Short-term hormonal contraceptives remain the most popular class of reversible contraceptives in the United States, despite the availability of longer-acting methods. Oral contraceptives (OCs), contraceptive patches, and contraceptive vaginal rings are extensively used not only because these methods are easy to initiate but also because their ongoing use remains under the control of the woman herself and also provides her with a wide range of important noncontraceptive benefits.

Despite the more than 60 years of innovation that have made hormonal contraceptives safer, more tolerable, and more convenient, there has been room for improvement. Over the last few years, 4 new hormonal methods have been introduced, and each addresses different limitations and problems associated with the existing, often generic, products.

Compared with the traditional norethindrone pill (Micronor and generics), a new drospirenone progestin-only pill (POP) increases ovulation suppression, offers an improved cyclical bleeding profile, and relaxes the tight missed-pill rules that are usually associated with POPs.

In contrast with the older norelgestromin patch (Evra, Xulane), a new contraceptive transdermal patch significantly decreases total estrogen exposure and pairs its estrogen with levonorgestrel, the progestin associated with the lowest venous thromboembolism (VTE) risk in combined hormonal pills.

While existing combination OCs are formulated with the potent estrogen ethinyl estradiol (EE), a new combination pill, formulated with estetrol (E4) and drospirenone, introduces the first new estrogen (estetrol) used in a contraceptive in more than 50 years. Estetrol, a native estrogen, has selective tissue activity with minimal hepatic and breast impacts. Combined with drospirenone, this formulation offers women good contraceptive efficacy and bleeding patterns.

A new contraceptive vaginal ring introduces a new long-acting, specific progestin (segesterone acetate) and pairs it with low-dose EE. These hormones are packaged in a soft vaginal ring that provides up to 13 cycles of contraceptive protection (3 weeks in/1 week out) with one ring, greatly increasing convenience for women.

Each of these new products represents important incremental improvement over existing options.

Continue to: 1. The drospirenone-only OC...

The new POP with drospirenone 4 mg (Slynd), which received US Food and Drug Administration (FDA) approval in 2019, is packaged in a 24/4 formulation (24 hormonally active tablets followed by 4 inactive tablets). This formulation results in more predictable bleeding than does the 0.35-mg norethindrone POP, which contains 28 hormonally active tablets in each pack. In the US clinical trials of drospirenone 4 mg, scheduled bleeding decreased from 81% in cycle 1 to 20% in cycle 13. Unscheduled spotting and bleeding decreased from 61% to 40% in the same timeframe. Notably, this bleeding pattern was well tolerated; only 0.4% of trial participants discontinued this drospirenone POP due to problems with irregular bleeding or amenorrhea.

In contrast to the continuous norethindrone POP, which is not sufficiently dosed to consistently suppress ovulation, the 4-mg daily dose of drospirenone in this new POP is higher than the 3 mg used in commonly prescribed combination OCs that contain EE and drospirenone. This results in a POP that has more consistent ovulation suppression. Because this drospirenone POP is appropriately dosed and based on a longer-acting progestin, it is more forgiving of inconsistent pill taking. Accordingly, the missed-pill rules for this pill are the same as with combination estrogen-progestin OCs.¹ The package labeling cites a first-year failure rate of 4%, but this includes unconfirmed pregnancies. The Pearl Index from the North American trials, based on confirmed pregnancies in nonbreastfeeding women, was 2.9.²

The package labeling for this drospirenone POP includes few contraindications. Conditions that preclude use include the US Medical Eligibility Criteria for contraception Category 4 condition (breast cancer in the last 5 years), renal impairment, and adrenal insufficiency. Other standard contraindications are listed in the prescribing information. Serum potassium levels should be checked (one time only) in the first cycle only for women who chronically use medications that could cause hyperkalemia, such as nonsteroidal anti-inflammatory drugs.

Given the ovulation suppression associated with this drospirenone POP, the safety of a progestin-only method, and the persistent popularity of OC pills, this pill should greatly increase the use of POPs beyond their traditional niche of postpartum and breastfeeding women. The advent of the drospirenone POP means that clinicians now have better options for women who have contraindications to estrogen and desire to control their own contraceptive use. It would be a logical consideration for over-the-counter accessibility.

2. Transdermal patch with ethinyl estradiol/levonorgestrel

The new EE/levonorgestrel transdermal contraceptive patch (Twirla) is soft and flexible, about the same size as other contraceptive patches, and contains EE 2.3 mg/levonorgestrel 2.6 mg. It provides total estrogen exposure that is similar to that of OCs with EE 30 µg and distinctly lower than estrogen levels seen with the original norelgestromin-containing patch or its 2 subsequent generic versions.³ This EE/levonorgestrel patch uses a new 5-layer drug delivery system that focuses the steroids for absorption beneath the patch; there is no peripheral spread of drug around the patch (FIGURE 1).

Transdermal patches offer the convenience of once-a-week dosing. One patch is used each week for 3 consecutive weeks followed by a patch-free week. Patches can be worn on the abdomen, buttock, or trunk (except breasts). Patches should not be placed consecutively on the same site; after a week’s rest, however, the first site can be reused. All transdermal contraceptive products are indicated for use only by women with a body mass index (BMI) <30 kg/m².⁴

While no head-to-head trials have compared this new lower-dose patch with older patches, each patch was compared against a standardized pill, so meaningful comparisons can be made.

In each case, the circulating estrogen levels associated with use of the EE/levonorgestrel patch were considerably lower than those of the comparator pill, while the older norelgestromin patch consistently delivered higher total estrogen levels than its 35-µg comparator pill (TABLE).³ Along these lines, no VTE events occurred in women in the clinical trial of the new patch among women with a BMI <30 kg/m².⁴

Women with a BMI <25 kg/m² experienced lower Pearl Index (PI) pregnancy rates (3.5%) compared with women with a BMI between 25 and 30 kg/m² (5.7%), according to clinical trial data cited in the package labeling. All the modern PI criteria were used to calculate these failure rates. Cycles in which no coitus occurred were excluded. Similarly, cycles in which another contraceptive method (for example, condoms) was added (even once) were excluded. Frequent pregnancy testing was done in the study centers and by the women at home. Bleeding patterns were well accepted; only 2.2% of study participants exited the study early due to menstrual disorders of any kind. Similarly, 3.1% of women discontinued use because of application site disorders. Women should be advised to press down on the patch edges after emerging from water exposure. Replacement patches are rapidly available from the manufacturer should permanent complete patch detachment occur.

Larger-scale phase 4 trials will be conducted to study the impact of this lower-dose patch on VTE rates.

Continue to: 3. A 1-year contraceptive vaginal ring...

The need to obtain new supplies every month or every 3 months contributes to high rates of contraceptive failure and unintended pregnancy among women using short-acting hormonal contraceptives (pills, patches, and vaginal rings).⁵ A woman-controlled contraceptive that would provide 1 year of protection against unintended pregnancy represents a step forward. A contraceptive vaginal ring (CVR) that releases the novel progestin segesterone acetate and EE provides woman-controlled contraception for up to 1 year. This CVR (Annovera) received FDA approval in 2018 and has been marketed in the United States since 2020.

The segesterone acetate/EE CVR is a soft, flexible ring that is opaque white in color and fabricated from nonbiodegradable silicone (FIGURE 2). The outside diameter is 5.6 cm, compared with the 5.4-cm outer diameter of the etonogestrel/EE vaginal ring (NuvaRing). The segesterone acetate/EE CVR has 2 channels: one releases segesterone acetate only and the other releases segesterone acetate and EE. In contrast with the etonogestrel/EE CVR, the segesterone acetate/EE CVR does not need to be refrigerated when stored.⁶

Continue to: 4. An OC with a novel estrogen...

4. An OC with a novel estrogen

Even as use of intrauterine devices and contraceptive implants continues to grow, OCs remain the reversible contraceptive most used by US women. While OCs have been widely studied and represent a safe method of contraception for most reproductive-age women, combination estrogen-progestin OCs are well recognized to increase the risk of VTE. Although the primary role of the progestin component of combination OCs is to suppress ovulation, estrogen is included in combination OCs to stimulate endometrial proliferation, thereby causing predictable bleeding. EE, the potent synthetic estrogen used in the great majority of current OC formulations, induces hepatic production of prothrombotic proteins while inhibiting synthesis of antithrombotic proteins. While the lower EE doses (10–35 µg) in today’s OC formulations are associated with a lower VTE risk than older OCs that contained higher doses of estrogen, VTE continues to represent the principal health risk associated with use of combination OCs. Accordingly, development of a combination OC that has less impact on risk of VTE would be appealing.

In April 2021, the FDA approved an OC formulation that combines 15 mg of the novel estrogen estetrol with 3 mg of drospirenone (Nextstellis). This dose of drospirenone is the same as that used in commonly prescribed EE/drospirenone OC formulations. Also known as E4, estetrol is a natural estrogen synthesized by the fetal liver. Plant-derived E4 is used in this new OC.

Depending on the tissue, E4 acts differently than other estrogens. Similar to other estrogens, E4 acts as an agonist on the nuclear receptor to produce beneficial effects in bone, vaginal mucosa, and heart.⁸ Unlike other estrogens, E4 inhibits proliferation of mammary gland cells and has a neutral impact on the liver.⁹

In contrast with EE, E4 is not inhibited by the liver’s P450 enzymes; accordingly, the risk of drug-drug interactions is reduced. Because E4 is primarily excreted through the urine and not through the biliary tract, the risk of gallstone formation may be lower than with an EE OC. Likewise, E4 has substantially less impact on triglycerides, which are increased with EE. Finally, because of E4’s reduced effect on the liver, the impact on clotting parameters is less than that observed with an OC formulated with EE.¹⁰ This latter observation raises the possibility that VTE risk is lower with the E4/drospirenone OC than an OC formulated with EE.

A 13-cycle phase 3 trial of the E4/drospirenone OC conducted in the United States and Canada enrolled 1,864 women aged 16 to 50 years, including 1,674 who were aged 16 to 35 years.¹¹ Among women in this latter age group, the PI was 2.65 per 100 woman-years. Bleeding/cycle control patterns were similar to those observed in recent trials of other combination contraceptives. Likewise, the proportion of trial participants who discontinued the study due to adverse effects was similar to or lower than that noted in recent trials of other combination contraceptives. Of particular note, no cases of VTE were noted among trial participants of any BMI, a finding which contrasts with recent phase 3 trials of other combination contraceptives. The result of this pivotal trial suggests that the theoretic advantages of E4 when used in a combination OC formulation may translate into a safer, effective, and well-tolerated contraceptive.

Refinements in hormonal contraceptives continue

The 4 new short-acting hormonal contraceptives we reviewed represent enhancements on existing pills, patches, and rings. We hope that, financially, women will have access to these innovative methods and, in particular, that third-party payers will facilitate women’s access to these enhanced short-acting hormonal contraceptives. ●

Short-term hormonal contraceptives remain the most popular class of reversible contraceptives in the United States, despite the availability of longer-acting methods. Oral contraceptives (OCs), contraceptive patches, and contraceptive vaginal rings are extensively used not only because these methods are easy to initiate but also because their ongoing use remains under the control of the woman herself and also provides her with a wide range of important noncontraceptive benefits.

Despite the more than 60 years of innovation that have made hormonal contraceptives safer, more tolerable, and more convenient, there has been room for improvement. Over the last few years, 4 new hormonal methods have been introduced, and each addresses different limitations and problems associated with the existing, often generic, products.

Compared with the traditional norethindrone pill (Micronor and generics), a new drospirenone progestin-only pill (POP) increases ovulation suppression, offers an improved cyclical bleeding profile, and relaxes the tight missed-pill rules that are usually associated with POPs.

In contrast with the older norelgestromin patch (Evra, Xulane), a new contraceptive transdermal patch significantly decreases total estrogen exposure and pairs its estrogen with levonorgestrel, the progestin associated with the lowest venous thromboembolism (VTE) risk in combined hormonal pills.

While existing combination OCs are formulated with the potent estrogen ethinyl estradiol (EE), a new combination pill, formulated with estetrol (E4) and drospirenone, introduces the first new estrogen (estetrol) used in a contraceptive in more than 50 years. Estetrol, a native estrogen, has selective tissue activity with minimal hepatic and breast impacts. Combined with drospirenone, this formulation offers women good contraceptive efficacy and bleeding patterns.

A new contraceptive vaginal ring introduces a new long-acting, specific progestin (segesterone acetate) and pairs it with low-dose EE. These hormones are packaged in a soft vaginal ring that provides up to 13 cycles of contraceptive protection (3 weeks in/1 week out) with one ring, greatly increasing convenience for women.

Each of these new products represents important incremental improvement over existing options.

Continue to: 1. The drospirenone-only OC...

The new POP with drospirenone 4 mg (Slynd), which received US Food and Drug Administration (FDA) approval in 2019, is packaged in a 24/4 formulation (24 hormonally active tablets followed by 4 inactive tablets). This formulation results in more predictable bleeding than does the 0.35-mg norethindrone POP, which contains 28 hormonally active tablets in each pack. In the US clinical trials of drospirenone 4 mg, scheduled bleeding decreased from 81% in cycle 1 to 20% in cycle 13. Unscheduled spotting and bleeding decreased from 61% to 40% in the same timeframe. Notably, this bleeding pattern was well tolerated; only 0.4% of trial participants discontinued this drospirenone POP due to problems with irregular bleeding or amenorrhea.

In contrast to the continuous norethindrone POP, which is not sufficiently dosed to consistently suppress ovulation, the 4-mg daily dose of drospirenone in this new POP is higher than the 3 mg used in commonly prescribed combination OCs that contain EE and drospirenone. This results in a POP that has more consistent ovulation suppression. Because this drospirenone POP is appropriately dosed and based on a longer-acting progestin, it is more forgiving of inconsistent pill taking. Accordingly, the missed-pill rules for this pill are the same as with combination estrogen-progestin OCs.¹ The package labeling cites a first-year failure rate of 4%, but this includes unconfirmed pregnancies. The Pearl Index from the North American trials, based on confirmed pregnancies in nonbreastfeeding women, was 2.9.²

The package labeling for this drospirenone POP includes few contraindications. Conditions that preclude use include the US Medical Eligibility Criteria for contraception Category 4 condition (breast cancer in the last 5 years), renal impairment, and adrenal insufficiency. Other standard contraindications are listed in the prescribing information. Serum potassium levels should be checked (one time only) in the first cycle only for women who chronically use medications that could cause hyperkalemia, such as nonsteroidal anti-inflammatory drugs.

Given the ovulation suppression associated with this drospirenone POP, the safety of a progestin-only method, and the persistent popularity of OC pills, this pill should greatly increase the use of POPs beyond their traditional niche of postpartum and breastfeeding women. The advent of the drospirenone POP means that clinicians now have better options for women who have contraindications to estrogen and desire to control their own contraceptive use. It would be a logical consideration for over-the-counter accessibility.

2. Transdermal patch with ethinyl estradiol/levonorgestrel

The new EE/levonorgestrel transdermal contraceptive patch (Twirla) is soft and flexible, about the same size as other contraceptive patches, and contains EE 2.3 mg/levonorgestrel 2.6 mg. It provides total estrogen exposure that is similar to that of OCs with EE 30 µg and distinctly lower than estrogen levels seen with the original norelgestromin-containing patch or its 2 subsequent generic versions.³ This EE/levonorgestrel patch uses a new 5-layer drug delivery system that focuses the steroids for absorption beneath the patch; there is no peripheral spread of drug around the patch (FIGURE 1).

Transdermal patches offer the convenience of once-a-week dosing. One patch is used each week for 3 consecutive weeks followed by a patch-free week. Patches can be worn on the abdomen, buttock, or trunk (except breasts). Patches should not be placed consecutively on the same site; after a week’s rest, however, the first site can be reused. All transdermal contraceptive products are indicated for use only by women with a body mass index (BMI) <30 kg/m².⁴

While no head-to-head trials have compared this new lower-dose patch with older patches, each patch was compared against a standardized pill, so meaningful comparisons can be made.

In each case, the circulating estrogen levels associated with use of the EE/levonorgestrel patch were considerably lower than those of the comparator pill, while the older norelgestromin patch consistently delivered higher total estrogen levels than its 35-µg comparator pill (TABLE).³ Along these lines, no VTE events occurred in women in the clinical trial of the new patch among women with a BMI <30 kg/m².⁴

Women with a BMI <25 kg/m² experienced lower Pearl Index (PI) pregnancy rates (3.5%) compared with women with a BMI between 25 and 30 kg/m² (5.7%), according to clinical trial data cited in the package labeling. All the modern PI criteria were used to calculate these failure rates. Cycles in which no coitus occurred were excluded. Similarly, cycles in which another contraceptive method (for example, condoms) was added (even once) were excluded. Frequent pregnancy testing was done in the study centers and by the women at home. Bleeding patterns were well accepted; only 2.2% of study participants exited the study early due to menstrual disorders of any kind. Similarly, 3.1% of women discontinued use because of application site disorders. Women should be advised to press down on the patch edges after emerging from water exposure. Replacement patches are rapidly available from the manufacturer should permanent complete patch detachment occur.

Larger-scale phase 4 trials will be conducted to study the impact of this lower-dose patch on VTE rates.

Continue to: 3. A 1-year contraceptive vaginal ring...

The need to obtain new supplies every month or every 3 months contributes to high rates of contraceptive failure and unintended pregnancy among women using short-acting hormonal contraceptives (pills, patches, and vaginal rings).⁵ A woman-controlled contraceptive that would provide 1 year of protection against unintended pregnancy represents a step forward. A contraceptive vaginal ring (CVR) that releases the novel progestin segesterone acetate and EE provides woman-controlled contraception for up to 1 year. This CVR (Annovera) received FDA approval in 2018 and has been marketed in the United States since 2020.

The segesterone acetate/EE CVR is a soft, flexible ring that is opaque white in color and fabricated from nonbiodegradable silicone (FIGURE 2). The outside diameter is 5.6 cm, compared with the 5.4-cm outer diameter of the etonogestrel/EE vaginal ring (NuvaRing). The segesterone acetate/EE CVR has 2 channels: one releases segesterone acetate only and the other releases segesterone acetate and EE. In contrast with the etonogestrel/EE CVR, the segesterone acetate/EE CVR does not need to be refrigerated when stored.⁶

Continue to: 4. An OC with a novel estrogen...

4. An OC with a novel estrogen

Even as use of intrauterine devices and contraceptive implants continues to grow, OCs remain the reversible contraceptive most used by US women. While OCs have been widely studied and represent a safe method of contraception for most reproductive-age women, combination estrogen-progestin OCs are well recognized to increase the risk of VTE. Although the primary role of the progestin component of combination OCs is to suppress ovulation, estrogen is included in combination OCs to stimulate endometrial proliferation, thereby causing predictable bleeding. EE, the potent synthetic estrogen used in the great majority of current OC formulations, induces hepatic production of prothrombotic proteins while inhibiting synthesis of antithrombotic proteins. While the lower EE doses (10–35 µg) in today’s OC formulations are associated with a lower VTE risk than older OCs that contained higher doses of estrogen, VTE continues to represent the principal health risk associated with use of combination OCs. Accordingly, development of a combination OC that has less impact on risk of VTE would be appealing.

In April 2021, the FDA approved an OC formulation that combines 15 mg of the novel estrogen estetrol with 3 mg of drospirenone (Nextstellis). This dose of drospirenone is the same as that used in commonly prescribed EE/drospirenone OC formulations. Also known as E4, estetrol is a natural estrogen synthesized by the fetal liver. Plant-derived E4 is used in this new OC.

Depending on the tissue, E4 acts differently than other estrogens. Similar to other estrogens, E4 acts as an agonist on the nuclear receptor to produce beneficial effects in bone, vaginal mucosa, and heart.⁸ Unlike other estrogens, E4 inhibits proliferation of mammary gland cells and has a neutral impact on the liver.⁹

In contrast with EE, E4 is not inhibited by the liver’s P450 enzymes; accordingly, the risk of drug-drug interactions is reduced. Because E4 is primarily excreted through the urine and not through the biliary tract, the risk of gallstone formation may be lower than with an EE OC. Likewise, E4 has substantially less impact on triglycerides, which are increased with EE. Finally, because of E4’s reduced effect on the liver, the impact on clotting parameters is less than that observed with an OC formulated with EE.¹⁰ This latter observation raises the possibility that VTE risk is lower with the E4/drospirenone OC than an OC formulated with EE.

A 13-cycle phase 3 trial of the E4/drospirenone OC conducted in the United States and Canada enrolled 1,864 women aged 16 to 50 years, including 1,674 who were aged 16 to 35 years.¹¹ Among women in this latter age group, the PI was 2.65 per 100 woman-years. Bleeding/cycle control patterns were similar to those observed in recent trials of other combination contraceptives. Likewise, the proportion of trial participants who discontinued the study due to adverse effects was similar to or lower than that noted in recent trials of other combination contraceptives. Of particular note, no cases of VTE were noted among trial participants of any BMI, a finding which contrasts with recent phase 3 trials of other combination contraceptives. The result of this pivotal trial suggests that the theoretic advantages of E4 when used in a combination OC formulation may translate into a safer, effective, and well-tolerated contraceptive.

Refinements in hormonal contraceptives continue

The 4 new short-acting hormonal contraceptives we reviewed represent enhancements on existing pills, patches, and rings. We hope that, financially, women will have access to these innovative methods and, in particular, that third-party payers will facilitate women’s access to these enhanced short-acting hormonal contraceptives. ●

Short-term hormonal contraceptives remain the most popular class of reversible contraceptives in the United States, despite the availability of longer-acting methods. Oral contraceptives (OCs), contraceptive patches, and contraceptive vaginal rings are extensively used not only because these methods are easy to initiate but also because their ongoing use remains under the control of the woman herself and also provides her with a wide range of important noncontraceptive benefits.

Despite the more than 60 years of innovation that have made hormonal contraceptives safer, more tolerable, and more convenient, there has been room for improvement. Over the last few years, 4 new hormonal methods have been introduced, and each addresses different limitations and problems associated with the existing, often generic, products.

Compared with the traditional norethindrone pill (Micronor and generics), a new drospirenone progestin-only pill (POP) increases ovulation suppression, offers an improved cyclical bleeding profile, and relaxes the tight missed-pill rules that are usually associated with POPs.

In contrast with the older norelgestromin patch (Evra, Xulane), a new contraceptive transdermal patch significantly decreases total estrogen exposure and pairs its estrogen with levonorgestrel, the progestin associated with the lowest venous thromboembolism (VTE) risk in combined hormonal pills.

While existing combination OCs are formulated with the potent estrogen ethinyl estradiol (EE), a new combination pill, formulated with estetrol (E4) and drospirenone, introduces the first new estrogen (estetrol) used in a contraceptive in more than 50 years. Estetrol, a native estrogen, has selective tissue activity with minimal hepatic and breast impacts. Combined with drospirenone, this formulation offers women good contraceptive efficacy and bleeding patterns.

A new contraceptive vaginal ring introduces a new long-acting, specific progestin (segesterone acetate) and pairs it with low-dose EE. These hormones are packaged in a soft vaginal ring that provides up to 13 cycles of contraceptive protection (3 weeks in/1 week out) with one ring, greatly increasing convenience for women.

Each of these new products represents important incremental improvement over existing options.

Continue to: 1. The drospirenone-only OC...

The new POP with drospirenone 4 mg (Slynd), which received US Food and Drug Administration (FDA) approval in 2019, is packaged in a 24/4 formulation (24 hormonally active tablets followed by 4 inactive tablets). This formulation results in more predictable bleeding than does the 0.35-mg norethindrone POP, which contains 28 hormonally active tablets in each pack. In the US clinical trials of drospirenone 4 mg, scheduled bleeding decreased from 81% in cycle 1 to 20% in cycle 13. Unscheduled spotting and bleeding decreased from 61% to 40% in the same timeframe. Notably, this bleeding pattern was well tolerated; only 0.4% of trial participants discontinued this drospirenone POP due to problems with irregular bleeding or amenorrhea.

In contrast to the continuous norethindrone POP, which is not sufficiently dosed to consistently suppress ovulation, the 4-mg daily dose of drospirenone in this new POP is higher than the 3 mg used in commonly prescribed combination OCs that contain EE and drospirenone. This results in a POP that has more consistent ovulation suppression. Because this drospirenone POP is appropriately dosed and based on a longer-acting progestin, it is more forgiving of inconsistent pill taking. Accordingly, the missed-pill rules for this pill are the same as with combination estrogen-progestin OCs.¹ The package labeling cites a first-year failure rate of 4%, but this includes unconfirmed pregnancies. The Pearl Index from the North American trials, based on confirmed pregnancies in nonbreastfeeding women, was 2.9.²

The package labeling for this drospirenone POP includes few contraindications. Conditions that preclude use include the US Medical Eligibility Criteria for contraception Category 4 condition (breast cancer in the last 5 years), renal impairment, and adrenal insufficiency. Other standard contraindications are listed in the prescribing information. Serum potassium levels should be checked (one time only) in the first cycle only for women who chronically use medications that could cause hyperkalemia, such as nonsteroidal anti-inflammatory drugs.

Given the ovulation suppression associated with this drospirenone POP, the safety of a progestin-only method, and the persistent popularity of OC pills, this pill should greatly increase the use of POPs beyond their traditional niche of postpartum and breastfeeding women. The advent of the drospirenone POP means that clinicians now have better options for women who have contraindications to estrogen and desire to control their own contraceptive use. It would be a logical consideration for over-the-counter accessibility.

2. Transdermal patch with ethinyl estradiol/levonorgestrel

The new EE/levonorgestrel transdermal contraceptive patch (Twirla) is soft and flexible, about the same size as other contraceptive patches, and contains EE 2.3 mg/levonorgestrel 2.6 mg. It provides total estrogen exposure that is similar to that of OCs with EE 30 µg and distinctly lower than estrogen levels seen with the original norelgestromin-containing patch or its 2 subsequent generic versions.³ This EE/levonorgestrel patch uses a new 5-layer drug delivery system that focuses the steroids for absorption beneath the patch; there is no peripheral spread of drug around the patch (FIGURE 1).

Transdermal patches offer the convenience of once-a-week dosing. One patch is used each week for 3 consecutive weeks followed by a patch-free week. Patches can be worn on the abdomen, buttock, or trunk (except breasts). Patches should not be placed consecutively on the same site; after a week’s rest, however, the first site can be reused. All transdermal contraceptive products are indicated for use only by women with a body mass index (BMI) <30 kg/m².⁴

While no head-to-head trials have compared this new lower-dose patch with older patches, each patch was compared against a standardized pill, so meaningful comparisons can be made.

In each case, the circulating estrogen levels associated with use of the EE/levonorgestrel patch were considerably lower than those of the comparator pill, while the older norelgestromin patch consistently delivered higher total estrogen levels than its 35-µg comparator pill (TABLE).³ Along these lines, no VTE events occurred in women in the clinical trial of the new patch among women with a BMI <30 kg/m².⁴

Women with a BMI <25 kg/m² experienced lower Pearl Index (PI) pregnancy rates (3.5%) compared with women with a BMI between 25 and 30 kg/m² (5.7%), according to clinical trial data cited in the package labeling. All the modern PI criteria were used to calculate these failure rates. Cycles in which no coitus occurred were excluded. Similarly, cycles in which another contraceptive method (for example, condoms) was added (even once) were excluded. Frequent pregnancy testing was done in the study centers and by the women at home. Bleeding patterns were well accepted; only 2.2% of study participants exited the study early due to menstrual disorders of any kind. Similarly, 3.1% of women discontinued use because of application site disorders. Women should be advised to press down on the patch edges after emerging from water exposure. Replacement patches are rapidly available from the manufacturer should permanent complete patch detachment occur.

Larger-scale phase 4 trials will be conducted to study the impact of this lower-dose patch on VTE rates.

Continue to: 3. A 1-year contraceptive vaginal ring...

The need to obtain new supplies every month or every 3 months contributes to high rates of contraceptive failure and unintended pregnancy among women using short-acting hormonal contraceptives (pills, patches, and vaginal rings).⁵ A woman-controlled contraceptive that would provide 1 year of protection against unintended pregnancy represents a step forward. A contraceptive vaginal ring (CVR) that releases the novel progestin segesterone acetate and EE provides woman-controlled contraception for up to 1 year. This CVR (Annovera) received FDA approval in 2018 and has been marketed in the United States since 2020.

The segesterone acetate/EE CVR is a soft, flexible ring that is opaque white in color and fabricated from nonbiodegradable silicone (FIGURE 2). The outside diameter is 5.6 cm, compared with the 5.4-cm outer diameter of the etonogestrel/EE vaginal ring (NuvaRing). The segesterone acetate/EE CVR has 2 channels: one releases segesterone acetate only and the other releases segesterone acetate and EE. In contrast with the etonogestrel/EE CVR, the segesterone acetate/EE CVR does not need to be refrigerated when stored.⁶

Continue to: 4. An OC with a novel estrogen...

4. An OC with a novel estrogen

Even as use of intrauterine devices and contraceptive implants continues to grow, OCs remain the reversible contraceptive most used by US women. While OCs have been widely studied and represent a safe method of contraception for most reproductive-age women, combination estrogen-progestin OCs are well recognized to increase the risk of VTE. Although the primary role of the progestin component of combination OCs is to suppress ovulation, estrogen is included in combination OCs to stimulate endometrial proliferation, thereby causing predictable bleeding. EE, the potent synthetic estrogen used in the great majority of current OC formulations, induces hepatic production of prothrombotic proteins while inhibiting synthesis of antithrombotic proteins. While the lower EE doses (10–35 µg) in today’s OC formulations are associated with a lower VTE risk than older OCs that contained higher doses of estrogen, VTE continues to represent the principal health risk associated with use of combination OCs. Accordingly, development of a combination OC that has less impact on risk of VTE would be appealing.

In April 2021, the FDA approved an OC formulation that combines 15 mg of the novel estrogen estetrol with 3 mg of drospirenone (Nextstellis). This dose of drospirenone is the same as that used in commonly prescribed EE/drospirenone OC formulations. Also known as E4, estetrol is a natural estrogen synthesized by the fetal liver. Plant-derived E4 is used in this new OC.

Depending on the tissue, E4 acts differently than other estrogens. Similar to other estrogens, E4 acts as an agonist on the nuclear receptor to produce beneficial effects in bone, vaginal mucosa, and heart.⁸ Unlike other estrogens, E4 inhibits proliferation of mammary gland cells and has a neutral impact on the liver.⁹

In contrast with EE, E4 is not inhibited by the liver’s P450 enzymes; accordingly, the risk of drug-drug interactions is reduced. Because E4 is primarily excreted through the urine and not through the biliary tract, the risk of gallstone formation may be lower than with an EE OC. Likewise, E4 has substantially less impact on triglycerides, which are increased with EE. Finally, because of E4’s reduced effect on the liver, the impact on clotting parameters is less than that observed with an OC formulated with EE.¹⁰ This latter observation raises the possibility that VTE risk is lower with the E4/drospirenone OC than an OC formulated with EE.

A 13-cycle phase 3 trial of the E4/drospirenone OC conducted in the United States and Canada enrolled 1,864 women aged 16 to 50 years, including 1,674 who were aged 16 to 35 years.¹¹ Among women in this latter age group, the PI was 2.65 per 100 woman-years. Bleeding/cycle control patterns were similar to those observed in recent trials of other combination contraceptives. Likewise, the proportion of trial participants who discontinued the study due to adverse effects was similar to or lower than that noted in recent trials of other combination contraceptives. Of particular note, no cases of VTE were noted among trial participants of any BMI, a finding which contrasts with recent phase 3 trials of other combination contraceptives. The result of this pivotal trial suggests that the theoretic advantages of E4 when used in a combination OC formulation may translate into a safer, effective, and well-tolerated contraceptive.

Refinements in hormonal contraceptives continue

The 4 new short-acting hormonal contraceptives we reviewed represent enhancements on existing pills, patches, and rings. We hope that, financially, women will have access to these innovative methods and, in particular, that third-party payers will facilitate women’s access to these enhanced short-acting hormonal contraceptives. ●

Uterine fibroids are a common condition that affects up to 80% of reproductive-age women.¹ Many women with fibroids are asymptomatic, but some experience symptoms that profoundly disrupt their lives, such as abnormal uterine bleeding, pelvic pain, and bulk symptoms including bladder and bowel dysfunction.² Although hysterectomy remains the definitive treatment for symptomatic fibroids, many women seek more conservative management. Hormonal treatment, such as contraceptive pills, levonorgestrel intrauterine devices, and gonadotropin-releasing hormone analogs, can improve heavy menstrual bleeding and anemia.³ Additionally, uterine artery embolization is a nonsurgical uterine-sparing option. However, these treatments are not ideal options for women who want to conceive.⁴ For reproductive-age women who desire future fertility, myomectomy has been the standard of care. Unfortunately, by the time patients become symptomatic from their fibroids and seek care, they may have numerous and/or sizable fibroids that result in high blood loss, surgical scarring, and the probable need for cesarean delivery (FIGURES 1 and 2).⁵

For patients who desire future conception, treatment of uterine fibroids poses a challenge in which optimizing symptomatic improvement must be balanced with protecting fertility and improving reproductive outcomes. In recent years, high-intensity focused ultrasound (FUS) and radiofrequency ablation (RFA) have been presented as less invasive, uterine-sparing alternatives for fibroid treatment that could potentially provide that balance.

In this article, we briefly review the available uterine-sparing fibroid treatments and their outcomes and then focus specifically on RFA as a possible option to address the fibroid treatment gap for reproductive-age women who desire future fertility.

Overview of uterine-sparing treatments

Two approaches can be pursued for conservative fibroid treatment: fibroid removal and fibroid necrosis (TABLE 1). We focus this review on outcomes for the most widely available of these treatments.

Myomectomy

For reproductive-age women who wish to conceive, surgical removal of fibroids has been the standard of care for symptomatic patients. Myomectomy can be performed via laparotomy, laparoscopy, robot-assisted surgery, and hysteroscopy. The mode of surgery depends on the fibroid characteristics (size, number, and location) and the surgeon’s skill set. Although some variation in the data exists, overall surgical outcomes, including blood loss, postoperative pain, and length of stay, are generally more favorable for minimally invasive approaches compared with laparotomy, with no significant differences in fibroid recurrence or reproductive outcomes (live birth rate, miscarriage rate, and cesarean delivery rate).⁶ This comes at the expense of longer operating time compared with laparotomy.⁷

While improvement in abnormal uterine bleeding and pelvic pain is reliable and usually significant after myomectomy,⁸ reproductive implications also warrant consideration. Myomectomy is associated with subsequent uterine adhesion formation, with some studies finding rates up to 83% to 94% depending on the surgical approach and the number of fibroids removed.⁹ These adhesions can impair fertility success.¹⁰ Myomectomy also is associated with high rates of cesarean delivery,⁵ invasive placentation (including placenta accreta spectrum),¹¹ and uterine rupture.¹² While the latter 2 complications are rare, they potentially can be catastrophic and should be kept in mind.

Continue to: Uterine artery embolization...

Uterine artery embolization

As a nonsurgical alternative to myomectomy, uterine artery embolization (UAE) has gained popularity as a conservative fibroid treatment since it was introduced in 1995. It is less invasive than myomectomy, a benefit for patients who decline surgery or are not ideal candidates for surgery.¹³ Evidence suggests that UAE produces overall comparable symptomatic improvement compared with myomectomy. One study showed no significant differences between UAE and myomectomy in terms of decreased uterine volume and menstrual bleeding at 6-month follow-up.¹⁴ In terms of long-term outcomes, a large multicenter study showed no significant difference in reintervention rates at 7 years posttreatment between UAE and myomectomy (8.9% vs 11.2%, respectively), and a significantly higher rate of improved menstrual bleeding with UAE (79.4% vs 49.5%), with no significant difference in bulk symptoms.¹⁵ The evidence is not entirely consistent, as other studies have shown increased rates of reintervention with UAE,^8,16 but overall UAE can be considered a reasonable alternative to myomectomy in terms of symptomatic improvement.

Pregnancy outcomes data, however, are mixed, and UAE often is not recommended for patients with future fertility plans. In a large review article that compared minimally invasive fibroid treatments, UAE was associated with a lower live birth rate compared with myomectomy and ablation techniques (60.6% for UAE, 75.6% for myomectomy, and 70.5% for ablation), and it also had the highest rate of miscarriage (27.4% for UAE vs 19.0% for myomectomy and 11.9% for ablation) and abnormal placentation.¹² While UAE remains an effective option for conservative treatment of symptomatic fibroids, it appears to have a worse impact on reproductive outcomes compared with myomectomy or ablative treatments.

Magnetic resonance–guided focused ultrasound

Emerging as a noninvasive ablation treatment for fibroids, magnetic resonance–guided focused ultrasound (MRgFUS) uses targeted high-intensity ultrasound pulses to cause thermal and mechanical fibroid tissue disruption.¹⁷ Data on this treatment are less robust given that it is newer than myomectomy or UAE. One study showed a decrease in fibroid volume by 12% at 1 month and 15% at 6 months, with 37.1% of patients reporting marked improvement in symptoms and an additional 31.4% reporting partial improvement; these are modest numbers compared with other treatment approaches.¹⁸ Another study showed more favorable outcomes, with 74% of patients reporting clinically significant improvement in bleeding and pain, and a 12.7% reintervention rate, comparable to rates reported for UAE and myomectomy.¹⁹

Because MRgFUS is newer than UAE or myomectomy, data are limited in terms of pregnancy outcomes, particularly because initial trials excluded women with future fertility plans due to lack of knowledge regarding pregnancy safety. A follow-up case series from one of the initial studies showed a decreased miscarriage rate compared with UAE, a term delivery rate of 93%, and a similar rate of abnormal placentation.²⁰ A more recent systematic review concluded that reproductive outcomes were noninferior to myomectomy; however, the outcomes data for MRgFUS were heterogenous and many studies did not report pregnancy rates.²¹

Overall, MRgFUS appears to be an effective alternative approach for symptomatic fibroids, but the long-term data are not yet conclusive and information on pregnancy safety and outcomes largely is lacking. Recent reviews have not made definitive statements on whether MRgFUS should be offered to patients desiring future fertility.

Continue to: RFA is a promising option...

RFA is a promising option

RFA is another noninvasive fibroid ablation technique that has become more widely adopted in recent years. Here, we describe the basics of RFA and its impact on fibroid symptoms and reproductive outcomes.

The RFA technique

RFA uses hyperthermic energy from a handpiece and real-time ultrasound for targeted coagulative necrosis via a laparoscopic (L-RFA) or transcervical (TC-RFA) approach.²² A comparison between the 2 devices available on the market in the United States is shown in TABLE 2. Ultrasound guidance allows placement of radiofrequency needles directly into the fibroid to target local treatment to the fibroid tissue only. Once the fibroid undergoes coagulative necrosis, the process of fibroid resorption and volume reduction occurs over weeks to months, depending on the fibroid size.

Impact on fibroid symptoms

Both laparoscopic and transcervical RFA approaches have shown significant decreases in pelvic pain and heavy menstrual bleeding associated with fibroids and a low reintervention rate that emphasizes the durability of their impact.

A feasibility and safety study of a TC-RFA device prior to the primary clinical trials found only a 4.3% reintervention rate in the first 18 months postprocedure.²³ The pivotal clinical trial of a TC-RFA device that followed also reported a low 5.5% reintervention rate in the first 24 months postprocedure, with significant improvement in health-related quality-of-life and high patient satisfaction²⁴ (results shown in TABLE 2, along with trial results for an L-RFA device). A subsequent study of TC-RFA reported that symptomatic improvement persisted at 3-year follow-up, with a 9.2% reintervention rate comparable to existing fibroid treatments such as myomectomy and UAE.²⁵ The original L-RFA trial also has shown similar positive results at 2-year follow-up, with a low reintervention rate of 4.8% after treatment, and similar patient satisfaction and quality-of-life improvements as TC-RFA.²⁶ While long-term data are limited by only recent approval by the Food and Drug Administration (FDA) of a TC-RFA device in 2018, one study followed clinical trial patients for a mean duration of 64 months. This study found no surgical reinterventions in the first 3.5 years posttreatment and a persistent reduction in fibroid symptoms from baseline 64.9 points to 27.6 points, as assessed by a validated symptom severity scale (out of 100 points).²⁷ Similar improvements in health-related quality-of life-were also found to persist for years posttreatment.⁴

In a large systematic review that compared L-RFA, MRgFUS, UAE, and myomectomy, L-RFA had similar improvement rates in quality-of-life and symptom severity scores compared with myomectomy, with no significant difference in reintervention rates.²⁸ This review also noted minimal heterogeneity among RFA meta-analyses data in contrast to significant heterogeneity among UAE and myomectomy data.

Reproductive outcomes

Similar to MRgFUS, the initial studies of RFA devices largely excluded women with future fertility plans, as data on safety were lacking. However, many RFA devices are now on the market across the globe, and subsequent pregnancies have been tracked and reported.

A large case series that included clinical trials and commercial settings reported a miscarriage rate (13.3%) similar to that of the general obstetric population and no cases of uterine rupture, invasive placentation, preterm delivery, or placental abruption.²⁹ Other case series have reported live birth rates similar those with myomectomy, and safe and favorable pregnancy outcomes with RFA have been supported by larger systematic reviews of all ablation techniques.¹²

Continue to: Uterine impact...

Uterine impact

One study of TC-RFA patients showed a greater than 65% reduction in fibroid volume (with a 90% reduction in fibroid volume for fibroids larger than 6 cm prior to RFA), and 54% of patients reported complete resolution of symptoms, with another 36% reporting decreased symptoms.³⁰ Similar decreases in fibroid volume, ranging from 65% to 84%, have been reported in numerous follow-up studies, with significant decreases in bleeding and pain in 78% to 88% of patients.^23,31-33 Additionally, a large secondary analysis of a TC-RFA clinical trial showed that patients did not have any significant decrease in uterine wall thickness or integrity on follow-up with magnetic resonance imaging compared with baseline measurements, and they did not have any new myometrial scars (assessed as nonperfused linear areas).²²

As with other ablation techniques, most data on RFA pregnancy outcomes come from case series, and further research and evaluation are needed. Existing studies, however, have demonstrated promising aspects of RFA that argue its usefulness in women with fertility plans.

A prospective trial that evaluated intrauterine adhesion formation with use of a TC-RFA device found no new adhesions on 6-week follow-up hysteroscopy compared with baseline pre-RFA hysteroscopy.³⁴ Because intrauterine adhesion formation and uterine rupture are both significant concerns with other uterine-sparing fibroid treatment approaches such as myomectomy, these findings suggest that RFA may be a better alternative for women who are planning future pregnancies, as they may have increased fertility success and decreased catastrophic complications.

The consensus is growing that RFA is a safe and effective option for women who desire minimally invasive fibroid treatment and want to preserve fertility.

Unique benefits of RFA

In this article, we highlight RFA as an emerging treatment option for fibroid management, particularly for women who desire a uterine-sparing approach to preserve their reproductive options. Although myomectomy has been the standard of care for many years, with UAE as the alternative nonsurgical treatment, neither approach provides the best balance between symptomatic improvement and reproductive outcomes, and neither is without pregnancy risks. In addition, many women with symptomatic fibroids do not desire future conception but decline fibroid removal for religious or personal reasons. RFA offers these women an alternative minimally invasive option for uterine-sparing fibroid treatment.

RFA presents a unique “incision-free” fibroid treatment that is truly minimally invasive. This technique minimizes the risks associated with myomectomy, such as intra-abdominal adhesions, intrauterine adhesions (Asherman syndrome), need for cesarean delivery, and pregnancy complications such as uterine rupture or invasive placentation. Furthermore, the evolution of an RFA transcervical approach has enabled treatment with no abdominal or uterine incisions, thus offering all the above reproductive benefits as well as the operative benefits of a faster recovery, less pain, and less risk of intraperitoneal surgical complications.

While many women desire uterine-sparing fibroid treatment even without future fertility plans, the larger question is whether we should treat fibroids more strategically for women who desire future fertility. Myomectomy and UAE are effective and reliable in terms of fibroid symptomatic improvement, but RFA promises more beneficial reproductive outcomes. The ability to avoid uterine myometrial incisions and still attain significant symptomatic improvement should be prioritized in these patients.

Currently, RFA is not approved by the FDA as a fertility-enabling treatment, and these patients have been largely excluded from RFA studies. However, the reproductive-age patient who desires future conception may benefit most from RFA. Furthermore, RFA technology also could address the gap in uterine-sparing treatment for reproductive-age women with adenomyosis. Although a complete review of adenomyosis treatment is beyond the scope of this article, recent studies show that RFA produces similar improvement in both uterine volume and symptom severity in women with adenomyosis.^35-37 ●

Uterine fibroids are a common condition that affects up to 80% of reproductive-age women.¹ Many women with fibroids are asymptomatic, but some experience symptoms that profoundly disrupt their lives, such as abnormal uterine bleeding, pelvic pain, and bulk symptoms including bladder and bowel dysfunction.² Although hysterectomy remains the definitive treatment for symptomatic fibroids, many women seek more conservative management. Hormonal treatment, such as contraceptive pills, levonorgestrel intrauterine devices, and gonadotropin-releasing hormone analogs, can improve heavy menstrual bleeding and anemia.³ Additionally, uterine artery embolization is a nonsurgical uterine-sparing option. However, these treatments are not ideal options for women who want to conceive.⁴ For reproductive-age women who desire future fertility, myomectomy has been the standard of care. Unfortunately, by the time patients become symptomatic from their fibroids and seek care, they may have numerous and/or sizable fibroids that result in high blood loss, surgical scarring, and the probable need for cesarean delivery (FIGURES 1 and 2).⁵

For patients who desire future conception, treatment of uterine fibroids poses a challenge in which optimizing symptomatic improvement must be balanced with protecting fertility and improving reproductive outcomes. In recent years, high-intensity focused ultrasound (FUS) and radiofrequency ablation (RFA) have been presented as less invasive, uterine-sparing alternatives for fibroid treatment that could potentially provide that balance.

In this article, we briefly review the available uterine-sparing fibroid treatments and their outcomes and then focus specifically on RFA as a possible option to address the fibroid treatment gap for reproductive-age women who desire future fertility.

Overview of uterine-sparing treatments

Two approaches can be pursued for conservative fibroid treatment: fibroid removal and fibroid necrosis (TABLE 1). We focus this review on outcomes for the most widely available of these treatments.

Myomectomy

For reproductive-age women who wish to conceive, surgical removal of fibroids has been the standard of care for symptomatic patients. Myomectomy can be performed via laparotomy, laparoscopy, robot-assisted surgery, and hysteroscopy. The mode of surgery depends on the fibroid characteristics (size, number, and location) and the surgeon’s skill set. Although some variation in the data exists, overall surgical outcomes, including blood loss, postoperative pain, and length of stay, are generally more favorable for minimally invasive approaches compared with laparotomy, with no significant differences in fibroid recurrence or reproductive outcomes (live birth rate, miscarriage rate, and cesarean delivery rate).⁶ This comes at the expense of longer operating time compared with laparotomy.⁷

While improvement in abnormal uterine bleeding and pelvic pain is reliable and usually significant after myomectomy,⁸ reproductive implications also warrant consideration. Myomectomy is associated with subsequent uterine adhesion formation, with some studies finding rates up to 83% to 94% depending on the surgical approach and the number of fibroids removed.⁹ These adhesions can impair fertility success.¹⁰ Myomectomy also is associated with high rates of cesarean delivery,⁵ invasive placentation (including placenta accreta spectrum),¹¹ and uterine rupture.¹² While the latter 2 complications are rare, they potentially can be catastrophic and should be kept in mind.

Continue to: Uterine artery embolization...

Uterine artery embolization

As a nonsurgical alternative to myomectomy, uterine artery embolization (UAE) has gained popularity as a conservative fibroid treatment since it was introduced in 1995. It is less invasive than myomectomy, a benefit for patients who decline surgery or are not ideal candidates for surgery.¹³ Evidence suggests that UAE produces overall comparable symptomatic improvement compared with myomectomy. One study showed no significant differences between UAE and myomectomy in terms of decreased uterine volume and menstrual bleeding at 6-month follow-up.¹⁴ In terms of long-term outcomes, a large multicenter study showed no significant difference in reintervention rates at 7 years posttreatment between UAE and myomectomy (8.9% vs 11.2%, respectively), and a significantly higher rate of improved menstrual bleeding with UAE (79.4% vs 49.5%), with no significant difference in bulk symptoms.¹⁵ The evidence is not entirely consistent, as other studies have shown increased rates of reintervention with UAE,^8,16 but overall UAE can be considered a reasonable alternative to myomectomy in terms of symptomatic improvement.

Pregnancy outcomes data, however, are mixed, and UAE often is not recommended for patients with future fertility plans. In a large review article that compared minimally invasive fibroid treatments, UAE was associated with a lower live birth rate compared with myomectomy and ablation techniques (60.6% for UAE, 75.6% for myomectomy, and 70.5% for ablation), and it also had the highest rate of miscarriage (27.4% for UAE vs 19.0% for myomectomy and 11.9% for ablation) and abnormal placentation.¹² While UAE remains an effective option for conservative treatment of symptomatic fibroids, it appears to have a worse impact on reproductive outcomes compared with myomectomy or ablative treatments.

Magnetic resonance–guided focused ultrasound

Emerging as a noninvasive ablation treatment for fibroids, magnetic resonance–guided focused ultrasound (MRgFUS) uses targeted high-intensity ultrasound pulses to cause thermal and mechanical fibroid tissue disruption.¹⁷ Data on this treatment are less robust given that it is newer than myomectomy or UAE. One study showed a decrease in fibroid volume by 12% at 1 month and 15% at 6 months, with 37.1% of patients reporting marked improvement in symptoms and an additional 31.4% reporting partial improvement; these are modest numbers compared with other treatment approaches.¹⁸ Another study showed more favorable outcomes, with 74% of patients reporting clinically significant improvement in bleeding and pain, and a 12.7% reintervention rate, comparable to rates reported for UAE and myomectomy.¹⁹

Because MRgFUS is newer than UAE or myomectomy, data are limited in terms of pregnancy outcomes, particularly because initial trials excluded women with future fertility plans due to lack of knowledge regarding pregnancy safety. A follow-up case series from one of the initial studies showed a decreased miscarriage rate compared with UAE, a term delivery rate of 93%, and a similar rate of abnormal placentation.²⁰ A more recent systematic review concluded that reproductive outcomes were noninferior to myomectomy; however, the outcomes data for MRgFUS were heterogenous and many studies did not report pregnancy rates.²¹

Overall, MRgFUS appears to be an effective alternative approach for symptomatic fibroids, but the long-term data are not yet conclusive and information on pregnancy safety and outcomes largely is lacking. Recent reviews have not made definitive statements on whether MRgFUS should be offered to patients desiring future fertility.

Continue to: RFA is a promising option...

RFA is a promising option

RFA is another noninvasive fibroid ablation technique that has become more widely adopted in recent years. Here, we describe the basics of RFA and its impact on fibroid symptoms and reproductive outcomes.

The RFA technique

RFA uses hyperthermic energy from a handpiece and real-time ultrasound for targeted coagulative necrosis via a laparoscopic (L-RFA) or transcervical (TC-RFA) approach.²² A comparison between the 2 devices available on the market in the United States is shown in TABLE 2. Ultrasound guidance allows placement of radiofrequency needles directly into the fibroid to target local treatment to the fibroid tissue only. Once the fibroid undergoes coagulative necrosis, the process of fibroid resorption and volume reduction occurs over weeks to months, depending on the fibroid size.

Impact on fibroid symptoms

Both laparoscopic and transcervical RFA approaches have shown significant decreases in pelvic pain and heavy menstrual bleeding associated with fibroids and a low reintervention rate that emphasizes the durability of their impact.

A feasibility and safety study of a TC-RFA device prior to the primary clinical trials found only a 4.3% reintervention rate in the first 18 months postprocedure.²³ The pivotal clinical trial of a TC-RFA device that followed also reported a low 5.5% reintervention rate in the first 24 months postprocedure, with significant improvement in health-related quality-of-life and high patient satisfaction²⁴ (results shown in TABLE 2, along with trial results for an L-RFA device). A subsequent study of TC-RFA reported that symptomatic improvement persisted at 3-year follow-up, with a 9.2% reintervention rate comparable to existing fibroid treatments such as myomectomy and UAE.²⁵ The original L-RFA trial also has shown similar positive results at 2-year follow-up, with a low reintervention rate of 4.8% after treatment, and similar patient satisfaction and quality-of-life improvements as TC-RFA.²⁶ While long-term data are limited by only recent approval by the Food and Drug Administration (FDA) of a TC-RFA device in 2018, one study followed clinical trial patients for a mean duration of 64 months. This study found no surgical reinterventions in the first 3.5 years posttreatment and a persistent reduction in fibroid symptoms from baseline 64.9 points to 27.6 points, as assessed by a validated symptom severity scale (out of 100 points).²⁷ Similar improvements in health-related quality-of life-were also found to persist for years posttreatment.⁴

In a large systematic review that compared L-RFA, MRgFUS, UAE, and myomectomy, L-RFA had similar improvement rates in quality-of-life and symptom severity scores compared with myomectomy, with no significant difference in reintervention rates.²⁸ This review also noted minimal heterogeneity among RFA meta-analyses data in contrast to significant heterogeneity among UAE and myomectomy data.

Reproductive outcomes

Similar to MRgFUS, the initial studies of RFA devices largely excluded women with future fertility plans, as data on safety were lacking. However, many RFA devices are now on the market across the globe, and subsequent pregnancies have been tracked and reported.

A large case series that included clinical trials and commercial settings reported a miscarriage rate (13.3%) similar to that of the general obstetric population and no cases of uterine rupture, invasive placentation, preterm delivery, or placental abruption.²⁹ Other case series have reported live birth rates similar those with myomectomy, and safe and favorable pregnancy outcomes with RFA have been supported by larger systematic reviews of all ablation techniques.¹²

Continue to: Uterine impact...

Uterine impact

One study of TC-RFA patients showed a greater than 65% reduction in fibroid volume (with a 90% reduction in fibroid volume for fibroids larger than 6 cm prior to RFA), and 54% of patients reported complete resolution of symptoms, with another 36% reporting decreased symptoms.³⁰ Similar decreases in fibroid volume, ranging from 65% to 84%, have been reported in numerous follow-up studies, with significant decreases in bleeding and pain in 78% to 88% of patients.^23,31-33 Additionally, a large secondary analysis of a TC-RFA clinical trial showed that patients did not have any significant decrease in uterine wall thickness or integrity on follow-up with magnetic resonance imaging compared with baseline measurements, and they did not have any new myometrial scars (assessed as nonperfused linear areas).²²

As with other ablation techniques, most data on RFA pregnancy outcomes come from case series, and further research and evaluation are needed. Existing studies, however, have demonstrated promising aspects of RFA that argue its usefulness in women with fertility plans.

A prospective trial that evaluated intrauterine adhesion formation with use of a TC-RFA device found no new adhesions on 6-week follow-up hysteroscopy compared with baseline pre-RFA hysteroscopy.³⁴ Because intrauterine adhesion formation and uterine rupture are both significant concerns with other uterine-sparing fibroid treatment approaches such as myomectomy, these findings suggest that RFA may be a better alternative for women who are planning future pregnancies, as they may have increased fertility success and decreased catastrophic complications.

The consensus is growing that RFA is a safe and effective option for women who desire minimally invasive fibroid treatment and want to preserve fertility.

Unique benefits of RFA

In this article, we highlight RFA as an emerging treatment option for fibroid management, particularly for women who desire a uterine-sparing approach to preserve their reproductive options. Although myomectomy has been the standard of care for many years, with UAE as the alternative nonsurgical treatment, neither approach provides the best balance between symptomatic improvement and reproductive outcomes, and neither is without pregnancy risks. In addition, many women with symptomatic fibroids do not desire future conception but decline fibroid removal for religious or personal reasons. RFA offers these women an alternative minimally invasive option for uterine-sparing fibroid treatment.

RFA presents a unique “incision-free” fibroid treatment that is truly minimally invasive. This technique minimizes the risks associated with myomectomy, such as intra-abdominal adhesions, intrauterine adhesions (Asherman syndrome), need for cesarean delivery, and pregnancy complications such as uterine rupture or invasive placentation. Furthermore, the evolution of an RFA transcervical approach has enabled treatment with no abdominal or uterine incisions, thus offering all the above reproductive benefits as well as the operative benefits of a faster recovery, less pain, and less risk of intraperitoneal surgical complications.

While many women desire uterine-sparing fibroid treatment even without future fertility plans, the larger question is whether we should treat fibroids more strategically for women who desire future fertility. Myomectomy and UAE are effective and reliable in terms of fibroid symptomatic improvement, but RFA promises more beneficial reproductive outcomes. The ability to avoid uterine myometrial incisions and still attain significant symptomatic improvement should be prioritized in these patients.

Currently, RFA is not approved by the FDA as a fertility-enabling treatment, and these patients have been largely excluded from RFA studies. However, the reproductive-age patient who desires future conception may benefit most from RFA. Furthermore, RFA technology also could address the gap in uterine-sparing treatment for reproductive-age women with adenomyosis. Although a complete review of adenomyosis treatment is beyond the scope of this article, recent studies show that RFA produces similar improvement in both uterine volume and symptom severity in women with adenomyosis.^35-37 ●

Uterine fibroids are a common condition that affects up to 80% of reproductive-age women.¹ Many women with fibroids are asymptomatic, but some experience symptoms that profoundly disrupt their lives, such as abnormal uterine bleeding, pelvic pain, and bulk symptoms including bladder and bowel dysfunction.² Although hysterectomy remains the definitive treatment for symptomatic fibroids, many women seek more conservative management. Hormonal treatment, such as contraceptive pills, levonorgestrel intrauterine devices, and gonadotropin-releasing hormone analogs, can improve heavy menstrual bleeding and anemia.³ Additionally, uterine artery embolization is a nonsurgical uterine-sparing option. However, these treatments are not ideal options for women who want to conceive.⁴ For reproductive-age women who desire future fertility, myomectomy has been the standard of care. Unfortunately, by the time patients become symptomatic from their fibroids and seek care, they may have numerous and/or sizable fibroids that result in high blood loss, surgical scarring, and the probable need for cesarean delivery (FIGURES 1 and 2).⁵

For patients who desire future conception, treatment of uterine fibroids poses a challenge in which optimizing symptomatic improvement must be balanced with protecting fertility and improving reproductive outcomes. In recent years, high-intensity focused ultrasound (FUS) and radiofrequency ablation (RFA) have been presented as less invasive, uterine-sparing alternatives for fibroid treatment that could potentially provide that balance.

In this article, we briefly review the available uterine-sparing fibroid treatments and their outcomes and then focus specifically on RFA as a possible option to address the fibroid treatment gap for reproductive-age women who desire future fertility.

Overview of uterine-sparing treatments

Two approaches can be pursued for conservative fibroid treatment: fibroid removal and fibroid necrosis (TABLE 1). We focus this review on outcomes for the most widely available of these treatments.

Myomectomy

For reproductive-age women who wish to conceive, surgical removal of fibroids has been the standard of care for symptomatic patients. Myomectomy can be performed via laparotomy, laparoscopy, robot-assisted surgery, and hysteroscopy. The mode of surgery depends on the fibroid characteristics (size, number, and location) and the surgeon’s skill set. Although some variation in the data exists, overall surgical outcomes, including blood loss, postoperative pain, and length of stay, are generally more favorable for minimally invasive approaches compared with laparotomy, with no significant differences in fibroid recurrence or reproductive outcomes (live birth rate, miscarriage rate, and cesarean delivery rate).⁶ This comes at the expense of longer operating time compared with laparotomy.⁷

While improvement in abnormal uterine bleeding and pelvic pain is reliable and usually significant after myomectomy,⁸ reproductive implications also warrant consideration. Myomectomy is associated with subsequent uterine adhesion formation, with some studies finding rates up to 83% to 94% depending on the surgical approach and the number of fibroids removed.⁹ These adhesions can impair fertility success.¹⁰ Myomectomy also is associated with high rates of cesarean delivery,⁵ invasive placentation (including placenta accreta spectrum),¹¹ and uterine rupture.¹² While the latter 2 complications are rare, they potentially can be catastrophic and should be kept in mind.

Continue to: Uterine artery embolization...

Uterine artery embolization

As a nonsurgical alternative to myomectomy, uterine artery embolization (UAE) has gained popularity as a conservative fibroid treatment since it was introduced in 1995. It is less invasive than myomectomy, a benefit for patients who decline surgery or are not ideal candidates for surgery.¹³ Evidence suggests that UAE produces overall comparable symptomatic improvement compared with myomectomy. One study showed no significant differences between UAE and myomectomy in terms of decreased uterine volume and menstrual bleeding at 6-month follow-up.¹⁴ In terms of long-term outcomes, a large multicenter study showed no significant difference in reintervention rates at 7 years posttreatment between UAE and myomectomy (8.9% vs 11.2%, respectively), and a significantly higher rate of improved menstrual bleeding with UAE (79.4% vs 49.5%), with no significant difference in bulk symptoms.¹⁵ The evidence is not entirely consistent, as other studies have shown increased rates of reintervention with UAE,^8,16 but overall UAE can be considered a reasonable alternative to myomectomy in terms of symptomatic improvement.

Pregnancy outcomes data, however, are mixed, and UAE often is not recommended for patients with future fertility plans. In a large review article that compared minimally invasive fibroid treatments, UAE was associated with a lower live birth rate compared with myomectomy and ablation techniques (60.6% for UAE, 75.6% for myomectomy, and 70.5% for ablation), and it also had the highest rate of miscarriage (27.4% for UAE vs 19.0% for myomectomy and 11.9% for ablation) and abnormal placentation.¹² While UAE remains an effective option for conservative treatment of symptomatic fibroids, it appears to have a worse impact on reproductive outcomes compared with myomectomy or ablative treatments.

Magnetic resonance–guided focused ultrasound

Emerging as a noninvasive ablation treatment for fibroids, magnetic resonance–guided focused ultrasound (MRgFUS) uses targeted high-intensity ultrasound pulses to cause thermal and mechanical fibroid tissue disruption.¹⁷ Data on this treatment are less robust given that it is newer than myomectomy or UAE. One study showed a decrease in fibroid volume by 12% at 1 month and 15% at 6 months, with 37.1% of patients reporting marked improvement in symptoms and an additional 31.4% reporting partial improvement; these are modest numbers compared with other treatment approaches.¹⁸ Another study showed more favorable outcomes, with 74% of patients reporting clinically significant improvement in bleeding and pain, and a 12.7% reintervention rate, comparable to rates reported for UAE and myomectomy.¹⁹

Because MRgFUS is newer than UAE or myomectomy, data are limited in terms of pregnancy outcomes, particularly because initial trials excluded women with future fertility plans due to lack of knowledge regarding pregnancy safety. A follow-up case series from one of the initial studies showed a decreased miscarriage rate compared with UAE, a term delivery rate of 93%, and a similar rate of abnormal placentation.²⁰ A more recent systematic review concluded that reproductive outcomes were noninferior to myomectomy; however, the outcomes data for MRgFUS were heterogenous and many studies did not report pregnancy rates.²¹

Overall, MRgFUS appears to be an effective alternative approach for symptomatic fibroids, but the long-term data are not yet conclusive and information on pregnancy safety and outcomes largely is lacking. Recent reviews have not made definitive statements on whether MRgFUS should be offered to patients desiring future fertility.

Continue to: RFA is a promising option...

RFA is a promising option

RFA is another noninvasive fibroid ablation technique that has become more widely adopted in recent years. Here, we describe the basics of RFA and its impact on fibroid symptoms and reproductive outcomes.

The RFA technique

RFA uses hyperthermic energy from a handpiece and real-time ultrasound for targeted coagulative necrosis via a laparoscopic (L-RFA) or transcervical (TC-RFA) approach.²² A comparison between the 2 devices available on the market in the United States is shown in TABLE 2. Ultrasound guidance allows placement of radiofrequency needles directly into the fibroid to target local treatment to the fibroid tissue only. Once the fibroid undergoes coagulative necrosis, the process of fibroid resorption and volume reduction occurs over weeks to months, depending on the fibroid size.

Impact on fibroid symptoms

Both laparoscopic and transcervical RFA approaches have shown significant decreases in pelvic pain and heavy menstrual bleeding associated with fibroids and a low reintervention rate that emphasizes the durability of their impact.

A feasibility and safety study of a TC-RFA device prior to the primary clinical trials found only a 4.3% reintervention rate in the first 18 months postprocedure.²³ The pivotal clinical trial of a TC-RFA device that followed also reported a low 5.5% reintervention rate in the first 24 months postprocedure, with significant improvement in health-related quality-of-life and high patient satisfaction²⁴ (results shown in TABLE 2, along with trial results for an L-RFA device). A subsequent study of TC-RFA reported that symptomatic improvement persisted at 3-year follow-up, with a 9.2% reintervention rate comparable to existing fibroid treatments such as myomectomy and UAE.²⁵ The original L-RFA trial also has shown similar positive results at 2-year follow-up, with a low reintervention rate of 4.8% after treatment, and similar patient satisfaction and quality-of-life improvements as TC-RFA.²⁶ While long-term data are limited by only recent approval by the Food and Drug Administration (FDA) of a TC-RFA device in 2018, one study followed clinical trial patients for a mean duration of 64 months. This study found no surgical reinterventions in the first 3.5 years posttreatment and a persistent reduction in fibroid symptoms from baseline 64.9 points to 27.6 points, as assessed by a validated symptom severity scale (out of 100 points).²⁷ Similar improvements in health-related quality-of life-were also found to persist for years posttreatment.⁴

In a large systematic review that compared L-RFA, MRgFUS, UAE, and myomectomy, L-RFA had similar improvement rates in quality-of-life and symptom severity scores compared with myomectomy, with no significant difference in reintervention rates.²⁸ This review also noted minimal heterogeneity among RFA meta-analyses data in contrast to significant heterogeneity among UAE and myomectomy data.

Reproductive outcomes

Similar to MRgFUS, the initial studies of RFA devices largely excluded women with future fertility plans, as data on safety were lacking. However, many RFA devices are now on the market across the globe, and subsequent pregnancies have been tracked and reported.

A large case series that included clinical trials and commercial settings reported a miscarriage rate (13.3%) similar to that of the general obstetric population and no cases of uterine rupture, invasive placentation, preterm delivery, or placental abruption.²⁹ Other case series have reported live birth rates similar those with myomectomy, and safe and favorable pregnancy outcomes with RFA have been supported by larger systematic reviews of all ablation techniques.¹²

Continue to: Uterine impact...

Uterine impact

One study of TC-RFA patients showed a greater than 65% reduction in fibroid volume (with a 90% reduction in fibroid volume for fibroids larger than 6 cm prior to RFA), and 54% of patients reported complete resolution of symptoms, with another 36% reporting decreased symptoms.³⁰ Similar decreases in fibroid volume, ranging from 65% to 84%, have been reported in numerous follow-up studies, with significant decreases in bleeding and pain in 78% to 88% of patients.^23,31-33 Additionally, a large secondary analysis of a TC-RFA clinical trial showed that patients did not have any significant decrease in uterine wall thickness or integrity on follow-up with magnetic resonance imaging compared with baseline measurements, and they did not have any new myometrial scars (assessed as nonperfused linear areas).²²

As with other ablation techniques, most data on RFA pregnancy outcomes come from case series, and further research and evaluation are needed. Existing studies, however, have demonstrated promising aspects of RFA that argue its usefulness in women with fertility plans.

A prospective trial that evaluated intrauterine adhesion formation with use of a TC-RFA device found no new adhesions on 6-week follow-up hysteroscopy compared with baseline pre-RFA hysteroscopy.³⁴ Because intrauterine adhesion formation and uterine rupture are both significant concerns with other uterine-sparing fibroid treatment approaches such as myomectomy, these findings suggest that RFA may be a better alternative for women who are planning future pregnancies, as they may have increased fertility success and decreased catastrophic complications.

The consensus is growing that RFA is a safe and effective option for women who desire minimally invasive fibroid treatment and want to preserve fertility.

Unique benefits of RFA

In this article, we highlight RFA as an emerging treatment option for fibroid management, particularly for women who desire a uterine-sparing approach to preserve their reproductive options. Although myomectomy has been the standard of care for many years, with UAE as the alternative nonsurgical treatment, neither approach provides the best balance between symptomatic improvement and reproductive outcomes, and neither is without pregnancy risks. In addition, many women with symptomatic fibroids do not desire future conception but decline fibroid removal for religious or personal reasons. RFA offers these women an alternative minimally invasive option for uterine-sparing fibroid treatment.

RFA presents a unique “incision-free” fibroid treatment that is truly minimally invasive. This technique minimizes the risks associated with myomectomy, such as intra-abdominal adhesions, intrauterine adhesions (Asherman syndrome), need for cesarean delivery, and pregnancy complications such as uterine rupture or invasive placentation. Furthermore, the evolution of an RFA transcervical approach has enabled treatment with no abdominal or uterine incisions, thus offering all the above reproductive benefits as well as the operative benefits of a faster recovery, less pain, and less risk of intraperitoneal surgical complications.

While many women desire uterine-sparing fibroid treatment even without future fertility plans, the larger question is whether we should treat fibroids more strategically for women who desire future fertility. Myomectomy and UAE are effective and reliable in terms of fibroid symptomatic improvement, but RFA promises more beneficial reproductive outcomes. The ability to avoid uterine myometrial incisions and still attain significant symptomatic improvement should be prioritized in these patients.

Currently, RFA is not approved by the FDA as a fertility-enabling treatment, and these patients have been largely excluded from RFA studies. However, the reproductive-age patient who desires future conception may benefit most from RFA. Furthermore, RFA technology also could address the gap in uterine-sparing treatment for reproductive-age women with adenomyosis. Although a complete review of adenomyosis treatment is beyond the scope of this article, recent studies show that RFA produces similar improvement in both uterine volume and symptom severity in women with adenomyosis.^35-37 ●

Susan Haney, MD, a board-certified emergency physician in Coos Bay, Ore., was 2 years into her career when she had her first manic episode, likely a side effect of the steroid prednisone, which she had been prescribed for an asthma flare-up. Her boss at Bay Area Hospital told her that if she wanted to return to work, she would need to have written clearance from the medical board.

In retrospect, Dr. Haney says, “I don’t think they had any idea of what they would set in motion.”

Dr. Haney says the Oregon Medical Board posted her name and the nondisciplinary action on their website and in their newsletter. Her local newspaper read it and ran a story about her. “They effectively announced my mental illness to the general public despite my objections,” she says.

During the next decade, she had two more manic episodes, and more board investigations and actions followed. Despite being cleared for work each time, Dr. Haney says the board actions decimated her career in emergency medicine and her income, which is about half of what she would have earned by now. She is frustrated, sad, and angry about what happened but considers herself lucky to be practicing medicine in urgent care.
 

Being investigated is scary

After her first manic episode in 2006, Dr. Haney contacted the board’s medical director, a retired general surgeon, who told her the only way the board would authorize her return to work was if she agreed to open a board investigation.

She gave them the green light because she thought she had nothing to fear – she was cooperating fully and wasn’t impaired. Now Dr. Haney says she was naive. “The board is not your friend,” she says.

Dr. Haney was also anxious to return to work. She worked in a seven-person emergency department, and two colleagues were on maternity leave or medical leave.

“My colleagues kept calling asking me when I was going to return to work, and I kept saying, ‘I don’t know because the board won’t tell me,’ “ she says.

She was also feeling a lot of financial pressure. She was 2 years out of residency, owed $100,000 in student loans, and had just bought a house.

“I was really scared – I didn’t know how long this would last or if they would let me return to work. Early on, I even got a fitness for duty evaluation from the state’s consulting psychiatrist, who cleared me for work, and the board still wouldn’t let me return. They told me I had to go through their bureaucracy and a board meeting, which didn’t make sense to me.”

Dr. Haney consented to give the board’s investigative staff access to her medical records because she feared that if she challenged them, they would suspend or revoke her license immediately.

After investigating her for 4 months, the board cleared Dr. Haney to return to work at Bay Area Hospital. She agreed to the board’s “corrective action” terms: She would continue to receive psychiatric care, maintain a physician-patient relationship with a primary care physician, and enroll in the Health Physicians Program (HPP) for substance abuse monitoring.

Dr. Haney suspects that the board investigation damaged her reputation at work. “Before this, my work evaluations were consistently excellent. Afterwards, they were all adequate. I don’t think that was a coincidence.”
 

Worst time of her life

Five years later, after taking prednisone for another asthma flare-up, Dr. Haney had a more severe manic episode and was hospitalized.

The consulting psychiatrist who evaluated her reported her case to the medical board, stating she had bipolar disorder, was mentally incompetent, and shouldn’t be practicing medicine. The board opened a second investigation of her in 2012, which lasted 4 months.

Dr. Haney had quit her job at Bay Area Hospital in 2011 because she was pregnant and was planning to take a year off to care for the baby at home.

“That was the worst time of my life. I lost the baby at 4 months, I wasn’t working, and now I was under investigation by the board again,” she says.

The board issued an “interim stipulated order” that required that she be monitored regularly for mental illness and substance abuse by the Health Professionals Services Program (HPSP) for 2 years. “The board accused me of abusing prednisone, which I wasn’t. I was using it as prescribed and medically indicated,” she said.

The board order was reported to the National Practitioner Databank and is now permanently in her record. Although the board cleared her to work, she could not find a permanent job in a hospital emergency department.

“The repeated ‘nondisciplinary’ public board orders have had the same net impact on my career as if I had been disciplined for killing or harming my patients. For all intents and purposes, people treat it as a disciplinary action for the rest of your career,” she said.

To keep afloat financially, she found locum tenens work in local emergency departments until 2019.
 

Mental health toll

Dr. Haney feels that the stress of repeated board investigations has affected her mental health. “Both times this happened, it made my mental health worse, made the mania worse, and subsequent depression worse.”

Particularly distressing to her was the fact that the administrative staff who investigated her were attorneys and persons in law enforcement, rather than medical professionals with mental health training.

“I was required to disclose intimate personal details of my psychological and psychiatric history to anybody at the board who requested them. These investigators were asking me about my childhood history. That was traumatic and none of their business!”

Dr. Haney had quietly managed episodes of major depression since she was in her early 20s with the help of a psychiatrist. Her third episode of mania, which occurred in 2014, triggered a more severe depression, which she says deepened when she learned that the HPSP had notified the board about her manic symptoms and that she would not be released from the 2-year monitoring contract. When the board notified her 2 weeks later that they were opening another investigation, Dr. Haney says she had an emotional crisis, attempted suicide, and was briefly hospitalized. Several weeks later, she decided to take a mood stabilizer, which she continues to take.

The board’s 2015 corrective action agreement required Dr. Haney to practice medicine only in settings that the board’s medical director preapproved and to obtain a preapproved monitoring health care provider who would send quarterly reports to the medical director. Dr. Haney says the “nondisciplinary” action agreement was also reported to the National Practitioner Data Bank.

She also agreed to ongoing monitoring by the HPSP for mental illness and substance abuse, which involved random drug testing. When she didn’t call in one day in 2019 and missed a scheduled test, the board opened another investigation on her that lasted 7 months until July 2020. Dr. Haney said this was despite three subsequent negative tests.

Dr. Haney believes that the “open investigation” doomed a job offer from a hospital emergency department in the Virgin Islands. “I had passed all the required credentialing and explained previous board orders. They pulled the rug from under me 1 week before I was supposed to move there,” says Dr. Haney.

Her license was inactivated again because she hadn’t practiced medicine for a year, which she says was a new board policy. Although Dr. Haney says the medical director reactivated her license after talking with her, “By the time I was able to apply emergency medicine jobs, no one was interested in me anymore.”
 

Financial toll

Dr. Haney started her medical career when she was 42 as a second career. She says the board investigations and actions have resulted in a significant loss of work and income. “I have only worked 14 of the past 17 years as a doctor. I live cheaply because I never know how much longer my career will last,” says Dr. Haney.

The ordeal has devastated her finances. She has shelled out at least $200,000 in legal fees – she hired an attorney in 2007 and filed a lawsuit against the board in Oregon district court alleging that members had violated several of her rights. The district judge sided with the state medical board, and it was upheld on appeal in 2012, referring to state laws that gave the board absolute immunity from civil lawsuits. “I had no legal recourse to contest their decisions, no matter how injurious or unjust,” says Dr. Haney.

She has also shelled out at least $100,000 to be evaluated and monitored by the health physician program (now HPSP) for several years. Physicians who agree to be monitored by these health programs have to pay their fees. The board finally agreed last July to end her HPSP participation.

Dr. Haney also filed a complaint in 2007 with the federal Department of Health & Human Services Office for Civil Rights, alleging that the board violated her civil rights under the Americans with Disabilities Act. She says that her lawsuit and the OCR investigation of the board enabled her to withdraw from the HPP in good standing in 2008..
 

What would she have done differently?

She regrets not hiring an attorney earlier because “most likely the board action would not have been made public. It snowballed after that -- any mistake I made in my career was viewed in the lens of potential impairment.”

She also regrets telling her employer about the nature of her illness and reporting it to the board. A psychiatrist she saw later shared advice he gives to other patients who want to remain anonymous: get help but go out of town, use a false name, and pay cash.

“I wish I had that advice when all this started. That was the best way to protect my career,” says Dr. Haney.
 

Protecting the public?

The Oregon Medical Board declined to comment on Dr. Haney’s experience because investigations are confidential, but the executive director, Nicole Krishnaswami, JD, answered questions in an email about how the current board operates.

She says the board has 11 medical professionals and employs a medical director and expert consultants in specialty-specific fields. MDs with mental health training are involved in investigating/reviewing cases involving doctors with mental illnesses.

“State medical boards have a responsibility to protect and inform the public. State laws further require state agencies to provide access and transparency regarding the board’s official actions. If the board receives a complaint that a licensee is impaired and thus unable to safely practice, the board has a responsibility to investigate and ensure the licensee is practicing medicine safely,” Ms. Krishnaswami said.

The HPSP is the monitoring program established by state law to provide oversight in order to ensure that licensees are not practicing while impaired. HPSP is separate from the board and the board adopted a statement outlining its perspective on the program in support of doctors with substance abuse and mental health disorder.

The board also founded the Oregon Wellness Program, which provides free, confidential counseling to all Oregon-licensed physicians and physician assistants.
 

Stigma continues

Dr. Haney feels there is huge stigma associated with mental illness in the medical profession. “If I had cancer twice, I wouldn’t have been put in this position and would be at the peak of my career,” she says.

Nearly half of the 862 emergency medicine physicians surveyed last October said they were reluctant to seek mental health treatment. The reasons included fear of professional repercussions and stigma in the workplace. Several physicians said they were concerned about potentially having to report the treatment on medical license applications in the future, according to a survey by the American College of Emergency Physicians.

In addition, 26% of the more than 12,000 physicians who responded to a Medscape survey last year said they didn’t want to risk disclosure (20%) or that they distrusted mental health professionals (6%).
 

Another physician fights back

Steven Miles, MD, an award-winning professor emeritus of medicine and bioethics at the Center for Bioethics at the University of Minnesota, in Minneapolis, understands their reluctance. In 1996, he disclosed on his license renewal application that he had recently been diagnosed with a mainly depressive type of bipolar disorder and was in treatment. He had already told his employer, who was supportive.

That set off a 14-month investigation of him by the Minnesota Board of Medical Practice. Dr. Miles and his psychiatrist refused to release his confidential records to a panel of physicians, most of whom had no expertise in mental health care. He also filed a federal claim that the board’s requests violated the ADA, and he won the case.

“Had the board given me evidence of impaired ability to practice with ordinary skill and safety, I would have cooperated. Instead, they proposed a course of action, which would have degraded the privacy of my relationship with my psychiatrist and arguably increased the barrier to getting proper care and the risk of impairment,” he said.

The board kept renewing his license, and Dr. Miles continued to work full time. “I was empowered and protected by my stature in the field at the time my mental illness was diagnosed. Early-career physicians do not yet have that protection and should be very careful of disclosing, given the still widespread stigma of mental illnesses,” he said.
 

His advocacy led to changes

Dr. Miles went public to mobilize support for his ADA claim. He wrote editorials that were published in JAMA and Minnesota Medicine that refer to the American Psychiatric Association’s 1984 position paper, which says that the mandatory disclosure of the physician’s confidential medical record is without merit. Dr. Miles adds that major newspapers ran stories based on his editorials.

The board backed down after Dr. Miles won his ADA case, and it met with him. “I said this is not good stewardship of the medical profession; you are injuring doctors by keeping them from psychiatric care, which is out of line with the medical view of the treatability of depression and that needs to change,” he says.

Dr. Miles says he won a victory because his practice continued. “I also won a victory in the way the board was handling these questions, which was an opening salvo in a process that continues to this day.”

The original form asked whether he had ever been diagnosed with or treated for manic depression, schizophrenia, compulsive gambling, or other psychiatric conditions.

The revised form asks, “Do you have a physical or mental condition that would affect your ability, with or without reasonable accommodation, to provide appropriate care to patients and otherwise perform the essential functions of a practitioner in your area of practice without posing a health or safety risk to your patients? If yes, what accommodations would help you provide appropriate care to patients and perform other essential functions?”

Dr. Miles says that the final wording wasn’t ideal and that it was confusing to physicians. He says this prompted additional changes in wording by the board. Starting in January, applicants will be asked, “Do you currently have any condition that is not being appropriately treated that is likely to impair or adversely affect your ability to practice medicine with reasonable skill and safety in a competent, ethical, and professional manner?” the medical board’s executive director, Ruth M. Martinez, said in an email.

When asked whether the board still investigates physicians who reveal mental illnesses on licensing applications, Ms. Martinez responded, “All disclosures are evaluated to assure that the practitioner is qualified and safe to practice.”

This article was updated 11/4/21.

A version of this article first appeared on Medscape.com.

Susan Haney, MD, a board-certified emergency physician in Coos Bay, Ore., was 2 years into her career when she had her first manic episode, likely a side effect of the steroid prednisone, which she had been prescribed for an asthma flare-up. Her boss at Bay Area Hospital told her that if she wanted to return to work, she would need to have written clearance from the medical board.

In retrospect, Dr. Haney says, “I don’t think they had any idea of what they would set in motion.”

Dr. Haney says the Oregon Medical Board posted her name and the nondisciplinary action on their website and in their newsletter. Her local newspaper read it and ran a story about her. “They effectively announced my mental illness to the general public despite my objections,” she says.

During the next decade, she had two more manic episodes, and more board investigations and actions followed. Despite being cleared for work each time, Dr. Haney says the board actions decimated her career in emergency medicine and her income, which is about half of what she would have earned by now. She is frustrated, sad, and angry about what happened but considers herself lucky to be practicing medicine in urgent care.
 

Being investigated is scary

After her first manic episode in 2006, Dr. Haney contacted the board’s medical director, a retired general surgeon, who told her the only way the board would authorize her return to work was if she agreed to open a board investigation.

She gave them the green light because she thought she had nothing to fear – she was cooperating fully and wasn’t impaired. Now Dr. Haney says she was naive. “The board is not your friend,” she says.

Dr. Haney was also anxious to return to work. She worked in a seven-person emergency department, and two colleagues were on maternity leave or medical leave.

“My colleagues kept calling asking me when I was going to return to work, and I kept saying, ‘I don’t know because the board won’t tell me,’ “ she says.

She was also feeling a lot of financial pressure. She was 2 years out of residency, owed $100,000 in student loans, and had just bought a house.

“I was really scared – I didn’t know how long this would last or if they would let me return to work. Early on, I even got a fitness for duty evaluation from the state’s consulting psychiatrist, who cleared me for work, and the board still wouldn’t let me return. They told me I had to go through their bureaucracy and a board meeting, which didn’t make sense to me.”

Dr. Haney consented to give the board’s investigative staff access to her medical records because she feared that if she challenged them, they would suspend or revoke her license immediately.

After investigating her for 4 months, the board cleared Dr. Haney to return to work at Bay Area Hospital. She agreed to the board’s “corrective action” terms: She would continue to receive psychiatric care, maintain a physician-patient relationship with a primary care physician, and enroll in the Health Physicians Program (HPP) for substance abuse monitoring.

Dr. Haney suspects that the board investigation damaged her reputation at work. “Before this, my work evaluations were consistently excellent. Afterwards, they were all adequate. I don’t think that was a coincidence.”
 

Worst time of her life

Five years later, after taking prednisone for another asthma flare-up, Dr. Haney had a more severe manic episode and was hospitalized.

The consulting psychiatrist who evaluated her reported her case to the medical board, stating she had bipolar disorder, was mentally incompetent, and shouldn’t be practicing medicine. The board opened a second investigation of her in 2012, which lasted 4 months.

Dr. Haney had quit her job at Bay Area Hospital in 2011 because she was pregnant and was planning to take a year off to care for the baby at home.

“That was the worst time of my life. I lost the baby at 4 months, I wasn’t working, and now I was under investigation by the board again,” she says.

The board issued an “interim stipulated order” that required that she be monitored regularly for mental illness and substance abuse by the Health Professionals Services Program (HPSP) for 2 years. “The board accused me of abusing prednisone, which I wasn’t. I was using it as prescribed and medically indicated,” she said.

The board order was reported to the National Practitioner Databank and is now permanently in her record. Although the board cleared her to work, she could not find a permanent job in a hospital emergency department.

“The repeated ‘nondisciplinary’ public board orders have had the same net impact on my career as if I had been disciplined for killing or harming my patients. For all intents and purposes, people treat it as a disciplinary action for the rest of your career,” she said.

To keep afloat financially, she found locum tenens work in local emergency departments until 2019.
 

Mental health toll

Dr. Haney feels that the stress of repeated board investigations has affected her mental health. “Both times this happened, it made my mental health worse, made the mania worse, and subsequent depression worse.”

Particularly distressing to her was the fact that the administrative staff who investigated her were attorneys and persons in law enforcement, rather than medical professionals with mental health training.

“I was required to disclose intimate personal details of my psychological and psychiatric history to anybody at the board who requested them. These investigators were asking me about my childhood history. That was traumatic and none of their business!”

Dr. Haney had quietly managed episodes of major depression since she was in her early 20s with the help of a psychiatrist. Her third episode of mania, which occurred in 2014, triggered a more severe depression, which she says deepened when she learned that the HPSP had notified the board about her manic symptoms and that she would not be released from the 2-year monitoring contract. When the board notified her 2 weeks later that they were opening another investigation, Dr. Haney says she had an emotional crisis, attempted suicide, and was briefly hospitalized. Several weeks later, she decided to take a mood stabilizer, which she continues to take.

The board’s 2015 corrective action agreement required Dr. Haney to practice medicine only in settings that the board’s medical director preapproved and to obtain a preapproved monitoring health care provider who would send quarterly reports to the medical director. Dr. Haney says the “nondisciplinary” action agreement was also reported to the National Practitioner Data Bank.

She also agreed to ongoing monitoring by the HPSP for mental illness and substance abuse, which involved random drug testing. When she didn’t call in one day in 2019 and missed a scheduled test, the board opened another investigation on her that lasted 7 months until July 2020. Dr. Haney said this was despite three subsequent negative tests.

Dr. Haney believes that the “open investigation” doomed a job offer from a hospital emergency department in the Virgin Islands. “I had passed all the required credentialing and explained previous board orders. They pulled the rug from under me 1 week before I was supposed to move there,” says Dr. Haney.

Her license was inactivated again because she hadn’t practiced medicine for a year, which she says was a new board policy. Although Dr. Haney says the medical director reactivated her license after talking with her, “By the time I was able to apply emergency medicine jobs, no one was interested in me anymore.”
 

Financial toll

Dr. Haney started her medical career when she was 42 as a second career. She says the board investigations and actions have resulted in a significant loss of work and income. “I have only worked 14 of the past 17 years as a doctor. I live cheaply because I never know how much longer my career will last,” says Dr. Haney.

The ordeal has devastated her finances. She has shelled out at least $200,000 in legal fees – she hired an attorney in 2007 and filed a lawsuit against the board in Oregon district court alleging that members had violated several of her rights. The district judge sided with the state medical board, and it was upheld on appeal in 2012, referring to state laws that gave the board absolute immunity from civil lawsuits. “I had no legal recourse to contest their decisions, no matter how injurious or unjust,” says Dr. Haney.

She has also shelled out at least $100,000 to be evaluated and monitored by the health physician program (now HPSP) for several years. Physicians who agree to be monitored by these health programs have to pay their fees. The board finally agreed last July to end her HPSP participation.

Dr. Haney also filed a complaint in 2007 with the federal Department of Health & Human Services Office for Civil Rights, alleging that the board violated her civil rights under the Americans with Disabilities Act. She says that her lawsuit and the OCR investigation of the board enabled her to withdraw from the HPP in good standing in 2008..
 

What would she have done differently?

She regrets not hiring an attorney earlier because “most likely the board action would not have been made public. It snowballed after that -- any mistake I made in my career was viewed in the lens of potential impairment.”

She also regrets telling her employer about the nature of her illness and reporting it to the board. A psychiatrist she saw later shared advice he gives to other patients who want to remain anonymous: get help but go out of town, use a false name, and pay cash.

“I wish I had that advice when all this started. That was the best way to protect my career,” says Dr. Haney.
 

Protecting the public?

The Oregon Medical Board declined to comment on Dr. Haney’s experience because investigations are confidential, but the executive director, Nicole Krishnaswami, JD, answered questions in an email about how the current board operates.

She says the board has 11 medical professionals and employs a medical director and expert consultants in specialty-specific fields. MDs with mental health training are involved in investigating/reviewing cases involving doctors with mental illnesses.

“State medical boards have a responsibility to protect and inform the public. State laws further require state agencies to provide access and transparency regarding the board’s official actions. If the board receives a complaint that a licensee is impaired and thus unable to safely practice, the board has a responsibility to investigate and ensure the licensee is practicing medicine safely,” Ms. Krishnaswami said.

The HPSP is the monitoring program established by state law to provide oversight in order to ensure that licensees are not practicing while impaired. HPSP is separate from the board and the board adopted a statement outlining its perspective on the program in support of doctors with substance abuse and mental health disorder.

The board also founded the Oregon Wellness Program, which provides free, confidential counseling to all Oregon-licensed physicians and physician assistants.
 

Stigma continues

Dr. Haney feels there is huge stigma associated with mental illness in the medical profession. “If I had cancer twice, I wouldn’t have been put in this position and would be at the peak of my career,” she says.

Nearly half of the 862 emergency medicine physicians surveyed last October said they were reluctant to seek mental health treatment. The reasons included fear of professional repercussions and stigma in the workplace. Several physicians said they were concerned about potentially having to report the treatment on medical license applications in the future, according to a survey by the American College of Emergency Physicians.

In addition, 26% of the more than 12,000 physicians who responded to a Medscape survey last year said they didn’t want to risk disclosure (20%) or that they distrusted mental health professionals (6%).
 

Another physician fights back

Steven Miles, MD, an award-winning professor emeritus of medicine and bioethics at the Center for Bioethics at the University of Minnesota, in Minneapolis, understands their reluctance. In 1996, he disclosed on his license renewal application that he had recently been diagnosed with a mainly depressive type of bipolar disorder and was in treatment. He had already told his employer, who was supportive.

That set off a 14-month investigation of him by the Minnesota Board of Medical Practice. Dr. Miles and his psychiatrist refused to release his confidential records to a panel of physicians, most of whom had no expertise in mental health care. He also filed a federal claim that the board’s requests violated the ADA, and he won the case.

“Had the board given me evidence of impaired ability to practice with ordinary skill and safety, I would have cooperated. Instead, they proposed a course of action, which would have degraded the privacy of my relationship with my psychiatrist and arguably increased the barrier to getting proper care and the risk of impairment,” he said.

The board kept renewing his license, and Dr. Miles continued to work full time. “I was empowered and protected by my stature in the field at the time my mental illness was diagnosed. Early-career physicians do not yet have that protection and should be very careful of disclosing, given the still widespread stigma of mental illnesses,” he said.
 

His advocacy led to changes

Dr. Miles went public to mobilize support for his ADA claim. He wrote editorials that were published in JAMA and Minnesota Medicine that refer to the American Psychiatric Association’s 1984 position paper, which says that the mandatory disclosure of the physician’s confidential medical record is without merit. Dr. Miles adds that major newspapers ran stories based on his editorials.

The board backed down after Dr. Miles won his ADA case, and it met with him. “I said this is not good stewardship of the medical profession; you are injuring doctors by keeping them from psychiatric care, which is out of line with the medical view of the treatability of depression and that needs to change,” he says.

Dr. Miles says he won a victory because his practice continued. “I also won a victory in the way the board was handling these questions, which was an opening salvo in a process that continues to this day.”

The original form asked whether he had ever been diagnosed with or treated for manic depression, schizophrenia, compulsive gambling, or other psychiatric conditions.

The revised form asks, “Do you have a physical or mental condition that would affect your ability, with or without reasonable accommodation, to provide appropriate care to patients and otherwise perform the essential functions of a practitioner in your area of practice without posing a health or safety risk to your patients? If yes, what accommodations would help you provide appropriate care to patients and perform other essential functions?”

Dr. Miles says that the final wording wasn’t ideal and that it was confusing to physicians. He says this prompted additional changes in wording by the board. Starting in January, applicants will be asked, “Do you currently have any condition that is not being appropriately treated that is likely to impair or adversely affect your ability to practice medicine with reasonable skill and safety in a competent, ethical, and professional manner?” the medical board’s executive director, Ruth M. Martinez, said in an email.

When asked whether the board still investigates physicians who reveal mental illnesses on licensing applications, Ms. Martinez responded, “All disclosures are evaluated to assure that the practitioner is qualified and safe to practice.”

This article was updated 11/4/21.

A version of this article first appeared on Medscape.com.

Susan Haney, MD, a board-certified emergency physician in Coos Bay, Ore., was 2 years into her career when she had her first manic episode, likely a side effect of the steroid prednisone, which she had been prescribed for an asthma flare-up. Her boss at Bay Area Hospital told her that if she wanted to return to work, she would need to have written clearance from the medical board.

In retrospect, Dr. Haney says, “I don’t think they had any idea of what they would set in motion.”

Dr. Haney says the Oregon Medical Board posted her name and the nondisciplinary action on their website and in their newsletter. Her local newspaper read it and ran a story about her. “They effectively announced my mental illness to the general public despite my objections,” she says.

During the next decade, she had two more manic episodes, and more board investigations and actions followed. Despite being cleared for work each time, Dr. Haney says the board actions decimated her career in emergency medicine and her income, which is about half of what she would have earned by now. She is frustrated, sad, and angry about what happened but considers herself lucky to be practicing medicine in urgent care.
 

Being investigated is scary

After her first manic episode in 2006, Dr. Haney contacted the board’s medical director, a retired general surgeon, who told her the only way the board would authorize her return to work was if she agreed to open a board investigation.

She gave them the green light because she thought she had nothing to fear – she was cooperating fully and wasn’t impaired. Now Dr. Haney says she was naive. “The board is not your friend,” she says.

Dr. Haney was also anxious to return to work. She worked in a seven-person emergency department, and two colleagues were on maternity leave or medical leave.

“My colleagues kept calling asking me when I was going to return to work, and I kept saying, ‘I don’t know because the board won’t tell me,’ “ she says.

She was also feeling a lot of financial pressure. She was 2 years out of residency, owed $100,000 in student loans, and had just bought a house.

“I was really scared – I didn’t know how long this would last or if they would let me return to work. Early on, I even got a fitness for duty evaluation from the state’s consulting psychiatrist, who cleared me for work, and the board still wouldn’t let me return. They told me I had to go through their bureaucracy and a board meeting, which didn’t make sense to me.”

Dr. Haney consented to give the board’s investigative staff access to her medical records because she feared that if she challenged them, they would suspend or revoke her license immediately.

After investigating her for 4 months, the board cleared Dr. Haney to return to work at Bay Area Hospital. She agreed to the board’s “corrective action” terms: She would continue to receive psychiatric care, maintain a physician-patient relationship with a primary care physician, and enroll in the Health Physicians Program (HPP) for substance abuse monitoring.

Dr. Haney suspects that the board investigation damaged her reputation at work. “Before this, my work evaluations were consistently excellent. Afterwards, they were all adequate. I don’t think that was a coincidence.”
 

Worst time of her life

Five years later, after taking prednisone for another asthma flare-up, Dr. Haney had a more severe manic episode and was hospitalized.

The consulting psychiatrist who evaluated her reported her case to the medical board, stating she had bipolar disorder, was mentally incompetent, and shouldn’t be practicing medicine. The board opened a second investigation of her in 2012, which lasted 4 months.

Dr. Haney had quit her job at Bay Area Hospital in 2011 because she was pregnant and was planning to take a year off to care for the baby at home.

“That was the worst time of my life. I lost the baby at 4 months, I wasn’t working, and now I was under investigation by the board again,” she says.

The board issued an “interim stipulated order” that required that she be monitored regularly for mental illness and substance abuse by the Health Professionals Services Program (HPSP) for 2 years. “The board accused me of abusing prednisone, which I wasn’t. I was using it as prescribed and medically indicated,” she said.

The board order was reported to the National Practitioner Databank and is now permanently in her record. Although the board cleared her to work, she could not find a permanent job in a hospital emergency department.

“The repeated ‘nondisciplinary’ public board orders have had the same net impact on my career as if I had been disciplined for killing or harming my patients. For all intents and purposes, people treat it as a disciplinary action for the rest of your career,” she said.

To keep afloat financially, she found locum tenens work in local emergency departments until 2019.
 

Mental health toll

Dr. Haney feels that the stress of repeated board investigations has affected her mental health. “Both times this happened, it made my mental health worse, made the mania worse, and subsequent depression worse.”

Particularly distressing to her was the fact that the administrative staff who investigated her were attorneys and persons in law enforcement, rather than medical professionals with mental health training.

“I was required to disclose intimate personal details of my psychological and psychiatric history to anybody at the board who requested them. These investigators were asking me about my childhood history. That was traumatic and none of their business!”

Dr. Haney had quietly managed episodes of major depression since she was in her early 20s with the help of a psychiatrist. Her third episode of mania, which occurred in 2014, triggered a more severe depression, which she says deepened when she learned that the HPSP had notified the board about her manic symptoms and that she would not be released from the 2-year monitoring contract. When the board notified her 2 weeks later that they were opening another investigation, Dr. Haney says she had an emotional crisis, attempted suicide, and was briefly hospitalized. Several weeks later, she decided to take a mood stabilizer, which she continues to take.

The board’s 2015 corrective action agreement required Dr. Haney to practice medicine only in settings that the board’s medical director preapproved and to obtain a preapproved monitoring health care provider who would send quarterly reports to the medical director. Dr. Haney says the “nondisciplinary” action agreement was also reported to the National Practitioner Data Bank.

She also agreed to ongoing monitoring by the HPSP for mental illness and substance abuse, which involved random drug testing. When she didn’t call in one day in 2019 and missed a scheduled test, the board opened another investigation on her that lasted 7 months until July 2020. Dr. Haney said this was despite three subsequent negative tests.

Dr. Haney believes that the “open investigation” doomed a job offer from a hospital emergency department in the Virgin Islands. “I had passed all the required credentialing and explained previous board orders. They pulled the rug from under me 1 week before I was supposed to move there,” says Dr. Haney.

Her license was inactivated again because she hadn’t practiced medicine for a year, which she says was a new board policy. Although Dr. Haney says the medical director reactivated her license after talking with her, “By the time I was able to apply emergency medicine jobs, no one was interested in me anymore.”
 

Financial toll

Dr. Haney started her medical career when she was 42 as a second career. She says the board investigations and actions have resulted in a significant loss of work and income. “I have only worked 14 of the past 17 years as a doctor. I live cheaply because I never know how much longer my career will last,” says Dr. Haney.

The ordeal has devastated her finances. She has shelled out at least $200,000 in legal fees – she hired an attorney in 2007 and filed a lawsuit against the board in Oregon district court alleging that members had violated several of her rights. The district judge sided with the state medical board, and it was upheld on appeal in 2012, referring to state laws that gave the board absolute immunity from civil lawsuits. “I had no legal recourse to contest their decisions, no matter how injurious or unjust,” says Dr. Haney.

She has also shelled out at least $100,000 to be evaluated and monitored by the health physician program (now HPSP) for several years. Physicians who agree to be monitored by these health programs have to pay their fees. The board finally agreed last July to end her HPSP participation.

Dr. Haney also filed a complaint in 2007 with the federal Department of Health & Human Services Office for Civil Rights, alleging that the board violated her civil rights under the Americans with Disabilities Act. She says that her lawsuit and the OCR investigation of the board enabled her to withdraw from the HPP in good standing in 2008..
 

What would she have done differently?

She regrets not hiring an attorney earlier because “most likely the board action would not have been made public. It snowballed after that -- any mistake I made in my career was viewed in the lens of potential impairment.”

She also regrets telling her employer about the nature of her illness and reporting it to the board. A psychiatrist she saw later shared advice he gives to other patients who want to remain anonymous: get help but go out of town, use a false name, and pay cash.

“I wish I had that advice when all this started. That was the best way to protect my career,” says Dr. Haney.
 

Protecting the public?

The Oregon Medical Board declined to comment on Dr. Haney’s experience because investigations are confidential, but the executive director, Nicole Krishnaswami, JD, answered questions in an email about how the current board operates.

She says the board has 11 medical professionals and employs a medical director and expert consultants in specialty-specific fields. MDs with mental health training are involved in investigating/reviewing cases involving doctors with mental illnesses.

“State medical boards have a responsibility to protect and inform the public. State laws further require state agencies to provide access and transparency regarding the board’s official actions. If the board receives a complaint that a licensee is impaired and thus unable to safely practice, the board has a responsibility to investigate and ensure the licensee is practicing medicine safely,” Ms. Krishnaswami said.

The HPSP is the monitoring program established by state law to provide oversight in order to ensure that licensees are not practicing while impaired. HPSP is separate from the board and the board adopted a statement outlining its perspective on the program in support of doctors with substance abuse and mental health disorder.

The board also founded the Oregon Wellness Program, which provides free, confidential counseling to all Oregon-licensed physicians and physician assistants.
 

Stigma continues

Dr. Haney feels there is huge stigma associated with mental illness in the medical profession. “If I had cancer twice, I wouldn’t have been put in this position and would be at the peak of my career,” she says.

Nearly half of the 862 emergency medicine physicians surveyed last October said they were reluctant to seek mental health treatment. The reasons included fear of professional repercussions and stigma in the workplace. Several physicians said they were concerned about potentially having to report the treatment on medical license applications in the future, according to a survey by the American College of Emergency Physicians.

In addition, 26% of the more than 12,000 physicians who responded to a Medscape survey last year said they didn’t want to risk disclosure (20%) or that they distrusted mental health professionals (6%).
 

Another physician fights back

Steven Miles, MD, an award-winning professor emeritus of medicine and bioethics at the Center for Bioethics at the University of Minnesota, in Minneapolis, understands their reluctance. In 1996, he disclosed on his license renewal application that he had recently been diagnosed with a mainly depressive type of bipolar disorder and was in treatment. He had already told his employer, who was supportive.

That set off a 14-month investigation of him by the Minnesota Board of Medical Practice. Dr. Miles and his psychiatrist refused to release his confidential records to a panel of physicians, most of whom had no expertise in mental health care. He also filed a federal claim that the board’s requests violated the ADA, and he won the case.

“Had the board given me evidence of impaired ability to practice with ordinary skill and safety, I would have cooperated. Instead, they proposed a course of action, which would have degraded the privacy of my relationship with my psychiatrist and arguably increased the barrier to getting proper care and the risk of impairment,” he said.

The board kept renewing his license, and Dr. Miles continued to work full time. “I was empowered and protected by my stature in the field at the time my mental illness was diagnosed. Early-career physicians do not yet have that protection and should be very careful of disclosing, given the still widespread stigma of mental illnesses,” he said.
 

His advocacy led to changes

Dr. Miles went public to mobilize support for his ADA claim. He wrote editorials that were published in JAMA and Minnesota Medicine that refer to the American Psychiatric Association’s 1984 position paper, which says that the mandatory disclosure of the physician’s confidential medical record is without merit. Dr. Miles adds that major newspapers ran stories based on his editorials.

The board backed down after Dr. Miles won his ADA case, and it met with him. “I said this is not good stewardship of the medical profession; you are injuring doctors by keeping them from psychiatric care, which is out of line with the medical view of the treatability of depression and that needs to change,” he says.

Dr. Miles says he won a victory because his practice continued. “I also won a victory in the way the board was handling these questions, which was an opening salvo in a process that continues to this day.”

The original form asked whether he had ever been diagnosed with or treated for manic depression, schizophrenia, compulsive gambling, or other psychiatric conditions.

The revised form asks, “Do you have a physical or mental condition that would affect your ability, with or without reasonable accommodation, to provide appropriate care to patients and otherwise perform the essential functions of a practitioner in your area of practice without posing a health or safety risk to your patients? If yes, what accommodations would help you provide appropriate care to patients and perform other essential functions?”

Dr. Miles says that the final wording wasn’t ideal and that it was confusing to physicians. He says this prompted additional changes in wording by the board. Starting in January, applicants will be asked, “Do you currently have any condition that is not being appropriately treated that is likely to impair or adversely affect your ability to practice medicine with reasonable skill and safety in a competent, ethical, and professional manner?” the medical board’s executive director, Ruth M. Martinez, said in an email.

When asked whether the board still investigates physicians who reveal mental illnesses on licensing applications, Ms. Martinez responded, “All disclosures are evaluated to assure that the practitioner is qualified and safe to practice.”

This article was updated 11/4/21.

A version of this article first appeared on Medscape.com.

_{Text copyright DenseBreast-info.org.}

Answer

C. Overall, tomosynthesis depicts an additional 1 to 2 cancers per thousand women screened in the first round of screening when added to standard digital mammography;^1-3 however, this improvement in cancer detection is only observed in women with fatty breasts (category A), scattered fibroglandular tissue (category B), and heterogeneously dense breasts (category C). Importantly, tomosynthesis does not significantly improve breast cancer detection in women with extremely dense breasts (category D).^2,4

Digital breast tomosynthesis, also referred to as “3-dimensional mammography” (3D mammography) or tomosynthesis, uses a dedicated electronic detector system to obtain multiple projection images that are reconstructed by the computer to create thin slices or slabs of multiple slices of the breast. These slices can be individually “scrolled through” by the radiologist to reduce tissue overlap that may obscure breast cancers on a standard mammogram. While tomosynthesis improves breast cancer detection in women with fatty, scattered fibroglandular density, and heterogeneously dense breasts, there is very little soft tissue contrast in extremely dense breasts due to insufficient fat, and some cancers will remain hidden by dense tissue even on sliced images through the breast.

FIGURE 2 shows an example of cancer that was missed on tomosynthesis in a 51-year-old woman with extremely dense breasts and right breast pain. The cancer was masked by extremely dense tissue on standard digital mammography and tomosynthesis; no abnormalities were detected. Ultrasonography showed a 1.6-cm, irregular, hypoechoic mass at the site of pain, and biopsy revealed a grade 3 triple-receptor negative invasive ductal carcinoma.

_{Text copyright DenseBreast-info.org.}

Answer

C. Overall, tomosynthesis depicts an additional 1 to 2 cancers per thousand women screened in the first round of screening when added to standard digital mammography;^1-3 however, this improvement in cancer detection is only observed in women with fatty breasts (category A), scattered fibroglandular tissue (category B), and heterogeneously dense breasts (category C). Importantly, tomosynthesis does not significantly improve breast cancer detection in women with extremely dense breasts (category D).^2,4

Digital breast tomosynthesis, also referred to as “3-dimensional mammography” (3D mammography) or tomosynthesis, uses a dedicated electronic detector system to obtain multiple projection images that are reconstructed by the computer to create thin slices or slabs of multiple slices of the breast. These slices can be individually “scrolled through” by the radiologist to reduce tissue overlap that may obscure breast cancers on a standard mammogram. While tomosynthesis improves breast cancer detection in women with fatty, scattered fibroglandular density, and heterogeneously dense breasts, there is very little soft tissue contrast in extremely dense breasts due to insufficient fat, and some cancers will remain hidden by dense tissue even on sliced images through the breast.

FIGURE 2 shows an example of cancer that was missed on tomosynthesis in a 51-year-old woman with extremely dense breasts and right breast pain. The cancer was masked by extremely dense tissue on standard digital mammography and tomosynthesis; no abnormalities were detected. Ultrasonography showed a 1.6-cm, irregular, hypoechoic mass at the site of pain, and biopsy revealed a grade 3 triple-receptor negative invasive ductal carcinoma.

_{Text copyright DenseBreast-info.org.}

Answer

C. Overall, tomosynthesis depicts an additional 1 to 2 cancers per thousand women screened in the first round of screening when added to standard digital mammography;^1-3 however, this improvement in cancer detection is only observed in women with fatty breasts (category A), scattered fibroglandular tissue (category B), and heterogeneously dense breasts (category C). Importantly, tomosynthesis does not significantly improve breast cancer detection in women with extremely dense breasts (category D).^2,4

Digital breast tomosynthesis, also referred to as “3-dimensional mammography” (3D mammography) or tomosynthesis, uses a dedicated electronic detector system to obtain multiple projection images that are reconstructed by the computer to create thin slices or slabs of multiple slices of the breast. These slices can be individually “scrolled through” by the radiologist to reduce tissue overlap that may obscure breast cancers on a standard mammogram. While tomosynthesis improves breast cancer detection in women with fatty, scattered fibroglandular density, and heterogeneously dense breasts, there is very little soft tissue contrast in extremely dense breasts due to insufficient fat, and some cancers will remain hidden by dense tissue even on sliced images through the breast.

FIGURE 2 shows an example of cancer that was missed on tomosynthesis in a 51-year-old woman with extremely dense breasts and right breast pain. The cancer was masked by extremely dense tissue on standard digital mammography and tomosynthesis; no abnormalities were detected. Ultrasonography showed a 1.6-cm, irregular, hypoechoic mass at the site of pain, and biopsy revealed a grade 3 triple-receptor negative invasive ductal carcinoma.

A clinical update from the American Gastroenterological Association focuses on bleeding and thrombosis-related questions in patients with cirrhosis. It provides guidance on test strategies for bleeding risk, preprocedure management of bleeding risk, venous thromboembolism (VTE) prophylaxis, screening for portal vein thrombosis (PVT), and anticoagulation therapies. It is aimed at primary care providers, gastroenterologists, and hepatologists, among other health care providers.

In cirrhosis, there are often changes to platelet (PLT) counts and prothrombin time/international normalized ratio (PT/INR), among other parameters, and historically these changes led to concerns that patients were at greater risk of bleeding or thrombosis. More recent evidence has led to a nuanced view. Neither factor necessarily suggests increased bleeding risk, and the severity of coagulopathy predicted by them does not predict the risk of bleeding complications.

Patients with cirrhosis are at greater risk of thrombosis, but clinicians may be hesitant to prescribe anticoagulants because of uncertain risk profiles, and test strategies employing PT/INR to estimate bleeding risk and track treatment endpoints in patients receiving vitamin K antagonists may not work in cirrhosis patients with alterations in procoagulant and anticoagulant measures. Recent efforts to address this led to testing of fibrin clot formation and lysis to better gauge the variety of abnormalities in cirrhosis patients.

The guideline, published in Gastroenterology, was informed by a technical review that focused on both bleeding-related and thrombosis-related questions. Bleeding-related questions included testing strategies and preprocedure prophylaxis to reduce bleeding risk. Thrombosis-related questions included whether VTE prophylaxis may be useful in hospitalized patients with cirrhosis, whether patients should be screened for PVT, potential therapies for nontumoral PVT, and whether or not anticoagulation is safe and effective when atrial fibrillation is present alongside cirrhosis.

Because of a lack of evidence, the guideline provides no recommendations on visco-elastic testing for bleeding risk in advance of common gastrointestinal procedures for patients with stable cirrhosis. It recommends against use of extensive preprocedural testing, such as repeated PT/INR or PLT count testing.

The guideline also looked at whether preprocedural efforts to correct coagulation parameters could reduce bleeding risk in patients with cirrhosis. It recommends against giving blood products ahead of the procedure for patients with stable cirrhosis without severe thrombocytopenia or severe coagulopathy. Such interventions can be considered for patients in the latter categories who are undergoing procedures with high bleeding risk after consideration of risks and benefits, and consultation with a hematologist.

Thrombopoietin receptor agonists (TPO-RAs) are also not recommended in patients with thrombocytopenia and stable cirrhosis undergoing common procedures, but they can be considered for patients who are more concerned about reduction of bleeding events and less concerned about the risk of PVT.

Patients who are hospitalized and meet the requirements should receive VTE prophylaxis. Although there is little available evidence about the effects of thromboprophylaxis in patients with cirrhosis, there is strong evidence of benefit in acutely ill hospitalized patients, and patients with cirrhosis are believed to be at a similar risk of VTE. There is evidence of increased bleed risk, but this is of very low certainty.

PVT should not be routinely tested for, but such testing can be offered to patients with a high level of concern over PVT and are not as worried about potential harms of treatment. This recommendation does not apply to patients waiting for a liver transplant.

Patients with non-umoral PVT should receive anticoagulation therapy, but patients who have high levels of concern about bleeding risk from anticoagulation and put a lower value on possible benefits of anticoagulation may choose not to receive it.

The guideline recommends anticoagulation for patients with atrial fibrillation and cirrhosis who are indicated for it. Patients with more concern about the bleeding risk of anticoagulation and place lower value on the reduction in stroke risk may choose to not receive anticoagulation. This is particularly true for those with more advanced cirrhosis (Child-Turcotte-Pugh Class C) and/or low CHA2DS2-VASC scores.

Nearly all of the recommendations in the guideline are conditional, reflecting a lack of data and a range of knowledge gaps that need filling. The authors call for additional research to identify specific patients who are at high risk for bleeding or thrombosis “to appropriately provide prophylaxis using blood product transfusion or TPO-RAs in patients at risk for clinically significant bleeding, to screen for and treat PVT, and to prevent clinically significant thromboembolic events.”

The development of the guideline was funded fully by the AGA. Members of the panel submitted conflict of interest information, and these statements are maintained at AGA headquarters.

A clinical update from the American Gastroenterological Association focuses on bleeding and thrombosis-related questions in patients with cirrhosis. It provides guidance on test strategies for bleeding risk, preprocedure management of bleeding risk, venous thromboembolism (VTE) prophylaxis, screening for portal vein thrombosis (PVT), and anticoagulation therapies. It is aimed at primary care providers, gastroenterologists, and hepatologists, among other health care providers.

In cirrhosis, there are often changes to platelet (PLT) counts and prothrombin time/international normalized ratio (PT/INR), among other parameters, and historically these changes led to concerns that patients were at greater risk of bleeding or thrombosis. More recent evidence has led to a nuanced view. Neither factor necessarily suggests increased bleeding risk, and the severity of coagulopathy predicted by them does not predict the risk of bleeding complications.

Patients with cirrhosis are at greater risk of thrombosis, but clinicians may be hesitant to prescribe anticoagulants because of uncertain risk profiles, and test strategies employing PT/INR to estimate bleeding risk and track treatment endpoints in patients receiving vitamin K antagonists may not work in cirrhosis patients with alterations in procoagulant and anticoagulant measures. Recent efforts to address this led to testing of fibrin clot formation and lysis to better gauge the variety of abnormalities in cirrhosis patients.

The guideline, published in Gastroenterology, was informed by a technical review that focused on both bleeding-related and thrombosis-related questions. Bleeding-related questions included testing strategies and preprocedure prophylaxis to reduce bleeding risk. Thrombosis-related questions included whether VTE prophylaxis may be useful in hospitalized patients with cirrhosis, whether patients should be screened for PVT, potential therapies for nontumoral PVT, and whether or not anticoagulation is safe and effective when atrial fibrillation is present alongside cirrhosis.

Because of a lack of evidence, the guideline provides no recommendations on visco-elastic testing for bleeding risk in advance of common gastrointestinal procedures for patients with stable cirrhosis. It recommends against use of extensive preprocedural testing, such as repeated PT/INR or PLT count testing.

The guideline also looked at whether preprocedural efforts to correct coagulation parameters could reduce bleeding risk in patients with cirrhosis. It recommends against giving blood products ahead of the procedure for patients with stable cirrhosis without severe thrombocytopenia or severe coagulopathy. Such interventions can be considered for patients in the latter categories who are undergoing procedures with high bleeding risk after consideration of risks and benefits, and consultation with a hematologist.

Thrombopoietin receptor agonists (TPO-RAs) are also not recommended in patients with thrombocytopenia and stable cirrhosis undergoing common procedures, but they can be considered for patients who are more concerned about reduction of bleeding events and less concerned about the risk of PVT.

Patients who are hospitalized and meet the requirements should receive VTE prophylaxis. Although there is little available evidence about the effects of thromboprophylaxis in patients with cirrhosis, there is strong evidence of benefit in acutely ill hospitalized patients, and patients with cirrhosis are believed to be at a similar risk of VTE. There is evidence of increased bleed risk, but this is of very low certainty.

PVT should not be routinely tested for, but such testing can be offered to patients with a high level of concern over PVT and are not as worried about potential harms of treatment. This recommendation does not apply to patients waiting for a liver transplant.

Patients with non-umoral PVT should receive anticoagulation therapy, but patients who have high levels of concern about bleeding risk from anticoagulation and put a lower value on possible benefits of anticoagulation may choose not to receive it.

The guideline recommends anticoagulation for patients with atrial fibrillation and cirrhosis who are indicated for it. Patients with more concern about the bleeding risk of anticoagulation and place lower value on the reduction in stroke risk may choose to not receive anticoagulation. This is particularly true for those with more advanced cirrhosis (Child-Turcotte-Pugh Class C) and/or low CHA2DS2-VASC scores.

Nearly all of the recommendations in the guideline are conditional, reflecting a lack of data and a range of knowledge gaps that need filling. The authors call for additional research to identify specific patients who are at high risk for bleeding or thrombosis “to appropriately provide prophylaxis using blood product transfusion or TPO-RAs in patients at risk for clinically significant bleeding, to screen for and treat PVT, and to prevent clinically significant thromboembolic events.”

The development of the guideline was funded fully by the AGA. Members of the panel submitted conflict of interest information, and these statements are maintained at AGA headquarters.

A clinical update from the American Gastroenterological Association focuses on bleeding and thrombosis-related questions in patients with cirrhosis. It provides guidance on test strategies for bleeding risk, preprocedure management of bleeding risk, venous thromboembolism (VTE) prophylaxis, screening for portal vein thrombosis (PVT), and anticoagulation therapies. It is aimed at primary care providers, gastroenterologists, and hepatologists, among other health care providers.

In cirrhosis, there are often changes to platelet (PLT) counts and prothrombin time/international normalized ratio (PT/INR), among other parameters, and historically these changes led to concerns that patients were at greater risk of bleeding or thrombosis. More recent evidence has led to a nuanced view. Neither factor necessarily suggests increased bleeding risk, and the severity of coagulopathy predicted by them does not predict the risk of bleeding complications.

Patients with cirrhosis are at greater risk of thrombosis, but clinicians may be hesitant to prescribe anticoagulants because of uncertain risk profiles, and test strategies employing PT/INR to estimate bleeding risk and track treatment endpoints in patients receiving vitamin K antagonists may not work in cirrhosis patients with alterations in procoagulant and anticoagulant measures. Recent efforts to address this led to testing of fibrin clot formation and lysis to better gauge the variety of abnormalities in cirrhosis patients.

The guideline, published in Gastroenterology, was informed by a technical review that focused on both bleeding-related and thrombosis-related questions. Bleeding-related questions included testing strategies and preprocedure prophylaxis to reduce bleeding risk. Thrombosis-related questions included whether VTE prophylaxis may be useful in hospitalized patients with cirrhosis, whether patients should be screened for PVT, potential therapies for nontumoral PVT, and whether or not anticoagulation is safe and effective when atrial fibrillation is present alongside cirrhosis.

Because of a lack of evidence, the guideline provides no recommendations on visco-elastic testing for bleeding risk in advance of common gastrointestinal procedures for patients with stable cirrhosis. It recommends against use of extensive preprocedural testing, such as repeated PT/INR or PLT count testing.

The guideline also looked at whether preprocedural efforts to correct coagulation parameters could reduce bleeding risk in patients with cirrhosis. It recommends against giving blood products ahead of the procedure for patients with stable cirrhosis without severe thrombocytopenia or severe coagulopathy. Such interventions can be considered for patients in the latter categories who are undergoing procedures with high bleeding risk after consideration of risks and benefits, and consultation with a hematologist.

Thrombopoietin receptor agonists (TPO-RAs) are also not recommended in patients with thrombocytopenia and stable cirrhosis undergoing common procedures, but they can be considered for patients who are more concerned about reduction of bleeding events and less concerned about the risk of PVT.

Patients who are hospitalized and meet the requirements should receive VTE prophylaxis. Although there is little available evidence about the effects of thromboprophylaxis in patients with cirrhosis, there is strong evidence of benefit in acutely ill hospitalized patients, and patients with cirrhosis are believed to be at a similar risk of VTE. There is evidence of increased bleed risk, but this is of very low certainty.

PVT should not be routinely tested for, but such testing can be offered to patients with a high level of concern over PVT and are not as worried about potential harms of treatment. This recommendation does not apply to patients waiting for a liver transplant.

Patients with non-umoral PVT should receive anticoagulation therapy, but patients who have high levels of concern about bleeding risk from anticoagulation and put a lower value on possible benefits of anticoagulation may choose not to receive it.

The guideline recommends anticoagulation for patients with atrial fibrillation and cirrhosis who are indicated for it. Patients with more concern about the bleeding risk of anticoagulation and place lower value on the reduction in stroke risk may choose to not receive anticoagulation. This is particularly true for those with more advanced cirrhosis (Child-Turcotte-Pugh Class C) and/or low CHA2DS2-VASC scores.

Nearly all of the recommendations in the guideline are conditional, reflecting a lack of data and a range of knowledge gaps that need filling. The authors call for additional research to identify specific patients who are at high risk for bleeding or thrombosis “to appropriately provide prophylaxis using blood product transfusion or TPO-RAs in patients at risk for clinically significant bleeding, to screen for and treat PVT, and to prevent clinically significant thromboembolic events.”

The development of the guideline was funded fully by the AGA. Members of the panel submitted conflict of interest information, and these statements are maintained at AGA headquarters.

According to the latest meta-analysis of sham-controlled randomized trials, catheter-based renal sympathetic denervation produces clinically meaningful reductions in blood pressure with acceptable safety, but the strategy is not yet regarded as ready for prime time, according to a summary of the results to be presented at the Transcatheter Cardiovascular Therapeutics annual meeting.

This meta-analysis was based on seven blinded trials, all of which associated denervation with a reduction in systolic ambulatory BP, according to Yousif Ahmad, BMBS, PhD, an interventional cardiologist at Yale University, New Haven, Conn.

Although the BP-lowering advantage in two of these studies did not reach statistical significance, the other five did, and all the data moved in the same direction.

For ambulatory diastolic pressure, the effect was more modest. One of the studies showed essentially a neutral effect. The reductions were statistically significant in only two, but, again, the data moved in the same direction in six of the studies, and a random-effects analysis suggested that the reductions, although modest, were potentially meaningful, according to Dr. Ahmad.

Overall, at a mean follow-up of 4.5 months, the reductions in ambulatory systolic and diastolic BPs were 3.61 and 1.85 mm Hg, respectively. The benefit was about the same whether renal denervation was or was not performed on the background of antihypertensive drugs, which was permitted in five of the seven trials. In the other two, all patients were off hypertensive medication.
 

Office-based systolic reduction: 6 mm Hg

When the same analysis was performed for office-based BP reductions, which were available for five of the seven trials, the overall reductions based on the meta-analysis were 5.86 and 3.63 mm Hg for the systolic and diastolic pressures, respectively. Again, background antihypertensive therapy was not a factor.

Of the seven trials, three randomized fewer than 100 patients. The largest, SYMPLICITY HTN-3, randomized 491 patients in 2:1 ratio to denervation or sham.

Three of the studies in the meta-analysis were trials of the Symplicity flex device. Another two evaluated the Symplicity Spyral catheter. Both deliver radiofrequency energy to for denervation. The Paradise device, the focus of the remaining two trials, employs energy in the form of ultrasound.

According to Dr. Ahmad, adverse events regardless of device were rare and not more common among those in the active treatment arm than in those treated with a sham procedure. Although one of these trials, RADIANCE-HTN SOLO associated denervation with efficacy and safety out to 12 months , Dr. Ahmad concluded that the mean follow-up of 4.5 months is not sufficient to consider long-term effects.

More than 20 meta-analyses published so far

By one count, there have been more than 20 meta-analyses of renal denervation published previously yet this intervention is still considered “controversial,” according to Dr. Ahmad. Relative to the previous meta-analyses, this included the RADIANCE-HTN TRIO trial, which is the latest such sham-controlled study and added 136 patients to the dataset of high-quality trials.

Basically, the results led Dr. Ahmad to conclude that, although the treatment effect is modest, it could be valuable in specific groups of patients, such as those reluctant or unable to take multiple medications or any medications at all. In addition to generating more data on efficacy and safety, he said longer follow-up is also needed for calculations of cost-effectiveness. Larger-scale observational studies might be one way of collecting these data, he reported.

The results of this study were published online in JACC Cardiovascular Interventions with an accompanying editorial by David E. Kandzari, MD, director of interventional cardiology, Piedmont Hart Institute, Atlanta.

Commenting on the large pile of meta-analyses, sometimes published months apart, Dr. Kandzari explained that their “short half-life” is a product of the continuous updating of data with new trials. For a procedure that remains controversial, he said these constant relooks are inevitable.

“My point is that, with more studies, we can expect to see more meta-analyses. It is just the way this is going to work,” Dr. Kandzari said in an interview.
 

Individual study data also relevant

Even as the authors of these analyses attempt to cull the best data from the most rigorously performed trials, “we are also going to have to look at the individual studies, because of the differences in the trial designs, particularly the devices used,” according to Dr. Kandzari, who was the principle investigator of the sham-controlled SPYRAL HTN-ON MED trial.

So far, the data, despite some inconsistencies, have supported “clinically meaningful” BP reductions and acceptable safety regardless of the device used, according to Dr. Kandzari. Although he also agrees with the basic premise that more long-term data are needed to better determine how renal denervation should be applied in management of hypertension, he does think it will eventually find a role that is “complimentary to, rather than a replacement for, drugs.”

“The effect is modest, but keep in mind that the effect size is similar to that of a single oral medication, and there are some features, such as an always-on 24-hour effect that could be useful,” he said.

“We have enough of a signal to start thinking of how this will be enveloped into routine care,” he said.

But it is not ready yet. This was the point made by Dr. Ahmad, and it was seconded by Dr. Kandzari. One of the senior authors of the meta-analysis, Deepak Bhatt, MD, executive director of interventional cardiovascular programs, Brigham and Women’s Health, Boston, was also asked to weigh on when it will be ready for prime time.

“At a minimum, I would recommend completion of ongoing sham-controlled randomized trials before considering clinical use of renal denervation. Longer term safety and durability data, as well as data on cost-effectiveness, are all still needed – preferably from randomized trials as opposed to registries,” he said.

“Ideally, larger sham-controlled trials with longer follow-up and clinical endpoints, as opposed to only blood pressure measurements, would be performed, although I am not aware of any plans at present,” he added.

Dr. Ahmad reported no financial relationships relevant to this research. Dr. Bhatt has financial relationships with more than 30 pharmaceutical companies, including those developing products relevant to hypertension and renal denervation. Dr. Kandzari reported financial relationships with Ablative Solutions and Medtronic.

According to the latest meta-analysis of sham-controlled randomized trials, catheter-based renal sympathetic denervation produces clinically meaningful reductions in blood pressure with acceptable safety, but the strategy is not yet regarded as ready for prime time, according to a summary of the results to be presented at the Transcatheter Cardiovascular Therapeutics annual meeting.

This meta-analysis was based on seven blinded trials, all of which associated denervation with a reduction in systolic ambulatory BP, according to Yousif Ahmad, BMBS, PhD, an interventional cardiologist at Yale University, New Haven, Conn.

Although the BP-lowering advantage in two of these studies did not reach statistical significance, the other five did, and all the data moved in the same direction.

For ambulatory diastolic pressure, the effect was more modest. One of the studies showed essentially a neutral effect. The reductions were statistically significant in only two, but, again, the data moved in the same direction in six of the studies, and a random-effects analysis suggested that the reductions, although modest, were potentially meaningful, according to Dr. Ahmad.

Overall, at a mean follow-up of 4.5 months, the reductions in ambulatory systolic and diastolic BPs were 3.61 and 1.85 mm Hg, respectively. The benefit was about the same whether renal denervation was or was not performed on the background of antihypertensive drugs, which was permitted in five of the seven trials. In the other two, all patients were off hypertensive medication.
 

Office-based systolic reduction: 6 mm Hg

When the same analysis was performed for office-based BP reductions, which were available for five of the seven trials, the overall reductions based on the meta-analysis were 5.86 and 3.63 mm Hg for the systolic and diastolic pressures, respectively. Again, background antihypertensive therapy was not a factor.

Of the seven trials, three randomized fewer than 100 patients. The largest, SYMPLICITY HTN-3, randomized 491 patients in 2:1 ratio to denervation or sham.

Three of the studies in the meta-analysis were trials of the Symplicity flex device. Another two evaluated the Symplicity Spyral catheter. Both deliver radiofrequency energy to for denervation. The Paradise device, the focus of the remaining two trials, employs energy in the form of ultrasound.

According to Dr. Ahmad, adverse events regardless of device were rare and not more common among those in the active treatment arm than in those treated with a sham procedure. Although one of these trials, RADIANCE-HTN SOLO associated denervation with efficacy and safety out to 12 months , Dr. Ahmad concluded that the mean follow-up of 4.5 months is not sufficient to consider long-term effects.

More than 20 meta-analyses published so far

By one count, there have been more than 20 meta-analyses of renal denervation published previously yet this intervention is still considered “controversial,” according to Dr. Ahmad. Relative to the previous meta-analyses, this included the RADIANCE-HTN TRIO trial, which is the latest such sham-controlled study and added 136 patients to the dataset of high-quality trials.

Basically, the results led Dr. Ahmad to conclude that, although the treatment effect is modest, it could be valuable in specific groups of patients, such as those reluctant or unable to take multiple medications or any medications at all. In addition to generating more data on efficacy and safety, he said longer follow-up is also needed for calculations of cost-effectiveness. Larger-scale observational studies might be one way of collecting these data, he reported.

The results of this study were published online in JACC Cardiovascular Interventions with an accompanying editorial by David E. Kandzari, MD, director of interventional cardiology, Piedmont Hart Institute, Atlanta.

Commenting on the large pile of meta-analyses, sometimes published months apart, Dr. Kandzari explained that their “short half-life” is a product of the continuous updating of data with new trials. For a procedure that remains controversial, he said these constant relooks are inevitable.

“My point is that, with more studies, we can expect to see more meta-analyses. It is just the way this is going to work,” Dr. Kandzari said in an interview.
 

Individual study data also relevant

Even as the authors of these analyses attempt to cull the best data from the most rigorously performed trials, “we are also going to have to look at the individual studies, because of the differences in the trial designs, particularly the devices used,” according to Dr. Kandzari, who was the principle investigator of the sham-controlled SPYRAL HTN-ON MED trial.

So far, the data, despite some inconsistencies, have supported “clinically meaningful” BP reductions and acceptable safety regardless of the device used, according to Dr. Kandzari. Although he also agrees with the basic premise that more long-term data are needed to better determine how renal denervation should be applied in management of hypertension, he does think it will eventually find a role that is “complimentary to, rather than a replacement for, drugs.”

“The effect is modest, but keep in mind that the effect size is similar to that of a single oral medication, and there are some features, such as an always-on 24-hour effect that could be useful,” he said.

“We have enough of a signal to start thinking of how this will be enveloped into routine care,” he said.

But it is not ready yet. This was the point made by Dr. Ahmad, and it was seconded by Dr. Kandzari. One of the senior authors of the meta-analysis, Deepak Bhatt, MD, executive director of interventional cardiovascular programs, Brigham and Women’s Health, Boston, was also asked to weigh on when it will be ready for prime time.

“At a minimum, I would recommend completion of ongoing sham-controlled randomized trials before considering clinical use of renal denervation. Longer term safety and durability data, as well as data on cost-effectiveness, are all still needed – preferably from randomized trials as opposed to registries,” he said.

“Ideally, larger sham-controlled trials with longer follow-up and clinical endpoints, as opposed to only blood pressure measurements, would be performed, although I am not aware of any plans at present,” he added.

Dr. Ahmad reported no financial relationships relevant to this research. Dr. Bhatt has financial relationships with more than 30 pharmaceutical companies, including those developing products relevant to hypertension and renal denervation. Dr. Kandzari reported financial relationships with Ablative Solutions and Medtronic.

According to the latest meta-analysis of sham-controlled randomized trials, catheter-based renal sympathetic denervation produces clinically meaningful reductions in blood pressure with acceptable safety, but the strategy is not yet regarded as ready for prime time, according to a summary of the results to be presented at the Transcatheter Cardiovascular Therapeutics annual meeting.

This meta-analysis was based on seven blinded trials, all of which associated denervation with a reduction in systolic ambulatory BP, according to Yousif Ahmad, BMBS, PhD, an interventional cardiologist at Yale University, New Haven, Conn.

Although the BP-lowering advantage in two of these studies did not reach statistical significance, the other five did, and all the data moved in the same direction.

For ambulatory diastolic pressure, the effect was more modest. One of the studies showed essentially a neutral effect. The reductions were statistically significant in only two, but, again, the data moved in the same direction in six of the studies, and a random-effects analysis suggested that the reductions, although modest, were potentially meaningful, according to Dr. Ahmad.

Overall, at a mean follow-up of 4.5 months, the reductions in ambulatory systolic and diastolic BPs were 3.61 and 1.85 mm Hg, respectively. The benefit was about the same whether renal denervation was or was not performed on the background of antihypertensive drugs, which was permitted in five of the seven trials. In the other two, all patients were off hypertensive medication.
 

Office-based systolic reduction: 6 mm Hg

When the same analysis was performed for office-based BP reductions, which were available for five of the seven trials, the overall reductions based on the meta-analysis were 5.86 and 3.63 mm Hg for the systolic and diastolic pressures, respectively. Again, background antihypertensive therapy was not a factor.

Of the seven trials, three randomized fewer than 100 patients. The largest, SYMPLICITY HTN-3, randomized 491 patients in 2:1 ratio to denervation or sham.

Three of the studies in the meta-analysis were trials of the Symplicity flex device. Another two evaluated the Symplicity Spyral catheter. Both deliver radiofrequency energy to for denervation. The Paradise device, the focus of the remaining two trials, employs energy in the form of ultrasound.

According to Dr. Ahmad, adverse events regardless of device were rare and not more common among those in the active treatment arm than in those treated with a sham procedure. Although one of these trials, RADIANCE-HTN SOLO associated denervation with efficacy and safety out to 12 months , Dr. Ahmad concluded that the mean follow-up of 4.5 months is not sufficient to consider long-term effects.

More than 20 meta-analyses published so far

By one count, there have been more than 20 meta-analyses of renal denervation published previously yet this intervention is still considered “controversial,” according to Dr. Ahmad. Relative to the previous meta-analyses, this included the RADIANCE-HTN TRIO trial, which is the latest such sham-controlled study and added 136 patients to the dataset of high-quality trials.

Basically, the results led Dr. Ahmad to conclude that, although the treatment effect is modest, it could be valuable in specific groups of patients, such as those reluctant or unable to take multiple medications or any medications at all. In addition to generating more data on efficacy and safety, he said longer follow-up is also needed for calculations of cost-effectiveness. Larger-scale observational studies might be one way of collecting these data, he reported.

The results of this study were published online in JACC Cardiovascular Interventions with an accompanying editorial by David E. Kandzari, MD, director of interventional cardiology, Piedmont Hart Institute, Atlanta.

Commenting on the large pile of meta-analyses, sometimes published months apart, Dr. Kandzari explained that their “short half-life” is a product of the continuous updating of data with new trials. For a procedure that remains controversial, he said these constant relooks are inevitable.

“My point is that, with more studies, we can expect to see more meta-analyses. It is just the way this is going to work,” Dr. Kandzari said in an interview.
 

Individual study data also relevant

Even as the authors of these analyses attempt to cull the best data from the most rigorously performed trials, “we are also going to have to look at the individual studies, because of the differences in the trial designs, particularly the devices used,” according to Dr. Kandzari, who was the principle investigator of the sham-controlled SPYRAL HTN-ON MED trial.

So far, the data, despite some inconsistencies, have supported “clinically meaningful” BP reductions and acceptable safety regardless of the device used, according to Dr. Kandzari. Although he also agrees with the basic premise that more long-term data are needed to better determine how renal denervation should be applied in management of hypertension, he does think it will eventually find a role that is “complimentary to, rather than a replacement for, drugs.”

“The effect is modest, but keep in mind that the effect size is similar to that of a single oral medication, and there are some features, such as an always-on 24-hour effect that could be useful,” he said.

“We have enough of a signal to start thinking of how this will be enveloped into routine care,” he said.

But it is not ready yet. This was the point made by Dr. Ahmad, and it was seconded by Dr. Kandzari. One of the senior authors of the meta-analysis, Deepak Bhatt, MD, executive director of interventional cardiovascular programs, Brigham and Women’s Health, Boston, was also asked to weigh on when it will be ready for prime time.

“At a minimum, I would recommend completion of ongoing sham-controlled randomized trials before considering clinical use of renal denervation. Longer term safety and durability data, as well as data on cost-effectiveness, are all still needed – preferably from randomized trials as opposed to registries,” he said.

“Ideally, larger sham-controlled trials with longer follow-up and clinical endpoints, as opposed to only blood pressure measurements, would be performed, although I am not aware of any plans at present,” he added.

Dr. Ahmad reported no financial relationships relevant to this research. Dr. Bhatt has financial relationships with more than 30 pharmaceutical companies, including those developing products relevant to hypertension and renal denervation. Dr. Kandzari reported financial relationships with Ablative Solutions and Medtronic.

No, Mr. Bond, I expect you to die

Movie watching usually requires a certain suspension of disbelief, and it’s safe to say James Bond movies require this more than most. Between the impossible gadgets and ludicrous doomsday plans, very few have ever stopped to consider the health risks of the James Bond universe.

Tumisu/Pixabay

Now, however, Bond, James Bond, has met his most formidable opponent: Wouter Graumans, a graduate student in epidemiology from the Netherlands. During a foray to Burkina Faso to study infectious diseases, Mr. Graumans came down with a case of food poisoning, which led him to wonder how 007 is able to trot across this big world of ours without contracting so much as a sinus infection.

Because Mr. Graumans is a man of science and conviction, mere speculation wasn’t enough. He and a group of coauthors wrote an entire paper on the health risks of the James Bond universe.

Doing so required watching over 3,000 minutes of numerous movies and analyzing Bond’s 86 total trips to 46 different countries based on current Centers for Disease Control and Prevention advice for travel to those countries. Time which, the authors state in the abstract, “could easily have been spent on more pressing societal issues or forms of relaxation that are more acceptable in academic circles.”

Naturally, Mr. Bond’s line of work entails exposure to unpleasant things, such as poison, dehydration, heatstroke, and dangerous wildlife (everything from ticks to crocodiles), though oddly enough he never succumbs to any of it. He’s also curiously immune to hangovers, despite rarely drinking anything nonalcoholic. There are also less obvious risks: For one, 007 rarely washes his hands. During one movie, he handles raw chicken to lure away a pack of crocodiles but fails to wash his hands afterward, leaving him at risk for multiple food-borne illnesses.

Of course, we must address the elephant in the bedroom: Mr. Bond’s numerous, er, encounters with women. One would imagine the biggest risk to those women would be from the various STDs that likely course through Bond’s body, but of the 27% who died shortly after … encountering … him, all involved violence, with disease playing no obvious role. Who knows, maybe he’s clean? Stranger things have happened.

The timing of this article may seem a bit suspicious. Was it a PR stunt by the studio? Rest assured, the authors addressed this, noting that they received no funding for the study, and that, “given the futility of its academic value, this is deemed entirely appropriate by all authors.” We love when a punchline writes itself.
 

How to see Atlanta on $688.35 a day

The world is always changing, so we have to change with it. This week, LOTME becomes a travel guide, and our first stop is the Big A, the Big Peach, Dogwood City, Empire City of the South, Wakanda.

There’s lots to do in Atlanta: Celebrate a World Series win, visit the College Football Hall of Fame or the World of Coca Cola, or take the Stranger Things/Upside Down film locations tour. Serious adventurers, however, get out of the city and go to Emory Decatur Hospital in – you guessed it – Decatur (unofficial motto: “Everything is Greater in Decatur”).

©Getty Images

Find the emergency room and ask for Taylor Davis, who will be your personal guide. She’ll show you how to check in at the desk, sit in the waiting room for 7 hours, and then leave without seeing any medical personnel or receiving any sort of attention whatsoever. All the things she did when she went there in July for a head injury.

Ms. Davis told Fox5 Atlanta: “I didn’t get my vitals taken, nobody called my name. I wasn’t seen at all.”

But wait! There’s more! By booking your trip through LOTMEgo* and using the code “Decatur,” you’ll get the Taylor Davis special, which includes a bill/cover charge for $688.35 from the hospital. An Emory Healthcare patient financial services employee told Ms. Davis that “you get charged before you are seen. Not for being seen.”

If all this has you ready to hop in your car (really?), then check out LOTMEgo* on Twittbook and InstaTok. You’ll also find trick-or-treating tips and discounts on haunted hospital tours.

*Does not actually exist

Breaking down the hot flash

Do you ever wonder why we scramble for cold things when we’re feeling nauseous? Whether it’s the cool air that needs to hit your face in the car or a cold, damp towel on the back of your neck, scientists think it could possibly be an evolutionary mechanism at the cellular level.

Piqsels

Motion sickness it’s actually a battle of body temperature, according to an article from LiveScience. Capillaries in the skin dilate, allowing for more blood flow near the skin’s surface and causing core temperature to fall. Once body temperature drops, the hypothalamus, which regulates temperature, tries to do its job by raising body temperature. Thus the hot flash!

The cold compress and cool air help fight the battle by counteracting the hypothalamus, but why the drop in body temperature to begin with?

There are a few theories. Dr. Robert Glatter, an emergency physician at Lenox Hill Hospital in New York, told LiveScience that the lack of oxygen needed in body tissue to survive at lower temperatures could be making it difficult to get oxygen to the body when a person is ill, and is “more likely an adaptive response influenced by poorly understood mechanisms at the cellular level.”

Another theory is that the nausea and body temperature shift is the body’s natural response to help people vomit.

Then there’s the theory of “defensive hypothermia,” which suggests that cold sweats are a possible mechanism to conserve energy so the body can fight off an intruder, which was supported by a 2014 study and a 2016 review.

It’s another one of the body’s many survival tricks.
 

Teachers were right: Pupils can do the math

Teachers liked to preach that we wouldn’t have calculators with us all the time, but that wound up not being true. Our phones have calculators at the press of a button. But maybe even calculators aren’t always needed because our pupils do more math than you think.

pxfuel

The pupil light reflex – constrict in light and dilate in darkness – is well known, but recent work shows that pupil size is also regulated by cognitive and perceptual factors. By presenting subjects with images of various numbers of dots and measuring pupil size, the investigators were able to show “that numerical information is intrinsically related to perception,” lead author Dr. Elisa Castaldi of Florence University noted in a written statement.

The researchers found that pupils are responsible for important survival techniques. Coauthor David Burr of the University of Sydney and the University of Florence gave an evolutionary perspective: “When we look around, we spontaneously perceive the form, size, movement and colour of a scene. Equally spontaneously, we perceive the number of items before us. This ability, shared with most other animals, is an evolutionary fundamental: It reveals immediately important quantities, such as how many apples there are on the tree, or how many enemies are attacking.”

Useful information, indeed, but our pupils seem to be more interested in the quantity of beers in the refrigerator.

No, Mr. Bond, I expect you to die

Movie watching usually requires a certain suspension of disbelief, and it’s safe to say James Bond movies require this more than most. Between the impossible gadgets and ludicrous doomsday plans, very few have ever stopped to consider the health risks of the James Bond universe.

Tumisu/Pixabay

Now, however, Bond, James Bond, has met his most formidable opponent: Wouter Graumans, a graduate student in epidemiology from the Netherlands. During a foray to Burkina Faso to study infectious diseases, Mr. Graumans came down with a case of food poisoning, which led him to wonder how 007 is able to trot across this big world of ours without contracting so much as a sinus infection.

Because Mr. Graumans is a man of science and conviction, mere speculation wasn’t enough. He and a group of coauthors wrote an entire paper on the health risks of the James Bond universe.

Doing so required watching over 3,000 minutes of numerous movies and analyzing Bond’s 86 total trips to 46 different countries based on current Centers for Disease Control and Prevention advice for travel to those countries. Time which, the authors state in the abstract, “could easily have been spent on more pressing societal issues or forms of relaxation that are more acceptable in academic circles.”

Naturally, Mr. Bond’s line of work entails exposure to unpleasant things, such as poison, dehydration, heatstroke, and dangerous wildlife (everything from ticks to crocodiles), though oddly enough he never succumbs to any of it. He’s also curiously immune to hangovers, despite rarely drinking anything nonalcoholic. There are also less obvious risks: For one, 007 rarely washes his hands. During one movie, he handles raw chicken to lure away a pack of crocodiles but fails to wash his hands afterward, leaving him at risk for multiple food-borne illnesses.

Of course, we must address the elephant in the bedroom: Mr. Bond’s numerous, er, encounters with women. One would imagine the biggest risk to those women would be from the various STDs that likely course through Bond’s body, but of the 27% who died shortly after … encountering … him, all involved violence, with disease playing no obvious role. Who knows, maybe he’s clean? Stranger things have happened.

The timing of this article may seem a bit suspicious. Was it a PR stunt by the studio? Rest assured, the authors addressed this, noting that they received no funding for the study, and that, “given the futility of its academic value, this is deemed entirely appropriate by all authors.” We love when a punchline writes itself.
 

How to see Atlanta on $688.35 a day

The world is always changing, so we have to change with it. This week, LOTME becomes a travel guide, and our first stop is the Big A, the Big Peach, Dogwood City, Empire City of the South, Wakanda.

There’s lots to do in Atlanta: Celebrate a World Series win, visit the College Football Hall of Fame or the World of Coca Cola, or take the Stranger Things/Upside Down film locations tour. Serious adventurers, however, get out of the city and go to Emory Decatur Hospital in – you guessed it – Decatur (unofficial motto: “Everything is Greater in Decatur”).

©Getty Images

Find the emergency room and ask for Taylor Davis, who will be your personal guide. She’ll show you how to check in at the desk, sit in the waiting room for 7 hours, and then leave without seeing any medical personnel or receiving any sort of attention whatsoever. All the things she did when she went there in July for a head injury.

Ms. Davis told Fox5 Atlanta: “I didn’t get my vitals taken, nobody called my name. I wasn’t seen at all.”

But wait! There’s more! By booking your trip through LOTMEgo* and using the code “Decatur,” you’ll get the Taylor Davis special, which includes a bill/cover charge for $688.35 from the hospital. An Emory Healthcare patient financial services employee told Ms. Davis that “you get charged before you are seen. Not for being seen.”

If all this has you ready to hop in your car (really?), then check out LOTMEgo* on Twittbook and InstaTok. You’ll also find trick-or-treating tips and discounts on haunted hospital tours.

*Does not actually exist

Breaking down the hot flash

Do you ever wonder why we scramble for cold things when we’re feeling nauseous? Whether it’s the cool air that needs to hit your face in the car or a cold, damp towel on the back of your neck, scientists think it could possibly be an evolutionary mechanism at the cellular level.

Piqsels

Motion sickness it’s actually a battle of body temperature, according to an article from LiveScience. Capillaries in the skin dilate, allowing for more blood flow near the skin’s surface and causing core temperature to fall. Once body temperature drops, the hypothalamus, which regulates temperature, tries to do its job by raising body temperature. Thus the hot flash!

The cold compress and cool air help fight the battle by counteracting the hypothalamus, but why the drop in body temperature to begin with?

There are a few theories. Dr. Robert Glatter, an emergency physician at Lenox Hill Hospital in New York, told LiveScience that the lack of oxygen needed in body tissue to survive at lower temperatures could be making it difficult to get oxygen to the body when a person is ill, and is “more likely an adaptive response influenced by poorly understood mechanisms at the cellular level.”

Another theory is that the nausea and body temperature shift is the body’s natural response to help people vomit.

Then there’s the theory of “defensive hypothermia,” which suggests that cold sweats are a possible mechanism to conserve energy so the body can fight off an intruder, which was supported by a 2014 study and a 2016 review.

It’s another one of the body’s many survival tricks.
 

Teachers were right: Pupils can do the math

Teachers liked to preach that we wouldn’t have calculators with us all the time, but that wound up not being true. Our phones have calculators at the press of a button. But maybe even calculators aren’t always needed because our pupils do more math than you think.

pxfuel

The pupil light reflex – constrict in light and dilate in darkness – is well known, but recent work shows that pupil size is also regulated by cognitive and perceptual factors. By presenting subjects with images of various numbers of dots and measuring pupil size, the investigators were able to show “that numerical information is intrinsically related to perception,” lead author Dr. Elisa Castaldi of Florence University noted in a written statement.

The researchers found that pupils are responsible for important survival techniques. Coauthor David Burr of the University of Sydney and the University of Florence gave an evolutionary perspective: “When we look around, we spontaneously perceive the form, size, movement and colour of a scene. Equally spontaneously, we perceive the number of items before us. This ability, shared with most other animals, is an evolutionary fundamental: It reveals immediately important quantities, such as how many apples there are on the tree, or how many enemies are attacking.”

Useful information, indeed, but our pupils seem to be more interested in the quantity of beers in the refrigerator.

No, Mr. Bond, I expect you to die

Movie watching usually requires a certain suspension of disbelief, and it’s safe to say James Bond movies require this more than most. Between the impossible gadgets and ludicrous doomsday plans, very few have ever stopped to consider the health risks of the James Bond universe.

Tumisu/Pixabay

Now, however, Bond, James Bond, has met his most formidable opponent: Wouter Graumans, a graduate student in epidemiology from the Netherlands. During a foray to Burkina Faso to study infectious diseases, Mr. Graumans came down with a case of food poisoning, which led him to wonder how 007 is able to trot across this big world of ours without contracting so much as a sinus infection.

Because Mr. Graumans is a man of science and conviction, mere speculation wasn’t enough. He and a group of coauthors wrote an entire paper on the health risks of the James Bond universe.

Doing so required watching over 3,000 minutes of numerous movies and analyzing Bond’s 86 total trips to 46 different countries based on current Centers for Disease Control and Prevention advice for travel to those countries. Time which, the authors state in the abstract, “could easily have been spent on more pressing societal issues or forms of relaxation that are more acceptable in academic circles.”

Naturally, Mr. Bond’s line of work entails exposure to unpleasant things, such as poison, dehydration, heatstroke, and dangerous wildlife (everything from ticks to crocodiles), though oddly enough he never succumbs to any of it. He’s also curiously immune to hangovers, despite rarely drinking anything nonalcoholic. There are also less obvious risks: For one, 007 rarely washes his hands. During one movie, he handles raw chicken to lure away a pack of crocodiles but fails to wash his hands afterward, leaving him at risk for multiple food-borne illnesses.

Of course, we must address the elephant in the bedroom: Mr. Bond’s numerous, er, encounters with women. One would imagine the biggest risk to those women would be from the various STDs that likely course through Bond’s body, but of the 27% who died shortly after … encountering … him, all involved violence, with disease playing no obvious role. Who knows, maybe he’s clean? Stranger things have happened.

The timing of this article may seem a bit suspicious. Was it a PR stunt by the studio? Rest assured, the authors addressed this, noting that they received no funding for the study, and that, “given the futility of its academic value, this is deemed entirely appropriate by all authors.” We love when a punchline writes itself.
 

How to see Atlanta on $688.35 a day

The world is always changing, so we have to change with it. This week, LOTME becomes a travel guide, and our first stop is the Big A, the Big Peach, Dogwood City, Empire City of the South, Wakanda.

There’s lots to do in Atlanta: Celebrate a World Series win, visit the College Football Hall of Fame or the World of Coca Cola, or take the Stranger Things/Upside Down film locations tour. Serious adventurers, however, get out of the city and go to Emory Decatur Hospital in – you guessed it – Decatur (unofficial motto: “Everything is Greater in Decatur”).

©Getty Images

Find the emergency room and ask for Taylor Davis, who will be your personal guide. She’ll show you how to check in at the desk, sit in the waiting room for 7 hours, and then leave without seeing any medical personnel or receiving any sort of attention whatsoever. All the things she did when she went there in July for a head injury.

Ms. Davis told Fox5 Atlanta: “I didn’t get my vitals taken, nobody called my name. I wasn’t seen at all.”

But wait! There’s more! By booking your trip through LOTMEgo* and using the code “Decatur,” you’ll get the Taylor Davis special, which includes a bill/cover charge for $688.35 from the hospital. An Emory Healthcare patient financial services employee told Ms. Davis that “you get charged before you are seen. Not for being seen.”

If all this has you ready to hop in your car (really?), then check out LOTMEgo* on Twittbook and InstaTok. You’ll also find trick-or-treating tips and discounts on haunted hospital tours.

*Does not actually exist

Breaking down the hot flash

Do you ever wonder why we scramble for cold things when we’re feeling nauseous? Whether it’s the cool air that needs to hit your face in the car or a cold, damp towel on the back of your neck, scientists think it could possibly be an evolutionary mechanism at the cellular level.

Piqsels

Motion sickness it’s actually a battle of body temperature, according to an article from LiveScience. Capillaries in the skin dilate, allowing for more blood flow near the skin’s surface and causing core temperature to fall. Once body temperature drops, the hypothalamus, which regulates temperature, tries to do its job by raising body temperature. Thus the hot flash!

The cold compress and cool air help fight the battle by counteracting the hypothalamus, but why the drop in body temperature to begin with?

There are a few theories. Dr. Robert Glatter, an emergency physician at Lenox Hill Hospital in New York, told LiveScience that the lack of oxygen needed in body tissue to survive at lower temperatures could be making it difficult to get oxygen to the body when a person is ill, and is “more likely an adaptive response influenced by poorly understood mechanisms at the cellular level.”

Another theory is that the nausea and body temperature shift is the body’s natural response to help people vomit.

Then there’s the theory of “defensive hypothermia,” which suggests that cold sweats are a possible mechanism to conserve energy so the body can fight off an intruder, which was supported by a 2014 study and a 2016 review.

It’s another one of the body’s many survival tricks.
 

Teachers were right: Pupils can do the math

Teachers liked to preach that we wouldn’t have calculators with us all the time, but that wound up not being true. Our phones have calculators at the press of a button. But maybe even calculators aren’t always needed because our pupils do more math than you think.

pxfuel

The pupil light reflex – constrict in light and dilate in darkness – is well known, but recent work shows that pupil size is also regulated by cognitive and perceptual factors. By presenting subjects with images of various numbers of dots and measuring pupil size, the investigators were able to show “that numerical information is intrinsically related to perception,” lead author Dr. Elisa Castaldi of Florence University noted in a written statement.

The researchers found that pupils are responsible for important survival techniques. Coauthor David Burr of the University of Sydney and the University of Florence gave an evolutionary perspective: “When we look around, we spontaneously perceive the form, size, movement and colour of a scene. Equally spontaneously, we perceive the number of items before us. This ability, shared with most other animals, is an evolutionary fundamental: It reveals immediately important quantities, such as how many apples there are on the tree, or how many enemies are attacking.”

Useful information, indeed, but our pupils seem to be more interested in the quantity of beers in the refrigerator.

In the longest study of bone loss in postmenopausal women to date, on average, bone mineral density (BMD) at the femoral neck (the most common location for a hip fracture) had dropped by 10% in 25 years – less than expected based on shorter studies.

Specifically, average BMD loss at the femoral neck was 0.4% per year during 25 years in this new study from Finland, compared with a drop of 1.6% per year over 15 years reported in other cohorts.

Five-year BMD change appeared to predict long-term bone loss. However, certain women had faster bone loss, indicating that they should be followed more closely.

“Although the average bone loss was 10.1% ... there is a significant variation in the bone loss rate” among women in the study, senior author Joonas Sirola, MD, PhD, associate professor, University of Eastern Finland, and coauthor Heikki Kröger, MD, PhD, a professor at the same university, explained to this news organization in an email, so “women with fast bone loss should receive special attention.

The findings from the Kuopio Osteoporosis Risk Factor and Prevention study by Anna Moilanen and colleagues were published online October 19 in the Journal of Bone and Mineral Research.

Several factors might explain the lower than expected drop in femoral neck BMD (the site that is used to diagnose osteoporosis), Dr. Sirola and Dr. Kröger said. BMD depends on a person’s age, race, sex, and genes. And compared with other countries, people in Finland consume more dairy products, and more postmenopausal women there take hormone replacement therapy (HRT).

“If otherwise indicated, HRT seemed to effectively protect from bone loss,” the researchers noted.

Also, the number of women who smoked or used corticosteroids was low, so bone loss in other populations may be higher. Moreover, the women who completed the study may have been healthier to start with, so the results should be interpreted with caution, they urge.

Nevertheless, the study sheds light on long-term changes in BMD in postmenopausal women and “stresses the importance of high peak bone mass before menopause and keeping a healthy weight” during aging to protect bone health, they say.

Indeed the work “changes our understanding of bone loss in older women,” said Dr. Kröger in a press release from the university.
 

Check BMD every 5 years after menopause

Invited to comment, American Society of Bone and Mineral Research President Peter R. Ebeling, MD, who was not involved with the research, noted key findings are that the rate of femoral neck bone loss after perimenopause was far less than previously expected, and 5-year BMD change appeared to predict long-term bone loss in postmenopausal women.

“We know bone loss begins 1 year before menopause and accelerates over the next 5 years,” Dr. Ebeling, from Monash University, Melbourne, added in an email. “This study indicates some stabilization of bone loss thereafter with lesser effects of low estrogen levels on bone.”

“It probably means bone density does not need to be measured as frequently following the menopause transition and could be every 5 years, rather than every 2 years, if there was concern about continuing bone loss.”
 

Baseline risk factors and long-term changes in BMD

For the study, researchers examined the association between risk factors for bone loss and long-term changes in femoral neck BMD in 2,695 women living in Kuopio who were 47 to 56 years old in 1989. The women were a mean age of 53 years, and 62% were postmenopausal.

They answered questionnaires and had femoral neck BMD measured by DEXA every 5 years.

A total of 2,695, 2,583, 2,482, 2,135, 1,305, and 686 women were assessed at baseline and 5-, 10-, 15-, 20- and 25-year follow-ups, respectively, indicating significant study drop-out by 25 years. 

By then, 17% of patients had died, 9% needed long-term care, some were unwilling to continue in the study, and others had factors that would have resulted in DEXA measurement errors (for example, hip implants, spine degeneration).

Researchers divided participants into quartiles of mean initial femoral neck BMD: 1.09 g/cm2, 0.97 g/cm2, 0.89 g/cm2, and 0.79 g/cm2, corresponding with quartiles 1 to 4 respectively (where quartile 1 had the highest initial femoral BMD and quartile 4 the lowest).

At 25 years, the mean femoral BMD had dropped to 0.97 g/cm2, 0.87 g/cm2, 0.80 g/cm2, and 0.73 g/cm2 in these respective quartiles.

Women lost 0.9%, 0.5%, 3.0%, and 1.0% of their initial BMD each year in quartiles 1 to 4, respectively.

And at 25 years, the women had lost 22.5%, 12.5%, 7.5%, and 2.5% of their initial BMD in the four quartiles, respectively.

Women in quartile 1 had the greatest drop in femoral BMD at 25 years, although their mean BMD at 25 years was higher than the mean initial BMD of the other women. 

The prevalence of bone-affecting diseases, smoking, and use of vitamin D/calcium supplementation, corticosteroids, or alcohol was similar in the four quartiles and was not associated with significant differences in annual bone loss.
 

The most important protective factor was HRT

However, body mass index (BMI) and HRT were significantly different in the four quartiles.

On average, women in quartile 1 had a mean BMI of 26.7 kg/m2 at baseline and 27.8 kg/m2 at 25 years. Women in quartile 4 (lowest initial BMD and lowest drop in BMD) had a mean BMI of 24.9 kg/m2 at baseline and 28.4 kg/m2 at 25 years.

Women in quartile 4 (lowest initial BMD and lowest drop in BMD) were more likely to take HRT than women in quartile 1 (highest initial BMD and highest drop in BMD), at 41% versus 26%, respectively.

“The average decrease in bone mineral density was lower than has been assumed on the basis of earlier, shorter follow-ups where the bone loss rate at the femoral neck has been estimated to be even more than 20%,” Dr. Sirola commented in the press release.

“There were also surprisingly few risk factors affecting bone mineral density. The most significant factor protecting against bone loss was hormone replacement therapy. Weight gain during the follow-up also protected against bone loss,” Dr. Sirola added.

The study was funded by the Academy of Finland, Finnish Ministry of Education and Culture, and the Päivikki and Sakari Sohlberg Foundation. The authors and Dr. Ebeling have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

In the longest study of bone loss in postmenopausal women to date, on average, bone mineral density (BMD) at the femoral neck (the most common location for a hip fracture) had dropped by 10% in 25 years – less than expected based on shorter studies.

Specifically, average BMD loss at the femoral neck was 0.4% per year during 25 years in this new study from Finland, compared with a drop of 1.6% per year over 15 years reported in other cohorts.

Five-year BMD change appeared to predict long-term bone loss. However, certain women had faster bone loss, indicating that they should be followed more closely.

“Although the average bone loss was 10.1% ... there is a significant variation in the bone loss rate” among women in the study, senior author Joonas Sirola, MD, PhD, associate professor, University of Eastern Finland, and coauthor Heikki Kröger, MD, PhD, a professor at the same university, explained to this news organization in an email, so “women with fast bone loss should receive special attention.

The findings from the Kuopio Osteoporosis Risk Factor and Prevention study by Anna Moilanen and colleagues were published online October 19 in the Journal of Bone and Mineral Research.

Several factors might explain the lower than expected drop in femoral neck BMD (the site that is used to diagnose osteoporosis), Dr. Sirola and Dr. Kröger said. BMD depends on a person’s age, race, sex, and genes. And compared with other countries, people in Finland consume more dairy products, and more postmenopausal women there take hormone replacement therapy (HRT).

“If otherwise indicated, HRT seemed to effectively protect from bone loss,” the researchers noted.

Also, the number of women who smoked or used corticosteroids was low, so bone loss in other populations may be higher. Moreover, the women who completed the study may have been healthier to start with, so the results should be interpreted with caution, they urge.

Nevertheless, the study sheds light on long-term changes in BMD in postmenopausal women and “stresses the importance of high peak bone mass before menopause and keeping a healthy weight” during aging to protect bone health, they say.

Indeed the work “changes our understanding of bone loss in older women,” said Dr. Kröger in a press release from the university.
 

Check BMD every 5 years after menopause

Invited to comment, American Society of Bone and Mineral Research President Peter R. Ebeling, MD, who was not involved with the research, noted key findings are that the rate of femoral neck bone loss after perimenopause was far less than previously expected, and 5-year BMD change appeared to predict long-term bone loss in postmenopausal women.

“We know bone loss begins 1 year before menopause and accelerates over the next 5 years,” Dr. Ebeling, from Monash University, Melbourne, added in an email. “This study indicates some stabilization of bone loss thereafter with lesser effects of low estrogen levels on bone.”

“It probably means bone density does not need to be measured as frequently following the menopause transition and could be every 5 years, rather than every 2 years, if there was concern about continuing bone loss.”
 

Baseline risk factors and long-term changes in BMD

For the study, researchers examined the association between risk factors for bone loss and long-term changes in femoral neck BMD in 2,695 women living in Kuopio who were 47 to 56 years old in 1989. The women were a mean age of 53 years, and 62% were postmenopausal.

They answered questionnaires and had femoral neck BMD measured by DEXA every 5 years.

A total of 2,695, 2,583, 2,482, 2,135, 1,305, and 686 women were assessed at baseline and 5-, 10-, 15-, 20- and 25-year follow-ups, respectively, indicating significant study drop-out by 25 years. 

By then, 17% of patients had died, 9% needed long-term care, some were unwilling to continue in the study, and others had factors that would have resulted in DEXA measurement errors (for example, hip implants, spine degeneration).

Researchers divided participants into quartiles of mean initial femoral neck BMD: 1.09 g/cm2, 0.97 g/cm2, 0.89 g/cm2, and 0.79 g/cm2, corresponding with quartiles 1 to 4 respectively (where quartile 1 had the highest initial femoral BMD and quartile 4 the lowest).

At 25 years, the mean femoral BMD had dropped to 0.97 g/cm2, 0.87 g/cm2, 0.80 g/cm2, and 0.73 g/cm2 in these respective quartiles.

Women lost 0.9%, 0.5%, 3.0%, and 1.0% of their initial BMD each year in quartiles 1 to 4, respectively.

And at 25 years, the women had lost 22.5%, 12.5%, 7.5%, and 2.5% of their initial BMD in the four quartiles, respectively.

Women in quartile 1 had the greatest drop in femoral BMD at 25 years, although their mean BMD at 25 years was higher than the mean initial BMD of the other women. 

The prevalence of bone-affecting diseases, smoking, and use of vitamin D/calcium supplementation, corticosteroids, or alcohol was similar in the four quartiles and was not associated with significant differences in annual bone loss.
 

The most important protective factor was HRT

However, body mass index (BMI) and HRT were significantly different in the four quartiles.

On average, women in quartile 1 had a mean BMI of 26.7 kg/m2 at baseline and 27.8 kg/m2 at 25 years. Women in quartile 4 (lowest initial BMD and lowest drop in BMD) had a mean BMI of 24.9 kg/m2 at baseline and 28.4 kg/m2 at 25 years.

Women in quartile 4 (lowest initial BMD and lowest drop in BMD) were more likely to take HRT than women in quartile 1 (highest initial BMD and highest drop in BMD), at 41% versus 26%, respectively.

“The average decrease in bone mineral density was lower than has been assumed on the basis of earlier, shorter follow-ups where the bone loss rate at the femoral neck has been estimated to be even more than 20%,” Dr. Sirola commented in the press release.

“There were also surprisingly few risk factors affecting bone mineral density. The most significant factor protecting against bone loss was hormone replacement therapy. Weight gain during the follow-up also protected against bone loss,” Dr. Sirola added.

The study was funded by the Academy of Finland, Finnish Ministry of Education and Culture, and the Päivikki and Sakari Sohlberg Foundation. The authors and Dr. Ebeling have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

In the longest study of bone loss in postmenopausal women to date, on average, bone mineral density (BMD) at the femoral neck (the most common location for a hip fracture) had dropped by 10% in 25 years – less than expected based on shorter studies.

Specifically, average BMD loss at the femoral neck was 0.4% per year during 25 years in this new study from Finland, compared with a drop of 1.6% per year over 15 years reported in other cohorts.

Five-year BMD change appeared to predict long-term bone loss. However, certain women had faster bone loss, indicating that they should be followed more closely.

“Although the average bone loss was 10.1% ... there is a significant variation in the bone loss rate” among women in the study, senior author Joonas Sirola, MD, PhD, associate professor, University of Eastern Finland, and coauthor Heikki Kröger, MD, PhD, a professor at the same university, explained to this news organization in an email, so “women with fast bone loss should receive special attention.

The findings from the Kuopio Osteoporosis Risk Factor and Prevention study by Anna Moilanen and colleagues were published online October 19 in the Journal of Bone and Mineral Research.

Several factors might explain the lower than expected drop in femoral neck BMD (the site that is used to diagnose osteoporosis), Dr. Sirola and Dr. Kröger said. BMD depends on a person’s age, race, sex, and genes. And compared with other countries, people in Finland consume more dairy products, and more postmenopausal women there take hormone replacement therapy (HRT).

“If otherwise indicated, HRT seemed to effectively protect from bone loss,” the researchers noted.

Also, the number of women who smoked or used corticosteroids was low, so bone loss in other populations may be higher. Moreover, the women who completed the study may have been healthier to start with, so the results should be interpreted with caution, they urge.

Nevertheless, the study sheds light on long-term changes in BMD in postmenopausal women and “stresses the importance of high peak bone mass before menopause and keeping a healthy weight” during aging to protect bone health, they say.

Indeed the work “changes our understanding of bone loss in older women,” said Dr. Kröger in a press release from the university.
 

Check BMD every 5 years after menopause

Invited to comment, American Society of Bone and Mineral Research President Peter R. Ebeling, MD, who was not involved with the research, noted key findings are that the rate of femoral neck bone loss after perimenopause was far less than previously expected, and 5-year BMD change appeared to predict long-term bone loss in postmenopausal women.

“We know bone loss begins 1 year before menopause and accelerates over the next 5 years,” Dr. Ebeling, from Monash University, Melbourne, added in an email. “This study indicates some stabilization of bone loss thereafter with lesser effects of low estrogen levels on bone.”

“It probably means bone density does not need to be measured as frequently following the menopause transition and could be every 5 years, rather than every 2 years, if there was concern about continuing bone loss.”
 

Baseline risk factors and long-term changes in BMD

For the study, researchers examined the association between risk factors for bone loss and long-term changes in femoral neck BMD in 2,695 women living in Kuopio who were 47 to 56 years old in 1989. The women were a mean age of 53 years, and 62% were postmenopausal.

They answered questionnaires and had femoral neck BMD measured by DEXA every 5 years.

A total of 2,695, 2,583, 2,482, 2,135, 1,305, and 686 women were assessed at baseline and 5-, 10-, 15-, 20- and 25-year follow-ups, respectively, indicating significant study drop-out by 25 years. 

By then, 17% of patients had died, 9% needed long-term care, some were unwilling to continue in the study, and others had factors that would have resulted in DEXA measurement errors (for example, hip implants, spine degeneration).

Researchers divided participants into quartiles of mean initial femoral neck BMD: 1.09 g/cm2, 0.97 g/cm2, 0.89 g/cm2, and 0.79 g/cm2, corresponding with quartiles 1 to 4 respectively (where quartile 1 had the highest initial femoral BMD and quartile 4 the lowest).

At 25 years, the mean femoral BMD had dropped to 0.97 g/cm2, 0.87 g/cm2, 0.80 g/cm2, and 0.73 g/cm2 in these respective quartiles.

Women lost 0.9%, 0.5%, 3.0%, and 1.0% of their initial BMD each year in quartiles 1 to 4, respectively.

And at 25 years, the women had lost 22.5%, 12.5%, 7.5%, and 2.5% of their initial BMD in the four quartiles, respectively.

Women in quartile 1 had the greatest drop in femoral BMD at 25 years, although their mean BMD at 25 years was higher than the mean initial BMD of the other women. 

The prevalence of bone-affecting diseases, smoking, and use of vitamin D/calcium supplementation, corticosteroids, or alcohol was similar in the four quartiles and was not associated with significant differences in annual bone loss.
 

The most important protective factor was HRT

However, body mass index (BMI) and HRT were significantly different in the four quartiles.

On average, women in quartile 1 had a mean BMI of 26.7 kg/m2 at baseline and 27.8 kg/m2 at 25 years. Women in quartile 4 (lowest initial BMD and lowest drop in BMD) had a mean BMI of 24.9 kg/m2 at baseline and 28.4 kg/m2 at 25 years.

Women in quartile 4 (lowest initial BMD and lowest drop in BMD) were more likely to take HRT than women in quartile 1 (highest initial BMD and highest drop in BMD), at 41% versus 26%, respectively.

“The average decrease in bone mineral density was lower than has been assumed on the basis of earlier, shorter follow-ups where the bone loss rate at the femoral neck has been estimated to be even more than 20%,” Dr. Sirola commented in the press release.

“There were also surprisingly few risk factors affecting bone mineral density. The most significant factor protecting against bone loss was hormone replacement therapy. Weight gain during the follow-up also protected against bone loss,” Dr. Sirola added.

The study was funded by the Academy of Finland, Finnish Ministry of Education and Culture, and the Päivikki and Sakari Sohlberg Foundation. The authors and Dr. Ebeling have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Clinical and dermoscopic features were consistent with a sporadic angiokeratoma, a benign ectasia of vessels associated with keratinization. Diagnosis was confirmed with shave biopsy.

Sporadic angiokeratomas are common and increase with age. They may occur anywhere on the skin, including mucous membranes. Dermoscopy of an angiokeratoma will reveal vascular lacunae—small pools of red or near black blood—as well as keratin scale, which appears as a white veil or shiny white lines.¹

Other subtypes of angiokeratomas may be more widespread, including angiokeratoma of Fordyce, which manifests on the vulva and scrotum (usually in adulthood), or angiokeratoma circumscriptum, which occurs congenitally. There are some rare syndromic conditions associated with widespread angiokeratomas, such as Fabry disease.

The differential diagnosis for this solitary, vascular-appearing papule or plaque includes cherry angioma, pyogenic granuloma, and melanoma. Over time, the keratinization may increase, and lesions may look like a wart. A punch or shave biopsy will distinguish an angiokeratoma from other types of lesions. When a lesion is small enough, it may also be curative.

Angiokeratomas do not require treatment. However, because they may occur in cosmetically sensitive areas or bleed when traumatized, remedies are often sought. Excision, cryotherapy, electrocautery, and vascular laser are all possible treatments.

In this case, the patient was treated with curettage and light electrocautery, which left a small scar.

‌

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

Clinical and dermoscopic features were consistent with a sporadic angiokeratoma, a benign ectasia of vessels associated with keratinization. Diagnosis was confirmed with shave biopsy.

Sporadic angiokeratomas are common and increase with age. They may occur anywhere on the skin, including mucous membranes. Dermoscopy of an angiokeratoma will reveal vascular lacunae—small pools of red or near black blood—as well as keratin scale, which appears as a white veil or shiny white lines.¹

Other subtypes of angiokeratomas may be more widespread, including angiokeratoma of Fordyce, which manifests on the vulva and scrotum (usually in adulthood), or angiokeratoma circumscriptum, which occurs congenitally. There are some rare syndromic conditions associated with widespread angiokeratomas, such as Fabry disease.

The differential diagnosis for this solitary, vascular-appearing papule or plaque includes cherry angioma, pyogenic granuloma, and melanoma. Over time, the keratinization may increase, and lesions may look like a wart. A punch or shave biopsy will distinguish an angiokeratoma from other types of lesions. When a lesion is small enough, it may also be curative.

Angiokeratomas do not require treatment. However, because they may occur in cosmetically sensitive areas or bleed when traumatized, remedies are often sought. Excision, cryotherapy, electrocautery, and vascular laser are all possible treatments.

In this case, the patient was treated with curettage and light electrocautery, which left a small scar.

‌

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

Clinical and dermoscopic features were consistent with a sporadic angiokeratoma, a benign ectasia of vessels associated with keratinization. Diagnosis was confirmed with shave biopsy.

Sporadic angiokeratomas are common and increase with age. They may occur anywhere on the skin, including mucous membranes. Dermoscopy of an angiokeratoma will reveal vascular lacunae—small pools of red or near black blood—as well as keratin scale, which appears as a white veil or shiny white lines.¹

Other subtypes of angiokeratomas may be more widespread, including angiokeratoma of Fordyce, which manifests on the vulva and scrotum (usually in adulthood), or angiokeratoma circumscriptum, which occurs congenitally. There are some rare syndromic conditions associated with widespread angiokeratomas, such as Fabry disease.

The differential diagnosis for this solitary, vascular-appearing papule or plaque includes cherry angioma, pyogenic granuloma, and melanoma. Over time, the keratinization may increase, and lesions may look like a wart. A punch or shave biopsy will distinguish an angiokeratoma from other types of lesions. When a lesion is small enough, it may also be curative.

Angiokeratomas do not require treatment. However, because they may occur in cosmetically sensitive areas or bleed when traumatized, remedies are often sought. Excision, cryotherapy, electrocautery, and vascular laser are all possible treatments.

In this case, the patient was treated with curettage and light electrocautery, which left a small scar.

‌

Text courtesy of Jonathan Karnes, MD, medical director, MDFMR Dermatology Services, Augusta, ME. Photos courtesy of Jonathan Karnes, MD (copyright retained).

To the Editor:

Photodynamic therapy (PDT) is a US Food and Drug Administration–approved treatment for actinic keratosis (AK). It also commonly is administered off label for basal cell carcinoma, Bowen disease, photoaging, and acne vulgaris and is being investigated for other applications.^1,2 In the context of treating AK, the mechanism employed in PDT most commonly involves the application of exogenous aminolevulinic acid (ALA), which is metabolized to the endogenous photosensitizer protoporphyrin IX (PpIX) in skin cells by enzymes in the heme biosynthetic pathway.³ The preferential uptake of ALA and conversion to PpIX is due to the altered and increased permeability of abnormal keratin layers of aging, sun-damaged cells, and skin tumors. Selectivity of ALA also occurs due to the preferential intracellular accumulation of PpIX in proliferating, relatively iron–deficient, precancerous and cancerous cells. The therapeutic effect is achieved with light exposure to blue light wavelength at 417 nm and corresponds to the excitation peak of PpIX,⁴ which activates PpIX and forms reactive oxygen species in the presence of oxygen that ultimately cause cell necrosis and apoptosis.⁵ Because it takes approximately 24 hours for PpIX to be completely metabolized from the skin, patients are counseled to avoid sun or artificial light exposure in the first 24 hours post-PDT, regardless of the indication, to avoid a severe phototoxic reaction.^3,6,7 Although it is normal and desirable for patients to experience some form of a phototoxic reaction, which may include erythema, edema, crusting, vesiculation, or erosion in most patients, these types of reactions most often are secondary to the intended exposure and incidental natural or artificial light exposures.⁶ We report a case of a severe phototoxic reaction in which a patient experienced painful erythema and purulence on the left side of the chin after being within an arm’s length of a flame in a fireplace following PDT treatment.

A 59-year-old man presented to our dermatology clinic for his second of 3 PDT sessions to treat AKs on the face. He had a history of a basal cell carcinoma on the left nasolabial fold that previously was treated with Mohs micrographic surgery and melanoma on the left ear that was previously treated with excision. The patient received the initial PDT session 1 month prior and experienced a mild reaction with minimal redness and peeling that resolved in 4 to 5 days. For the second treatment, per standard protocol at our clinic, ALA was applied to the face, after which the patient incubated for 1 hour prior to blue light exposure (mean [SD] peak output of 417 [5] nm for 1000 seconds and 10 J/cm²).

After blue light exposure, broad-spectrum sunscreen (sun protection factor 47) was applied to our patient’s face, and he wore a wide-brimmed hat upon leaving the clinic and walking to his car. Similar to the first PDT session 1 month prior, he experienced minimal pain immediately after treatment. Once home and approximately 4 to 5 hours after PDT, he tended to a fire using his left hand and leaned into the fireplace with the left side of his face, which was within an arm’s length of the flames. Although his skin did not come in direct contact with the flames, the brief 2- to 3-minute exposure to the flame’s light and heat produced an immediate intense burning pain that the patient likened to the pain of blue light exposure. Within 24 hours, he developed a severe inflammatory reaction that included erythema, edema, desquamation, and pustules on the left side of the chin and cheek that produced a purulent discharge (Figure). The purulence resolved the next day; however, the other clinical manifestations persisted for 1 week. Despite the discomfort and symptoms, our patient did not seek medical attention and instead managed his symptoms conservatively with cold compresses. Although he noticed an overall subjective improvement in the appearance of his face after this second treatment, he received a third treatment with PDT approximately 1 month later, which resulted in a response that was similar to his first visit.

Photodynamic therapy is an increasingly accepted treatment modality for a plethora of benign and malignant dermatologic conditions. Although blue and red light are the most common light sources utilized with PDT because their wavelengths (404–420 nm and 635 nm, respectively) correspond to the excitation peaks of photosensitizers, alternative light sources increasingly are being explored. There is increasing interest in utilizing infrared (IR) light sources (700–1,000,000 nm) to penetrate deeper into the skin in the treatment of precancerous and cancerous lesions. Exposure to IR radiation is known to raise skin temperature via inside-out dermal water absorption and is thought to be useful in PDT-ALA by promoting ALA penetration and its conversion to PpIX.⁸ In a randomized controlled trial by Giehl et al,⁹ visible light plus water-filtered IR-A light was shown to produce considerably less pain in ALA-PDT compared to placebo, though efficacy was not statistically affected. There are burgeoning trials examining the role of IR in treating dermatologic conditions such as acne, but research is still needed on ALA-PDT activated by IR radiation to target AKs.

Although the PDT side-effect profile of phototoxicity, dyspigmentation, and hypersensitivity is well documented, phototoxicity secondary to flame exposure is rare. In our patient, the synergistic effect of light and heat produced an exuberant phototoxic reaction. As the applications for PDT continue to broaden, this case may represent the importance of addressing additional precautions, such as avoiding open flames in the house or while camping, in the PDT aftercare instructions to maximize patient safety.

To the Editor:

Photodynamic therapy (PDT) is a US Food and Drug Administration–approved treatment for actinic keratosis (AK). It also commonly is administered off label for basal cell carcinoma, Bowen disease, photoaging, and acne vulgaris and is being investigated for other applications.^1,2 In the context of treating AK, the mechanism employed in PDT most commonly involves the application of exogenous aminolevulinic acid (ALA), which is metabolized to the endogenous photosensitizer protoporphyrin IX (PpIX) in skin cells by enzymes in the heme biosynthetic pathway.³ The preferential uptake of ALA and conversion to PpIX is due to the altered and increased permeability of abnormal keratin layers of aging, sun-damaged cells, and skin tumors. Selectivity of ALA also occurs due to the preferential intracellular accumulation of PpIX in proliferating, relatively iron–deficient, precancerous and cancerous cells. The therapeutic effect is achieved with light exposure to blue light wavelength at 417 nm and corresponds to the excitation peak of PpIX,⁴ which activates PpIX and forms reactive oxygen species in the presence of oxygen that ultimately cause cell necrosis and apoptosis.⁵ Because it takes approximately 24 hours for PpIX to be completely metabolized from the skin, patients are counseled to avoid sun or artificial light exposure in the first 24 hours post-PDT, regardless of the indication, to avoid a severe phototoxic reaction.^3,6,7 Although it is normal and desirable for patients to experience some form of a phototoxic reaction, which may include erythema, edema, crusting, vesiculation, or erosion in most patients, these types of reactions most often are secondary to the intended exposure and incidental natural or artificial light exposures.⁶ We report a case of a severe phototoxic reaction in which a patient experienced painful erythema and purulence on the left side of the chin after being within an arm’s length of a flame in a fireplace following PDT treatment.

A 59-year-old man presented to our dermatology clinic for his second of 3 PDT sessions to treat AKs on the face. He had a history of a basal cell carcinoma on the left nasolabial fold that previously was treated with Mohs micrographic surgery and melanoma on the left ear that was previously treated with excision. The patient received the initial PDT session 1 month prior and experienced a mild reaction with minimal redness and peeling that resolved in 4 to 5 days. For the second treatment, per standard protocol at our clinic, ALA was applied to the face, after which the patient incubated for 1 hour prior to blue light exposure (mean [SD] peak output of 417 [5] nm for 1000 seconds and 10 J/cm²).

After blue light exposure, broad-spectrum sunscreen (sun protection factor 47) was applied to our patient’s face, and he wore a wide-brimmed hat upon leaving the clinic and walking to his car. Similar to the first PDT session 1 month prior, he experienced minimal pain immediately after treatment. Once home and approximately 4 to 5 hours after PDT, he tended to a fire using his left hand and leaned into the fireplace with the left side of his face, which was within an arm’s length of the flames. Although his skin did not come in direct contact with the flames, the brief 2- to 3-minute exposure to the flame’s light and heat produced an immediate intense burning pain that the patient likened to the pain of blue light exposure. Within 24 hours, he developed a severe inflammatory reaction that included erythema, edema, desquamation, and pustules on the left side of the chin and cheek that produced a purulent discharge (Figure). The purulence resolved the next day; however, the other clinical manifestations persisted for 1 week. Despite the discomfort and symptoms, our patient did not seek medical attention and instead managed his symptoms conservatively with cold compresses. Although he noticed an overall subjective improvement in the appearance of his face after this second treatment, he received a third treatment with PDT approximately 1 month later, which resulted in a response that was similar to his first visit.

Photodynamic therapy is an increasingly accepted treatment modality for a plethora of benign and malignant dermatologic conditions. Although blue and red light are the most common light sources utilized with PDT because their wavelengths (404–420 nm and 635 nm, respectively) correspond to the excitation peaks of photosensitizers, alternative light sources increasingly are being explored. There is increasing interest in utilizing infrared (IR) light sources (700–1,000,000 nm) to penetrate deeper into the skin in the treatment of precancerous and cancerous lesions. Exposure to IR radiation is known to raise skin temperature via inside-out dermal water absorption and is thought to be useful in PDT-ALA by promoting ALA penetration and its conversion to PpIX.⁸ In a randomized controlled trial by Giehl et al,⁹ visible light plus water-filtered IR-A light was shown to produce considerably less pain in ALA-PDT compared to placebo, though efficacy was not statistically affected. There are burgeoning trials examining the role of IR in treating dermatologic conditions such as acne, but research is still needed on ALA-PDT activated by IR radiation to target AKs.

Although the PDT side-effect profile of phototoxicity, dyspigmentation, and hypersensitivity is well documented, phototoxicity secondary to flame exposure is rare. In our patient, the synergistic effect of light and heat produced an exuberant phototoxic reaction. As the applications for PDT continue to broaden, this case may represent the importance of addressing additional precautions, such as avoiding open flames in the house or while camping, in the PDT aftercare instructions to maximize patient safety.

To the Editor:

Photodynamic therapy (PDT) is a US Food and Drug Administration–approved treatment for actinic keratosis (AK). It also commonly is administered off label for basal cell carcinoma, Bowen disease, photoaging, and acne vulgaris and is being investigated for other applications.^1,2 In the context of treating AK, the mechanism employed in PDT most commonly involves the application of exogenous aminolevulinic acid (ALA), which is metabolized to the endogenous photosensitizer protoporphyrin IX (PpIX) in skin cells by enzymes in the heme biosynthetic pathway.³ The preferential uptake of ALA and conversion to PpIX is due to the altered and increased permeability of abnormal keratin layers of aging, sun-damaged cells, and skin tumors. Selectivity of ALA also occurs due to the preferential intracellular accumulation of PpIX in proliferating, relatively iron–deficient, precancerous and cancerous cells. The therapeutic effect is achieved with light exposure to blue light wavelength at 417 nm and corresponds to the excitation peak of PpIX,⁴ which activates PpIX and forms reactive oxygen species in the presence of oxygen that ultimately cause cell necrosis and apoptosis.⁵ Because it takes approximately 24 hours for PpIX to be completely metabolized from the skin, patients are counseled to avoid sun or artificial light exposure in the first 24 hours post-PDT, regardless of the indication, to avoid a severe phototoxic reaction.^3,6,7 Although it is normal and desirable for patients to experience some form of a phototoxic reaction, which may include erythema, edema, crusting, vesiculation, or erosion in most patients, these types of reactions most often are secondary to the intended exposure and incidental natural or artificial light exposures.⁶ We report a case of a severe phototoxic reaction in which a patient experienced painful erythema and purulence on the left side of the chin after being within an arm’s length of a flame in a fireplace following PDT treatment.

A 59-year-old man presented to our dermatology clinic for his second of 3 PDT sessions to treat AKs on the face. He had a history of a basal cell carcinoma on the left nasolabial fold that previously was treated with Mohs micrographic surgery and melanoma on the left ear that was previously treated with excision. The patient received the initial PDT session 1 month prior and experienced a mild reaction with minimal redness and peeling that resolved in 4 to 5 days. For the second treatment, per standard protocol at our clinic, ALA was applied to the face, after which the patient incubated for 1 hour prior to blue light exposure (mean [SD] peak output of 417 [5] nm for 1000 seconds and 10 J/cm²).

After blue light exposure, broad-spectrum sunscreen (sun protection factor 47) was applied to our patient’s face, and he wore a wide-brimmed hat upon leaving the clinic and walking to his car. Similar to the first PDT session 1 month prior, he experienced minimal pain immediately after treatment. Once home and approximately 4 to 5 hours after PDT, he tended to a fire using his left hand and leaned into the fireplace with the left side of his face, which was within an arm’s length of the flames. Although his skin did not come in direct contact with the flames, the brief 2- to 3-minute exposure to the flame’s light and heat produced an immediate intense burning pain that the patient likened to the pain of blue light exposure. Within 24 hours, he developed a severe inflammatory reaction that included erythema, edema, desquamation, and pustules on the left side of the chin and cheek that produced a purulent discharge (Figure). The purulence resolved the next day; however, the other clinical manifestations persisted for 1 week. Despite the discomfort and symptoms, our patient did not seek medical attention and instead managed his symptoms conservatively with cold compresses. Although he noticed an overall subjective improvement in the appearance of his face after this second treatment, he received a third treatment with PDT approximately 1 month later, which resulted in a response that was similar to his first visit.

Photodynamic therapy is an increasingly accepted treatment modality for a plethora of benign and malignant dermatologic conditions. Although blue and red light are the most common light sources utilized with PDT because their wavelengths (404–420 nm and 635 nm, respectively) correspond to the excitation peaks of photosensitizers, alternative light sources increasingly are being explored. There is increasing interest in utilizing infrared (IR) light sources (700–1,000,000 nm) to penetrate deeper into the skin in the treatment of precancerous and cancerous lesions. Exposure to IR radiation is known to raise skin temperature via inside-out dermal water absorption and is thought to be useful in PDT-ALA by promoting ALA penetration and its conversion to PpIX.⁸ In a randomized controlled trial by Giehl et al,⁹ visible light plus water-filtered IR-A light was shown to produce considerably less pain in ALA-PDT compared to placebo, though efficacy was not statistically affected. There are burgeoning trials examining the role of IR in treating dermatologic conditions such as acne, but research is still needed on ALA-PDT activated by IR radiation to target AKs.

Although the PDT side-effect profile of phototoxicity, dyspigmentation, and hypersensitivity is well documented, phototoxicity secondary to flame exposure is rare. In our patient, the synergistic effect of light and heat produced an exuberant phototoxic reaction. As the applications for PDT continue to broaden, this case may represent the importance of addressing additional precautions, such as avoiding open flames in the house or while camping, in the PDT aftercare instructions to maximize patient safety.