Reproductive Endocrinology

PHILADELPHIA – Factors such as primary fibroid volume, fibroid stage, and uterine volume did not appear to affect the efficacy of elagolix in improving heavy menstrual bleeding associated with uterine fibroids, according to results presented at the annual meeting of the American Society for Reproductive Medicine.

Ayman Al-Hendy, MD, PhD, director of translational research at the University of Illinois at Chicago, and associates, analyzed a pooled subgroup of 790 patients from the Elaris UF-1 and UF-2 trials who received elagolix twice daily at a dose of 300 mg (199 patients), elagolix 300 mg twice daily with add-back therapy (1 mg of estradiol plus 0.5 mg of norethindrone acetate; 395 patients), and a placebo group (196 patients) for treatment of heavy menstrual bleeding. Patients were premenopausal women aged 18-51 years with more than 80 mL of menstrual blood loss per cycle. The study design included a washout period, followed by a 2.5-month to 3.5-month screening period, and patients were randomized to 6 months of treatment with placebo, elagolix alone, or elagolix with add-back therapy in a 1:1:2 ratio. Researchers evaluated whether patients had less than 80 mL of menstrual blood loss per cycle and a 50% or more reduction in menstrual blood loss per cycle by the end of the study.

In a subgroup analysis, they also analyzed primary fibroid volume, fibroid stage, and uterine volume. The median primary fibroid volume was 36.2 cm³ (range, 1.0-1,081.5 cm³). Fibroid location was classified using the International Federation of Gynecology and Obstetrics (FIGO) staging system, and researchers placed fibroids into FIGO 0-3, FIGO 4, and FIGO 5-8 groups. At baseline, characteristics between groups were similar, but the patients who received elagolix alone had a lower number of fibroids classified as FIGO 0-3 and had a greater percentage of fibroids less than 36.2 cm³. The median uterine volume was 356.5 cm³ (range, 71.6-3,347.9 cm³).

At final follow-up, 81% of patients receiving elagolix alone and 72% of patients receiving elagolix with add-back therapy responded to treatment, compared with placebo (9%).

Patients receiving elagolix plus add-back therapy responded to treatment better than placebo, and there were no significant differences in outcomes in terms of FIGO stage: Response was as follows for patients with FIGO 0-3 classified fibroids (78% of 47 patients vs. 9% of 25 patients), FIGO 4 fibroids (68% of 177 patients vs. 15% of 85 patients) and FIGO 5-8 fibroids (74% of 165 patients vs. 4% of 82 patients). The same was true in terms of both primary fibroid volume and uterine volume in patients who received elagolix plus add-back therapy, compared with those who received placebo: Patients with a primary fibroid volume of less than 36.2 cm³ (74% of 189 patients vs. 15% of 92 patients) responded similarly to elagolix plus add-back therapy as did patients with a primary fibroid volume greater than 36.2 cm³ (70% of 200 patients vs. 5% of 100 patients), and there were no significant differences between the treatment response of patients with a uterine volume less than 365.5 cm³ (75% of 203 patients vs. 15% of 88 patients) and a uterine volume greater than 365.5 cm³ (70% of 192 patients vs. 5% of 108 patients).

“These really are very encouraging results and suggests that, in women with different fibroids, elagolix with add-back therapy would be an effective treatment option despite uterine and fibroid volume and location of fibroids,” said Dr. Al-Hendy.

Dr. Al-Hendy noted there are ongoing studies analyzing elagolix with add-back in women with fibroids, in women with endometriosis, and elagolix in women with polycystic ovary syndrome.

AbbVie recently submitted a new drug application to the Food and Drug Administration for elagolix based on results from these two trials. Elagolix, an oral GnRh receptor antagonist, is an FDA-approved oral medication for the management of endometriosis with associated moderate to severe pain.

This study was funded by AbbVie, and the company was involved in the study design, research, data collection, analysis and interpretation of the data, as well as the writing, reviewing and approving of the study for publication. The authors reported various relationships with industry, pharmaceutical companies, government entities, and other organizations.
 

SOURCE: Al-Hendy A et al. ASRM 2019, Abstract O-205.

PHILADELPHIA – Factors such as primary fibroid volume, fibroid stage, and uterine volume did not appear to affect the efficacy of elagolix in improving heavy menstrual bleeding associated with uterine fibroids, according to results presented at the annual meeting of the American Society for Reproductive Medicine.

Ayman Al-Hendy, MD, PhD, director of translational research at the University of Illinois at Chicago, and associates, analyzed a pooled subgroup of 790 patients from the Elaris UF-1 and UF-2 trials who received elagolix twice daily at a dose of 300 mg (199 patients), elagolix 300 mg twice daily with add-back therapy (1 mg of estradiol plus 0.5 mg of norethindrone acetate; 395 patients), and a placebo group (196 patients) for treatment of heavy menstrual bleeding. Patients were premenopausal women aged 18-51 years with more than 80 mL of menstrual blood loss per cycle. The study design included a washout period, followed by a 2.5-month to 3.5-month screening period, and patients were randomized to 6 months of treatment with placebo, elagolix alone, or elagolix with add-back therapy in a 1:1:2 ratio. Researchers evaluated whether patients had less than 80 mL of menstrual blood loss per cycle and a 50% or more reduction in menstrual blood loss per cycle by the end of the study.

In a subgroup analysis, they also analyzed primary fibroid volume, fibroid stage, and uterine volume. The median primary fibroid volume was 36.2 cm³ (range, 1.0-1,081.5 cm³). Fibroid location was classified using the International Federation of Gynecology and Obstetrics (FIGO) staging system, and researchers placed fibroids into FIGO 0-3, FIGO 4, and FIGO 5-8 groups. At baseline, characteristics between groups were similar, but the patients who received elagolix alone had a lower number of fibroids classified as FIGO 0-3 and had a greater percentage of fibroids less than 36.2 cm³. The median uterine volume was 356.5 cm³ (range, 71.6-3,347.9 cm³).

At final follow-up, 81% of patients receiving elagolix alone and 72% of patients receiving elagolix with add-back therapy responded to treatment, compared with placebo (9%).

Patients receiving elagolix plus add-back therapy responded to treatment better than placebo, and there were no significant differences in outcomes in terms of FIGO stage: Response was as follows for patients with FIGO 0-3 classified fibroids (78% of 47 patients vs. 9% of 25 patients), FIGO 4 fibroids (68% of 177 patients vs. 15% of 85 patients) and FIGO 5-8 fibroids (74% of 165 patients vs. 4% of 82 patients). The same was true in terms of both primary fibroid volume and uterine volume in patients who received elagolix plus add-back therapy, compared with those who received placebo: Patients with a primary fibroid volume of less than 36.2 cm³ (74% of 189 patients vs. 15% of 92 patients) responded similarly to elagolix plus add-back therapy as did patients with a primary fibroid volume greater than 36.2 cm³ (70% of 200 patients vs. 5% of 100 patients), and there were no significant differences between the treatment response of patients with a uterine volume less than 365.5 cm³ (75% of 203 patients vs. 15% of 88 patients) and a uterine volume greater than 365.5 cm³ (70% of 192 patients vs. 5% of 108 patients).

“These really are very encouraging results and suggests that, in women with different fibroids, elagolix with add-back therapy would be an effective treatment option despite uterine and fibroid volume and location of fibroids,” said Dr. Al-Hendy.

Dr. Al-Hendy noted there are ongoing studies analyzing elagolix with add-back in women with fibroids, in women with endometriosis, and elagolix in women with polycystic ovary syndrome.

AbbVie recently submitted a new drug application to the Food and Drug Administration for elagolix based on results from these two trials. Elagolix, an oral GnRh receptor antagonist, is an FDA-approved oral medication for the management of endometriosis with associated moderate to severe pain.

This study was funded by AbbVie, and the company was involved in the study design, research, data collection, analysis and interpretation of the data, as well as the writing, reviewing and approving of the study for publication. The authors reported various relationships with industry, pharmaceutical companies, government entities, and other organizations.
 

SOURCE: Al-Hendy A et al. ASRM 2019, Abstract O-205.

PHILADELPHIA – Factors such as primary fibroid volume, fibroid stage, and uterine volume did not appear to affect the efficacy of elagolix in improving heavy menstrual bleeding associated with uterine fibroids, according to results presented at the annual meeting of the American Society for Reproductive Medicine.

Ayman Al-Hendy, MD, PhD, director of translational research at the University of Illinois at Chicago, and associates, analyzed a pooled subgroup of 790 patients from the Elaris UF-1 and UF-2 trials who received elagolix twice daily at a dose of 300 mg (199 patients), elagolix 300 mg twice daily with add-back therapy (1 mg of estradiol plus 0.5 mg of norethindrone acetate; 395 patients), and a placebo group (196 patients) for treatment of heavy menstrual bleeding. Patients were premenopausal women aged 18-51 years with more than 80 mL of menstrual blood loss per cycle. The study design included a washout period, followed by a 2.5-month to 3.5-month screening period, and patients were randomized to 6 months of treatment with placebo, elagolix alone, or elagolix with add-back therapy in a 1:1:2 ratio. Researchers evaluated whether patients had less than 80 mL of menstrual blood loss per cycle and a 50% or more reduction in menstrual blood loss per cycle by the end of the study.

In a subgroup analysis, they also analyzed primary fibroid volume, fibroid stage, and uterine volume. The median primary fibroid volume was 36.2 cm³ (range, 1.0-1,081.5 cm³). Fibroid location was classified using the International Federation of Gynecology and Obstetrics (FIGO) staging system, and researchers placed fibroids into FIGO 0-3, FIGO 4, and FIGO 5-8 groups. At baseline, characteristics between groups were similar, but the patients who received elagolix alone had a lower number of fibroids classified as FIGO 0-3 and had a greater percentage of fibroids less than 36.2 cm³. The median uterine volume was 356.5 cm³ (range, 71.6-3,347.9 cm³).

At final follow-up, 81% of patients receiving elagolix alone and 72% of patients receiving elagolix with add-back therapy responded to treatment, compared with placebo (9%).

Patients receiving elagolix plus add-back therapy responded to treatment better than placebo, and there were no significant differences in outcomes in terms of FIGO stage: Response was as follows for patients with FIGO 0-3 classified fibroids (78% of 47 patients vs. 9% of 25 patients), FIGO 4 fibroids (68% of 177 patients vs. 15% of 85 patients) and FIGO 5-8 fibroids (74% of 165 patients vs. 4% of 82 patients). The same was true in terms of both primary fibroid volume and uterine volume in patients who received elagolix plus add-back therapy, compared with those who received placebo: Patients with a primary fibroid volume of less than 36.2 cm³ (74% of 189 patients vs. 15% of 92 patients) responded similarly to elagolix plus add-back therapy as did patients with a primary fibroid volume greater than 36.2 cm³ (70% of 200 patients vs. 5% of 100 patients), and there were no significant differences between the treatment response of patients with a uterine volume less than 365.5 cm³ (75% of 203 patients vs. 15% of 88 patients) and a uterine volume greater than 365.5 cm³ (70% of 192 patients vs. 5% of 108 patients).

“These really are very encouraging results and suggests that, in women with different fibroids, elagolix with add-back therapy would be an effective treatment option despite uterine and fibroid volume and location of fibroids,” said Dr. Al-Hendy.

Dr. Al-Hendy noted there are ongoing studies analyzing elagolix with add-back in women with fibroids, in women with endometriosis, and elagolix in women with polycystic ovary syndrome.

AbbVie recently submitted a new drug application to the Food and Drug Administration for elagolix based on results from these two trials. Elagolix, an oral GnRh receptor antagonist, is an FDA-approved oral medication for the management of endometriosis with associated moderate to severe pain.

This study was funded by AbbVie, and the company was involved in the study design, research, data collection, analysis and interpretation of the data, as well as the writing, reviewing and approving of the study for publication. The authors reported various relationships with industry, pharmaceutical companies, government entities, and other organizations.
 

SOURCE: Al-Hendy A et al. ASRM 2019, Abstract O-205.

PHILADELPHIA – Women with ovarian torsion had a lower rate of perioperative complications when treated with conservative surgery, compared with oophorectomy, according to results from a retrospective study presented at the annual meeting of the American Society for Reproductive Medicine.

Jeff Craven/MDedge News

The effectiveness of laparoscopy and conservative surgery has increased in recent years, but over 75% of women with ovarian torsion in the study were treated with oophorectomy and 60% underwent a laparotomy, said Rachel S. Mandelbaum, MD, of the department of obstetrics & gynecology at the University of Southern California, Los Angeles.

“We believe that conservative surgery should be performed whenever possible in young women with ovarian torsion regardless of the appearance of the ovary intraoperatively,” said Dr. Mandelbaum.

The researchers performed a retrospective, observational study of 89,801 women in the Nationwide Inpatient Sample who were younger than age 50 years, were diagnosed with ovarian torsion during Jan. 2001–Sept. 2015, and were treated with conservative surgery or oophorectomy. Patients were excluded if they had malignancy, were older than 50 years of age, or their surgery information was unavailable. The majority of patients in the study were white (46%), nonobese (91%), without comorbidities, privately insured (59%), and were seen at a large (61%) urban hospital (51% teaching; 38% nonteaching).

Dr. Mandelbaum and colleagues found 78% of patients received a cystectomy, 19% had cyst drainage, 11% had detorsion alone, and 0.5% had an oophoropexy, with less than 10% of patients having a combination of cystectomy, cyst drainage, and oophoropexy. According to a multivariable analysis, patients who were treated with conservative surgery were more likely to be young, have a high income, live in the northeastern United States, be treated with laparoscopy, and be seen at a large hospital or teaching hospital (P less than .001). Oophorectomy was more common in patients with a high number of comorbidities and in patients with morbid obesity (P less than .001).

Between 2001 and 2015, the rate of conservative surgery increased from 19% to 25% (P less than .001); however, the rate of conservative surgery by age was nearly 40% in pediatric patients up to 15 years old, while the rate of conservative surgery declined by almost half until 35 years, followed by a further decline until age 50 years, said Dr. Mandelbaum. Use of laparoscopy also increased from 31% in 2001 to 42% in 2015 (P less than .001).

Overall, 20,643 patients underwent conservative surgery and 69,157 patients received an oophorectomy. Patients in the conservative surgery group were more likely to undergo a conservative surgery with a laparoscopic surgical approach (51%) than a laparotomy (41%), while patients receiving an oophorectomy were more likely to have a laparotomy (67%) than a laparoscopic surgical approach (33%). In 1,663 conservative surgeries (8%), the approach was unknown.

Postoperative complications were higher in the oophorectomy group (12%) than the conservative surgery (8%) group (odds ratio, 0.57; 95% confidence interval, 0.57-0.78; P less than .001), but there was a similar rate of venous thromboembolism (0.3% vs. 0.2%; P equals .568) and sepsis (0.3% vs. 0.3%; P equals .865) in each group.

Dr. Mandelbaum attributed the high rate of oophorectomies in the study to “differential uptake of evidence” in different areas of the United States, fear of complications from leaving an infected ovary in situ, or the surgeon’s belief that the ovary is not viable because of its color intraoperatively. “We know from animal and human studies that the intraoperative appearance of the ovary does not correlate to viability, and that 90% of black or blue ovaries regain function and subsequently appear normal on both transvaginal ultrasound or on a second look grossly,” she said. Oophorectomy rates also vary by surgeon, and gynecologists are more likely to perform conservative surgery, she added.

The researchers said they were unable to obtain data on specific surgical variables such as the size of the mass, time to surgery, intraoperative appearance, laterality, fertility wishes of the patient, and surgeon type. There were also no postdischarge data, or information on the timing of complications.

Dr. Mandelbaum reported no relevant conflicts of interest.

SOURCE: Mandelbaum RS et al. ASRM 2019. Abstract O-96.

PHILADELPHIA – Women with ovarian torsion had a lower rate of perioperative complications when treated with conservative surgery, compared with oophorectomy, according to results from a retrospective study presented at the annual meeting of the American Society for Reproductive Medicine.

Jeff Craven/MDedge News

The effectiveness of laparoscopy and conservative surgery has increased in recent years, but over 75% of women with ovarian torsion in the study were treated with oophorectomy and 60% underwent a laparotomy, said Rachel S. Mandelbaum, MD, of the department of obstetrics & gynecology at the University of Southern California, Los Angeles.

“We believe that conservative surgery should be performed whenever possible in young women with ovarian torsion regardless of the appearance of the ovary intraoperatively,” said Dr. Mandelbaum.

The researchers performed a retrospective, observational study of 89,801 women in the Nationwide Inpatient Sample who were younger than age 50 years, were diagnosed with ovarian torsion during Jan. 2001–Sept. 2015, and were treated with conservative surgery or oophorectomy. Patients were excluded if they had malignancy, were older than 50 years of age, or their surgery information was unavailable. The majority of patients in the study were white (46%), nonobese (91%), without comorbidities, privately insured (59%), and were seen at a large (61%) urban hospital (51% teaching; 38% nonteaching).

Dr. Mandelbaum and colleagues found 78% of patients received a cystectomy, 19% had cyst drainage, 11% had detorsion alone, and 0.5% had an oophoropexy, with less than 10% of patients having a combination of cystectomy, cyst drainage, and oophoropexy. According to a multivariable analysis, patients who were treated with conservative surgery were more likely to be young, have a high income, live in the northeastern United States, be treated with laparoscopy, and be seen at a large hospital or teaching hospital (P less than .001). Oophorectomy was more common in patients with a high number of comorbidities and in patients with morbid obesity (P less than .001).

Between 2001 and 2015, the rate of conservative surgery increased from 19% to 25% (P less than .001); however, the rate of conservative surgery by age was nearly 40% in pediatric patients up to 15 years old, while the rate of conservative surgery declined by almost half until 35 years, followed by a further decline until age 50 years, said Dr. Mandelbaum. Use of laparoscopy also increased from 31% in 2001 to 42% in 2015 (P less than .001).

Overall, 20,643 patients underwent conservative surgery and 69,157 patients received an oophorectomy. Patients in the conservative surgery group were more likely to undergo a conservative surgery with a laparoscopic surgical approach (51%) than a laparotomy (41%), while patients receiving an oophorectomy were more likely to have a laparotomy (67%) than a laparoscopic surgical approach (33%). In 1,663 conservative surgeries (8%), the approach was unknown.

Postoperative complications were higher in the oophorectomy group (12%) than the conservative surgery (8%) group (odds ratio, 0.57; 95% confidence interval, 0.57-0.78; P less than .001), but there was a similar rate of venous thromboembolism (0.3% vs. 0.2%; P equals .568) and sepsis (0.3% vs. 0.3%; P equals .865) in each group.

Dr. Mandelbaum attributed the high rate of oophorectomies in the study to “differential uptake of evidence” in different areas of the United States, fear of complications from leaving an infected ovary in situ, or the surgeon’s belief that the ovary is not viable because of its color intraoperatively. “We know from animal and human studies that the intraoperative appearance of the ovary does not correlate to viability, and that 90% of black or blue ovaries regain function and subsequently appear normal on both transvaginal ultrasound or on a second look grossly,” she said. Oophorectomy rates also vary by surgeon, and gynecologists are more likely to perform conservative surgery, she added.

The researchers said they were unable to obtain data on specific surgical variables such as the size of the mass, time to surgery, intraoperative appearance, laterality, fertility wishes of the patient, and surgeon type. There were also no postdischarge data, or information on the timing of complications.

Dr. Mandelbaum reported no relevant conflicts of interest.

SOURCE: Mandelbaum RS et al. ASRM 2019. Abstract O-96.

PHILADELPHIA – Women with ovarian torsion had a lower rate of perioperative complications when treated with conservative surgery, compared with oophorectomy, according to results from a retrospective study presented at the annual meeting of the American Society for Reproductive Medicine.

Jeff Craven/MDedge News

The effectiveness of laparoscopy and conservative surgery has increased in recent years, but over 75% of women with ovarian torsion in the study were treated with oophorectomy and 60% underwent a laparotomy, said Rachel S. Mandelbaum, MD, of the department of obstetrics & gynecology at the University of Southern California, Los Angeles.

“We believe that conservative surgery should be performed whenever possible in young women with ovarian torsion regardless of the appearance of the ovary intraoperatively,” said Dr. Mandelbaum.

The researchers performed a retrospective, observational study of 89,801 women in the Nationwide Inpatient Sample who were younger than age 50 years, were diagnosed with ovarian torsion during Jan. 2001–Sept. 2015, and were treated with conservative surgery or oophorectomy. Patients were excluded if they had malignancy, were older than 50 years of age, or their surgery information was unavailable. The majority of patients in the study were white (46%), nonobese (91%), without comorbidities, privately insured (59%), and were seen at a large (61%) urban hospital (51% teaching; 38% nonteaching).

Dr. Mandelbaum and colleagues found 78% of patients received a cystectomy, 19% had cyst drainage, 11% had detorsion alone, and 0.5% had an oophoropexy, with less than 10% of patients having a combination of cystectomy, cyst drainage, and oophoropexy. According to a multivariable analysis, patients who were treated with conservative surgery were more likely to be young, have a high income, live in the northeastern United States, be treated with laparoscopy, and be seen at a large hospital or teaching hospital (P less than .001). Oophorectomy was more common in patients with a high number of comorbidities and in patients with morbid obesity (P less than .001).

Between 2001 and 2015, the rate of conservative surgery increased from 19% to 25% (P less than .001); however, the rate of conservative surgery by age was nearly 40% in pediatric patients up to 15 years old, while the rate of conservative surgery declined by almost half until 35 years, followed by a further decline until age 50 years, said Dr. Mandelbaum. Use of laparoscopy also increased from 31% in 2001 to 42% in 2015 (P less than .001).

Overall, 20,643 patients underwent conservative surgery and 69,157 patients received an oophorectomy. Patients in the conservative surgery group were more likely to undergo a conservative surgery with a laparoscopic surgical approach (51%) than a laparotomy (41%), while patients receiving an oophorectomy were more likely to have a laparotomy (67%) than a laparoscopic surgical approach (33%). In 1,663 conservative surgeries (8%), the approach was unknown.

Postoperative complications were higher in the oophorectomy group (12%) than the conservative surgery (8%) group (odds ratio, 0.57; 95% confidence interval, 0.57-0.78; P less than .001), but there was a similar rate of venous thromboembolism (0.3% vs. 0.2%; P equals .568) and sepsis (0.3% vs. 0.3%; P equals .865) in each group.

Dr. Mandelbaum attributed the high rate of oophorectomies in the study to “differential uptake of evidence” in different areas of the United States, fear of complications from leaving an infected ovary in situ, or the surgeon’s belief that the ovary is not viable because of its color intraoperatively. “We know from animal and human studies that the intraoperative appearance of the ovary does not correlate to viability, and that 90% of black or blue ovaries regain function and subsequently appear normal on both transvaginal ultrasound or on a second look grossly,” she said. Oophorectomy rates also vary by surgeon, and gynecologists are more likely to perform conservative surgery, she added.

The researchers said they were unable to obtain data on specific surgical variables such as the size of the mass, time to surgery, intraoperative appearance, laterality, fertility wishes of the patient, and surgeon type. There were also no postdischarge data, or information on the timing of complications.

Dr. Mandelbaum reported no relevant conflicts of interest.

SOURCE: Mandelbaum RS et al. ASRM 2019. Abstract O-96.

PHILADELPHIA – Women taking SSRIs may experience reduced fecundity and a lower live birth rate than women who were not exposed to antidepressants, Lindsey A. Sjaarda, PhD, reported at the annual meeting of the American Society for Reproductive Medicine.

Jeff Craven/MDedge News

In addition, women in a subgroup receiving fluoxetine experienced a lower live birth rate and greater incidence of pregnancy loss than women taking other SSRIs, but the results were not statistically significant, said Dr. Sjaarda of the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

“[It] is biologically plausible that fluoxetine might have some different effects,” she noted. “It does have some different interaction with [cytochrome] P-450 enzyme activity, and this translates to it having a much longer half-life as well. It’s different in terms of drug metabolism and in its interaction with the hormone biosynthesis pathway.”

Most of the research on antidepressants and SSRIs in pregnancy has focused on the safety of the agents, rather than the effect on pregnancy for women trying to conceive, explained Dr. Sjaarda. Previous research also has shown inconsistent findings for fecundability in women of reproductive age taking SSRIs, and the risk of specific SSRI compounds on pregnancy loss is unclear.

The researchers performed a longitudinal exposure assessment of the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial, which consisted of 1,228 women aged between 18 and 40 years trying to conceive. Patients were included if they had one to two prior pregnancy losses, up to two live births, and had been trying to become pregnant for six menstrual cycles; they were excluded if they had a severe history of mental illness. There were 1,035 women who had no preconception antidepressant exposure and 183 who did have preconception antidepressant exposure.

Patients provided longitudinal urine samples at various time points, including while trying to conceive and in early pregnancy, during the menses phase of each menstrual cycle and at their last menstrual cycle, and at 4 and 8 weeks’ gestation if they become pregnant. The urine samples were collected at home or in clinic; human chorionic gonadotropin levels were measured on the stored samples. The researchers defined pregnancy loss as any kind of loss measured after detecting human chorionic gonadotropin, and they used the patient’s medical record to determine live birth. The fecundability odds ratio was used to estimate the odds of conception in menstrual cycles.

Wavebreakmedia Ltd/Thinkstock

Aypical and tricyclic antidepressants and SSRIs such as sertraline, fluoxetine, and citalopram/escitalopram were analyzed, as well as use of opioids, cannabinoids, and benzodiazepines. In total, 172 women used SSRIs, which represented 94% of the patient group analyzed, said Dr. Sjaarda. “This cohort really represents women who are successfully controlled with first-line agents.”

Patients in both the SSRI and no-antidepressant groups had similar baseline characteristics, but there were differences with regard to body mass index (26 kg/m² vs. 28 kg/m²), employment status (77% vs. 67%), perceived stress (1.0 vs. 0.9), and opioid exposure (16% vs. 23%).

The researchers found use of any SSRI was associated with a 23% reduction in fecundability, with patients using fluoxetine, sertraline, and citalopram/escitalopram having a similar reduction in fecundability, compared with patients not using SSRIs.

Patients who received SSRIs also had approximately a 53% live birth rate overall. When analyzed by individual SSRI, however, there was a statistically significant reduction in the live birth rate for patients who were using fluoxetine, compared with patients using sertraline and citalopram/escitalopram. “This suggests that there was something besides just reduced fecundability going on with the fluoxetine-exposed women,” said Dr. Sjaarda.

When SSRI use was analyzed with regard to pregnancy loss, there was a generally null effect between women exposed to SSRIs overall versus those not exposed at the time before conception, at last menstrual period, and at 4 or 8 weeks’ gestation. But when grouped by specific SSRI, patients receiving fluoxetine had increased risk of pregnancy loss prior to conception, compared with patients not taking fluoxetine (34% vs. 24%; adjusted risk ratio, 1.41; 95% confidence interval, 0.94-2.12) , as well as at their last menstrual period (34% vs. 24%; adjusted RR, 1.48; 95% CI, 0.98-2.24) and at 4 weeks of pregnancy (31% vs. 22%; adjusted RR, 1.61; 95% CI, 0.94-2.78). “This was about a 40%-60% increase in pregnancy loss, even though the sample size is generally small when you divide it into these groups,” said Dr. Sjaarda.

Mental health care is an important public health and maternal health issue, and SSRIs as a drug class are essential for helping to appropriately manage mental health, noted Dr. Sjaarda.

Because “patients’ disease severities all vary and the reactions to different drugs vary, no one-size-fits-all recommendation can be made for people planning a pregnancy while using SSRIs,” concluded Dr. Sjaarda. “However, we’re hoping that women and their physicians can now consider these new data, which are based on objective and longitudinally measured exposure, as well as prospectively-assessed outcomes for these most common antidepressants and develop to a more informed and individualized plan for women who are trying to conceive and use SSRIs.”

Dr. Sjaarda reported no relevant conflicts of interest.

SOURCE: Sjaarda L et al. ASRM 2019, Abstract O-1.

PHILADELPHIA – Women taking SSRIs may experience reduced fecundity and a lower live birth rate than women who were not exposed to antidepressants, Lindsey A. Sjaarda, PhD, reported at the annual meeting of the American Society for Reproductive Medicine.

Jeff Craven/MDedge News

In addition, women in a subgroup receiving fluoxetine experienced a lower live birth rate and greater incidence of pregnancy loss than women taking other SSRIs, but the results were not statistically significant, said Dr. Sjaarda of the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

“[It] is biologically plausible that fluoxetine might have some different effects,” she noted. “It does have some different interaction with [cytochrome] P-450 enzyme activity, and this translates to it having a much longer half-life as well. It’s different in terms of drug metabolism and in its interaction with the hormone biosynthesis pathway.”

Most of the research on antidepressants and SSRIs in pregnancy has focused on the safety of the agents, rather than the effect on pregnancy for women trying to conceive, explained Dr. Sjaarda. Previous research also has shown inconsistent findings for fecundability in women of reproductive age taking SSRIs, and the risk of specific SSRI compounds on pregnancy loss is unclear.

The researchers performed a longitudinal exposure assessment of the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial, which consisted of 1,228 women aged between 18 and 40 years trying to conceive. Patients were included if they had one to two prior pregnancy losses, up to two live births, and had been trying to become pregnant for six menstrual cycles; they were excluded if they had a severe history of mental illness. There were 1,035 women who had no preconception antidepressant exposure and 183 who did have preconception antidepressant exposure.

Patients provided longitudinal urine samples at various time points, including while trying to conceive and in early pregnancy, during the menses phase of each menstrual cycle and at their last menstrual cycle, and at 4 and 8 weeks’ gestation if they become pregnant. The urine samples were collected at home or in clinic; human chorionic gonadotropin levels were measured on the stored samples. The researchers defined pregnancy loss as any kind of loss measured after detecting human chorionic gonadotropin, and they used the patient’s medical record to determine live birth. The fecundability odds ratio was used to estimate the odds of conception in menstrual cycles.

Wavebreakmedia Ltd/Thinkstock

Aypical and tricyclic antidepressants and SSRIs such as sertraline, fluoxetine, and citalopram/escitalopram were analyzed, as well as use of opioids, cannabinoids, and benzodiazepines. In total, 172 women used SSRIs, which represented 94% of the patient group analyzed, said Dr. Sjaarda. “This cohort really represents women who are successfully controlled with first-line agents.”

Patients in both the SSRI and no-antidepressant groups had similar baseline characteristics, but there were differences with regard to body mass index (26 kg/m² vs. 28 kg/m²), employment status (77% vs. 67%), perceived stress (1.0 vs. 0.9), and opioid exposure (16% vs. 23%).

The researchers found use of any SSRI was associated with a 23% reduction in fecundability, with patients using fluoxetine, sertraline, and citalopram/escitalopram having a similar reduction in fecundability, compared with patients not using SSRIs.

Patients who received SSRIs also had approximately a 53% live birth rate overall. When analyzed by individual SSRI, however, there was a statistically significant reduction in the live birth rate for patients who were using fluoxetine, compared with patients using sertraline and citalopram/escitalopram. “This suggests that there was something besides just reduced fecundability going on with the fluoxetine-exposed women,” said Dr. Sjaarda.

When SSRI use was analyzed with regard to pregnancy loss, there was a generally null effect between women exposed to SSRIs overall versus those not exposed at the time before conception, at last menstrual period, and at 4 or 8 weeks’ gestation. But when grouped by specific SSRI, patients receiving fluoxetine had increased risk of pregnancy loss prior to conception, compared with patients not taking fluoxetine (34% vs. 24%; adjusted risk ratio, 1.41; 95% confidence interval, 0.94-2.12) , as well as at their last menstrual period (34% vs. 24%; adjusted RR, 1.48; 95% CI, 0.98-2.24) and at 4 weeks of pregnancy (31% vs. 22%; adjusted RR, 1.61; 95% CI, 0.94-2.78). “This was about a 40%-60% increase in pregnancy loss, even though the sample size is generally small when you divide it into these groups,” said Dr. Sjaarda.

Mental health care is an important public health and maternal health issue, and SSRIs as a drug class are essential for helping to appropriately manage mental health, noted Dr. Sjaarda.

Because “patients’ disease severities all vary and the reactions to different drugs vary, no one-size-fits-all recommendation can be made for people planning a pregnancy while using SSRIs,” concluded Dr. Sjaarda. “However, we’re hoping that women and their physicians can now consider these new data, which are based on objective and longitudinally measured exposure, as well as prospectively-assessed outcomes for these most common antidepressants and develop to a more informed and individualized plan for women who are trying to conceive and use SSRIs.”

Dr. Sjaarda reported no relevant conflicts of interest.

SOURCE: Sjaarda L et al. ASRM 2019, Abstract O-1.

PHILADELPHIA – Women taking SSRIs may experience reduced fecundity and a lower live birth rate than women who were not exposed to antidepressants, Lindsey A. Sjaarda, PhD, reported at the annual meeting of the American Society for Reproductive Medicine.

Jeff Craven/MDedge News

In addition, women in a subgroup receiving fluoxetine experienced a lower live birth rate and greater incidence of pregnancy loss than women taking other SSRIs, but the results were not statistically significant, said Dr. Sjaarda of the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

“[It] is biologically plausible that fluoxetine might have some different effects,” she noted. “It does have some different interaction with [cytochrome] P-450 enzyme activity, and this translates to it having a much longer half-life as well. It’s different in terms of drug metabolism and in its interaction with the hormone biosynthesis pathway.”

Most of the research on antidepressants and SSRIs in pregnancy has focused on the safety of the agents, rather than the effect on pregnancy for women trying to conceive, explained Dr. Sjaarda. Previous research also has shown inconsistent findings for fecundability in women of reproductive age taking SSRIs, and the risk of specific SSRI compounds on pregnancy loss is unclear.

The researchers performed a longitudinal exposure assessment of the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial, which consisted of 1,228 women aged between 18 and 40 years trying to conceive. Patients were included if they had one to two prior pregnancy losses, up to two live births, and had been trying to become pregnant for six menstrual cycles; they were excluded if they had a severe history of mental illness. There were 1,035 women who had no preconception antidepressant exposure and 183 who did have preconception antidepressant exposure.

Patients provided longitudinal urine samples at various time points, including while trying to conceive and in early pregnancy, during the menses phase of each menstrual cycle and at their last menstrual cycle, and at 4 and 8 weeks’ gestation if they become pregnant. The urine samples were collected at home or in clinic; human chorionic gonadotropin levels were measured on the stored samples. The researchers defined pregnancy loss as any kind of loss measured after detecting human chorionic gonadotropin, and they used the patient’s medical record to determine live birth. The fecundability odds ratio was used to estimate the odds of conception in menstrual cycles.

Wavebreakmedia Ltd/Thinkstock

Aypical and tricyclic antidepressants and SSRIs such as sertraline, fluoxetine, and citalopram/escitalopram were analyzed, as well as use of opioids, cannabinoids, and benzodiazepines. In total, 172 women used SSRIs, which represented 94% of the patient group analyzed, said Dr. Sjaarda. “This cohort really represents women who are successfully controlled with first-line agents.”

Patients in both the SSRI and no-antidepressant groups had similar baseline characteristics, but there were differences with regard to body mass index (26 kg/m² vs. 28 kg/m²), employment status (77% vs. 67%), perceived stress (1.0 vs. 0.9), and opioid exposure (16% vs. 23%).

The researchers found use of any SSRI was associated with a 23% reduction in fecundability, with patients using fluoxetine, sertraline, and citalopram/escitalopram having a similar reduction in fecundability, compared with patients not using SSRIs.

Patients who received SSRIs also had approximately a 53% live birth rate overall. When analyzed by individual SSRI, however, there was a statistically significant reduction in the live birth rate for patients who were using fluoxetine, compared with patients using sertraline and citalopram/escitalopram. “This suggests that there was something besides just reduced fecundability going on with the fluoxetine-exposed women,” said Dr. Sjaarda.

When SSRI use was analyzed with regard to pregnancy loss, there was a generally null effect between women exposed to SSRIs overall versus those not exposed at the time before conception, at last menstrual period, and at 4 or 8 weeks’ gestation. But when grouped by specific SSRI, patients receiving fluoxetine had increased risk of pregnancy loss prior to conception, compared with patients not taking fluoxetine (34% vs. 24%; adjusted risk ratio, 1.41; 95% confidence interval, 0.94-2.12) , as well as at their last menstrual period (34% vs. 24%; adjusted RR, 1.48; 95% CI, 0.98-2.24) and at 4 weeks of pregnancy (31% vs. 22%; adjusted RR, 1.61; 95% CI, 0.94-2.78). “This was about a 40%-60% increase in pregnancy loss, even though the sample size is generally small when you divide it into these groups,” said Dr. Sjaarda.

Mental health care is an important public health and maternal health issue, and SSRIs as a drug class are essential for helping to appropriately manage mental health, noted Dr. Sjaarda.

Because “patients’ disease severities all vary and the reactions to different drugs vary, no one-size-fits-all recommendation can be made for people planning a pregnancy while using SSRIs,” concluded Dr. Sjaarda. “However, we’re hoping that women and their physicians can now consider these new data, which are based on objective and longitudinally measured exposure, as well as prospectively-assessed outcomes for these most common antidepressants and develop to a more informed and individualized plan for women who are trying to conceive and use SSRIs.”

Dr. Sjaarda reported no relevant conflicts of interest.

SOURCE: Sjaarda L et al. ASRM 2019, Abstract O-1.

The recent drop in U.S. twin birthrates after more than three decades of increases was not distributed evenly among demographic groups, according to the National Center for Health Statistics.

The twin birthrate, which had increased by 79% during 1980-2014, fell by 4% during 2014-2018, but that decline was “not universal across maternal age and race and Hispanic-origin groups,” the NCHS investigators said.

Twin birthrates fell by at least 10% for mothers aged 30 years and older from 2014 to 2018 but held steady for women in their twenties. Over that same period, the twin birthrate fell by a significant 7% among non-Hispanic white women (36.7 to 34.3 per 1,000 total births) but increased just slightly for non-Hispanic black women (40.0 to 40.5 per 1,000) and Hispanic women (24.1 to 24.4), the investigators reported.

For women 30 years and older, the drops in twin births got larger as age increased and were significant for each age group. The rate for women aged 30-34 years fell 10% as it went from 40.3 per 1,000 total births in 2014 to 36.2 per 1,000. The decrease was 12% (from 48.6 per 1,000 to 42.8) for women aged 35-39 and 23% (from 66.0 to 51.1) for those aged 40 years and older, they said based on data from the National Vital Statistics System.

The rates were basically unchanged for women in their 20s, from 23.0 to 23.2 in 20- to 24-year-olds and 30.5 to 30.4 in 25- to 29-year-olds – but there was a significant increase for the youngest group with rates among those younger than 20 years going from 16.0 to 17.1 per 1,000, the report showed.

[email protected]

The recent drop in U.S. twin birthrates after more than three decades of increases was not distributed evenly among demographic groups, according to the National Center for Health Statistics.

The twin birthrate, which had increased by 79% during 1980-2014, fell by 4% during 2014-2018, but that decline was “not universal across maternal age and race and Hispanic-origin groups,” the NCHS investigators said.

Twin birthrates fell by at least 10% for mothers aged 30 years and older from 2014 to 2018 but held steady for women in their twenties. Over that same period, the twin birthrate fell by a significant 7% among non-Hispanic white women (36.7 to 34.3 per 1,000 total births) but increased just slightly for non-Hispanic black women (40.0 to 40.5 per 1,000) and Hispanic women (24.1 to 24.4), the investigators reported.

For women 30 years and older, the drops in twin births got larger as age increased and were significant for each age group. The rate for women aged 30-34 years fell 10% as it went from 40.3 per 1,000 total births in 2014 to 36.2 per 1,000. The decrease was 12% (from 48.6 per 1,000 to 42.8) for women aged 35-39 and 23% (from 66.0 to 51.1) for those aged 40 years and older, they said based on data from the National Vital Statistics System.

The rates were basically unchanged for women in their 20s, from 23.0 to 23.2 in 20- to 24-year-olds and 30.5 to 30.4 in 25- to 29-year-olds – but there was a significant increase for the youngest group with rates among those younger than 20 years going from 16.0 to 17.1 per 1,000, the report showed.

[email protected]

The recent drop in U.S. twin birthrates after more than three decades of increases was not distributed evenly among demographic groups, according to the National Center for Health Statistics.

The twin birthrate, which had increased by 79% during 1980-2014, fell by 4% during 2014-2018, but that decline was “not universal across maternal age and race and Hispanic-origin groups,” the NCHS investigators said.

Twin birthrates fell by at least 10% for mothers aged 30 years and older from 2014 to 2018 but held steady for women in their twenties. Over that same period, the twin birthrate fell by a significant 7% among non-Hispanic white women (36.7 to 34.3 per 1,000 total births) but increased just slightly for non-Hispanic black women (40.0 to 40.5 per 1,000) and Hispanic women (24.1 to 24.4), the investigators reported.

For women 30 years and older, the drops in twin births got larger as age increased and were significant for each age group. The rate for women aged 30-34 years fell 10% as it went from 40.3 per 1,000 total births in 2014 to 36.2 per 1,000. The decrease was 12% (from 48.6 per 1,000 to 42.8) for women aged 35-39 and 23% (from 66.0 to 51.1) for those aged 40 years and older, they said based on data from the National Vital Statistics System.

The rates were basically unchanged for women in their 20s, from 23.0 to 23.2 in 20- to 24-year-olds and 30.5 to 30.4 in 25- to 29-year-olds – but there was a significant increase for the youngest group with rates among those younger than 20 years going from 16.0 to 17.1 per 1,000, the report showed.

[email protected]

Children born to mothers with high blood levels of lead have an increased risk of being overweight or obese, particularly if their mothers are also overweight, according to new research.

Creatas Images

Adequate maternal plasma levels of folate, however, mitigated this risk.

“When considered simultaneously, maternal lead exposure, rather than early childhood lead exposure, contributed to overweight/obesity risk in a dose-response fashion across multiple developmental stages (preschool age, school age and early adolescence) and amplified intergenerational overweight/obesity risk (additively with maternal overweight/obesity),” Guoying Wang, MD, PhD, of Johns Hopkins Bloomberg School of Public Health, Baltimore, and associates, reported in JAMA Network Open.

“These findings support the hypothesis that the obesity epidemic could be related to environmental chemical exposures in utero and raise the possibility that optimal maternal folate supplementation may help counteract the adverse effects of environmental lead exposure,” the authors wrote.

The prospective urban, low-income cohort study, which ran from 2002 to 2013, involved 1,442 mother-child pairs who joined the study when the children were born and attended follow-up visits at Boston Medical Center. The mean age of the mothers was 29 years, and the children were, on average, 8 years old at follow-up. Half the children were male; 67% of mothers were black, and 20% were Latina.

The researchers collected maternal blood samples within 24-72 hours after birth to measure red blood cell lead levels and plasma folate levels. Children’s whole-blood lead levels were measured during the first lead screening of their well child visits, at a median 10 months of age. Researchers tracked children’s body mass index Z-score and defined overweight/obesity as exceeding the 85th national percentile for their age and sex.

Detectable lead was present in all the mothers’ blood samples. The median maternal red blood cell lead level was 2.5 mcg/dL, although black mothers tended to have higher lead exposure than that of other racial groups. Median maternal plasma folate level was 32 nmol/L. Children’s blood lead levels were a median 1.4 mcg/dL, and their median BMI Z-score was 0.78.

Children whose mothers had red blood cell lead levels of 5.0 mcg/dL or greater (16%) had 65% greater odds of being overweight or obese compared with children whose mothers’ lead level was less than 2 mcg/dL, after adjustment for maternal education, race/ethnicity, smoking status, parity, diabetes, hypertensive disorder, preterm birth, fetal growth, and breastfeeding status (odds ratio [OR], 1.65; 95% confidence internal [CI], 1.18-2.32). Only 5.2% of children had whole-blood lead levels of 5 mcg/dL or greater.

“Mothers with the highest red blood cell lead levels were older and multiparous, were more likely to be black and nonsmokers, had lower plasma folate levels and were more likely to have prepregnancy overweight/obesity and diabetes,” the authors reported.

The dose-response association did not lose significance when the researchers adjusted for children’s blood lead levels, maternal age, cesarean delivery, term births only, and black race. Nor did it change in a subset of children when the researchers adjusted for children’s physical activity.

The strength of the association increased when mothers also had a BMI greater than the average/healthy range. Children were more than four times more likely to be overweight or obese if their mothers were overweight or obese and had lead levels greater than 5.0 mcg/dL, compared with nonoverweight mothers with levels below 2 mcg/dL (OR, 4.24; 95% CI, 2.64-6.82).

Among children whose mothers were overweight/obese and had high blood lead levels, however, high folate levels appeared protective against obesity. These children had a 41% lower risk of being overweight or obese, compared with others in their group, if their mothers had plasma folate levels of at least 20 nmol/L (OR, 0.59 CI, 0.36-0.95; P = .03).

According to an invited commentary, “approximately 140,000 new chemicals and pesticides have appeared since 1950,” with “universal human exposure to approximately 5,000 of those,” wrote Marco Sanchez-Guerra, PhD, of the National Institute of Perinatology in Mexico City, and coauthors Andres Cardenas, PhD, of the University of California, Berkeley, and Citlalli Osorio-Yáñez, PhD, of the National Autonomous University of Mexico in Mexico City. Yet fewer than half of those chemicals have been tested for safety or toxic effect, the editorialists wrote, and scientists know little of their potential reproductive harm.

Dr. Sanchez-Guerra, Dr. Cardenas, and Dr. Osorio-Yáñez agreed with the study authors that elevated lead exposures, especially from gasoline before lead was removed in the United States in 1975, may partly explain the current epidemic of obesity.

“Identifying preventable prenatal causes of obesity is a cornerstone in the fight against the obesity epidemic,” the editorialists said. While most recommendations center on changes to diet and physical activity, environmental factors during pregnancy could be involved in childhood obesity as well.

“The study by Wang et al. opens the door to new questions about whether adequate folate intake might modify the adverse effects of other chemical exposures,” they continued, noting other research suggesting a protective effect from folate against health effects of air pollution exposure. “These efforts could yield substantial public health benefits and represent novel tools in fighting the obesity epidemic,” they concluded.

The research was funded by the National Institutes of Health and the U.S. Department of Health and Human Services. Neither the study authors nor the editorialists had industry financial disclosures.

SOURCES: Wang G et al. JAMA Netw Open. 2019;2(10):e1912343. doi: 10.1001/jamanetworkopen.2019.12343; Sanchez-Guerra M et al. JAMA Netw Open. 2019;2(10):e1912334. doi: 10.1001/jamanetworkopen.2019.12334.

Children born to mothers with high blood levels of lead have an increased risk of being overweight or obese, particularly if their mothers are also overweight, according to new research.

Creatas Images

Adequate maternal plasma levels of folate, however, mitigated this risk.

“When considered simultaneously, maternal lead exposure, rather than early childhood lead exposure, contributed to overweight/obesity risk in a dose-response fashion across multiple developmental stages (preschool age, school age and early adolescence) and amplified intergenerational overweight/obesity risk (additively with maternal overweight/obesity),” Guoying Wang, MD, PhD, of Johns Hopkins Bloomberg School of Public Health, Baltimore, and associates, reported in JAMA Network Open.

“These findings support the hypothesis that the obesity epidemic could be related to environmental chemical exposures in utero and raise the possibility that optimal maternal folate supplementation may help counteract the adverse effects of environmental lead exposure,” the authors wrote.

The prospective urban, low-income cohort study, which ran from 2002 to 2013, involved 1,442 mother-child pairs who joined the study when the children were born and attended follow-up visits at Boston Medical Center. The mean age of the mothers was 29 years, and the children were, on average, 8 years old at follow-up. Half the children were male; 67% of mothers were black, and 20% were Latina.

The researchers collected maternal blood samples within 24-72 hours after birth to measure red blood cell lead levels and plasma folate levels. Children’s whole-blood lead levels were measured during the first lead screening of their well child visits, at a median 10 months of age. Researchers tracked children’s body mass index Z-score and defined overweight/obesity as exceeding the 85th national percentile for their age and sex.

Detectable lead was present in all the mothers’ blood samples. The median maternal red blood cell lead level was 2.5 mcg/dL, although black mothers tended to have higher lead exposure than that of other racial groups. Median maternal plasma folate level was 32 nmol/L. Children’s blood lead levels were a median 1.4 mcg/dL, and their median BMI Z-score was 0.78.

Children whose mothers had red blood cell lead levels of 5.0 mcg/dL or greater (16%) had 65% greater odds of being overweight or obese compared with children whose mothers’ lead level was less than 2 mcg/dL, after adjustment for maternal education, race/ethnicity, smoking status, parity, diabetes, hypertensive disorder, preterm birth, fetal growth, and breastfeeding status (odds ratio [OR], 1.65; 95% confidence internal [CI], 1.18-2.32). Only 5.2% of children had whole-blood lead levels of 5 mcg/dL or greater.

“Mothers with the highest red blood cell lead levels were older and multiparous, were more likely to be black and nonsmokers, had lower plasma folate levels and were more likely to have prepregnancy overweight/obesity and diabetes,” the authors reported.

The dose-response association did not lose significance when the researchers adjusted for children’s blood lead levels, maternal age, cesarean delivery, term births only, and black race. Nor did it change in a subset of children when the researchers adjusted for children’s physical activity.

The strength of the association increased when mothers also had a BMI greater than the average/healthy range. Children were more than four times more likely to be overweight or obese if their mothers were overweight or obese and had lead levels greater than 5.0 mcg/dL, compared with nonoverweight mothers with levels below 2 mcg/dL (OR, 4.24; 95% CI, 2.64-6.82).

Among children whose mothers were overweight/obese and had high blood lead levels, however, high folate levels appeared protective against obesity. These children had a 41% lower risk of being overweight or obese, compared with others in their group, if their mothers had plasma folate levels of at least 20 nmol/L (OR, 0.59 CI, 0.36-0.95; P = .03).

According to an invited commentary, “approximately 140,000 new chemicals and pesticides have appeared since 1950,” with “universal human exposure to approximately 5,000 of those,” wrote Marco Sanchez-Guerra, PhD, of the National Institute of Perinatology in Mexico City, and coauthors Andres Cardenas, PhD, of the University of California, Berkeley, and Citlalli Osorio-Yáñez, PhD, of the National Autonomous University of Mexico in Mexico City. Yet fewer than half of those chemicals have been tested for safety or toxic effect, the editorialists wrote, and scientists know little of their potential reproductive harm.

Dr. Sanchez-Guerra, Dr. Cardenas, and Dr. Osorio-Yáñez agreed with the study authors that elevated lead exposures, especially from gasoline before lead was removed in the United States in 1975, may partly explain the current epidemic of obesity.

“Identifying preventable prenatal causes of obesity is a cornerstone in the fight against the obesity epidemic,” the editorialists said. While most recommendations center on changes to diet and physical activity, environmental factors during pregnancy could be involved in childhood obesity as well.

“The study by Wang et al. opens the door to new questions about whether adequate folate intake might modify the adverse effects of other chemical exposures,” they continued, noting other research suggesting a protective effect from folate against health effects of air pollution exposure. “These efforts could yield substantial public health benefits and represent novel tools in fighting the obesity epidemic,” they concluded.

The research was funded by the National Institutes of Health and the U.S. Department of Health and Human Services. Neither the study authors nor the editorialists had industry financial disclosures.

SOURCES: Wang G et al. JAMA Netw Open. 2019;2(10):e1912343. doi: 10.1001/jamanetworkopen.2019.12343; Sanchez-Guerra M et al. JAMA Netw Open. 2019;2(10):e1912334. doi: 10.1001/jamanetworkopen.2019.12334.

Children born to mothers with high blood levels of lead have an increased risk of being overweight or obese, particularly if their mothers are also overweight, according to new research.

Creatas Images

Adequate maternal plasma levels of folate, however, mitigated this risk.

“When considered simultaneously, maternal lead exposure, rather than early childhood lead exposure, contributed to overweight/obesity risk in a dose-response fashion across multiple developmental stages (preschool age, school age and early adolescence) and amplified intergenerational overweight/obesity risk (additively with maternal overweight/obesity),” Guoying Wang, MD, PhD, of Johns Hopkins Bloomberg School of Public Health, Baltimore, and associates, reported in JAMA Network Open.

“These findings support the hypothesis that the obesity epidemic could be related to environmental chemical exposures in utero and raise the possibility that optimal maternal folate supplementation may help counteract the adverse effects of environmental lead exposure,” the authors wrote.

The prospective urban, low-income cohort study, which ran from 2002 to 2013, involved 1,442 mother-child pairs who joined the study when the children were born and attended follow-up visits at Boston Medical Center. The mean age of the mothers was 29 years, and the children were, on average, 8 years old at follow-up. Half the children were male; 67% of mothers were black, and 20% were Latina.

The researchers collected maternal blood samples within 24-72 hours after birth to measure red blood cell lead levels and plasma folate levels. Children’s whole-blood lead levels were measured during the first lead screening of their well child visits, at a median 10 months of age. Researchers tracked children’s body mass index Z-score and defined overweight/obesity as exceeding the 85th national percentile for their age and sex.

Detectable lead was present in all the mothers’ blood samples. The median maternal red blood cell lead level was 2.5 mcg/dL, although black mothers tended to have higher lead exposure than that of other racial groups. Median maternal plasma folate level was 32 nmol/L. Children’s blood lead levels were a median 1.4 mcg/dL, and their median BMI Z-score was 0.78.

Children whose mothers had red blood cell lead levels of 5.0 mcg/dL or greater (16%) had 65% greater odds of being overweight or obese compared with children whose mothers’ lead level was less than 2 mcg/dL, after adjustment for maternal education, race/ethnicity, smoking status, parity, diabetes, hypertensive disorder, preterm birth, fetal growth, and breastfeeding status (odds ratio [OR], 1.65; 95% confidence internal [CI], 1.18-2.32). Only 5.2% of children had whole-blood lead levels of 5 mcg/dL or greater.

“Mothers with the highest red blood cell lead levels were older and multiparous, were more likely to be black and nonsmokers, had lower plasma folate levels and were more likely to have prepregnancy overweight/obesity and diabetes,” the authors reported.

The dose-response association did not lose significance when the researchers adjusted for children’s blood lead levels, maternal age, cesarean delivery, term births only, and black race. Nor did it change in a subset of children when the researchers adjusted for children’s physical activity.

The strength of the association increased when mothers also had a BMI greater than the average/healthy range. Children were more than four times more likely to be overweight or obese if their mothers were overweight or obese and had lead levels greater than 5.0 mcg/dL, compared with nonoverweight mothers with levels below 2 mcg/dL (OR, 4.24; 95% CI, 2.64-6.82).

Among children whose mothers were overweight/obese and had high blood lead levels, however, high folate levels appeared protective against obesity. These children had a 41% lower risk of being overweight or obese, compared with others in their group, if their mothers had plasma folate levels of at least 20 nmol/L (OR, 0.59 CI, 0.36-0.95; P = .03).

According to an invited commentary, “approximately 140,000 new chemicals and pesticides have appeared since 1950,” with “universal human exposure to approximately 5,000 of those,” wrote Marco Sanchez-Guerra, PhD, of the National Institute of Perinatology in Mexico City, and coauthors Andres Cardenas, PhD, of the University of California, Berkeley, and Citlalli Osorio-Yáñez, PhD, of the National Autonomous University of Mexico in Mexico City. Yet fewer than half of those chemicals have been tested for safety or toxic effect, the editorialists wrote, and scientists know little of their potential reproductive harm.

Dr. Sanchez-Guerra, Dr. Cardenas, and Dr. Osorio-Yáñez agreed with the study authors that elevated lead exposures, especially from gasoline before lead was removed in the United States in 1975, may partly explain the current epidemic of obesity.

“Identifying preventable prenatal causes of obesity is a cornerstone in the fight against the obesity epidemic,” the editorialists said. While most recommendations center on changes to diet and physical activity, environmental factors during pregnancy could be involved in childhood obesity as well.

“The study by Wang et al. opens the door to new questions about whether adequate folate intake might modify the adverse effects of other chemical exposures,” they continued, noting other research suggesting a protective effect from folate against health effects of air pollution exposure. “These efforts could yield substantial public health benefits and represent novel tools in fighting the obesity epidemic,” they concluded.

The research was funded by the National Institutes of Health and the U.S. Department of Health and Human Services. Neither the study authors nor the editorialists had industry financial disclosures.

SOURCES: Wang G et al. JAMA Netw Open. 2019;2(10):e1912343. doi: 10.1001/jamanetworkopen.2019.12343; Sanchez-Guerra M et al. JAMA Netw Open. 2019;2(10):e1912334. doi: 10.1001/jamanetworkopen.2019.12334.

A new international position statement on testosterone therapy for women concludes that a trial of testosterone is appropriate for postmenopausal women with hypoactive sexual desire dysfunction (HSDD) and that its use for any other condition, symptom, or reason is not supported by available evidence.

The seven-page position statement, developed by an international task force of experts from the Endocrine Society, the American College of Gynecologists and Obstetricians, and multiple other medical societies, also emphasized that blood concentrations of testosterone should approximate premenopausal physiological conditions.

“When testosterone therapy is given, the resultant blood levels should not be above those seen in healthy young women,” said lead author Susan Ruth Davis, PhD, MBBS, of Monash University in Melbourne, Australia, in a press release issued by the Endocrine Society. Dr. Davis is president of the International Menopause Society, which coordinated the panel.

The statement was published in the Journal of Clinical Endocrinology & Metabolism and three other medical journals.

Margaret E. Wierman, MD, who represented the Endocrine Society on the task force, said in an interview that there has been “growing concern about testosterone being prescribed for a variety of signs and symptoms without data to support” such use. At the same time, there is significant concern about the ongoing lack of approved formulations licensed specifically for women, she said.

In part, the statement is about a renewed “call to industry to make some [female-specific] formulations so that we can examine other potential roles of testosterone in women,” said Dr. Wierman, professor of medicine and physiology at the University of Colorado at Denver, Aurora, and chief of endocrinology at the Rocky Mountain Regional Veterans Affairs Medical Center in Aurora.

“Testosterone may be useful [for indications other than HSDD], but we don’t know. There may be no [breast or cardiovascular disease risk], but we don’t know,” she said. “And without a formulation to study potential benefits and risks, it’s good to be cautious. It’s good to really outline where we have data and where we don’t.”

The Endocrine Society’s 2014 clinical practice guideline on androgen therapy in women, for which Dr. Wierman was the lead author, also recommended against the off-label use of testosterone for sexual dysfunction other than HSDD or for any other reason, such as cognitive, cardiovascular, metabolic, or bone health. As with the new statement, the society’s position statement was guided by an international, multisociety task force, albeit a smaller one.

For the new global position statement, the task force’s review of evidence includes a recently published systematic review and meta-analysis of randomized controlled trial data – of at least 12 weeks’ duration – on the use of testosterone for sexual function, cardiometabolic variables, cognitive measures, and musculoskeletal health. Some of the data from the randomized controlled trials were unpublished.

The meta-analysis, led by Dr. Davis and published in July in the Lancet Diabetes & Endocrinology, found that, compared with placebo or a comparator (such as estrogen, with or without progesterone), testosterone in either oral or transdermal form significantly improved sexual function in postmenopausal women. However, data about the effects of testosterone for other indications, its long-term safety, and its use in premenopausal women, were insufficient for drawing any conclusions (Lancet Diabetes Endocrinol. 2019 Jul 25. doi: 10.1016/S2213-8587[19]30189-5).

In addition, testosterone administered orally – but not nonorally (patch or cream) – was associated with adverse lipid profiles, Dr. Davis and her colleagues reported.

Another systematic review and meta-analysis, published in Fertility and Sterility in 2017 and included in the task force’s evidence review, focused specifically on transdermal testosterone for menopausal women with HSDD, with or without estrogen and progestin therapy. It also showed short-term efficacy in terms of improvement in sexual function, as well as short-term safety (Fertil Steril. 2017;107(2):475-82).

The new position statement warns about the lack of long-term safety data, stating that “safety data for testosterone in physiologic doses are not available beyond 24 months of treatment.”

In the short term, testosterone therapy for postmenopausal women (in doses approximating testosterone concentrations for premenopausal women), is associated with mild increases in acne and body/facial hair growth in some women, but not with alopecia, clitoromegaly, or voice change. Short-term transdermal therapy also does not seem to affect breast cancer risk or have any significant effects on lipid profiles, the statement says.

The panel points out, however, that randomized controlled trials with testosterone therapy have excluded women who are at high risk of cardiometabolic disease, and that women with a previous diagnosis of breast cancer have also been excluded from randomized trials of testosterone in women with HSDD. This is a “big issue,” said Dr. Wierman, and means that recommendations regarding the effect of testosterone in postmenopausal women with HSDD may not be generalizable to possible at-risk subpopulations.

The panel endorsed testosterone therapy specifically for women with HSDD because most of the studies reporting on sexual function have recruited women with diagnosed HSDD. Demonstrated benefits of testosterone in these cases include improved sexual desire, arousal, orgasm, and pleasure, and reduced concerns and distress about sex. HSDD should be diagnosed after formal biopsychosocial assessment, the statement notes.

“We don’t completely understand the control of sexual function in women, but it’s very dependent on estrogen status. And it’s also dependent on psychosocial factors, emotional health, relationship issues, and physical issues,” Dr. Wierman said in the interview.

“In practice, we look at all these issues, and we first optimize estrogen status. Once that’s done, and we’ve looked at all the other components of sexual function, then we can consider off-label use of testosterone,” she said. “If there’s no response in 3-6 months, we stop it.”

Testosterone levels do not correlate with sexual dysfunction, Dr. Wierman emphasized, and direct assays for the measurement of total and free testosterone are unreliable. The statement acknowledges that but still recommends measurement of testosterone using direct assays, in cases in which liquid/gas chromatography and tandem mass spectrometry assay (which has “high accuracy and reproducibility”) are not available. This is “to exclude high baseline concentrations and also to exclude supraphysiological concentrations during treatment,” the panel said.

Most endocrinologists and other experts who prescribe testosterone therapy for women use an approved male formulation off label and adjust it – an approach that the panel says is reasonable as long as hormone concentrations are “maintained in the physiologic female range.”

Compounded “bioidentical” testosterone therapy “cannot be recommended for the treatment of HSDD because of the lack of evidence for safety and efficacy,” the statement says.

“A big concern of many endocrinologists,” Dr. Wierman added, “is the recent explosion of using pharmacological levels of both estrogen and testosterone in either [injections] or pellets.” The Endocrine Society and other societies have alerted the Food and Drug Administration to “this new cottage industry, which may have significant side effects and risks for our patients,” she said.
Dr. Wierman reported received funding from Corcept Therapeutics, Novartis, and the Cancer League of Colorado, and honoraria or consultation fees from Pfizer to review ASPIRE grant applications for studies of acromegaly as well as Endocrine Society honorarium for teaching in the Endocrine Board Review and Clinical Endocrine Update. Dr. Davis reported receiving funding from a National Health and Medical Research Council Project Grant, a National Breast Foundation accelerator grant, and the Grollo-Ruzenne Foundation, as well as honoraria from Besins and Pfizer Australia. She has been a consultant to Besins Healthcare, Mayne Pharmaceuticals, Lawley Pharmaceuticals, and Que Oncology. Disclosures for other authors of the position statement are listed with the statement.

SOURCE: Davis SR et al. J Clin Endocrinol Metab. 2019 Sep 2. doi: 10.1210/jc.2019-01603.
 

A new international position statement on testosterone therapy for women concludes that a trial of testosterone is appropriate for postmenopausal women with hypoactive sexual desire dysfunction (HSDD) and that its use for any other condition, symptom, or reason is not supported by available evidence.

The seven-page position statement, developed by an international task force of experts from the Endocrine Society, the American College of Gynecologists and Obstetricians, and multiple other medical societies, also emphasized that blood concentrations of testosterone should approximate premenopausal physiological conditions.

“When testosterone therapy is given, the resultant blood levels should not be above those seen in healthy young women,” said lead author Susan Ruth Davis, PhD, MBBS, of Monash University in Melbourne, Australia, in a press release issued by the Endocrine Society. Dr. Davis is president of the International Menopause Society, which coordinated the panel.

The statement was published in the Journal of Clinical Endocrinology & Metabolism and three other medical journals.

Margaret E. Wierman, MD, who represented the Endocrine Society on the task force, said in an interview that there has been “growing concern about testosterone being prescribed for a variety of signs and symptoms without data to support” such use. At the same time, there is significant concern about the ongoing lack of approved formulations licensed specifically for women, she said.

In part, the statement is about a renewed “call to industry to make some [female-specific] formulations so that we can examine other potential roles of testosterone in women,” said Dr. Wierman, professor of medicine and physiology at the University of Colorado at Denver, Aurora, and chief of endocrinology at the Rocky Mountain Regional Veterans Affairs Medical Center in Aurora.

“Testosterone may be useful [for indications other than HSDD], but we don’t know. There may be no [breast or cardiovascular disease risk], but we don’t know,” she said. “And without a formulation to study potential benefits and risks, it’s good to be cautious. It’s good to really outline where we have data and where we don’t.”

The Endocrine Society’s 2014 clinical practice guideline on androgen therapy in women, for which Dr. Wierman was the lead author, also recommended against the off-label use of testosterone for sexual dysfunction other than HSDD or for any other reason, such as cognitive, cardiovascular, metabolic, or bone health. As with the new statement, the society’s position statement was guided by an international, multisociety task force, albeit a smaller one.

For the new global position statement, the task force’s review of evidence includes a recently published systematic review and meta-analysis of randomized controlled trial data – of at least 12 weeks’ duration – on the use of testosterone for sexual function, cardiometabolic variables, cognitive measures, and musculoskeletal health. Some of the data from the randomized controlled trials were unpublished.

The meta-analysis, led by Dr. Davis and published in July in the Lancet Diabetes & Endocrinology, found that, compared with placebo or a comparator (such as estrogen, with or without progesterone), testosterone in either oral or transdermal form significantly improved sexual function in postmenopausal women. However, data about the effects of testosterone for other indications, its long-term safety, and its use in premenopausal women, were insufficient for drawing any conclusions (Lancet Diabetes Endocrinol. 2019 Jul 25. doi: 10.1016/S2213-8587[19]30189-5).

In addition, testosterone administered orally – but not nonorally (patch or cream) – was associated with adverse lipid profiles, Dr. Davis and her colleagues reported.

Another systematic review and meta-analysis, published in Fertility and Sterility in 2017 and included in the task force’s evidence review, focused specifically on transdermal testosterone for menopausal women with HSDD, with or without estrogen and progestin therapy. It also showed short-term efficacy in terms of improvement in sexual function, as well as short-term safety (Fertil Steril. 2017;107(2):475-82).

The new position statement warns about the lack of long-term safety data, stating that “safety data for testosterone in physiologic doses are not available beyond 24 months of treatment.”

In the short term, testosterone therapy for postmenopausal women (in doses approximating testosterone concentrations for premenopausal women), is associated with mild increases in acne and body/facial hair growth in some women, but not with alopecia, clitoromegaly, or voice change. Short-term transdermal therapy also does not seem to affect breast cancer risk or have any significant effects on lipid profiles, the statement says.

The panel points out, however, that randomized controlled trials with testosterone therapy have excluded women who are at high risk of cardiometabolic disease, and that women with a previous diagnosis of breast cancer have also been excluded from randomized trials of testosterone in women with HSDD. This is a “big issue,” said Dr. Wierman, and means that recommendations regarding the effect of testosterone in postmenopausal women with HSDD may not be generalizable to possible at-risk subpopulations.

The panel endorsed testosterone therapy specifically for women with HSDD because most of the studies reporting on sexual function have recruited women with diagnosed HSDD. Demonstrated benefits of testosterone in these cases include improved sexual desire, arousal, orgasm, and pleasure, and reduced concerns and distress about sex. HSDD should be diagnosed after formal biopsychosocial assessment, the statement notes.

“We don’t completely understand the control of sexual function in women, but it’s very dependent on estrogen status. And it’s also dependent on psychosocial factors, emotional health, relationship issues, and physical issues,” Dr. Wierman said in the interview.

“In practice, we look at all these issues, and we first optimize estrogen status. Once that’s done, and we’ve looked at all the other components of sexual function, then we can consider off-label use of testosterone,” she said. “If there’s no response in 3-6 months, we stop it.”

Testosterone levels do not correlate with sexual dysfunction, Dr. Wierman emphasized, and direct assays for the measurement of total and free testosterone are unreliable. The statement acknowledges that but still recommends measurement of testosterone using direct assays, in cases in which liquid/gas chromatography and tandem mass spectrometry assay (which has “high accuracy and reproducibility”) are not available. This is “to exclude high baseline concentrations and also to exclude supraphysiological concentrations during treatment,” the panel said.

Most endocrinologists and other experts who prescribe testosterone therapy for women use an approved male formulation off label and adjust it – an approach that the panel says is reasonable as long as hormone concentrations are “maintained in the physiologic female range.”

Compounded “bioidentical” testosterone therapy “cannot be recommended for the treatment of HSDD because of the lack of evidence for safety and efficacy,” the statement says.

“A big concern of many endocrinologists,” Dr. Wierman added, “is the recent explosion of using pharmacological levels of both estrogen and testosterone in either [injections] or pellets.” The Endocrine Society and other societies have alerted the Food and Drug Administration to “this new cottage industry, which may have significant side effects and risks for our patients,” she said.
Dr. Wierman reported received funding from Corcept Therapeutics, Novartis, and the Cancer League of Colorado, and honoraria or consultation fees from Pfizer to review ASPIRE grant applications for studies of acromegaly as well as Endocrine Society honorarium for teaching in the Endocrine Board Review and Clinical Endocrine Update. Dr. Davis reported receiving funding from a National Health and Medical Research Council Project Grant, a National Breast Foundation accelerator grant, and the Grollo-Ruzenne Foundation, as well as honoraria from Besins and Pfizer Australia. She has been a consultant to Besins Healthcare, Mayne Pharmaceuticals, Lawley Pharmaceuticals, and Que Oncology. Disclosures for other authors of the position statement are listed with the statement.

SOURCE: Davis SR et al. J Clin Endocrinol Metab. 2019 Sep 2. doi: 10.1210/jc.2019-01603.
 

A new international position statement on testosterone therapy for women concludes that a trial of testosterone is appropriate for postmenopausal women with hypoactive sexual desire dysfunction (HSDD) and that its use for any other condition, symptom, or reason is not supported by available evidence.

The seven-page position statement, developed by an international task force of experts from the Endocrine Society, the American College of Gynecologists and Obstetricians, and multiple other medical societies, also emphasized that blood concentrations of testosterone should approximate premenopausal physiological conditions.

“When testosterone therapy is given, the resultant blood levels should not be above those seen in healthy young women,” said lead author Susan Ruth Davis, PhD, MBBS, of Monash University in Melbourne, Australia, in a press release issued by the Endocrine Society. Dr. Davis is president of the International Menopause Society, which coordinated the panel.

The statement was published in the Journal of Clinical Endocrinology & Metabolism and three other medical journals.

Margaret E. Wierman, MD, who represented the Endocrine Society on the task force, said in an interview that there has been “growing concern about testosterone being prescribed for a variety of signs and symptoms without data to support” such use. At the same time, there is significant concern about the ongoing lack of approved formulations licensed specifically for women, she said.

In part, the statement is about a renewed “call to industry to make some [female-specific] formulations so that we can examine other potential roles of testosterone in women,” said Dr. Wierman, professor of medicine and physiology at the University of Colorado at Denver, Aurora, and chief of endocrinology at the Rocky Mountain Regional Veterans Affairs Medical Center in Aurora.

“Testosterone may be useful [for indications other than HSDD], but we don’t know. There may be no [breast or cardiovascular disease risk], but we don’t know,” she said. “And without a formulation to study potential benefits and risks, it’s good to be cautious. It’s good to really outline where we have data and where we don’t.”

The Endocrine Society’s 2014 clinical practice guideline on androgen therapy in women, for which Dr. Wierman was the lead author, also recommended against the off-label use of testosterone for sexual dysfunction other than HSDD or for any other reason, such as cognitive, cardiovascular, metabolic, or bone health. As with the new statement, the society’s position statement was guided by an international, multisociety task force, albeit a smaller one.

For the new global position statement, the task force’s review of evidence includes a recently published systematic review and meta-analysis of randomized controlled trial data – of at least 12 weeks’ duration – on the use of testosterone for sexual function, cardiometabolic variables, cognitive measures, and musculoskeletal health. Some of the data from the randomized controlled trials were unpublished.

The meta-analysis, led by Dr. Davis and published in July in the Lancet Diabetes & Endocrinology, found that, compared with placebo or a comparator (such as estrogen, with or without progesterone), testosterone in either oral or transdermal form significantly improved sexual function in postmenopausal women. However, data about the effects of testosterone for other indications, its long-term safety, and its use in premenopausal women, were insufficient for drawing any conclusions (Lancet Diabetes Endocrinol. 2019 Jul 25. doi: 10.1016/S2213-8587[19]30189-5).

In addition, testosterone administered orally – but not nonorally (patch or cream) – was associated with adverse lipid profiles, Dr. Davis and her colleagues reported.

Another systematic review and meta-analysis, published in Fertility and Sterility in 2017 and included in the task force’s evidence review, focused specifically on transdermal testosterone for menopausal women with HSDD, with or without estrogen and progestin therapy. It also showed short-term efficacy in terms of improvement in sexual function, as well as short-term safety (Fertil Steril. 2017;107(2):475-82).

The new position statement warns about the lack of long-term safety data, stating that “safety data for testosterone in physiologic doses are not available beyond 24 months of treatment.”

In the short term, testosterone therapy for postmenopausal women (in doses approximating testosterone concentrations for premenopausal women), is associated with mild increases in acne and body/facial hair growth in some women, but not with alopecia, clitoromegaly, or voice change. Short-term transdermal therapy also does not seem to affect breast cancer risk or have any significant effects on lipid profiles, the statement says.

The panel points out, however, that randomized controlled trials with testosterone therapy have excluded women who are at high risk of cardiometabolic disease, and that women with a previous diagnosis of breast cancer have also been excluded from randomized trials of testosterone in women with HSDD. This is a “big issue,” said Dr. Wierman, and means that recommendations regarding the effect of testosterone in postmenopausal women with HSDD may not be generalizable to possible at-risk subpopulations.

The panel endorsed testosterone therapy specifically for women with HSDD because most of the studies reporting on sexual function have recruited women with diagnosed HSDD. Demonstrated benefits of testosterone in these cases include improved sexual desire, arousal, orgasm, and pleasure, and reduced concerns and distress about sex. HSDD should be diagnosed after formal biopsychosocial assessment, the statement notes.

“We don’t completely understand the control of sexual function in women, but it’s very dependent on estrogen status. And it’s also dependent on psychosocial factors, emotional health, relationship issues, and physical issues,” Dr. Wierman said in the interview.

“In practice, we look at all these issues, and we first optimize estrogen status. Once that’s done, and we’ve looked at all the other components of sexual function, then we can consider off-label use of testosterone,” she said. “If there’s no response in 3-6 months, we stop it.”

Testosterone levels do not correlate with sexual dysfunction, Dr. Wierman emphasized, and direct assays for the measurement of total and free testosterone are unreliable. The statement acknowledges that but still recommends measurement of testosterone using direct assays, in cases in which liquid/gas chromatography and tandem mass spectrometry assay (which has “high accuracy and reproducibility”) are not available. This is “to exclude high baseline concentrations and also to exclude supraphysiological concentrations during treatment,” the panel said.

Most endocrinologists and other experts who prescribe testosterone therapy for women use an approved male formulation off label and adjust it – an approach that the panel says is reasonable as long as hormone concentrations are “maintained in the physiologic female range.”

Compounded “bioidentical” testosterone therapy “cannot be recommended for the treatment of HSDD because of the lack of evidence for safety and efficacy,” the statement says.

“A big concern of many endocrinologists,” Dr. Wierman added, “is the recent explosion of using pharmacological levels of both estrogen and testosterone in either [injections] or pellets.” The Endocrine Society and other societies have alerted the Food and Drug Administration to “this new cottage industry, which may have significant side effects and risks for our patients,” she said.
Dr. Wierman reported received funding from Corcept Therapeutics, Novartis, and the Cancer League of Colorado, and honoraria or consultation fees from Pfizer to review ASPIRE grant applications for studies of acromegaly as well as Endocrine Society honorarium for teaching in the Endocrine Board Review and Clinical Endocrine Update. Dr. Davis reported receiving funding from a National Health and Medical Research Council Project Grant, a National Breast Foundation accelerator grant, and the Grollo-Ruzenne Foundation, as well as honoraria from Besins and Pfizer Australia. She has been a consultant to Besins Healthcare, Mayne Pharmaceuticals, Lawley Pharmaceuticals, and Que Oncology. Disclosures for other authors of the position statement are listed with the statement.

SOURCE: Davis SR et al. J Clin Endocrinol Metab. 2019 Sep 2. doi: 10.1210/jc.2019-01603.
 

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Postpartum teenage mothers who use long-acting reversible contraceptives (LARC) reported using condoms half as often as their peers using non-LARC methods such as the birth control pill, vaginal ring, contraceptive patch, or injection, according to research in JAMA Pediatrics.

This highlights a need for education to lower the risk of sexually transmitted infections in this population.

©Florea Marius Catalin/iStockphoto.com

SOURCE: Kortsmit K et al. JAMA Pediatr. 2019. doi: 10.1001/jamapediatrics.2019.1136; Hoopes AJ et al. JAMA Pediatr. 2019. doi: 10.1001/jamapediatrics.2019.1133.

Postpartum teenage mothers who use long-acting reversible contraceptives (LARC) reported using condoms half as often as their peers using non-LARC methods such as the birth control pill, vaginal ring, contraceptive patch, or injection, according to research in JAMA Pediatrics.

This highlights a need for education to lower the risk of sexually transmitted infections in this population.

©Florea Marius Catalin/iStockphoto.com

SOURCE: Kortsmit K et al. JAMA Pediatr. 2019. doi: 10.1001/jamapediatrics.2019.1136; Hoopes AJ et al. JAMA Pediatr. 2019. doi: 10.1001/jamapediatrics.2019.1133.

Postpartum teenage mothers who use long-acting reversible contraceptives (LARC) reported using condoms half as often as their peers using non-LARC methods such as the birth control pill, vaginal ring, contraceptive patch, or injection, according to research in JAMA Pediatrics.

This highlights a need for education to lower the risk of sexually transmitted infections in this population.

©Florea Marius Catalin/iStockphoto.com

SOURCE: Kortsmit K et al. JAMA Pediatr. 2019. doi: 10.1001/jamapediatrics.2019.1136; Hoopes AJ et al. JAMA Pediatr. 2019. doi: 10.1001/jamapediatrics.2019.1133.

The decision to undergo preimplantation genetic testing for aneuploidy is associated with a small but not unimportant amount of regret among some patients undergoing fertility treatment, research suggests.

In a report published in Human Reproduction, researchers did an anonymous survey of 69 patients undergoing their first cycle of autologous preimplantation genetic testing for aneuploidy (PGT-A) at a single fertility center.

“Despite the known distress associated with many aspects of assisted reproductive technology (ART) and the many opportunities for distress among patients pursuing PGT-A, little is known about the associated patient experience and psychological risks,” wrote Dr. Kara N. Goldman of New York University Langone Fertility Center, and coauthors.

“A ‘failure’ after PGT-A can present in many forms well before other IVF losses may be experienced: Embryos may not meet criteria for biopsy, PGT-A may result in an all-aneuploid embryo cohort, or a euploid embryo may fail to implant,” the authors continued.

The mean overall decision regret scale score was 8.5 on a scale of 0-100 – with a median of 0 – and 61% of respondents said they had no regrets about undergoing preimplantation genetic testing for aneuploidy; the remaining 39% reported “any degree of regret.”

This “one-third of respondents reported some degree of regret, suggesting an important opportunity for pretest counseling and support among patients pursuing PGT-A,” Dr. Goldman and associates emphasized.

Of the respondents who then underwent euploid embryo transfer, and who had a known pregnancy outcome, the 36 with an ongoing or delivered pregnancy had significantly less decision regret than the 24 who experienced a negative pregnancy test or a miscarriage.

The study found no differences in decision regret between those aged under or over 35 years of age, those with different levels of educational attainment, or between patients who paid exclusively out of pocket compared with those with any insurance coverage.

However, greater levels of decision regret were seen in patients who had experienced a longer time since retrieval of oocytes and those who said they would consider pregnancy with donor oocytes if they were unsuccessful with IVF and PGT-A.

“Completing a cycle of IVF with PGT-A and obtaining no usable, euploid embryos results in distress, but this distress must be weighed against the alternative scenario in which a patient invests valuable time, energy, and resources into a futile embryo transfer cycle resulting in a negative pregnancy test, miscarriage, or aneuploid gestation,” the authors wrote.

When assessing the dependence of the decision regret score on demographic factors, the researchers found that patients who had learned about PGT-A from their physicians, rather than from other sources such as friends or the Internet, had the highest levels of decision regret.

There was no external funding. One coauthor declared personal fees and other support from the fertility and pharmaceutical sector. No other conflicts of interest were declared.

SOURCE: Goldman KN et al. Hum Reprod. 2019 Jun 21. doi: 10.1093/humrep/dez080.

The decision to undergo preimplantation genetic testing for aneuploidy is associated with a small but not unimportant amount of regret among some patients undergoing fertility treatment, research suggests.

In a report published in Human Reproduction, researchers did an anonymous survey of 69 patients undergoing their first cycle of autologous preimplantation genetic testing for aneuploidy (PGT-A) at a single fertility center.

“Despite the known distress associated with many aspects of assisted reproductive technology (ART) and the many opportunities for distress among patients pursuing PGT-A, little is known about the associated patient experience and psychological risks,” wrote Dr. Kara N. Goldman of New York University Langone Fertility Center, and coauthors.

“A ‘failure’ after PGT-A can present in many forms well before other IVF losses may be experienced: Embryos may not meet criteria for biopsy, PGT-A may result in an all-aneuploid embryo cohort, or a euploid embryo may fail to implant,” the authors continued.

The mean overall decision regret scale score was 8.5 on a scale of 0-100 – with a median of 0 – and 61% of respondents said they had no regrets about undergoing preimplantation genetic testing for aneuploidy; the remaining 39% reported “any degree of regret.”

This “one-third of respondents reported some degree of regret, suggesting an important opportunity for pretest counseling and support among patients pursuing PGT-A,” Dr. Goldman and associates emphasized.

Of the respondents who then underwent euploid embryo transfer, and who had a known pregnancy outcome, the 36 with an ongoing or delivered pregnancy had significantly less decision regret than the 24 who experienced a negative pregnancy test or a miscarriage.

The study found no differences in decision regret between those aged under or over 35 years of age, those with different levels of educational attainment, or between patients who paid exclusively out of pocket compared with those with any insurance coverage.

However, greater levels of decision regret were seen in patients who had experienced a longer time since retrieval of oocytes and those who said they would consider pregnancy with donor oocytes if they were unsuccessful with IVF and PGT-A.

“Completing a cycle of IVF with PGT-A and obtaining no usable, euploid embryos results in distress, but this distress must be weighed against the alternative scenario in which a patient invests valuable time, energy, and resources into a futile embryo transfer cycle resulting in a negative pregnancy test, miscarriage, or aneuploid gestation,” the authors wrote.

When assessing the dependence of the decision regret score on demographic factors, the researchers found that patients who had learned about PGT-A from their physicians, rather than from other sources such as friends or the Internet, had the highest levels of decision regret.

There was no external funding. One coauthor declared personal fees and other support from the fertility and pharmaceutical sector. No other conflicts of interest were declared.

SOURCE: Goldman KN et al. Hum Reprod. 2019 Jun 21. doi: 10.1093/humrep/dez080.

The decision to undergo preimplantation genetic testing for aneuploidy is associated with a small but not unimportant amount of regret among some patients undergoing fertility treatment, research suggests.

In a report published in Human Reproduction, researchers did an anonymous survey of 69 patients undergoing their first cycle of autologous preimplantation genetic testing for aneuploidy (PGT-A) at a single fertility center.

“Despite the known distress associated with many aspects of assisted reproductive technology (ART) and the many opportunities for distress among patients pursuing PGT-A, little is known about the associated patient experience and psychological risks,” wrote Dr. Kara N. Goldman of New York University Langone Fertility Center, and coauthors.

“A ‘failure’ after PGT-A can present in many forms well before other IVF losses may be experienced: Embryos may not meet criteria for biopsy, PGT-A may result in an all-aneuploid embryo cohort, or a euploid embryo may fail to implant,” the authors continued.

The mean overall decision regret scale score was 8.5 on a scale of 0-100 – with a median of 0 – and 61% of respondents said they had no regrets about undergoing preimplantation genetic testing for aneuploidy; the remaining 39% reported “any degree of regret.”

This “one-third of respondents reported some degree of regret, suggesting an important opportunity for pretest counseling and support among patients pursuing PGT-A,” Dr. Goldman and associates emphasized.

Of the respondents who then underwent euploid embryo transfer, and who had a known pregnancy outcome, the 36 with an ongoing or delivered pregnancy had significantly less decision regret than the 24 who experienced a negative pregnancy test or a miscarriage.

The study found no differences in decision regret between those aged under or over 35 years of age, those with different levels of educational attainment, or between patients who paid exclusively out of pocket compared with those with any insurance coverage.

However, greater levels of decision regret were seen in patients who had experienced a longer time since retrieval of oocytes and those who said they would consider pregnancy with donor oocytes if they were unsuccessful with IVF and PGT-A.

“Completing a cycle of IVF with PGT-A and obtaining no usable, euploid embryos results in distress, but this distress must be weighed against the alternative scenario in which a patient invests valuable time, energy, and resources into a futile embryo transfer cycle resulting in a negative pregnancy test, miscarriage, or aneuploid gestation,” the authors wrote.

When assessing the dependence of the decision regret score on demographic factors, the researchers found that patients who had learned about PGT-A from their physicians, rather than from other sources such as friends or the Internet, had the highest levels of decision regret.

There was no external funding. One coauthor declared personal fees and other support from the fertility and pharmaceutical sector. No other conflicts of interest were declared.

SOURCE: Goldman KN et al. Hum Reprod. 2019 Jun 21. doi: 10.1093/humrep/dez080.

Cutaneous endometriosis should be considered as a diagnosis when umbilical lesions are present, especially if there is a history of pain flares during menses, according to Liza Raffi of the University of Southern California, Los Angeles, and associates.

KatarzynaBialasiewicz/Thinkstock

The report, published in the International Journal of Women’s Dermatology, detailed a case of a woman aged 41 years who presented with a 5-month history of a painful firm subcutaneous nodule in the umbilicus and flares of pain during menstrual periods. Her past history indicated a missed miscarriage (removed by dilation and curettage) and laparoscopic left salpingectomy for a ruptured ectopic pregnancy.

At presentation, the woman reported undergoing fertility treatments including subcutaneous injections of follitropin beta and choriogonadotropin alfa.

Because of the patient’s history of salpingectomy and painful menstrual periods, her physicians suspected cutaneous endometriosis. An ultrasound was performed to rule out fistula, and then a punch biopsy of the nodule was performed. The biopsy showed endometrial glands with encompassing fibrotic stroma, which was consistent with cutaneous endometriosis, likely transplanted during the laparoscopic port site entry during salpingectomy.

The patient chose to undergo surgery for excision of the nodule, declining hormonal therapy because she was undergoing fertility treatment.

“The differential diagnosis of umbilical lesions with similar presentation includes keloid, dermatofibroma, dermatofibrosarcoma protuberans, and cutaneous metastasis of cancer,” the investigators wrote. “Ultimately, patients should be referred to obstetrics & gynecology if they describe classic symptoms including pain with menses, dyspareunia, and infertility and wish to explore diagnostic and therapeutic options.”

Ms. Raffi and associates reported they had no conflicts of interest. There was no external funding.

[email protected]

SOURCE: Raffi L et al. Int J Womens Dermatol. 2019 Jul 2. doi: 10.1016/j.ijwd.2019.06.025.

Cutaneous endometriosis should be considered as a diagnosis when umbilical lesions are present, especially if there is a history of pain flares during menses, according to Liza Raffi of the University of Southern California, Los Angeles, and associates.

KatarzynaBialasiewicz/Thinkstock

The report, published in the International Journal of Women’s Dermatology, detailed a case of a woman aged 41 years who presented with a 5-month history of a painful firm subcutaneous nodule in the umbilicus and flares of pain during menstrual periods. Her past history indicated a missed miscarriage (removed by dilation and curettage) and laparoscopic left salpingectomy for a ruptured ectopic pregnancy.

At presentation, the woman reported undergoing fertility treatments including subcutaneous injections of follitropin beta and choriogonadotropin alfa.

Because of the patient’s history of salpingectomy and painful menstrual periods, her physicians suspected cutaneous endometriosis. An ultrasound was performed to rule out fistula, and then a punch biopsy of the nodule was performed. The biopsy showed endometrial glands with encompassing fibrotic stroma, which was consistent with cutaneous endometriosis, likely transplanted during the laparoscopic port site entry during salpingectomy.

The patient chose to undergo surgery for excision of the nodule, declining hormonal therapy because she was undergoing fertility treatment.

“The differential diagnosis of umbilical lesions with similar presentation includes keloid, dermatofibroma, dermatofibrosarcoma protuberans, and cutaneous metastasis of cancer,” the investigators wrote. “Ultimately, patients should be referred to obstetrics & gynecology if they describe classic symptoms including pain with menses, dyspareunia, and infertility and wish to explore diagnostic and therapeutic options.”

Ms. Raffi and associates reported they had no conflicts of interest. There was no external funding.

[email protected]

SOURCE: Raffi L et al. Int J Womens Dermatol. 2019 Jul 2. doi: 10.1016/j.ijwd.2019.06.025.

Cutaneous endometriosis should be considered as a diagnosis when umbilical lesions are present, especially if there is a history of pain flares during menses, according to Liza Raffi of the University of Southern California, Los Angeles, and associates.

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The report, published in the International Journal of Women’s Dermatology, detailed a case of a woman aged 41 years who presented with a 5-month history of a painful firm subcutaneous nodule in the umbilicus and flares of pain during menstrual periods. Her past history indicated a missed miscarriage (removed by dilation and curettage) and laparoscopic left salpingectomy for a ruptured ectopic pregnancy.

At presentation, the woman reported undergoing fertility treatments including subcutaneous injections of follitropin beta and choriogonadotropin alfa.

Because of the patient’s history of salpingectomy and painful menstrual periods, her physicians suspected cutaneous endometriosis. An ultrasound was performed to rule out fistula, and then a punch biopsy of the nodule was performed. The biopsy showed endometrial glands with encompassing fibrotic stroma, which was consistent with cutaneous endometriosis, likely transplanted during the laparoscopic port site entry during salpingectomy.

The patient chose to undergo surgery for excision of the nodule, declining hormonal therapy because she was undergoing fertility treatment.

“The differential diagnosis of umbilical lesions with similar presentation includes keloid, dermatofibroma, dermatofibrosarcoma protuberans, and cutaneous metastasis of cancer,” the investigators wrote. “Ultimately, patients should be referred to obstetrics & gynecology if they describe classic symptoms including pain with menses, dyspareunia, and infertility and wish to explore diagnostic and therapeutic options.”

Ms. Raffi and associates reported they had no conflicts of interest. There was no external funding.

[email protected]

SOURCE: Raffi L et al. Int J Womens Dermatol. 2019 Jul 2. doi: 10.1016/j.ijwd.2019.06.025.