Menopause

EXPERT COMMENTARY

Vinogradova Y, Coupland C, Hippisley-Cox J. Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ. 2019;364:k4810.

The Women’s Health Initiative trials, in which menopausal women were randomly assigned to treatment with oral CEE or placebo, found that statistically the largest risk associated with menopausal hormone therapy (HT) was increased VTE.¹ Recently, investigators in the United Kingdom (UK) published results of their research aimed at determining the association between the risk of VTE and the use of different types of HT.²

Details of the study

Vinogradova and colleagues used 2 UK primary care research databases, QResearch and Clinical Practice Research Datalink, to identify cases of incident VTE in general practice records, hospital admissions, and mortality records. They identified 80,396 women (aged 40 to 79 years) diagnosed with VTE between 1998 and 2017 and 391,494 control women matched by age and general practice. The mean age of the case and control women was approximately 64 years; the great majority of women were white. Analyses were adjusted for smoking, body mass index (BMI), family history of VTE, and comorbidities associated with VTE.

Types of HT used. The investigators found that 5,795 (7.2%) women with VTE and 21,670 (5.5%) controls were exposed to HT in the 90 days before the index date (the first date of VTE diagnosis for cases became the index date for matched controls). In those exposed to HT:

• 4,915 (85%) cases and 16,938 (78%) controls used oral preparations (including 102 [1.8%] cases and 312 [1.4%] controls who also had transdermal preparations)
• 880 (14%) cases and 4,731 (19%) controls used transdermal HT only.

Association of VTE with HT. Risk of VTE was increased with all oral HT formulations, including combined (estrogen plus progestogen) and estrogen-only preparations. Use of oral CEE (odds ratio [OR], 1.49) and estradiol (OR, 1.27) were both associated with an elevated risk of VTE (P<.05 for both comparisons). In contrast, use of transdermal estradiol (the great majority of which was administered by patch) was not associated with an elevated risk of VTE (OR, 0.96).

Direct comparison of oral estradiol and CEE found that the lower VTE risk with oral estradiol achieved statistical significance (P = .005). Direct comparison of oral and transdermal estrogen revealed an OR of 1.7 for the oral route of administration (P<.001)

Continue to: Study strengths and weaknesses

Study strengths and weaknesses

This study used data from the 2 largest primary care databases in the United Kingdom. Analyses were adjusted for numerous confounding factors, including acute and chronic conditions, lifestyle factors, and social deprivation. Additional sensitivity analyses were conducted and yielded results similar to those of the main analysis.

Several limitations could have resulted in some residual confounding bias. For example, drug exposure information was based on HT prescriptions and not actual use; data on some factors were not available, such as indications for HT, age at menopause, and education level; and for a small proportion of women, some data (smoking status, alcohol consumption, BMI) were missing and had to be imputed for analysis.

EXPERT COMMENTARY

Vinogradova Y, Coupland C, Hippisley-Cox J. Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ. 2019;364:k4810.

The Women’s Health Initiative trials, in which menopausal women were randomly assigned to treatment with oral CEE or placebo, found that statistically the largest risk associated with menopausal hormone therapy (HT) was increased VTE.¹ Recently, investigators in the United Kingdom (UK) published results of their research aimed at determining the association between the risk of VTE and the use of different types of HT.²

Details of the study

Vinogradova and colleagues used 2 UK primary care research databases, QResearch and Clinical Practice Research Datalink, to identify cases of incident VTE in general practice records, hospital admissions, and mortality records. They identified 80,396 women (aged 40 to 79 years) diagnosed with VTE between 1998 and 2017 and 391,494 control women matched by age and general practice. The mean age of the case and control women was approximately 64 years; the great majority of women were white. Analyses were adjusted for smoking, body mass index (BMI), family history of VTE, and comorbidities associated with VTE.

Types of HT used. The investigators found that 5,795 (7.2%) women with VTE and 21,670 (5.5%) controls were exposed to HT in the 90 days before the index date (the first date of VTE diagnosis for cases became the index date for matched controls). In those exposed to HT:

• 4,915 (85%) cases and 16,938 (78%) controls used oral preparations (including 102 [1.8%] cases and 312 [1.4%] controls who also had transdermal preparations)
• 880 (14%) cases and 4,731 (19%) controls used transdermal HT only.

Association of VTE with HT. Risk of VTE was increased with all oral HT formulations, including combined (estrogen plus progestogen) and estrogen-only preparations. Use of oral CEE (odds ratio [OR], 1.49) and estradiol (OR, 1.27) were both associated with an elevated risk of VTE (P<.05 for both comparisons). In contrast, use of transdermal estradiol (the great majority of which was administered by patch) was not associated with an elevated risk of VTE (OR, 0.96).

Direct comparison of oral estradiol and CEE found that the lower VTE risk with oral estradiol achieved statistical significance (P = .005). Direct comparison of oral and transdermal estrogen revealed an OR of 1.7 for the oral route of administration (P<.001)

Continue to: Study strengths and weaknesses

Study strengths and weaknesses

This study used data from the 2 largest primary care databases in the United Kingdom. Analyses were adjusted for numerous confounding factors, including acute and chronic conditions, lifestyle factors, and social deprivation. Additional sensitivity analyses were conducted and yielded results similar to those of the main analysis.

Several limitations could have resulted in some residual confounding bias. For example, drug exposure information was based on HT prescriptions and not actual use; data on some factors were not available, such as indications for HT, age at menopause, and education level; and for a small proportion of women, some data (smoking status, alcohol consumption, BMI) were missing and had to be imputed for analysis.

EXPERT COMMENTARY

Vinogradova Y, Coupland C, Hippisley-Cox J. Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ. 2019;364:k4810.

The Women’s Health Initiative trials, in which menopausal women were randomly assigned to treatment with oral CEE or placebo, found that statistically the largest risk associated with menopausal hormone therapy (HT) was increased VTE.¹ Recently, investigators in the United Kingdom (UK) published results of their research aimed at determining the association between the risk of VTE and the use of different types of HT.²

Details of the study

Vinogradova and colleagues used 2 UK primary care research databases, QResearch and Clinical Practice Research Datalink, to identify cases of incident VTE in general practice records, hospital admissions, and mortality records. They identified 80,396 women (aged 40 to 79 years) diagnosed with VTE between 1998 and 2017 and 391,494 control women matched by age and general practice. The mean age of the case and control women was approximately 64 years; the great majority of women were white. Analyses were adjusted for smoking, body mass index (BMI), family history of VTE, and comorbidities associated with VTE.

Types of HT used. The investigators found that 5,795 (7.2%) women with VTE and 21,670 (5.5%) controls were exposed to HT in the 90 days before the index date (the first date of VTE diagnosis for cases became the index date for matched controls). In those exposed to HT:

• 4,915 (85%) cases and 16,938 (78%) controls used oral preparations (including 102 [1.8%] cases and 312 [1.4%] controls who also had transdermal preparations)
• 880 (14%) cases and 4,731 (19%) controls used transdermal HT only.

Association of VTE with HT. Risk of VTE was increased with all oral HT formulations, including combined (estrogen plus progestogen) and estrogen-only preparations. Use of oral CEE (odds ratio [OR], 1.49) and estradiol (OR, 1.27) were both associated with an elevated risk of VTE (P<.05 for both comparisons). In contrast, use of transdermal estradiol (the great majority of which was administered by patch) was not associated with an elevated risk of VTE (OR, 0.96).

Direct comparison of oral estradiol and CEE found that the lower VTE risk with oral estradiol achieved statistical significance (P = .005). Direct comparison of oral and transdermal estrogen revealed an OR of 1.7 for the oral route of administration (P<.001)

Continue to: Study strengths and weaknesses

Study strengths and weaknesses

This study used data from the 2 largest primary care databases in the United Kingdom. Analyses were adjusted for numerous confounding factors, including acute and chronic conditions, lifestyle factors, and social deprivation. Additional sensitivity analyses were conducted and yielded results similar to those of the main analysis.

Several limitations could have resulted in some residual confounding bias. For example, drug exposure information was based on HT prescriptions and not actual use; data on some factors were not available, such as indications for HT, age at menopause, and education level; and for a small proportion of women, some data (smoking status, alcohol consumption, BMI) were missing and had to be imputed for analysis.

Estrogen and androgen deficiency from menopause causes vulvovaginal and urogenital changes and a plethora of symptoms, most prominently dyspareunia. 

Read the supplement and earn CME credit for your knowledge of the following:

• The pathophysiology of dyspareunia due to vulvovaginal atrophy (VVA) of menopause.
• The underrecognition and undertreatment of dyspareunia due to VVA.
• Efficacy results of randomized placebo controlled trials of ospemifene.
• Adverse events associated with ospemifene.
• Safety data of ospemifine as well as other oral selective estrogen receptor modulators and estrogens.

Click on the image above or here to read the supplement and earn credit

Estrogen and androgen deficiency from menopause causes vulvovaginal and urogenital changes and a plethora of symptoms, most prominently dyspareunia. 

Read the supplement and earn CME credit for your knowledge of the following:

• The pathophysiology of dyspareunia due to vulvovaginal atrophy (VVA) of menopause.
• The underrecognition and undertreatment of dyspareunia due to VVA.
• Efficacy results of randomized placebo controlled trials of ospemifene.
• Adverse events associated with ospemifene.
• Safety data of ospemifine as well as other oral selective estrogen receptor modulators and estrogens.

Click on the image above or here to read the supplement and earn credit

Estrogen and androgen deficiency from menopause causes vulvovaginal and urogenital changes and a plethora of symptoms, most prominently dyspareunia. 

Read the supplement and earn CME credit for your knowledge of the following:

• The pathophysiology of dyspareunia due to vulvovaginal atrophy (VVA) of menopause.
• The underrecognition and undertreatment of dyspareunia due to VVA.
• Efficacy results of randomized placebo controlled trials of ospemifene.
• Adverse events associated with ospemifene.
• Safety data of ospemifine as well as other oral selective estrogen receptor modulators and estrogens.

Click on the image above or here to read the supplement and earn credit

A cohort of Chinese women who are breast cancer survivors had no increased mortality from soy intake, according to a new study.

margouillatphotos/iStock/Getty Images Plus

The work adds to the existing body of evidence that women with breast cancer, or risk for breast cancer, don’t need to modify their soy intake to mitigate risk, said the study’s first author, Suzanne C. Ho, PhD.

Speaking at the annual meeting of the North American Menopause Society, Dr. Ho noted that the combination of increasing breast cancer incidence and improved outcome has resulted in larger numbers of breast cancer survivors in Hong Kong, where she is professor emerita at the Chinese University of Hong Kong.

The prospective, ongoing study examines the association between soy intake pre- and postdiagnosis and total mortality for Chinese women who are breast cancer survivors. Dr. Ho said that she and her colleagues hypothesized that they would not see higher mortality among women who had higher soy intake – and this was the case.

Of 1,497 breast cancer survivors drawn from two facilities in Hong Kong, those who consumed higher quantities of dietary soy did not have increased risk of all-cause mortality, compared with those in the lowest tertile of soy consumption.

There are theoretical underpinnings for thinking that soy could be a player in cancer risk, but the biochemistry and epidemiology behind the studies are complicated. Estrogen plays a role in human breast cancer, and many modern breast cancer treatments actually dampen endogenous estrogens.

However, epidemiologic data have shown that consumption of soy-based foods – which contain phytoestrogens, primarily in the form of isoflavones – is inversely associated with developing breast cancer.

This is all part of why soy-based foods have been thought of as a mixed bag with regard to breast cancer: Soy isoflavones are, said Dr. Ho, “Natural estrogen receptor modulators that possess both estrogenlike and antiestrogenic properties.”

Other chemicals contained in soy may fight cancer, with effects that are antioxidative and strengthen immune response. Soy constituents also inhibit DNA topoisomerase I and II, proteases, tyrosine kinases, and inositol phosphate, effects that can slow tumor growth. Still, one soy isoflavone, genistein, actually can promote growth of estrogen-dependent tumors in rats, said Dr. Ho

Dr. Ho and her colleagues enrolled Hong Kong residents for the study of mortality among breast cancer survivors. Participants were included if they were Chinese, female, aged 24-77 years, and had their first primary breast cancer histologically confirmed within 12 months of entering the study. Cancer had to be graded below stage III.

Using a 109-item validated food questionnaire, investigators gathered information about participants’ soy intake and general diet for the year prior to breast cancer diagnosis. Other patient characteristics, relevant prognostic information from medical records, and anthropometric data were collected at baseline, and repeated at 18, 36, and 60 months.

The primary outcome measure – all-cause mortality during the follow-up period – was tracked for a mean 50.9 months, with a 78% retention rate for study participants, said Dr. Ho. In total, 96 patients died during follow-up, making up 5.9% of the premenopausal and 7% of the postmenopausal participants.

Statistical analysis corrected for potential confounders, including patient and disease characteristics and treatment modalities, as well as overall energy consumption.

Patients were evenly divided into tertiles of soy isoflavone intake, with cutpoints of 3.77 mg/1,000 kcal and 10.05 mg/1,000 kcal for the lower limit of the two higher tertiles. For the highest tertile, though, mean isoflavone intake was actually 20.87 mg/1,000 kcal.

Patient, disease, and treatment characteristics did not differ significantly among the tertiles.

An adjusted statistical analysis looked at pre- and postmenopausal women separately by tertile of soy isoflavone consumption, setting the hazard ratio for all-cause mortality at 1.00 for women in the lowest tertile of soy consumption.

For premenopausal women in the middle tertile, the HR was 0.45 (95% confidence interval, 0.20-1.00), and 0.86 for those in the highest tertile (95% CI, 0.43-1.72); 782 participants, in all, were premenopausal.

For the 715 postmenopausal women, the HR for those in the middle tertile of soy consumption was 0.94 (95% CI, 0.43-2.05), and 1.11 in the highest (95% CI, 0.54-2.29).

Taking all pre- and postmenopausal participants together, those in the middle tertile of soy isoflavone intake had an all-cause mortality HR of 0.63 (95% CI, 0.37-1.09). For the highest tertile of the full cohort, the HR was 0.95 (95% CI, 0.58-1.55).

Confidence intervals were wide in these findings, but Dr. Ho noted that “moderate soy food intake might be associated with better survival.”

“Prediagnosis soy intake did not increase the risk of all-cause mortality in breast cancer survivors,” said Dr. Ho, findings she called “consistent with the literature that soy consumption does not adversely effect breast cancer survival.”

The study is ongoing, she explained, and “longer follow-up will provide further evidence on the effect of pre- and postdiagnosis soy intake on breast cancer outcomes.”

The study had a homogeneous population of southern Chinese women, with fairly good retention and robust statistical adjustment for confounders. However, it wasn’t possible to assess bioavailability of isoflavones and their metabolites, which can vary according to individual microbiota. Also, researchers did not track whether patients used traditional Chinese medicine.

The World Cancer Research Fund International supported the study. Dr. Ho reported no conflicts of interest.

[email protected]

SOURCE: Ho S et al. NAMS 2018, Abstract S-23.

A cohort of Chinese women who are breast cancer survivors had no increased mortality from soy intake, according to a new study.

margouillatphotos/iStock/Getty Images Plus

The work adds to the existing body of evidence that women with breast cancer, or risk for breast cancer, don’t need to modify their soy intake to mitigate risk, said the study’s first author, Suzanne C. Ho, PhD.

Speaking at the annual meeting of the North American Menopause Society, Dr. Ho noted that the combination of increasing breast cancer incidence and improved outcome has resulted in larger numbers of breast cancer survivors in Hong Kong, where she is professor emerita at the Chinese University of Hong Kong.

The prospective, ongoing study examines the association between soy intake pre- and postdiagnosis and total mortality for Chinese women who are breast cancer survivors. Dr. Ho said that she and her colleagues hypothesized that they would not see higher mortality among women who had higher soy intake – and this was the case.

Of 1,497 breast cancer survivors drawn from two facilities in Hong Kong, those who consumed higher quantities of dietary soy did not have increased risk of all-cause mortality, compared with those in the lowest tertile of soy consumption.

There are theoretical underpinnings for thinking that soy could be a player in cancer risk, but the biochemistry and epidemiology behind the studies are complicated. Estrogen plays a role in human breast cancer, and many modern breast cancer treatments actually dampen endogenous estrogens.

However, epidemiologic data have shown that consumption of soy-based foods – which contain phytoestrogens, primarily in the form of isoflavones – is inversely associated with developing breast cancer.

This is all part of why soy-based foods have been thought of as a mixed bag with regard to breast cancer: Soy isoflavones are, said Dr. Ho, “Natural estrogen receptor modulators that possess both estrogenlike and antiestrogenic properties.”

Other chemicals contained in soy may fight cancer, with effects that are antioxidative and strengthen immune response. Soy constituents also inhibit DNA topoisomerase I and II, proteases, tyrosine kinases, and inositol phosphate, effects that can slow tumor growth. Still, one soy isoflavone, genistein, actually can promote growth of estrogen-dependent tumors in rats, said Dr. Ho

Dr. Ho and her colleagues enrolled Hong Kong residents for the study of mortality among breast cancer survivors. Participants were included if they were Chinese, female, aged 24-77 years, and had their first primary breast cancer histologically confirmed within 12 months of entering the study. Cancer had to be graded below stage III.

Using a 109-item validated food questionnaire, investigators gathered information about participants’ soy intake and general diet for the year prior to breast cancer diagnosis. Other patient characteristics, relevant prognostic information from medical records, and anthropometric data were collected at baseline, and repeated at 18, 36, and 60 months.

The primary outcome measure – all-cause mortality during the follow-up period – was tracked for a mean 50.9 months, with a 78% retention rate for study participants, said Dr. Ho. In total, 96 patients died during follow-up, making up 5.9% of the premenopausal and 7% of the postmenopausal participants.

Statistical analysis corrected for potential confounders, including patient and disease characteristics and treatment modalities, as well as overall energy consumption.

Patients were evenly divided into tertiles of soy isoflavone intake, with cutpoints of 3.77 mg/1,000 kcal and 10.05 mg/1,000 kcal for the lower limit of the two higher tertiles. For the highest tertile, though, mean isoflavone intake was actually 20.87 mg/1,000 kcal.

Patient, disease, and treatment characteristics did not differ significantly among the tertiles.

An adjusted statistical analysis looked at pre- and postmenopausal women separately by tertile of soy isoflavone consumption, setting the hazard ratio for all-cause mortality at 1.00 for women in the lowest tertile of soy consumption.

For premenopausal women in the middle tertile, the HR was 0.45 (95% confidence interval, 0.20-1.00), and 0.86 for those in the highest tertile (95% CI, 0.43-1.72); 782 participants, in all, were premenopausal.

For the 715 postmenopausal women, the HR for those in the middle tertile of soy consumption was 0.94 (95% CI, 0.43-2.05), and 1.11 in the highest (95% CI, 0.54-2.29).

Taking all pre- and postmenopausal participants together, those in the middle tertile of soy isoflavone intake had an all-cause mortality HR of 0.63 (95% CI, 0.37-1.09). For the highest tertile of the full cohort, the HR was 0.95 (95% CI, 0.58-1.55).

Confidence intervals were wide in these findings, but Dr. Ho noted that “moderate soy food intake might be associated with better survival.”

“Prediagnosis soy intake did not increase the risk of all-cause mortality in breast cancer survivors,” said Dr. Ho, findings she called “consistent with the literature that soy consumption does not adversely effect breast cancer survival.”

The study is ongoing, she explained, and “longer follow-up will provide further evidence on the effect of pre- and postdiagnosis soy intake on breast cancer outcomes.”

The study had a homogeneous population of southern Chinese women, with fairly good retention and robust statistical adjustment for confounders. However, it wasn’t possible to assess bioavailability of isoflavones and their metabolites, which can vary according to individual microbiota. Also, researchers did not track whether patients used traditional Chinese medicine.

The World Cancer Research Fund International supported the study. Dr. Ho reported no conflicts of interest.

[email protected]

SOURCE: Ho S et al. NAMS 2018, Abstract S-23.

A cohort of Chinese women who are breast cancer survivors had no increased mortality from soy intake, according to a new study.

margouillatphotos/iStock/Getty Images Plus

The work adds to the existing body of evidence that women with breast cancer, or risk for breast cancer, don’t need to modify their soy intake to mitigate risk, said the study’s first author, Suzanne C. Ho, PhD.

Speaking at the annual meeting of the North American Menopause Society, Dr. Ho noted that the combination of increasing breast cancer incidence and improved outcome has resulted in larger numbers of breast cancer survivors in Hong Kong, where she is professor emerita at the Chinese University of Hong Kong.

The prospective, ongoing study examines the association between soy intake pre- and postdiagnosis and total mortality for Chinese women who are breast cancer survivors. Dr. Ho said that she and her colleagues hypothesized that they would not see higher mortality among women who had higher soy intake – and this was the case.

Of 1,497 breast cancer survivors drawn from two facilities in Hong Kong, those who consumed higher quantities of dietary soy did not have increased risk of all-cause mortality, compared with those in the lowest tertile of soy consumption.

There are theoretical underpinnings for thinking that soy could be a player in cancer risk, but the biochemistry and epidemiology behind the studies are complicated. Estrogen plays a role in human breast cancer, and many modern breast cancer treatments actually dampen endogenous estrogens.

However, epidemiologic data have shown that consumption of soy-based foods – which contain phytoestrogens, primarily in the form of isoflavones – is inversely associated with developing breast cancer.

This is all part of why soy-based foods have been thought of as a mixed bag with regard to breast cancer: Soy isoflavones are, said Dr. Ho, “Natural estrogen receptor modulators that possess both estrogenlike and antiestrogenic properties.”

Other chemicals contained in soy may fight cancer, with effects that are antioxidative and strengthen immune response. Soy constituents also inhibit DNA topoisomerase I and II, proteases, tyrosine kinases, and inositol phosphate, effects that can slow tumor growth. Still, one soy isoflavone, genistein, actually can promote growth of estrogen-dependent tumors in rats, said Dr. Ho

Dr. Ho and her colleagues enrolled Hong Kong residents for the study of mortality among breast cancer survivors. Participants were included if they were Chinese, female, aged 24-77 years, and had their first primary breast cancer histologically confirmed within 12 months of entering the study. Cancer had to be graded below stage III.

Using a 109-item validated food questionnaire, investigators gathered information about participants’ soy intake and general diet for the year prior to breast cancer diagnosis. Other patient characteristics, relevant prognostic information from medical records, and anthropometric data were collected at baseline, and repeated at 18, 36, and 60 months.

The primary outcome measure – all-cause mortality during the follow-up period – was tracked for a mean 50.9 months, with a 78% retention rate for study participants, said Dr. Ho. In total, 96 patients died during follow-up, making up 5.9% of the premenopausal and 7% of the postmenopausal participants.

Statistical analysis corrected for potential confounders, including patient and disease characteristics and treatment modalities, as well as overall energy consumption.

Patients were evenly divided into tertiles of soy isoflavone intake, with cutpoints of 3.77 mg/1,000 kcal and 10.05 mg/1,000 kcal for the lower limit of the two higher tertiles. For the highest tertile, though, mean isoflavone intake was actually 20.87 mg/1,000 kcal.

Patient, disease, and treatment characteristics did not differ significantly among the tertiles.

An adjusted statistical analysis looked at pre- and postmenopausal women separately by tertile of soy isoflavone consumption, setting the hazard ratio for all-cause mortality at 1.00 for women in the lowest tertile of soy consumption.

For premenopausal women in the middle tertile, the HR was 0.45 (95% confidence interval, 0.20-1.00), and 0.86 for those in the highest tertile (95% CI, 0.43-1.72); 782 participants, in all, were premenopausal.

For the 715 postmenopausal women, the HR for those in the middle tertile of soy consumption was 0.94 (95% CI, 0.43-2.05), and 1.11 in the highest (95% CI, 0.54-2.29).

Taking all pre- and postmenopausal participants together, those in the middle tertile of soy isoflavone intake had an all-cause mortality HR of 0.63 (95% CI, 0.37-1.09). For the highest tertile of the full cohort, the HR was 0.95 (95% CI, 0.58-1.55).

Confidence intervals were wide in these findings, but Dr. Ho noted that “moderate soy food intake might be associated with better survival.”

“Prediagnosis soy intake did not increase the risk of all-cause mortality in breast cancer survivors,” said Dr. Ho, findings she called “consistent with the literature that soy consumption does not adversely effect breast cancer survival.”

The study is ongoing, she explained, and “longer follow-up will provide further evidence on the effect of pre- and postdiagnosis soy intake on breast cancer outcomes.”

The study had a homogeneous population of southern Chinese women, with fairly good retention and robust statistical adjustment for confounders. However, it wasn’t possible to assess bioavailability of isoflavones and their metabolites, which can vary according to individual microbiota. Also, researchers did not track whether patients used traditional Chinese medicine.

The World Cancer Research Fund International supported the study. Dr. Ho reported no conflicts of interest.

[email protected]

SOURCE: Ho S et al. NAMS 2018, Abstract S-23.

Transdermal hormone replacement therapy is associated with the lowest risk of venous thromboembolism, yet still is relatively underused compared to oral preparations, researchers say.

Alexander Raths/Fotolia

Writing in the BMJ, Yana Vinogradova, PhD, of the University of Nottingham (England) and her associates reported the results of two nested case-control studies of hormone replacement therapy (HRT) and venous thromboembolism (VTE) from Jan. 1998 to Feb. 2017 that altogether included 80,396 women aged 40-79 years with a primary diagnosis of VTE matched to 391,494 female controls.

Overall, 7% of the women with VTE had been exposed to HRT in the 90 days before the index date versus 5.5% of controls.

The greatest increase in risk of VTE, compared with no exposure, was seen with oral conjugated equine estrogen with medroxyprogesterone acetate, which was associated with a more than twofold increase in risk (odds ratio, 2.10; 95% confidence interval, 1.92-2.31; P less than .01).

However transdermal HRT use was not associated with any increase in risk, compared with no HRT exposure. The data even pointed to a slight decrease in risk, which the authors suggested may be the result of some residual confounding or indication bias.

Oral HRT generally was associated with a 58% increased risk of VTE, which amounted to a number needed to harm of 1,076 and nine extra cases of VTE per 10,000 women taking oral HRT.

Dr. Vinogradova and her colleagues noted that the vast majority of women in the study were being prescribed oral HRT for menopausal symptoms despite previous studies showing transdermal HRT has much lower risk.

“When women with menopausal symptoms already have an increased VTE risk because of comorbidities or obesity, these women and their doctors should give greater consideration to transdermal HRT,” they wrote.

Lubna Pal, MBBS, director of the menopause program and professor of obstetrics, gynecology, and reproductive sciences at Yale University, New Haven, Conn., commented in an interview, “These data are tremendously reassuring. The reported findings are: 1) reaffirm what we have already known , i.e. that advancing age, higher body mass index, and higher doses of exogenous systemic estrogen therapy are associated with increased risk for VTE; 2) offer greater granularity in risk for VTE with different formulations of estrogens and progestins and different regimens than understood thus far, 3) reaffirm that, unlike oral estrogen, transdermal estrogen formulations in doses commonly utilized in clinical practice are not associated with VTE risk, and 4) provide reassurance that the absolute risk, while exaggerated with oral estrogen or combination estrogen and progestin use, is nonetheless small as reflected in the number needed to harm with oral hormone therapy being 1,076, and the number of extra VTE cases attributable to oral HT being 9 per 10,000 woman years. 

“The authors are to be commended on this massive analytic undertaking that allows an improved understanding of HRT-related risk for VTE and offers meaningful guidance to the practitioner,” said Dr. Pal, who was not involved in the study.*

Estrogen-only preparations had a 40% higher risk and combined preparations had a 73% higher risk, compared with no exposure.

In estrogen-only preparations, the lowest risk was seen with estradiol, compared with conjugated equine estrogens or combined preparations.

The lowest risk of VTE among oral preparations was seen with estradiol plus dydrogesterone, which only showed a nonsignificant 18% increase in risk.

In an attempt to account for possible increased risk of VTE, the authors conducted a sensitivity analysis in a subgroup of women who had not previously used anticoagulants, but they found similar results to the main analysis.

“This sensitivity analysis indicates that most of the excluded women had probably used anticoagulants because of atrial fibrillation or hip replacement operations rather than an earlier unrecorded VTE,” they wrote.

One author declared directorship of a clinical software company, but no other conflicts of interest were declared. There was no external funding. Dr. Pal reported that she was a coinvestigator in the Kronos Early Estrogen Prevention Study and on an AMAG Pharmaceuticals advisory board and member of their speaker’s bureau. 

SOURCE: Vinogradova Y et al. BMJ. 2019 Jan 9. doi: 10.1136/bmj.k4810.

*This article was updated 1/11/19.
 

Transdermal hormone replacement therapy is associated with the lowest risk of venous thromboembolism, yet still is relatively underused compared to oral preparations, researchers say.

Alexander Raths/Fotolia

Writing in the BMJ, Yana Vinogradova, PhD, of the University of Nottingham (England) and her associates reported the results of two nested case-control studies of hormone replacement therapy (HRT) and venous thromboembolism (VTE) from Jan. 1998 to Feb. 2017 that altogether included 80,396 women aged 40-79 years with a primary diagnosis of VTE matched to 391,494 female controls.

Overall, 7% of the women with VTE had been exposed to HRT in the 90 days before the index date versus 5.5% of controls.

The greatest increase in risk of VTE, compared with no exposure, was seen with oral conjugated equine estrogen with medroxyprogesterone acetate, which was associated with a more than twofold increase in risk (odds ratio, 2.10; 95% confidence interval, 1.92-2.31; P less than .01).

However transdermal HRT use was not associated with any increase in risk, compared with no HRT exposure. The data even pointed to a slight decrease in risk, which the authors suggested may be the result of some residual confounding or indication bias.

Oral HRT generally was associated with a 58% increased risk of VTE, which amounted to a number needed to harm of 1,076 and nine extra cases of VTE per 10,000 women taking oral HRT.

Dr. Vinogradova and her colleagues noted that the vast majority of women in the study were being prescribed oral HRT for menopausal symptoms despite previous studies showing transdermal HRT has much lower risk.

“When women with menopausal symptoms already have an increased VTE risk because of comorbidities or obesity, these women and their doctors should give greater consideration to transdermal HRT,” they wrote.

Lubna Pal, MBBS, director of the menopause program and professor of obstetrics, gynecology, and reproductive sciences at Yale University, New Haven, Conn., commented in an interview, “These data are tremendously reassuring. The reported findings are: 1) reaffirm what we have already known , i.e. that advancing age, higher body mass index, and higher doses of exogenous systemic estrogen therapy are associated with increased risk for VTE; 2) offer greater granularity in risk for VTE with different formulations of estrogens and progestins and different regimens than understood thus far, 3) reaffirm that, unlike oral estrogen, transdermal estrogen formulations in doses commonly utilized in clinical practice are not associated with VTE risk, and 4) provide reassurance that the absolute risk, while exaggerated with oral estrogen or combination estrogen and progestin use, is nonetheless small as reflected in the number needed to harm with oral hormone therapy being 1,076, and the number of extra VTE cases attributable to oral HT being 9 per 10,000 woman years. 

“The authors are to be commended on this massive analytic undertaking that allows an improved understanding of HRT-related risk for VTE and offers meaningful guidance to the practitioner,” said Dr. Pal, who was not involved in the study.*

Estrogen-only preparations had a 40% higher risk and combined preparations had a 73% higher risk, compared with no exposure.

In estrogen-only preparations, the lowest risk was seen with estradiol, compared with conjugated equine estrogens or combined preparations.

The lowest risk of VTE among oral preparations was seen with estradiol plus dydrogesterone, which only showed a nonsignificant 18% increase in risk.

In an attempt to account for possible increased risk of VTE, the authors conducted a sensitivity analysis in a subgroup of women who had not previously used anticoagulants, but they found similar results to the main analysis.

“This sensitivity analysis indicates that most of the excluded women had probably used anticoagulants because of atrial fibrillation or hip replacement operations rather than an earlier unrecorded VTE,” they wrote.

One author declared directorship of a clinical software company, but no other conflicts of interest were declared. There was no external funding. Dr. Pal reported that she was a coinvestigator in the Kronos Early Estrogen Prevention Study and on an AMAG Pharmaceuticals advisory board and member of their speaker’s bureau. 

SOURCE: Vinogradova Y et al. BMJ. 2019 Jan 9. doi: 10.1136/bmj.k4810.

*This article was updated 1/11/19.
 

Transdermal hormone replacement therapy is associated with the lowest risk of venous thromboembolism, yet still is relatively underused compared to oral preparations, researchers say.

Alexander Raths/Fotolia

Writing in the BMJ, Yana Vinogradova, PhD, of the University of Nottingham (England) and her associates reported the results of two nested case-control studies of hormone replacement therapy (HRT) and venous thromboembolism (VTE) from Jan. 1998 to Feb. 2017 that altogether included 80,396 women aged 40-79 years with a primary diagnosis of VTE matched to 391,494 female controls.

Overall, 7% of the women with VTE had been exposed to HRT in the 90 days before the index date versus 5.5% of controls.

The greatest increase in risk of VTE, compared with no exposure, was seen with oral conjugated equine estrogen with medroxyprogesterone acetate, which was associated with a more than twofold increase in risk (odds ratio, 2.10; 95% confidence interval, 1.92-2.31; P less than .01).

However transdermal HRT use was not associated with any increase in risk, compared with no HRT exposure. The data even pointed to a slight decrease in risk, which the authors suggested may be the result of some residual confounding or indication bias.

Oral HRT generally was associated with a 58% increased risk of VTE, which amounted to a number needed to harm of 1,076 and nine extra cases of VTE per 10,000 women taking oral HRT.

Dr. Vinogradova and her colleagues noted that the vast majority of women in the study were being prescribed oral HRT for menopausal symptoms despite previous studies showing transdermal HRT has much lower risk.

“When women with menopausal symptoms already have an increased VTE risk because of comorbidities or obesity, these women and their doctors should give greater consideration to transdermal HRT,” they wrote.

Lubna Pal, MBBS, director of the menopause program and professor of obstetrics, gynecology, and reproductive sciences at Yale University, New Haven, Conn., commented in an interview, “These data are tremendously reassuring. The reported findings are: 1) reaffirm what we have already known , i.e. that advancing age, higher body mass index, and higher doses of exogenous systemic estrogen therapy are associated with increased risk for VTE; 2) offer greater granularity in risk for VTE with different formulations of estrogens and progestins and different regimens than understood thus far, 3) reaffirm that, unlike oral estrogen, transdermal estrogen formulations in doses commonly utilized in clinical practice are not associated with VTE risk, and 4) provide reassurance that the absolute risk, while exaggerated with oral estrogen or combination estrogen and progestin use, is nonetheless small as reflected in the number needed to harm with oral hormone therapy being 1,076, and the number of extra VTE cases attributable to oral HT being 9 per 10,000 woman years. 

“The authors are to be commended on this massive analytic undertaking that allows an improved understanding of HRT-related risk for VTE and offers meaningful guidance to the practitioner,” said Dr. Pal, who was not involved in the study.*

Estrogen-only preparations had a 40% higher risk and combined preparations had a 73% higher risk, compared with no exposure.

In estrogen-only preparations, the lowest risk was seen with estradiol, compared with conjugated equine estrogens or combined preparations.

The lowest risk of VTE among oral preparations was seen with estradiol plus dydrogesterone, which only showed a nonsignificant 18% increase in risk.

In an attempt to account for possible increased risk of VTE, the authors conducted a sensitivity analysis in a subgroup of women who had not previously used anticoagulants, but they found similar results to the main analysis.

“This sensitivity analysis indicates that most of the excluded women had probably used anticoagulants because of atrial fibrillation or hip replacement operations rather than an earlier unrecorded VTE,” they wrote.

One author declared directorship of a clinical software company, but no other conflicts of interest were declared. There was no external funding. Dr. Pal reported that she was a coinvestigator in the Kronos Early Estrogen Prevention Study and on an AMAG Pharmaceuticals advisory board and member of their speaker’s bureau. 

SOURCE: Vinogradova Y et al. BMJ. 2019 Jan 9. doi: 10.1136/bmj.k4810.

*This article was updated 1/11/19.
 

Expert Commentary 

Sriprasert I, Hodis HN, Karim R, et al. Differential effect of plasma estradiol on subclinical atherosclerosis progression in early versus late postmenopause. J Clin Endocrinol Metab. 2019;104:293-300. doi:10.1210/jc.2018-01600.

In 2016, the primary findings of the Early versus Late Intervention Trial with Estradiol (ELITE) demonstrated that oral E2 administered to women who were less than 6 years postmenopause slowed progression of subclinical atherosclerosis as assessed by carotid artery intima-media thickness (CIMT), while it had no effect in women who were at least 10 years postmenopause.¹

That trial included 643 healthy women without cardiovascular disease who at enrollment had a median age of 55.4 years in the early postmenopause group (median 3.5 years since menopause) and 63.6 years in the late postmenopause group (median 14.3 years since menopause). The study medications were oral estradiol 1 mg daily plus progesterone vaginal gel for women with a uterus or placebo and placebo gel for a median of 5 years.

The investigators found also that, in contrast with CIMT, cardiac computed tomography (CT) measures of atherosclerosis did not differ significantly between the estradiol and placebo groups, regardless of age.¹

Posttrial data analysis revealed a new finding

In a secondary analysis of data from the ELITE trial, Sriprasert and colleagues dug deeper to assess the impact of plasma E2 levels on progression of subclinical atherosclerosis.²

Among 596 women (69.6% white non-Hispanic, 8.7% black, 13.3% Hispanic, and 8.4% Asian/Pacific Islander), E2 levels were available in 248 women in early postmenopause (mean age, 54.7 years) and 348 women in late postmenopause (median age, 63.6 years).

For women in the estradiol-treated group, mean E2 levels during the trial as well as change of E2 levels from baseline were significantly higher in the early postmenopause group than in the late postmenopause group, even though both groups had similar adherence based on pill count. For those in the placebo group, mean E2 levels and change of E2 levels from baseline were equivalent in early and late menopause.

In the E2-treated group and the placebo group combined, the mixed effects analysis of the CIMT progression rate (based on the mean E2 level during the trial) demonstrated that a higher level of E2 was inversely associated with the CIMT progression rate in early postmenopausal women (beta coefficient = -0.04 [95% confidence interval (CI), -0.09 to -0.001] μm CIMT per year per 1 pg/mL estradiol; P = .04). However, a higher level of E2 was positively associated (beta coefficient = 0.063 [95% CI, 0.018 to 0.107] μm CIMT per year per 1 pg/mL estradiol; P = .006) with CIMT progression rate in the late postmenopausal women.

Continue to: Bottom line...

Bottom line. E2 levels resulting from administration of oral estradiol were inversely associated with atherosclerosis progression in women in early menopause, but they were positively associated with progression in late postmenopause participants.

Expert Commentary 

Sriprasert I, Hodis HN, Karim R, et al. Differential effect of plasma estradiol on subclinical atherosclerosis progression in early versus late postmenopause. J Clin Endocrinol Metab. 2019;104:293-300. doi:10.1210/jc.2018-01600.

In 2016, the primary findings of the Early versus Late Intervention Trial with Estradiol (ELITE) demonstrated that oral E2 administered to women who were less than 6 years postmenopause slowed progression of subclinical atherosclerosis as assessed by carotid artery intima-media thickness (CIMT), while it had no effect in women who were at least 10 years postmenopause.¹

That trial included 643 healthy women without cardiovascular disease who at enrollment had a median age of 55.4 years in the early postmenopause group (median 3.5 years since menopause) and 63.6 years in the late postmenopause group (median 14.3 years since menopause). The study medications were oral estradiol 1 mg daily plus progesterone vaginal gel for women with a uterus or placebo and placebo gel for a median of 5 years.

The investigators found also that, in contrast with CIMT, cardiac computed tomography (CT) measures of atherosclerosis did not differ significantly between the estradiol and placebo groups, regardless of age.¹

Posttrial data analysis revealed a new finding

In a secondary analysis of data from the ELITE trial, Sriprasert and colleagues dug deeper to assess the impact of plasma E2 levels on progression of subclinical atherosclerosis.²

Among 596 women (69.6% white non-Hispanic, 8.7% black, 13.3% Hispanic, and 8.4% Asian/Pacific Islander), E2 levels were available in 248 women in early postmenopause (mean age, 54.7 years) and 348 women in late postmenopause (median age, 63.6 years).

For women in the estradiol-treated group, mean E2 levels during the trial as well as change of E2 levels from baseline were significantly higher in the early postmenopause group than in the late postmenopause group, even though both groups had similar adherence based on pill count. For those in the placebo group, mean E2 levels and change of E2 levels from baseline were equivalent in early and late menopause.

In the E2-treated group and the placebo group combined, the mixed effects analysis of the CIMT progression rate (based on the mean E2 level during the trial) demonstrated that a higher level of E2 was inversely associated with the CIMT progression rate in early postmenopausal women (beta coefficient = -0.04 [95% confidence interval (CI), -0.09 to -0.001] μm CIMT per year per 1 pg/mL estradiol; P = .04). However, a higher level of E2 was positively associated (beta coefficient = 0.063 [95% CI, 0.018 to 0.107] μm CIMT per year per 1 pg/mL estradiol; P = .006) with CIMT progression rate in the late postmenopausal women.

Continue to: Bottom line...

Bottom line. E2 levels resulting from administration of oral estradiol were inversely associated with atherosclerosis progression in women in early menopause, but they were positively associated with progression in late postmenopause participants.

Expert Commentary 

Sriprasert I, Hodis HN, Karim R, et al. Differential effect of plasma estradiol on subclinical atherosclerosis progression in early versus late postmenopause. J Clin Endocrinol Metab. 2019;104:293-300. doi:10.1210/jc.2018-01600.

In 2016, the primary findings of the Early versus Late Intervention Trial with Estradiol (ELITE) demonstrated that oral E2 administered to women who were less than 6 years postmenopause slowed progression of subclinical atherosclerosis as assessed by carotid artery intima-media thickness (CIMT), while it had no effect in women who were at least 10 years postmenopause.¹

That trial included 643 healthy women without cardiovascular disease who at enrollment had a median age of 55.4 years in the early postmenopause group (median 3.5 years since menopause) and 63.6 years in the late postmenopause group (median 14.3 years since menopause). The study medications were oral estradiol 1 mg daily plus progesterone vaginal gel for women with a uterus or placebo and placebo gel for a median of 5 years.

The investigators found also that, in contrast with CIMT, cardiac computed tomography (CT) measures of atherosclerosis did not differ significantly between the estradiol and placebo groups, regardless of age.¹

Posttrial data analysis revealed a new finding

In a secondary analysis of data from the ELITE trial, Sriprasert and colleagues dug deeper to assess the impact of plasma E2 levels on progression of subclinical atherosclerosis.²

Among 596 women (69.6% white non-Hispanic, 8.7% black, 13.3% Hispanic, and 8.4% Asian/Pacific Islander), E2 levels were available in 248 women in early postmenopause (mean age, 54.7 years) and 348 women in late postmenopause (median age, 63.6 years).

For women in the estradiol-treated group, mean E2 levels during the trial as well as change of E2 levels from baseline were significantly higher in the early postmenopause group than in the late postmenopause group, even though both groups had similar adherence based on pill count. For those in the placebo group, mean E2 levels and change of E2 levels from baseline were equivalent in early and late menopause.

In the E2-treated group and the placebo group combined, the mixed effects analysis of the CIMT progression rate (based on the mean E2 level during the trial) demonstrated that a higher level of E2 was inversely associated with the CIMT progression rate in early postmenopausal women (beta coefficient = -0.04 [95% confidence interval (CI), -0.09 to -0.001] μm CIMT per year per 1 pg/mL estradiol; P = .04). However, a higher level of E2 was positively associated (beta coefficient = 0.063 [95% CI, 0.018 to 0.107] μm CIMT per year per 1 pg/mL estradiol; P = .006) with CIMT progression rate in the late postmenopausal women.

Continue to: Bottom line...

Bottom line. E2 levels resulting from administration of oral estradiol were inversely associated with atherosclerosis progression in women in early menopause, but they were positively associated with progression in late postmenopause participants.

Breast cancer survivors entering menopause face the risk of several menopausal symptoms:

• Hot flashes, the most common symptom, occur in more than 75% of women during menopause and have the potential to persist for as long as 15 years.¹ That lengthy interval becomes a major issue for patients, especially when hot flashes are associated with other menopausal symptoms, including sleep disruption, difficulty concentrating, and emotional instability (crying, irritability).

• Painful intercourse and loss of interest in sexual activity often develop as a result of vaginal atrophy and dryness.

• Urinary tract symptoms include urgency and, compared to the patient’s history, more frequent infections.
• Bone loss is a concern for many women after breast cancer, especially if they are, or have been, on aromatase inhibitor therapy.

• Depression might be related to hormonal changes due to menopause or hormonal therapies, a consequence of merely having a diagnosis of cancer, or an adverse effect of chemotherapy.

In this brief review, I’ll examine options for treating symptoms of menopause by strategy—lifestyle modifications, over-the-counter treatments, and prescription drugs. Separately, I’ll look at options for managing genitourinary syndrome of menopause (GSM).

CASE 1

Rose is a 56-year-old woman who presents to clinic with a new breast mass, felt on breast self exam. The mass is about 1 cm, mobile, and firm. Diagnostic mammogram and ultrasound confirm a worrisome mass; biopsy returns positive with a 9-mm invasive, estrogen-receptor positive, ductal carcinoma with negative sentinel nodes at the time of lumpectomy. Radiation therapy was completed. She then met with oncology and decided against chemotherapy. Instead, she began an aromatase inhibitor 3 months ago. Bone density showed osteopenia. She presents to your office reporting frequent bothersome hot flashes and disrupted sleep.

Strategy #1: Lifestyle adaptations

First-line interventions for menopausal women who have had breast cancer usually involve taking a critical look at lifestyle and undertaking modifications that can alleviate discomfort. Because overall health is important for women who have had breast cancer, you should, across the spectrum of patients, encourage them to:

• increase physical activity
• reduce body weight by approximately 10% (if overweight or obese)
• reduce alcohol consumption
• stop smoking
• ensure adequate intake of calcium (1,200 mg, preferably by diet)
• optimize the level of vitamin D, including by increasing intake of fresh fish, eggs, and numerous other fortified foods.

The value of nondrug therapy for hot flashes is difficult to prove. Certain lifestyle changes are sensible, even if not evidence-based, and will help some women (but not others). We suggest that patients try lowering the temperature in the home (65–68˚ at night); running a fan; wearing clothing that can be removed in layers; and avoiding triggers such as spicy food, alcohol, cigarettes, and hot drinks. Hypnosis and cognitive behavioral therapy (CBT) have been shown to help in clinical trials. Measures with benefit and minimal risks, but effectiveness not established, include acupuncture (sham worked as well as traditional), exercise, yoga, paced respiration, relaxation training, and mindfulness-based stress reduction.

Continue to: Strategy #2: OTC compounds...

Strategy #2: OTC compounds

Over-the-counter products—from soy products to black cohosh to flax seed, and including dong quai, evening primrose oil, maca, omegas, pollen extract, ginseng, and red clover,² or several compounds formulated in combination—have not been proven to be of more benefit for relieving symptoms of menopause than placebo in randomized trials, and thus might or might not be effective in a given patient. S-equol, a metabolite of a soy isoflavone taken by women who are non-equol producers, is available under the trade name Equelle and has shown some benefit. Note: There is concern that supplements that contain estrogen-like compounds, like soy products, might actually increase the risk of breast cancer. Dietary soy is not felt to be a concern.

Ask questions about the severity of a patient’s hot flashes. When a patient reports hot flashes, and is requesting help to relieve her discomfort, inquire 1) how often she has hot flashes, 2) how severe they are, and 3) how bothered she is by them (not all women are equally troubled, of course). The patient’s answers to these questions will help you decide which treatment option to offer, based on evidence and your experience.

CASE 1 Continued

Rose tried black cohosh OTC without improvement. She was interested in hypnosis but did not find it effective for her. She returned 3 months later stating that she is miserable, exhausted, not getting enough sleep, and her hot flashes and night sweats are affecting both her work and her relationship.

Strategy #3: Prescription medication

When addressing hot flashes, consider whether they occur more at night or during the day, or do not follow a day–night pattern. For women whose hot flashes occur mostly at night, and might therefore make sleeping difficult and cause fatigue and irritability, gabapentin, taken approximately 1 hour before bed, can be helpful. If tolerated without excessive somnolence the next day, the dose can be increased at night or additional doses provided during the day depending on hot flash response. For women who have hot flashes day and night, we often prescribe a low-dose antidepressant from the selective serotonin-reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) class.

When prescribing an antidepressant, we make a distinction between breast cancer patients who are taking tamoxifen and those who are not, to avoid cytochrome P450 2D6 inhibitors in women taking tamoxifen.³ Better choices for women taking tamoxifen include desvenlafaxine, venlafaxine, escitalopram, or gabapentin or pregabalin.

For women with breast cancer who are taking an aromatase inhibitor, and who are also experiencing mood changes with their hot flashes, we often choose a trial of a low-dose antidepressant, either an SSRI or SNRI. One drug is approved by the US Food and Drug Administration (FDA) for the treatment of hot flashes (but not for mood disorder). This is low-dose salt of paroxetine, 7.5 mg/d, which has the advantage of exerting no adverse effect on libido or weight (but is sometimes difficult to obtain because it is a branded product that might not be covered, or not covered fully, by a given patient’s insurance plan). Other antidepressants can be used in doses lower than needed for depression, with more rapid onset of effect on hot flashes, often within 2 weeks.

Last, transdermal clonidine, an antihypertensive, also has been found to relieve hot flashes.

Continue to: Not a recommended strategy: Systemic hormone therapy

Not a recommended strategy: Systemic hormone therapy

Although hormone therapy is, in general, the gold standard for alleviating hot flashes, it is contraindicated in most women with breast cancer.⁴ At our institution, we avoid systemic hormone therapy for hot flashes in almost all breast cancer patients.

CASE 2

Sarah first presented with hot flashes that improved while taking escitalopram 10 mg. Her night sweats persisted, however. Gabapentin 300 mg was added to take nightly. With this regimen, she finally felt that she was coping better. Six months later, she reported that she and her long-term partner had not been able to resume vaginal intercourse post–breast cancer treatment because of pain.

The challenge of managing GSM

What if your patient says, “Doctor, I’m really doing OK with my hot flashes, but sex has become painful. I don’t have any interest. I have vaginal dryness, and it’s affecting my quality of life”?

Studies have shown that GSM affects up to 50% of women, and even more than that among women who have had breast cancer.⁵ The condition interferes with sexual intimacy, disrupts quality of life, and can sour a partnership—significant quality-of-life concerns for breast cancer survivors.

For mild symptoms, encourage patients to apply a lubricant just before intercourse or a vaginal moisturizer twice weekly; moisturizers improve vaginal pH, too. These treatments do not fix the problem of a lack of superficial cells due to estrogen loss, however; to accomplish that, consider prescribing low-dose vaginal estrogen therapy or intravaginal dehydroepiandrosterone (DHEA). This strategy is felt to be safe for many breast cancer survivors, as systemic absorption of estrogen is minimal if dosed low, keeping levels in the postmenopausal range.

The American College of Obstetricians and Gynecologists (ACOG), the North American Menopause Society (NAMS), and the Endocrine Society agree that vaginal estrogen therapy may be a good option for many women with breast cancer for whom moisturizers and lubricants are inadequate.⁶ Delivery options include vaginal creams, tablets, suppositories used 2 or 3 times per week, or the low-dose vaginal estrogen ring, replaced every 3 months. We are concerned about using vaginal estrogen in women who have had aromatase inhibitor (AI) therapy; their estrogen levels are so low that absorbing even a small amount might make a difference in terms of effectiveness of AI. For women who need more than lubricants or vaginal moisturizers, particularly those taking anti-estrogen therapy (aromatase therapy), the use of low-dose vaginal hormones may be considered on an individual basis, but should include the oncologist in decision making.^1,3

Beyond low-dose vaginal estrogen therapies, there are additional options that can be considered but with less supporting data for treating GSM in women with breast cancer.

Oral ospemifene, a selective estrogen-receptor modulator (SERM; Osphena), might be neutral or even protective in its effect on the breast, as demonstrated in preclinical trials.⁷ In human trials, the drug is approved only for painful intercourse, not for loss of libido, and has not been tested in breast cancer patients.

Intravaginal DHEA (Prasterone), has been on the market for almost 1 year. The drug is approved for treating painful intercourse, but it also reverses vaginal atrophy and alleviates urinary symptoms. Because DHEA is a prohormone, it is converted to estrogen and androgen in the vagina. Again, absorption appears minimal. Intravaginal DHEA does not have the US Food and Drug Administration (FDA) black-box warning that vaginal estrogen products do, but it is accompanied by a warning that it has not been tested in women with breast cancer.

Tissue selective estrogen receptor modulator is a conjugated estrogen combined with a third-generation SERM bazedoxifene, which treats hot flashes and reverses vaginal atrophy. This new systemic agent is probably neutral on the breast (at least that is the finding in clinical trials at 2 years⁸); again, however, it has not been tested in patients with breast cancer.

Continue to: Nonhormone therapies...

Nonhormone therapies

Topical lidocaine for insertional dyspareunia has been studied in postmenopausal women with breast cancer with severe GSM, dyspareunia, increased sexual distress scores, or abnormal sexual function with improvement seen using 4% aqueous lidocaine versus saline applied with a cotton ball to the vestibule for 3 minutes before vaginal penetration.⁹

Vaginal laser therapy has the potential to ameliorate distressing GSM without the need for local hormone intervention; however, placebo or active-controlled trials and long-term safety follow-up are needed.⁵

Treatment begins with a conversation

Most importantly, we need to listen to our patients in discomfort because of their menopausal symptoms. Consider proceeding along these lines: “You’ve been treated for breast cancer; now, let’s look at the medical issues that are affecting your quality of life. Are you depressed? Are you having hot flashes? Are you getting enough sleep? Have you stopped having sex or not restarted after your breast cancer treatment? Are you having painful sex or avoiding sex due to fear of pain? Let’s discuss options and work with your oncologist to try to relieve your symptoms and make your life better.”

First-line therapy for the treatment of menopausal symptoms in women with a history of breast cancer should start with lifestyle changes and nonhormone therapies. For GSM, lubricants and vaginal moisturizers should be tried first and may be effective. Reassure patients that there are many treatment options, even though not all of them have been well-tested in breast cancer patients, and that new modalities are under investigation and review (see “Newly arrived and on the horizon,”). Become familiar with published data on the safety and effectiveness of the range of available treatments; guide patients through the process of finding what works best for them; and invite their oncologist into the therapeutic partnership. If you do not feel comfortable with these issues in women who are breast cancer survivors, find a menopause specialist to help, available by zip code at Find a Provider, http://www.menopause.org.

Breast cancer survivors entering menopause face the risk of several menopausal symptoms:

• Hot flashes, the most common symptom, occur in more than 75% of women during menopause and have the potential to persist for as long as 15 years.¹ That lengthy interval becomes a major issue for patients, especially when hot flashes are associated with other menopausal symptoms, including sleep disruption, difficulty concentrating, and emotional instability (crying, irritability).

• Painful intercourse and loss of interest in sexual activity often develop as a result of vaginal atrophy and dryness.

• Urinary tract symptoms include urgency and, compared to the patient’s history, more frequent infections.
• Bone loss is a concern for many women after breast cancer, especially if they are, or have been, on aromatase inhibitor therapy.

• Depression might be related to hormonal changes due to menopause or hormonal therapies, a consequence of merely having a diagnosis of cancer, or an adverse effect of chemotherapy.

In this brief review, I’ll examine options for treating symptoms of menopause by strategy—lifestyle modifications, over-the-counter treatments, and prescription drugs. Separately, I’ll look at options for managing genitourinary syndrome of menopause (GSM).

CASE 1

Rose is a 56-year-old woman who presents to clinic with a new breast mass, felt on breast self exam. The mass is about 1 cm, mobile, and firm. Diagnostic mammogram and ultrasound confirm a worrisome mass; biopsy returns positive with a 9-mm invasive, estrogen-receptor positive, ductal carcinoma with negative sentinel nodes at the time of lumpectomy. Radiation therapy was completed. She then met with oncology and decided against chemotherapy. Instead, she began an aromatase inhibitor 3 months ago. Bone density showed osteopenia. She presents to your office reporting frequent bothersome hot flashes and disrupted sleep.

Strategy #1: Lifestyle adaptations

First-line interventions for menopausal women who have had breast cancer usually involve taking a critical look at lifestyle and undertaking modifications that can alleviate discomfort. Because overall health is important for women who have had breast cancer, you should, across the spectrum of patients, encourage them to:

• increase physical activity
• reduce body weight by approximately 10% (if overweight or obese)
• reduce alcohol consumption
• stop smoking
• ensure adequate intake of calcium (1,200 mg, preferably by diet)
• optimize the level of vitamin D, including by increasing intake of fresh fish, eggs, and numerous other fortified foods.

The value of nondrug therapy for hot flashes is difficult to prove. Certain lifestyle changes are sensible, even if not evidence-based, and will help some women (but not others). We suggest that patients try lowering the temperature in the home (65–68˚ at night); running a fan; wearing clothing that can be removed in layers; and avoiding triggers such as spicy food, alcohol, cigarettes, and hot drinks. Hypnosis and cognitive behavioral therapy (CBT) have been shown to help in clinical trials. Measures with benefit and minimal risks, but effectiveness not established, include acupuncture (sham worked as well as traditional), exercise, yoga, paced respiration, relaxation training, and mindfulness-based stress reduction.

Continue to: Strategy #2: OTC compounds...

Strategy #2: OTC compounds

Over-the-counter products—from soy products to black cohosh to flax seed, and including dong quai, evening primrose oil, maca, omegas, pollen extract, ginseng, and red clover,² or several compounds formulated in combination—have not been proven to be of more benefit for relieving symptoms of menopause than placebo in randomized trials, and thus might or might not be effective in a given patient. S-equol, a metabolite of a soy isoflavone taken by women who are non-equol producers, is available under the trade name Equelle and has shown some benefit. Note: There is concern that supplements that contain estrogen-like compounds, like soy products, might actually increase the risk of breast cancer. Dietary soy is not felt to be a concern.

Ask questions about the severity of a patient’s hot flashes. When a patient reports hot flashes, and is requesting help to relieve her discomfort, inquire 1) how often she has hot flashes, 2) how severe they are, and 3) how bothered she is by them (not all women are equally troubled, of course). The patient’s answers to these questions will help you decide which treatment option to offer, based on evidence and your experience.

CASE 1 Continued

Rose tried black cohosh OTC without improvement. She was interested in hypnosis but did not find it effective for her. She returned 3 months later stating that she is miserable, exhausted, not getting enough sleep, and her hot flashes and night sweats are affecting both her work and her relationship.

Strategy #3: Prescription medication

When addressing hot flashes, consider whether they occur more at night or during the day, or do not follow a day–night pattern. For women whose hot flashes occur mostly at night, and might therefore make sleeping difficult and cause fatigue and irritability, gabapentin, taken approximately 1 hour before bed, can be helpful. If tolerated without excessive somnolence the next day, the dose can be increased at night or additional doses provided during the day depending on hot flash response. For women who have hot flashes day and night, we often prescribe a low-dose antidepressant from the selective serotonin-reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) class.

When prescribing an antidepressant, we make a distinction between breast cancer patients who are taking tamoxifen and those who are not, to avoid cytochrome P450 2D6 inhibitors in women taking tamoxifen.³ Better choices for women taking tamoxifen include desvenlafaxine, venlafaxine, escitalopram, or gabapentin or pregabalin.

For women with breast cancer who are taking an aromatase inhibitor, and who are also experiencing mood changes with their hot flashes, we often choose a trial of a low-dose antidepressant, either an SSRI or SNRI. One drug is approved by the US Food and Drug Administration (FDA) for the treatment of hot flashes (but not for mood disorder). This is low-dose salt of paroxetine, 7.5 mg/d, which has the advantage of exerting no adverse effect on libido or weight (but is sometimes difficult to obtain because it is a branded product that might not be covered, or not covered fully, by a given patient’s insurance plan). Other antidepressants can be used in doses lower than needed for depression, with more rapid onset of effect on hot flashes, often within 2 weeks.

Last, transdermal clonidine, an antihypertensive, also has been found to relieve hot flashes.

Continue to: Not a recommended strategy: Systemic hormone therapy

Not a recommended strategy: Systemic hormone therapy

Although hormone therapy is, in general, the gold standard for alleviating hot flashes, it is contraindicated in most women with breast cancer.⁴ At our institution, we avoid systemic hormone therapy for hot flashes in almost all breast cancer patients.

CASE 2

Sarah first presented with hot flashes that improved while taking escitalopram 10 mg. Her night sweats persisted, however. Gabapentin 300 mg was added to take nightly. With this regimen, she finally felt that she was coping better. Six months later, she reported that she and her long-term partner had not been able to resume vaginal intercourse post–breast cancer treatment because of pain.

The challenge of managing GSM

What if your patient says, “Doctor, I’m really doing OK with my hot flashes, but sex has become painful. I don’t have any interest. I have vaginal dryness, and it’s affecting my quality of life”?

Studies have shown that GSM affects up to 50% of women, and even more than that among women who have had breast cancer.⁵ The condition interferes with sexual intimacy, disrupts quality of life, and can sour a partnership—significant quality-of-life concerns for breast cancer survivors.

For mild symptoms, encourage patients to apply a lubricant just before intercourse or a vaginal moisturizer twice weekly; moisturizers improve vaginal pH, too. These treatments do not fix the problem of a lack of superficial cells due to estrogen loss, however; to accomplish that, consider prescribing low-dose vaginal estrogen therapy or intravaginal dehydroepiandrosterone (DHEA). This strategy is felt to be safe for many breast cancer survivors, as systemic absorption of estrogen is minimal if dosed low, keeping levels in the postmenopausal range.

The American College of Obstetricians and Gynecologists (ACOG), the North American Menopause Society (NAMS), and the Endocrine Society agree that vaginal estrogen therapy may be a good option for many women with breast cancer for whom moisturizers and lubricants are inadequate.⁶ Delivery options include vaginal creams, tablets, suppositories used 2 or 3 times per week, or the low-dose vaginal estrogen ring, replaced every 3 months. We are concerned about using vaginal estrogen in women who have had aromatase inhibitor (AI) therapy; their estrogen levels are so low that absorbing even a small amount might make a difference in terms of effectiveness of AI. For women who need more than lubricants or vaginal moisturizers, particularly those taking anti-estrogen therapy (aromatase therapy), the use of low-dose vaginal hormones may be considered on an individual basis, but should include the oncologist in decision making.^1,3

Beyond low-dose vaginal estrogen therapies, there are additional options that can be considered but with less supporting data for treating GSM in women with breast cancer.

Oral ospemifene, a selective estrogen-receptor modulator (SERM; Osphena), might be neutral or even protective in its effect on the breast, as demonstrated in preclinical trials.⁷ In human trials, the drug is approved only for painful intercourse, not for loss of libido, and has not been tested in breast cancer patients.

Intravaginal DHEA (Prasterone), has been on the market for almost 1 year. The drug is approved for treating painful intercourse, but it also reverses vaginal atrophy and alleviates urinary symptoms. Because DHEA is a prohormone, it is converted to estrogen and androgen in the vagina. Again, absorption appears minimal. Intravaginal DHEA does not have the US Food and Drug Administration (FDA) black-box warning that vaginal estrogen products do, but it is accompanied by a warning that it has not been tested in women with breast cancer.

Tissue selective estrogen receptor modulator is a conjugated estrogen combined with a third-generation SERM bazedoxifene, which treats hot flashes and reverses vaginal atrophy. This new systemic agent is probably neutral on the breast (at least that is the finding in clinical trials at 2 years⁸); again, however, it has not been tested in patients with breast cancer.

Continue to: Nonhormone therapies...

Nonhormone therapies

Topical lidocaine for insertional dyspareunia has been studied in postmenopausal women with breast cancer with severe GSM, dyspareunia, increased sexual distress scores, or abnormal sexual function with improvement seen using 4% aqueous lidocaine versus saline applied with a cotton ball to the vestibule for 3 minutes before vaginal penetration.⁹

Vaginal laser therapy has the potential to ameliorate distressing GSM without the need for local hormone intervention; however, placebo or active-controlled trials and long-term safety follow-up are needed.⁵

Treatment begins with a conversation

Most importantly, we need to listen to our patients in discomfort because of their menopausal symptoms. Consider proceeding along these lines: “You’ve been treated for breast cancer; now, let’s look at the medical issues that are affecting your quality of life. Are you depressed? Are you having hot flashes? Are you getting enough sleep? Have you stopped having sex or not restarted after your breast cancer treatment? Are you having painful sex or avoiding sex due to fear of pain? Let’s discuss options and work with your oncologist to try to relieve your symptoms and make your life better.”

First-line therapy for the treatment of menopausal symptoms in women with a history of breast cancer should start with lifestyle changes and nonhormone therapies. For GSM, lubricants and vaginal moisturizers should be tried first and may be effective. Reassure patients that there are many treatment options, even though not all of them have been well-tested in breast cancer patients, and that new modalities are under investigation and review (see “Newly arrived and on the horizon,”). Become familiar with published data on the safety and effectiveness of the range of available treatments; guide patients through the process of finding what works best for them; and invite their oncologist into the therapeutic partnership. If you do not feel comfortable with these issues in women who are breast cancer survivors, find a menopause specialist to help, available by zip code at Find a Provider, http://www.menopause.org.

Breast cancer survivors entering menopause face the risk of several menopausal symptoms:

• Hot flashes, the most common symptom, occur in more than 75% of women during menopause and have the potential to persist for as long as 15 years.¹ That lengthy interval becomes a major issue for patients, especially when hot flashes are associated with other menopausal symptoms, including sleep disruption, difficulty concentrating, and emotional instability (crying, irritability).

• Painful intercourse and loss of interest in sexual activity often develop as a result of vaginal atrophy and dryness.

• Urinary tract symptoms include urgency and, compared to the patient’s history, more frequent infections.
• Bone loss is a concern for many women after breast cancer, especially if they are, or have been, on aromatase inhibitor therapy.

• Depression might be related to hormonal changes due to menopause or hormonal therapies, a consequence of merely having a diagnosis of cancer, or an adverse effect of chemotherapy.

In this brief review, I’ll examine options for treating symptoms of menopause by strategy—lifestyle modifications, over-the-counter treatments, and prescription drugs. Separately, I’ll look at options for managing genitourinary syndrome of menopause (GSM).

CASE 1

Rose is a 56-year-old woman who presents to clinic with a new breast mass, felt on breast self exam. The mass is about 1 cm, mobile, and firm. Diagnostic mammogram and ultrasound confirm a worrisome mass; biopsy returns positive with a 9-mm invasive, estrogen-receptor positive, ductal carcinoma with negative sentinel nodes at the time of lumpectomy. Radiation therapy was completed. She then met with oncology and decided against chemotherapy. Instead, she began an aromatase inhibitor 3 months ago. Bone density showed osteopenia. She presents to your office reporting frequent bothersome hot flashes and disrupted sleep.

Strategy #1: Lifestyle adaptations

First-line interventions for menopausal women who have had breast cancer usually involve taking a critical look at lifestyle and undertaking modifications that can alleviate discomfort. Because overall health is important for women who have had breast cancer, you should, across the spectrum of patients, encourage them to:

• increase physical activity
• reduce body weight by approximately 10% (if overweight or obese)
• reduce alcohol consumption
• stop smoking
• ensure adequate intake of calcium (1,200 mg, preferably by diet)
• optimize the level of vitamin D, including by increasing intake of fresh fish, eggs, and numerous other fortified foods.

The value of nondrug therapy for hot flashes is difficult to prove. Certain lifestyle changes are sensible, even if not evidence-based, and will help some women (but not others). We suggest that patients try lowering the temperature in the home (65–68˚ at night); running a fan; wearing clothing that can be removed in layers; and avoiding triggers such as spicy food, alcohol, cigarettes, and hot drinks. Hypnosis and cognitive behavioral therapy (CBT) have been shown to help in clinical trials. Measures with benefit and minimal risks, but effectiveness not established, include acupuncture (sham worked as well as traditional), exercise, yoga, paced respiration, relaxation training, and mindfulness-based stress reduction.

Continue to: Strategy #2: OTC compounds...

Strategy #2: OTC compounds

Over-the-counter products—from soy products to black cohosh to flax seed, and including dong quai, evening primrose oil, maca, omegas, pollen extract, ginseng, and red clover,² or several compounds formulated in combination—have not been proven to be of more benefit for relieving symptoms of menopause than placebo in randomized trials, and thus might or might not be effective in a given patient. S-equol, a metabolite of a soy isoflavone taken by women who are non-equol producers, is available under the trade name Equelle and has shown some benefit. Note: There is concern that supplements that contain estrogen-like compounds, like soy products, might actually increase the risk of breast cancer. Dietary soy is not felt to be a concern.

Ask questions about the severity of a patient’s hot flashes. When a patient reports hot flashes, and is requesting help to relieve her discomfort, inquire 1) how often she has hot flashes, 2) how severe they are, and 3) how bothered she is by them (not all women are equally troubled, of course). The patient’s answers to these questions will help you decide which treatment option to offer, based on evidence and your experience.

CASE 1 Continued

Rose tried black cohosh OTC without improvement. She was interested in hypnosis but did not find it effective for her. She returned 3 months later stating that she is miserable, exhausted, not getting enough sleep, and her hot flashes and night sweats are affecting both her work and her relationship.

Strategy #3: Prescription medication

When addressing hot flashes, consider whether they occur more at night or during the day, or do not follow a day–night pattern. For women whose hot flashes occur mostly at night, and might therefore make sleeping difficult and cause fatigue and irritability, gabapentin, taken approximately 1 hour before bed, can be helpful. If tolerated without excessive somnolence the next day, the dose can be increased at night or additional doses provided during the day depending on hot flash response. For women who have hot flashes day and night, we often prescribe a low-dose antidepressant from the selective serotonin-reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) class.

When prescribing an antidepressant, we make a distinction between breast cancer patients who are taking tamoxifen and those who are not, to avoid cytochrome P450 2D6 inhibitors in women taking tamoxifen.³ Better choices for women taking tamoxifen include desvenlafaxine, venlafaxine, escitalopram, or gabapentin or pregabalin.

For women with breast cancer who are taking an aromatase inhibitor, and who are also experiencing mood changes with their hot flashes, we often choose a trial of a low-dose antidepressant, either an SSRI or SNRI. One drug is approved by the US Food and Drug Administration (FDA) for the treatment of hot flashes (but not for mood disorder). This is low-dose salt of paroxetine, 7.5 mg/d, which has the advantage of exerting no adverse effect on libido or weight (but is sometimes difficult to obtain because it is a branded product that might not be covered, or not covered fully, by a given patient’s insurance plan). Other antidepressants can be used in doses lower than needed for depression, with more rapid onset of effect on hot flashes, often within 2 weeks.

Last, transdermal clonidine, an antihypertensive, also has been found to relieve hot flashes.

Continue to: Not a recommended strategy: Systemic hormone therapy

Not a recommended strategy: Systemic hormone therapy

Although hormone therapy is, in general, the gold standard for alleviating hot flashes, it is contraindicated in most women with breast cancer.⁴ At our institution, we avoid systemic hormone therapy for hot flashes in almost all breast cancer patients.

CASE 2

Sarah first presented with hot flashes that improved while taking escitalopram 10 mg. Her night sweats persisted, however. Gabapentin 300 mg was added to take nightly. With this regimen, she finally felt that she was coping better. Six months later, she reported that she and her long-term partner had not been able to resume vaginal intercourse post–breast cancer treatment because of pain.

The challenge of managing GSM

What if your patient says, “Doctor, I’m really doing OK with my hot flashes, but sex has become painful. I don’t have any interest. I have vaginal dryness, and it’s affecting my quality of life”?

Studies have shown that GSM affects up to 50% of women, and even more than that among women who have had breast cancer.⁵ The condition interferes with sexual intimacy, disrupts quality of life, and can sour a partnership—significant quality-of-life concerns for breast cancer survivors.

For mild symptoms, encourage patients to apply a lubricant just before intercourse or a vaginal moisturizer twice weekly; moisturizers improve vaginal pH, too. These treatments do not fix the problem of a lack of superficial cells due to estrogen loss, however; to accomplish that, consider prescribing low-dose vaginal estrogen therapy or intravaginal dehydroepiandrosterone (DHEA). This strategy is felt to be safe for many breast cancer survivors, as systemic absorption of estrogen is minimal if dosed low, keeping levels in the postmenopausal range.

The American College of Obstetricians and Gynecologists (ACOG), the North American Menopause Society (NAMS), and the Endocrine Society agree that vaginal estrogen therapy may be a good option for many women with breast cancer for whom moisturizers and lubricants are inadequate.⁶ Delivery options include vaginal creams, tablets, suppositories used 2 or 3 times per week, or the low-dose vaginal estrogen ring, replaced every 3 months. We are concerned about using vaginal estrogen in women who have had aromatase inhibitor (AI) therapy; their estrogen levels are so low that absorbing even a small amount might make a difference in terms of effectiveness of AI. For women who need more than lubricants or vaginal moisturizers, particularly those taking anti-estrogen therapy (aromatase therapy), the use of low-dose vaginal hormones may be considered on an individual basis, but should include the oncologist in decision making.^1,3

Beyond low-dose vaginal estrogen therapies, there are additional options that can be considered but with less supporting data for treating GSM in women with breast cancer.

Oral ospemifene, a selective estrogen-receptor modulator (SERM; Osphena), might be neutral or even protective in its effect on the breast, as demonstrated in preclinical trials.⁷ In human trials, the drug is approved only for painful intercourse, not for loss of libido, and has not been tested in breast cancer patients.

Intravaginal DHEA (Prasterone), has been on the market for almost 1 year. The drug is approved for treating painful intercourse, but it also reverses vaginal atrophy and alleviates urinary symptoms. Because DHEA is a prohormone, it is converted to estrogen and androgen in the vagina. Again, absorption appears minimal. Intravaginal DHEA does not have the US Food and Drug Administration (FDA) black-box warning that vaginal estrogen products do, but it is accompanied by a warning that it has not been tested in women with breast cancer.

Tissue selective estrogen receptor modulator is a conjugated estrogen combined with a third-generation SERM bazedoxifene, which treats hot flashes and reverses vaginal atrophy. This new systemic agent is probably neutral on the breast (at least that is the finding in clinical trials at 2 years⁸); again, however, it has not been tested in patients with breast cancer.

Continue to: Nonhormone therapies...

Nonhormone therapies

Topical lidocaine for insertional dyspareunia has been studied in postmenopausal women with breast cancer with severe GSM, dyspareunia, increased sexual distress scores, or abnormal sexual function with improvement seen using 4% aqueous lidocaine versus saline applied with a cotton ball to the vestibule for 3 minutes before vaginal penetration.⁹

Vaginal laser therapy has the potential to ameliorate distressing GSM without the need for local hormone intervention; however, placebo or active-controlled trials and long-term safety follow-up are needed.⁵

Treatment begins with a conversation

Most importantly, we need to listen to our patients in discomfort because of their menopausal symptoms. Consider proceeding along these lines: “You’ve been treated for breast cancer; now, let’s look at the medical issues that are affecting your quality of life. Are you depressed? Are you having hot flashes? Are you getting enough sleep? Have you stopped having sex or not restarted after your breast cancer treatment? Are you having painful sex or avoiding sex due to fear of pain? Let’s discuss options and work with your oncologist to try to relieve your symptoms and make your life better.”

First-line therapy for the treatment of menopausal symptoms in women with a history of breast cancer should start with lifestyle changes and nonhormone therapies. For GSM, lubricants and vaginal moisturizers should be tried first and may be effective. Reassure patients that there are many treatment options, even though not all of them have been well-tested in breast cancer patients, and that new modalities are under investigation and review (see “Newly arrived and on the horizon,”). Become familiar with published data on the safety and effectiveness of the range of available treatments; guide patients through the process of finding what works best for them; and invite their oncologist into the therapeutic partnership. If you do not feel comfortable with these issues in women who are breast cancer survivors, find a menopause specialist to help, available by zip code at Find a Provider, http://www.menopause.org.

The conventional bone mineral density threshold for initiating treatment to prevent fragility fractures is a T-score of less than -2.5 (the World Health Organization criteria for osteoporosis).¹ However, most fractures experienced by postmenopausal women occur not in osteoporotic women but in those with low bone mass (osteopenia).²

Investigators in New Zealand recently published the results of a randomized controlled trial they conducted to determine the efficacy of zoledronate (zoledronic acid) in preventing fractures in postmenopausal women.³ They enrolled women age 65 years or older with osteopenia of the hip and randomly assigned the participants to 4 intravenous infusions of 5 mg zoledronic acid or placebo at 18-month intervals for 6 years.

Zoledronic acid reduced fracture risk

The trial included 2,000 postmenopausal women (mean age at baseline, 71 years; 94% European ethnicity) with a T-score of -1.0 to -2.5 at either the total hip or the femoral neck on either side. Both hips were assessed. The women received either zoledronic acid treatment or placebo in a 1:1 ratio. Candidates were excluded if they regularly used bone-active drugs in the previous year.

Fragility fractures were noted in 190 women in the placebo group and in 122 women treated with zoledronic acid (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.50–0.79, P<.001). The number of women that would need to be treated to prevent the occurrence of a fracture in 1 woman was 15.

Compared with placebo, zoledronic acid also lowered the risk of nonvertebral, symptomatic, and vertebral fractures as well as height loss (P≤.003 for these 4 comparisons). Relatively few adverse events occurred with zoledronic acid treatment. No atypical femoral fractures or cases of osteonecrosis of the jaw occurred in either group.

Trial closes the knowledge gap regarding treatment thresholds

This trial’s findings underscore the importance of age as a risk factor for fragility fracture and clarify that pharmacologic treatment is appropriate not only for women with osteoporosis but also for older postmenopausal women with osteopenia.

As the authors point out, administration of zoledronic acid less often than annually can be highly effective in preventing fractures; they recommend future trials of administration of this intravenous bisphosphonate at intervals less frequent than 18 months. Although the absence of atypical femoral fractures or cases of osteonecrosis of the jaw is reassuring, the authors note that their trial was underpowered to assess these uncommon events.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

The conventional bone mineral density threshold for initiating treatment to prevent fragility fractures is a T-score of less than -2.5 (the World Health Organization criteria for osteoporosis).¹ However, most fractures experienced by postmenopausal women occur not in osteoporotic women but in those with low bone mass (osteopenia).²

Investigators in New Zealand recently published the results of a randomized controlled trial they conducted to determine the efficacy of zoledronate (zoledronic acid) in preventing fractures in postmenopausal women.³ They enrolled women age 65 years or older with osteopenia of the hip and randomly assigned the participants to 4 intravenous infusions of 5 mg zoledronic acid or placebo at 18-month intervals for 6 years.

Zoledronic acid reduced fracture risk

The trial included 2,000 postmenopausal women (mean age at baseline, 71 years; 94% European ethnicity) with a T-score of -1.0 to -2.5 at either the total hip or the femoral neck on either side. Both hips were assessed. The women received either zoledronic acid treatment or placebo in a 1:1 ratio. Candidates were excluded if they regularly used bone-active drugs in the previous year.

Fragility fractures were noted in 190 women in the placebo group and in 122 women treated with zoledronic acid (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.50–0.79, P<.001). The number of women that would need to be treated to prevent the occurrence of a fracture in 1 woman was 15.

Compared with placebo, zoledronic acid also lowered the risk of nonvertebral, symptomatic, and vertebral fractures as well as height loss (P≤.003 for these 4 comparisons). Relatively few adverse events occurred with zoledronic acid treatment. No atypical femoral fractures or cases of osteonecrosis of the jaw occurred in either group.

Trial closes the knowledge gap regarding treatment thresholds

This trial’s findings underscore the importance of age as a risk factor for fragility fracture and clarify that pharmacologic treatment is appropriate not only for women with osteoporosis but also for older postmenopausal women with osteopenia.

As the authors point out, administration of zoledronic acid less often than annually can be highly effective in preventing fractures; they recommend future trials of administration of this intravenous bisphosphonate at intervals less frequent than 18 months. Although the absence of atypical femoral fractures or cases of osteonecrosis of the jaw is reassuring, the authors note that their trial was underpowered to assess these uncommon events.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

The conventional bone mineral density threshold for initiating treatment to prevent fragility fractures is a T-score of less than -2.5 (the World Health Organization criteria for osteoporosis).¹ However, most fractures experienced by postmenopausal women occur not in osteoporotic women but in those with low bone mass (osteopenia).²

Investigators in New Zealand recently published the results of a randomized controlled trial they conducted to determine the efficacy of zoledronate (zoledronic acid) in preventing fractures in postmenopausal women.³ They enrolled women age 65 years or older with osteopenia of the hip and randomly assigned the participants to 4 intravenous infusions of 5 mg zoledronic acid or placebo at 18-month intervals for 6 years.

Zoledronic acid reduced fracture risk

The trial included 2,000 postmenopausal women (mean age at baseline, 71 years; 94% European ethnicity) with a T-score of -1.0 to -2.5 at either the total hip or the femoral neck on either side. Both hips were assessed. The women received either zoledronic acid treatment or placebo in a 1:1 ratio. Candidates were excluded if they regularly used bone-active drugs in the previous year.

Fragility fractures were noted in 190 women in the placebo group and in 122 women treated with zoledronic acid (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.50–0.79, P<.001). The number of women that would need to be treated to prevent the occurrence of a fracture in 1 woman was 15.

Compared with placebo, zoledronic acid also lowered the risk of nonvertebral, symptomatic, and vertebral fractures as well as height loss (P≤.003 for these 4 comparisons). Relatively few adverse events occurred with zoledronic acid treatment. No atypical femoral fractures or cases of osteonecrosis of the jaw occurred in either group.

Trial closes the knowledge gap regarding treatment thresholds

This trial’s findings underscore the importance of age as a risk factor for fragility fracture and clarify that pharmacologic treatment is appropriate not only for women with osteoporosis but also for older postmenopausal women with osteopenia.

As the authors point out, administration of zoledronic acid less often than annually can be highly effective in preventing fractures; they recommend future trials of administration of this intravenous bisphosphonate at intervals less frequent than 18 months. Although the absence of atypical femoral fractures or cases of osteonecrosis of the jaw is reassuring, the authors note that their trial was underpowered to assess these uncommon events.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

As ObGyns, we are the first-line health care providers for our menopausal patients in terms of identifying, preventing, and initiating treatment for women at risk for fragility fractures. Osteoporosis is probably the most important risk factor for bone health, although sarcopenia, frailty, poor eyesight, and falls also play a significant role in bone health and fragility fracture.

In 2005, more than 2 million incident fractures were reported in the United States, with a total cost of $17 billion.¹ By 2025, annual fractures and costs are expected to rise by almost 50%. People who are 65 to 74 years of age will likely experience the largest increase in fracture—greater than 87%.¹

Findings from the Women’s Health Initiative study showed that the number of women who had a clinical fracture in 1 year exceeded all the cases of myocardial infarction, stroke, and breast cancer combined.² Furthermore, the morbidity and mortality rates for fractures are staggering. Thirty percent of women with a hip fracture will be dead within 1 year.³ So, although many patients fear developing breast cancer, and cardiovascular disease remains the number 1 cause of death, the impact of maintaining and protecting bone health cannot be emphasized enough.

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WHI incidental findings: Hormone-treated menopausal women had decreased hip fracture rate

Manson JE, Aragaki AK, Rossouw JE, et al; WHI Investigators. Menopausal hormone therapy and long-term all-cause and cause-specific mortality: the Women’s Health Initiative randomized trials. JAMA. 2017;318:927-938.

Manson and colleagues examined the total and cause-specific cumulative mortality of the 2 Women’s Health Initiative (WHI) hormone therapy trials. This was an observational follow-up of US multiethnic postmenopausal women aged 50 to 79 years (mean age at baseline, 63.4 years) enrolled in 2 randomized clinical trials between 1993 and 1998 and followed up through December 31, 2014. A total of 27,347 women were randomly assigned to treatment.

Treatment groups

Depending on the presence or absence of a uterus, women received conjugated equine estrogens (CEE, 0.625 mg/d) plus medroxyprogesterone acetate (MPA, 2.5 mg/d) (n = 8,506) or placebo (n = 8,102) for a median of 5.6 years or CEE alone (n = 5,310) versus placebo (n = 5,429) for a median of 7.2 years. All-cause mortality (the primary outcome) and cause-specific mortality (cardiovascular disease mortality, cancer mortality, and other major causes of mortality) were analyzed in the 2 trials pooled and in each trial individually.

All-cause and cause-specific mortality findings

Mortality follow-up was available for more than 98% of participants. During the cumulative 18-year follow-up, 7,489 deaths occurred. In the overall pooled cohort, all-cause mortality in the hormone therapy group was 27.1% compared with 27.6% in the placebo group (hazard ratio [HR], 0.99 [95% confidence interval (CI), 0.94–1.03]). In the CEE plus MPA group, the HR was 1.02 (95% CI, 0.96–1.08). For those in the CEE-alone group, the HR was 0.94 (95% CI, 0.88–1.01).

In the pooled cohort for cardiovascular mortality, the HR was 1.00 (95% CI, 0.92–1.08 [8.9% with hormone therapy vs 9.0% with placebo]). For total cancer mortality, the HR was 1.03 (95% CI, 0.95–1.12 [8.2% with hormone therapy vs 8.0% with placebo]). For other causes, the HR was 0.95 (95% CI, 0.88–1.02 [10.0% with hormone therapy vs 10.7% with placebo]). Results did not differ significantly between trials.

Key takeaway

The study authors concluded that among postmenopausal women, hormone therapy with CEE plus MPA for a median of 5.6 years or with CEE alone for a median of 7.2 years was not associated with risk of all-cause, cardiovascular, or cancer mortality during a cumulative follow-up of 18 years.

Continue to: Appropriate to defer DXA testing to age 65...

Gourlay ML, Overman RA, Fine JP, et al; Women’s Health Initiative Investigators. Time to clinically relevant fracture risk scores in postmenopausal women. Am J Med. 2017;130:862.e15-862.e23.

Gourlay ML, Fine JP, Preisser JS, et al; Study of Osteoporotic Fractures Research Group. Bone-density testing interval and transition to osteoporosis in older women. N Engl J Med. 2012;366:225-233.

Many clinicians used to (and still do) order bone mineral density (BMD) testing at 23-month intervals because that was what insurance would allow. Gourlay and colleagues previously published a study on BMD testing intervals and the time it takes to develop osteoporosis. I covered that information in previous Updates.^4,5

To recap, Gourlay and colleagues studied 4,957 women, 67 years of age or older, with normal BMD or osteopenia and with no history of hip or clinical vertebral fracture or of treatment for osteoporosis; the women were followed prospectively for up to 15 years. The estimated time for 10% of women to make the transition to osteoporosis was 16.8 years for those with normal BMD, 4.7 years for those with moderate osteopenia, and 1.1 years for women with advanced osteopenia.

Today, FRAX is recommended to assess need for treatment

Older treatment recommendations involved determining various osteopenic BMD levels and the presence or absence of certain risk factors. More recently, the National Osteoporosis Foundation and many medical societies, including the American College of Obstetricians and Gynecologists, have recommended using the FRAX fracture prediction algorithm (available at https://www.sheffield.ac.uk/FRAX/) instead of T-scores to consider initiating pharmacotherapy.

The FRAX calculation tool uses information such as the country where the patient lives, age, sex, height, weight, history of previous fracture, parental fracture, current smoking, glucocorticoid use, rheumatoid arthritis, secondary osteoporosis, alcohol use of 3 or more units per day, and, if available, BMD determination at the femoral neck. It then yields the 10-year absolute risk of hip fracture and any major osteoporotic fracture for that individual or, more precisely, for an individual like that.

In the United States, accepted levels for cost-effective pharmacotherapy are a 10-year absolute risk of hip fracture of 3% or major osteoporotic fracture of 20%.

Continue to: Age also is a key factor in fracture risk assessment

Gourlay and colleagues more recently conducted a retrospective analysis of new occurrence of treatment-level fracture risk scores in postmenopausal women (50 years of age and older) before they received pharmacologic treatment and before they experienced a first hip or clinical vertebral fracture.

In 54,280 postmenopausal women aged 50 to 64 without a BMD test, the time for 10% to develop a treatment-level FRAX score could not be estimated accurately because of the rarity of treatment-level scores. In 6,096 women who had FRAX scores calculated with their BMD score, the estimated time to treatment-level FRAX was 7.6 years for those 65 to 69 and 5.1 years for 75 to 79 year olds. Furthermore, of 17,967 women aged 50 to 64 with a screening-level FRAX at baseline, only 100 (0.6%) experienced a hip or clinical vertebral fracture by age 65.

The investigators concluded that, “Postmenopausal women with sub-threshold fracture risk scores at baseline were unlikely to develop a treatment-level FRAX score between ages 50 and 64 years. After age 65, the increased incidence of treatment-level fracture risk scores, osteoporosis, and major osteoporotic fracture supports more frequent consideration of FRAX and bone mineral density testing.”

Continue to: USPSTF offers updated recommendations for osteoporosis screening

US Preventive Services Task Force, Curry SJ, Krist AH, Owens DK, et al. Screening for osteoporosis to prevent fractures: US Preventive Services Task Force recommendation statement. JAMA. 2018;319:2521-2531.

The 2018 updated osteoporosis screening recommendations from the United States Preventative Services Task Force (USPSTF) may seem contradictory to the conclusions of Gourlay and colleagues discussed above. They are not.

The USPSTF authors point out that by 2020, about 12.3 million US individuals older than 50 years are expected to have osteoporosis. Osteoporotic fractures (especially hip fractures) are associated with limitations in ambulation, chronic pain and disability, loss of independence, and decreased quality of life. In fact, 21% to 30% of people who sustain a hip fracture die within 1 year. As the US population continues to age, the potential preventable burden will likely increase.

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Evidence on bone measurement tests, risk assessment tools, and drug therapy efficacy

The USPSTF conducted an evidence review on screening for and treatment of osteoporotic fractures in women as well as risk assessment tools. The task force found the evidence convincing that bone measurement tests are accurate for detecting osteoporosis and predicting osteoporotic fractures. In addition, there is adequate evidence that clinical risk assessment tools are moderately accurate in identifying risk of osteoporosis and osteoporotic fractures. Furthermore, there is convincing evidence that drug therapies reduce subsequent fracture rates in postmenopausal women.

The USPSTF recommends the following:

• For women aged 65 and older, screen for osteoporosis with bone measurement testing to prevent osteoporotic fractures.
• For women younger than 65 who are at increased risk for osteoporosis based on formal clinical risk assessment tools, screen for osteoporosis with bone measurement testing to prevent osteoporotic fractures.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

As ObGyns, we are the first-line health care providers for our menopausal patients in terms of identifying, preventing, and initiating treatment for women at risk for fragility fractures. Osteoporosis is probably the most important risk factor for bone health, although sarcopenia, frailty, poor eyesight, and falls also play a significant role in bone health and fragility fracture.

In 2005, more than 2 million incident fractures were reported in the United States, with a total cost of $17 billion.¹ By 2025, annual fractures and costs are expected to rise by almost 50%. People who are 65 to 74 years of age will likely experience the largest increase in fracture—greater than 87%.¹

Findings from the Women’s Health Initiative study showed that the number of women who had a clinical fracture in 1 year exceeded all the cases of myocardial infarction, stroke, and breast cancer combined.² Furthermore, the morbidity and mortality rates for fractures are staggering. Thirty percent of women with a hip fracture will be dead within 1 year.³ So, although many patients fear developing breast cancer, and cardiovascular disease remains the number 1 cause of death, the impact of maintaining and protecting bone health cannot be emphasized enough.

Image

_

WHI incidental findings: Hormone-treated menopausal women had decreased hip fracture rate

Manson JE, Aragaki AK, Rossouw JE, et al; WHI Investigators. Menopausal hormone therapy and long-term all-cause and cause-specific mortality: the Women’s Health Initiative randomized trials. JAMA. 2017;318:927-938.

Manson and colleagues examined the total and cause-specific cumulative mortality of the 2 Women’s Health Initiative (WHI) hormone therapy trials. This was an observational follow-up of US multiethnic postmenopausal women aged 50 to 79 years (mean age at baseline, 63.4 years) enrolled in 2 randomized clinical trials between 1993 and 1998 and followed up through December 31, 2014. A total of 27,347 women were randomly assigned to treatment.

Treatment groups

Depending on the presence or absence of a uterus, women received conjugated equine estrogens (CEE, 0.625 mg/d) plus medroxyprogesterone acetate (MPA, 2.5 mg/d) (n = 8,506) or placebo (n = 8,102) for a median of 5.6 years or CEE alone (n = 5,310) versus placebo (n = 5,429) for a median of 7.2 years. All-cause mortality (the primary outcome) and cause-specific mortality (cardiovascular disease mortality, cancer mortality, and other major causes of mortality) were analyzed in the 2 trials pooled and in each trial individually.

All-cause and cause-specific mortality findings

Mortality follow-up was available for more than 98% of participants. During the cumulative 18-year follow-up, 7,489 deaths occurred. In the overall pooled cohort, all-cause mortality in the hormone therapy group was 27.1% compared with 27.6% in the placebo group (hazard ratio [HR], 0.99 [95% confidence interval (CI), 0.94–1.03]). In the CEE plus MPA group, the HR was 1.02 (95% CI, 0.96–1.08). For those in the CEE-alone group, the HR was 0.94 (95% CI, 0.88–1.01).

In the pooled cohort for cardiovascular mortality, the HR was 1.00 (95% CI, 0.92–1.08 [8.9% with hormone therapy vs 9.0% with placebo]). For total cancer mortality, the HR was 1.03 (95% CI, 0.95–1.12 [8.2% with hormone therapy vs 8.0% with placebo]). For other causes, the HR was 0.95 (95% CI, 0.88–1.02 [10.0% with hormone therapy vs 10.7% with placebo]). Results did not differ significantly between trials.

Key takeaway

The study authors concluded that among postmenopausal women, hormone therapy with CEE plus MPA for a median of 5.6 years or with CEE alone for a median of 7.2 years was not associated with risk of all-cause, cardiovascular, or cancer mortality during a cumulative follow-up of 18 years.

Continue to: Appropriate to defer DXA testing to age 65...

Gourlay ML, Overman RA, Fine JP, et al; Women’s Health Initiative Investigators. Time to clinically relevant fracture risk scores in postmenopausal women. Am J Med. 2017;130:862.e15-862.e23.

Gourlay ML, Fine JP, Preisser JS, et al; Study of Osteoporotic Fractures Research Group. Bone-density testing interval and transition to osteoporosis in older women. N Engl J Med. 2012;366:225-233.

Many clinicians used to (and still do) order bone mineral density (BMD) testing at 23-month intervals because that was what insurance would allow. Gourlay and colleagues previously published a study on BMD testing intervals and the time it takes to develop osteoporosis. I covered that information in previous Updates.^4,5

To recap, Gourlay and colleagues studied 4,957 women, 67 years of age or older, with normal BMD or osteopenia and with no history of hip or clinical vertebral fracture or of treatment for osteoporosis; the women were followed prospectively for up to 15 years. The estimated time for 10% of women to make the transition to osteoporosis was 16.8 years for those with normal BMD, 4.7 years for those with moderate osteopenia, and 1.1 years for women with advanced osteopenia.

Today, FRAX is recommended to assess need for treatment

Older treatment recommendations involved determining various osteopenic BMD levels and the presence or absence of certain risk factors. More recently, the National Osteoporosis Foundation and many medical societies, including the American College of Obstetricians and Gynecologists, have recommended using the FRAX fracture prediction algorithm (available at https://www.sheffield.ac.uk/FRAX/) instead of T-scores to consider initiating pharmacotherapy.

The FRAX calculation tool uses information such as the country where the patient lives, age, sex, height, weight, history of previous fracture, parental fracture, current smoking, glucocorticoid use, rheumatoid arthritis, secondary osteoporosis, alcohol use of 3 or more units per day, and, if available, BMD determination at the femoral neck. It then yields the 10-year absolute risk of hip fracture and any major osteoporotic fracture for that individual or, more precisely, for an individual like that.

In the United States, accepted levels for cost-effective pharmacotherapy are a 10-year absolute risk of hip fracture of 3% or major osteoporotic fracture of 20%.

Continue to: Age also is a key factor in fracture risk assessment

Gourlay and colleagues more recently conducted a retrospective analysis of new occurrence of treatment-level fracture risk scores in postmenopausal women (50 years of age and older) before they received pharmacologic treatment and before they experienced a first hip or clinical vertebral fracture.

In 54,280 postmenopausal women aged 50 to 64 without a BMD test, the time for 10% to develop a treatment-level FRAX score could not be estimated accurately because of the rarity of treatment-level scores. In 6,096 women who had FRAX scores calculated with their BMD score, the estimated time to treatment-level FRAX was 7.6 years for those 65 to 69 and 5.1 years for 75 to 79 year olds. Furthermore, of 17,967 women aged 50 to 64 with a screening-level FRAX at baseline, only 100 (0.6%) experienced a hip or clinical vertebral fracture by age 65.

The investigators concluded that, “Postmenopausal women with sub-threshold fracture risk scores at baseline were unlikely to develop a treatment-level FRAX score between ages 50 and 64 years. After age 65, the increased incidence of treatment-level fracture risk scores, osteoporosis, and major osteoporotic fracture supports more frequent consideration of FRAX and bone mineral density testing.”

Continue to: USPSTF offers updated recommendations for osteoporosis screening

US Preventive Services Task Force, Curry SJ, Krist AH, Owens DK, et al. Screening for osteoporosis to prevent fractures: US Preventive Services Task Force recommendation statement. JAMA. 2018;319:2521-2531.

The 2018 updated osteoporosis screening recommendations from the United States Preventative Services Task Force (USPSTF) may seem contradictory to the conclusions of Gourlay and colleagues discussed above. They are not.

The USPSTF authors point out that by 2020, about 12.3 million US individuals older than 50 years are expected to have osteoporosis. Osteoporotic fractures (especially hip fractures) are associated with limitations in ambulation, chronic pain and disability, loss of independence, and decreased quality of life. In fact, 21% to 30% of people who sustain a hip fracture die within 1 year. As the US population continues to age, the potential preventable burden will likely increase.

_

Evidence on bone measurement tests, risk assessment tools, and drug therapy efficacy

The USPSTF conducted an evidence review on screening for and treatment of osteoporotic fractures in women as well as risk assessment tools. The task force found the evidence convincing that bone measurement tests are accurate for detecting osteoporosis and predicting osteoporotic fractures. In addition, there is adequate evidence that clinical risk assessment tools are moderately accurate in identifying risk of osteoporosis and osteoporotic fractures. Furthermore, there is convincing evidence that drug therapies reduce subsequent fracture rates in postmenopausal women.

The USPSTF recommends the following:

• For women aged 65 and older, screen for osteoporosis with bone measurement testing to prevent osteoporotic fractures.
• For women younger than 65 who are at increased risk for osteoporosis based on formal clinical risk assessment tools, screen for osteoporosis with bone measurement testing to prevent osteoporotic fractures.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

As ObGyns, we are the first-line health care providers for our menopausal patients in terms of identifying, preventing, and initiating treatment for women at risk for fragility fractures. Osteoporosis is probably the most important risk factor for bone health, although sarcopenia, frailty, poor eyesight, and falls also play a significant role in bone health and fragility fracture.

In 2005, more than 2 million incident fractures were reported in the United States, with a total cost of $17 billion.¹ By 2025, annual fractures and costs are expected to rise by almost 50%. People who are 65 to 74 years of age will likely experience the largest increase in fracture—greater than 87%.¹

Findings from the Women’s Health Initiative study showed that the number of women who had a clinical fracture in 1 year exceeded all the cases of myocardial infarction, stroke, and breast cancer combined.² Furthermore, the morbidity and mortality rates for fractures are staggering. Thirty percent of women with a hip fracture will be dead within 1 year.³ So, although many patients fear developing breast cancer, and cardiovascular disease remains the number 1 cause of death, the impact of maintaining and protecting bone health cannot be emphasized enough.

Image

_

WHI incidental findings: Hormone-treated menopausal women had decreased hip fracture rate

Manson JE, Aragaki AK, Rossouw JE, et al; WHI Investigators. Menopausal hormone therapy and long-term all-cause and cause-specific mortality: the Women’s Health Initiative randomized trials. JAMA. 2017;318:927-938.

Manson and colleagues examined the total and cause-specific cumulative mortality of the 2 Women’s Health Initiative (WHI) hormone therapy trials. This was an observational follow-up of US multiethnic postmenopausal women aged 50 to 79 years (mean age at baseline, 63.4 years) enrolled in 2 randomized clinical trials between 1993 and 1998 and followed up through December 31, 2014. A total of 27,347 women were randomly assigned to treatment.

Treatment groups

Depending on the presence or absence of a uterus, women received conjugated equine estrogens (CEE, 0.625 mg/d) plus medroxyprogesterone acetate (MPA, 2.5 mg/d) (n = 8,506) or placebo (n = 8,102) for a median of 5.6 years or CEE alone (n = 5,310) versus placebo (n = 5,429) for a median of 7.2 years. All-cause mortality (the primary outcome) and cause-specific mortality (cardiovascular disease mortality, cancer mortality, and other major causes of mortality) were analyzed in the 2 trials pooled and in each trial individually.

All-cause and cause-specific mortality findings

Mortality follow-up was available for more than 98% of participants. During the cumulative 18-year follow-up, 7,489 deaths occurred. In the overall pooled cohort, all-cause mortality in the hormone therapy group was 27.1% compared with 27.6% in the placebo group (hazard ratio [HR], 0.99 [95% confidence interval (CI), 0.94–1.03]). In the CEE plus MPA group, the HR was 1.02 (95% CI, 0.96–1.08). For those in the CEE-alone group, the HR was 0.94 (95% CI, 0.88–1.01).

In the pooled cohort for cardiovascular mortality, the HR was 1.00 (95% CI, 0.92–1.08 [8.9% with hormone therapy vs 9.0% with placebo]). For total cancer mortality, the HR was 1.03 (95% CI, 0.95–1.12 [8.2% with hormone therapy vs 8.0% with placebo]). For other causes, the HR was 0.95 (95% CI, 0.88–1.02 [10.0% with hormone therapy vs 10.7% with placebo]). Results did not differ significantly between trials.

Key takeaway

The study authors concluded that among postmenopausal women, hormone therapy with CEE plus MPA for a median of 5.6 years or with CEE alone for a median of 7.2 years was not associated with risk of all-cause, cardiovascular, or cancer mortality during a cumulative follow-up of 18 years.

Continue to: Appropriate to defer DXA testing to age 65...

Gourlay ML, Overman RA, Fine JP, et al; Women’s Health Initiative Investigators. Time to clinically relevant fracture risk scores in postmenopausal women. Am J Med. 2017;130:862.e15-862.e23.

Gourlay ML, Fine JP, Preisser JS, et al; Study of Osteoporotic Fractures Research Group. Bone-density testing interval and transition to osteoporosis in older women. N Engl J Med. 2012;366:225-233.

Many clinicians used to (and still do) order bone mineral density (BMD) testing at 23-month intervals because that was what insurance would allow. Gourlay and colleagues previously published a study on BMD testing intervals and the time it takes to develop osteoporosis. I covered that information in previous Updates.^4,5

To recap, Gourlay and colleagues studied 4,957 women, 67 years of age or older, with normal BMD or osteopenia and with no history of hip or clinical vertebral fracture or of treatment for osteoporosis; the women were followed prospectively for up to 15 years. The estimated time for 10% of women to make the transition to osteoporosis was 16.8 years for those with normal BMD, 4.7 years for those with moderate osteopenia, and 1.1 years for women with advanced osteopenia.

Today, FRAX is recommended to assess need for treatment

Older treatment recommendations involved determining various osteopenic BMD levels and the presence or absence of certain risk factors. More recently, the National Osteoporosis Foundation and many medical societies, including the American College of Obstetricians and Gynecologists, have recommended using the FRAX fracture prediction algorithm (available at https://www.sheffield.ac.uk/FRAX/) instead of T-scores to consider initiating pharmacotherapy.

The FRAX calculation tool uses information such as the country where the patient lives, age, sex, height, weight, history of previous fracture, parental fracture, current smoking, glucocorticoid use, rheumatoid arthritis, secondary osteoporosis, alcohol use of 3 or more units per day, and, if available, BMD determination at the femoral neck. It then yields the 10-year absolute risk of hip fracture and any major osteoporotic fracture for that individual or, more precisely, for an individual like that.

In the United States, accepted levels for cost-effective pharmacotherapy are a 10-year absolute risk of hip fracture of 3% or major osteoporotic fracture of 20%.

Continue to: Age also is a key factor in fracture risk assessment

Gourlay and colleagues more recently conducted a retrospective analysis of new occurrence of treatment-level fracture risk scores in postmenopausal women (50 years of age and older) before they received pharmacologic treatment and before they experienced a first hip or clinical vertebral fracture.

In 54,280 postmenopausal women aged 50 to 64 without a BMD test, the time for 10% to develop a treatment-level FRAX score could not be estimated accurately because of the rarity of treatment-level scores. In 6,096 women who had FRAX scores calculated with their BMD score, the estimated time to treatment-level FRAX was 7.6 years for those 65 to 69 and 5.1 years for 75 to 79 year olds. Furthermore, of 17,967 women aged 50 to 64 with a screening-level FRAX at baseline, only 100 (0.6%) experienced a hip or clinical vertebral fracture by age 65.

The investigators concluded that, “Postmenopausal women with sub-threshold fracture risk scores at baseline were unlikely to develop a treatment-level FRAX score between ages 50 and 64 years. After age 65, the increased incidence of treatment-level fracture risk scores, osteoporosis, and major osteoporotic fracture supports more frequent consideration of FRAX and bone mineral density testing.”

Continue to: USPSTF offers updated recommendations for osteoporosis screening

US Preventive Services Task Force, Curry SJ, Krist AH, Owens DK, et al. Screening for osteoporosis to prevent fractures: US Preventive Services Task Force recommendation statement. JAMA. 2018;319:2521-2531.

The 2018 updated osteoporosis screening recommendations from the United States Preventative Services Task Force (USPSTF) may seem contradictory to the conclusions of Gourlay and colleagues discussed above. They are not.

The USPSTF authors point out that by 2020, about 12.3 million US individuals older than 50 years are expected to have osteoporosis. Osteoporotic fractures (especially hip fractures) are associated with limitations in ambulation, chronic pain and disability, loss of independence, and decreased quality of life. In fact, 21% to 30% of people who sustain a hip fracture die within 1 year. As the US population continues to age, the potential preventable burden will likely increase.

_

Evidence on bone measurement tests, risk assessment tools, and drug therapy efficacy

The USPSTF conducted an evidence review on screening for and treatment of osteoporotic fractures in women as well as risk assessment tools. The task force found the evidence convincing that bone measurement tests are accurate for detecting osteoporosis and predicting osteoporotic fractures. In addition, there is adequate evidence that clinical risk assessment tools are moderately accurate in identifying risk of osteoporosis and osteoporotic fractures. Furthermore, there is convincing evidence that drug therapies reduce subsequent fracture rates in postmenopausal women.

The USPSTF recommends the following:

• For women aged 65 and older, screen for osteoporosis with bone measurement testing to prevent osteoporotic fractures.
• For women younger than 65 who are at increased risk for osteoporosis based on formal clinical risk assessment tools, screen for osteoporosis with bone measurement testing to prevent osteoporotic fractures.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Women who have a healthier lifestyle during the menopausal transition could significantly reduce their risk of cardiovascular disease, new research suggests.

kali9/E+

Because women experience a steeper increase in CVD risk during and after the menopausal transition, researchers analyzed data from the Study of Women’s Health Across the Nation (SWAN), a prospective longitudinal cohort study of 1,143 women aged 42-52 years. The report is in JAHA: Journal of the American Heart Association.

The analysis revealed that women with the highest average Healthy Lifestyle Score – a composite score of dietary quality, levels of physical activity, and smoking – over 10 years of follow-up had a 0.024-mm smaller common carotid artery intima-media thickness and 0.16-mm smaller adventitial diameter, compared to those with the lowest average score. This was after adjustment for confounders and physiological risk factors such as ethnicity, age, menopausal status, body mass index, and cholesterol levels.

“Smoking, unhealthy diet, and lack of physical activity are three well-known modifiable behavioral risk factors for CVD,” wrote Dongqing Wang of the University of Michigan, Ann Arbor, and his coauthors. “Even after adjusting for the lifestyle-related physiological risk factors, the adherence to a healthy lifestyle composed of abstinence from smoking, healthy diet, and regular engagement in physical activity is inversely associated with atherosclerosis in midlife women.”

Women with higher average health lifestyle score also had lower levels of carotid plaque after adjustment for confounding factors, but this was no longer significant after adjustment for physiological risk factors.

The authors analyzed the three components of the healthy lifestyle score separately, and found that not smoking was strongly and significantly associated with lower scores for all three measures of subclinical atherosclerosis. Women who never smoked across the duration of the study had a 49% lower odds of having a high carotid plaque index compared with women who smoked at some point during the follow-up period.

The analysis showed an inverse association between average Alternate Healthy Eating Index score – a measure of diet quality – and smaller common carotid artery adventitial diameter, although after adjustment for BMI this association was no longer statistically significant. Likewise, the association between dietary quality and intima-media thickness was only marginally significant and lost that significance after adjustment for BMI.

Long-term physical activity was only marginally significantly associated with common carotid artery intima-media thickness, but this was not significant after adjustment for physiological risk factors. No association was found between physical activity and common carotid artery adventitial diameter or carotid plaque.

The authors said that 1.7% of the study population managed to stay in the top category for all three components of healthy lifestyle at all three follow-up time points in the study.

“The low prevalence of a healthy lifestyle in midlife women highlights the potential for lifestyle interventions aimed at this vulnerable population,” they wrote.

In particular, they highlighted abstinence from smoking as having the strongest impact on all three measures of subclinical atherosclerosis, which is known to affect women more than men. However, the outcomes from diet and physical activity weren’t so strong: The authors suggested that BMI could partly mediate the effects of healthier diet and greater levels of physical activity.

One strength of the study was its ethnically diverse population, which included African American, Chinese, and Hispanic women in addition to non-Hispanic white women. However, the study was not powered to examine the impacts ethnicity may have had on outcomes, the researchers wrote.

The Study of Women’s Health Across the Nation is supported by the National Institutes of Health. No conflicts of interest were declared.

SOURCE: Wang D et al. JAHA 2018 Nov. 28.

Women who have a healthier lifestyle during the menopausal transition could significantly reduce their risk of cardiovascular disease, new research suggests.

kali9/E+

Because women experience a steeper increase in CVD risk during and after the menopausal transition, researchers analyzed data from the Study of Women’s Health Across the Nation (SWAN), a prospective longitudinal cohort study of 1,143 women aged 42-52 years. The report is in JAHA: Journal of the American Heart Association.

The analysis revealed that women with the highest average Healthy Lifestyle Score – a composite score of dietary quality, levels of physical activity, and smoking – over 10 years of follow-up had a 0.024-mm smaller common carotid artery intima-media thickness and 0.16-mm smaller adventitial diameter, compared to those with the lowest average score. This was after adjustment for confounders and physiological risk factors such as ethnicity, age, menopausal status, body mass index, and cholesterol levels.

“Smoking, unhealthy diet, and lack of physical activity are three well-known modifiable behavioral risk factors for CVD,” wrote Dongqing Wang of the University of Michigan, Ann Arbor, and his coauthors. “Even after adjusting for the lifestyle-related physiological risk factors, the adherence to a healthy lifestyle composed of abstinence from smoking, healthy diet, and regular engagement in physical activity is inversely associated with atherosclerosis in midlife women.”

Women with higher average health lifestyle score also had lower levels of carotid plaque after adjustment for confounding factors, but this was no longer significant after adjustment for physiological risk factors.

The authors analyzed the three components of the healthy lifestyle score separately, and found that not smoking was strongly and significantly associated with lower scores for all three measures of subclinical atherosclerosis. Women who never smoked across the duration of the study had a 49% lower odds of having a high carotid plaque index compared with women who smoked at some point during the follow-up period.

The analysis showed an inverse association between average Alternate Healthy Eating Index score – a measure of diet quality – and smaller common carotid artery adventitial diameter, although after adjustment for BMI this association was no longer statistically significant. Likewise, the association between dietary quality and intima-media thickness was only marginally significant and lost that significance after adjustment for BMI.

Long-term physical activity was only marginally significantly associated with common carotid artery intima-media thickness, but this was not significant after adjustment for physiological risk factors. No association was found between physical activity and common carotid artery adventitial diameter or carotid plaque.

The authors said that 1.7% of the study population managed to stay in the top category for all three components of healthy lifestyle at all three follow-up time points in the study.

“The low prevalence of a healthy lifestyle in midlife women highlights the potential for lifestyle interventions aimed at this vulnerable population,” they wrote.

In particular, they highlighted abstinence from smoking as having the strongest impact on all three measures of subclinical atherosclerosis, which is known to affect women more than men. However, the outcomes from diet and physical activity weren’t so strong: The authors suggested that BMI could partly mediate the effects of healthier diet and greater levels of physical activity.

One strength of the study was its ethnically diverse population, which included African American, Chinese, and Hispanic women in addition to non-Hispanic white women. However, the study was not powered to examine the impacts ethnicity may have had on outcomes, the researchers wrote.

The Study of Women’s Health Across the Nation is supported by the National Institutes of Health. No conflicts of interest were declared.

SOURCE: Wang D et al. JAHA 2018 Nov. 28.

Women who have a healthier lifestyle during the menopausal transition could significantly reduce their risk of cardiovascular disease, new research suggests.

kali9/E+

Because women experience a steeper increase in CVD risk during and after the menopausal transition, researchers analyzed data from the Study of Women’s Health Across the Nation (SWAN), a prospective longitudinal cohort study of 1,143 women aged 42-52 years. The report is in JAHA: Journal of the American Heart Association.

The analysis revealed that women with the highest average Healthy Lifestyle Score – a composite score of dietary quality, levels of physical activity, and smoking – over 10 years of follow-up had a 0.024-mm smaller common carotid artery intima-media thickness and 0.16-mm smaller adventitial diameter, compared to those with the lowest average score. This was after adjustment for confounders and physiological risk factors such as ethnicity, age, menopausal status, body mass index, and cholesterol levels.

“Smoking, unhealthy diet, and lack of physical activity are three well-known modifiable behavioral risk factors for CVD,” wrote Dongqing Wang of the University of Michigan, Ann Arbor, and his coauthors. “Even after adjusting for the lifestyle-related physiological risk factors, the adherence to a healthy lifestyle composed of abstinence from smoking, healthy diet, and regular engagement in physical activity is inversely associated with atherosclerosis in midlife women.”

Women with higher average health lifestyle score also had lower levels of carotid plaque after adjustment for confounding factors, but this was no longer significant after adjustment for physiological risk factors.

The authors analyzed the three components of the healthy lifestyle score separately, and found that not smoking was strongly and significantly associated with lower scores for all three measures of subclinical atherosclerosis. Women who never smoked across the duration of the study had a 49% lower odds of having a high carotid plaque index compared with women who smoked at some point during the follow-up period.

The analysis showed an inverse association between average Alternate Healthy Eating Index score – a measure of diet quality – and smaller common carotid artery adventitial diameter, although after adjustment for BMI this association was no longer statistically significant. Likewise, the association between dietary quality and intima-media thickness was only marginally significant and lost that significance after adjustment for BMI.

Long-term physical activity was only marginally significantly associated with common carotid artery intima-media thickness, but this was not significant after adjustment for physiological risk factors. No association was found between physical activity and common carotid artery adventitial diameter or carotid plaque.

The authors said that 1.7% of the study population managed to stay in the top category for all three components of healthy lifestyle at all three follow-up time points in the study.

“The low prevalence of a healthy lifestyle in midlife women highlights the potential for lifestyle interventions aimed at this vulnerable population,” they wrote.

In particular, they highlighted abstinence from smoking as having the strongest impact on all three measures of subclinical atherosclerosis, which is known to affect women more than men. However, the outcomes from diet and physical activity weren’t so strong: The authors suggested that BMI could partly mediate the effects of healthier diet and greater levels of physical activity.

One strength of the study was its ethnically diverse population, which included African American, Chinese, and Hispanic women in addition to non-Hispanic white women. However, the study was not powered to examine the impacts ethnicity may have had on outcomes, the researchers wrote.

The Study of Women’s Health Across the Nation is supported by the National Institutes of Health. No conflicts of interest were declared.

SOURCE: Wang D et al. JAHA 2018 Nov. 28.

Intimate partner violence or sexual assault may have a significant effect on menopausal symptoms in women, according to a cohort study published in JAMA Internal Medicine.

Karen Winton/iStockphoto

Researchers analyzed data from 2,016 women aged 40 years or older who were enrolled in the observational Reproductive Risks of Incontinence Study; 40% were non-Latina white, 21% were black, 20% were Latina or Hispanic, and 19% were Asian. Of this cohort, 21% had experienced emotional intimate partner violence (IPV) – 64 (3.2%) in the past 12 months – 16% had experienced physical IPV, 14% had experienced both, and 19% reported sexual assault. More than one in five women (23%) met the criteria for clinically significant PTSD.

Women who had experienced emotional domestic abuse were 36% more likely to report difficulty sleeping, 50% more like to experience night sweats, and 60% more likely to experience pain with intercourse, compared with women who had not experienced any abuse.

Physical abuse was associated with 33% higher odds of night sweats, and sexual assault was associated with 41% higher odds of vaginal dryness, 42% higher odds of vaginal irritation, and 44% higher odds of pain with intercourse.

Women with clinically significant PTSD symptoms were significantly more likely to experience all the symptoms of menopause, including twofold higher odds of pain with intercourse and threefold higher odds of difficulty sleeping. When authors accounted for the effect of PTSD symptoms in the cohort, they found that only the association between emotional abuse and night sweats or pain with intercourse, and between sexual assault and vaginal dryness, remained independently significant.

Carolyn J. Gibson, PhD, MPH, of the San Francisco Veterans Affairs Health Care System, and coauthors said that the biological and hormonal changes that underpin menopausal symptoms, as well as health risk behaviors, cardiometabolic risk factors, and other chronic health conditions associated with menopause, all are impacted by trauma and its psychological effects.

“Chronic hyperarousal and hypervigilance, common in individuals who have experienced trauma and characteristic symptoms of PTSD, may affect sleep and symptom sensitivity,” they wrote.

The reverse is also true; that the symptoms of menopause can impact the symptoms of PTSD by affecting a woman’s sense of self-efficacy, interpersonal engagements, and heighten the stress associated with this period of transition.

“The clinical management of menopause symptoms may also be enhanced by trauma-informed care, including recognition of challenges that may impair efforts to address menopause-related concerns among women affected by trauma,” the authors wrote.

Clinicians also could help by providing education about the link between trauma and health, providing their patients with a safe and supportive treatment environment, and facilitating referrals for psychological or trauma-specific services when needed, they said.

The research was supported by the San Francisco Veterans Affairs Medical Center and Kaiser Permanente Northern California, and funded by the University of California San Francisco–Kaiser Permanente Grants Program for Delivery Science, the Office of Research on Women’s Health Specialized Center of Research, and grants from the National Institute of Diabetes and Digestive and Kidney Diseases.

SOURCE: Gibson C et al. JAMA Intern Med. 2018 Nov 19. doi: 10.1001/jamainternmed.2018.5233.

Intimate partner violence or sexual assault may have a significant effect on menopausal symptoms in women, according to a cohort study published in JAMA Internal Medicine.

Karen Winton/iStockphoto

Researchers analyzed data from 2,016 women aged 40 years or older who were enrolled in the observational Reproductive Risks of Incontinence Study; 40% were non-Latina white, 21% were black, 20% were Latina or Hispanic, and 19% were Asian. Of this cohort, 21% had experienced emotional intimate partner violence (IPV) – 64 (3.2%) in the past 12 months – 16% had experienced physical IPV, 14% had experienced both, and 19% reported sexual assault. More than one in five women (23%) met the criteria for clinically significant PTSD.

Women who had experienced emotional domestic abuse were 36% more likely to report difficulty sleeping, 50% more like to experience night sweats, and 60% more likely to experience pain with intercourse, compared with women who had not experienced any abuse.

Physical abuse was associated with 33% higher odds of night sweats, and sexual assault was associated with 41% higher odds of vaginal dryness, 42% higher odds of vaginal irritation, and 44% higher odds of pain with intercourse.

Women with clinically significant PTSD symptoms were significantly more likely to experience all the symptoms of menopause, including twofold higher odds of pain with intercourse and threefold higher odds of difficulty sleeping. When authors accounted for the effect of PTSD symptoms in the cohort, they found that only the association between emotional abuse and night sweats or pain with intercourse, and between sexual assault and vaginal dryness, remained independently significant.

Carolyn J. Gibson, PhD, MPH, of the San Francisco Veterans Affairs Health Care System, and coauthors said that the biological and hormonal changes that underpin menopausal symptoms, as well as health risk behaviors, cardiometabolic risk factors, and other chronic health conditions associated with menopause, all are impacted by trauma and its psychological effects.

“Chronic hyperarousal and hypervigilance, common in individuals who have experienced trauma and characteristic symptoms of PTSD, may affect sleep and symptom sensitivity,” they wrote.

The reverse is also true; that the symptoms of menopause can impact the symptoms of PTSD by affecting a woman’s sense of self-efficacy, interpersonal engagements, and heighten the stress associated with this period of transition.

“The clinical management of menopause symptoms may also be enhanced by trauma-informed care, including recognition of challenges that may impair efforts to address menopause-related concerns among women affected by trauma,” the authors wrote.

Clinicians also could help by providing education about the link between trauma and health, providing their patients with a safe and supportive treatment environment, and facilitating referrals for psychological or trauma-specific services when needed, they said.

The research was supported by the San Francisco Veterans Affairs Medical Center and Kaiser Permanente Northern California, and funded by the University of California San Francisco–Kaiser Permanente Grants Program for Delivery Science, the Office of Research on Women’s Health Specialized Center of Research, and grants from the National Institute of Diabetes and Digestive and Kidney Diseases.

SOURCE: Gibson C et al. JAMA Intern Med. 2018 Nov 19. doi: 10.1001/jamainternmed.2018.5233.

Intimate partner violence or sexual assault may have a significant effect on menopausal symptoms in women, according to a cohort study published in JAMA Internal Medicine.

Karen Winton/iStockphoto

Researchers analyzed data from 2,016 women aged 40 years or older who were enrolled in the observational Reproductive Risks of Incontinence Study; 40% were non-Latina white, 21% were black, 20% were Latina or Hispanic, and 19% were Asian. Of this cohort, 21% had experienced emotional intimate partner violence (IPV) – 64 (3.2%) in the past 12 months – 16% had experienced physical IPV, 14% had experienced both, and 19% reported sexual assault. More than one in five women (23%) met the criteria for clinically significant PTSD.

Women who had experienced emotional domestic abuse were 36% more likely to report difficulty sleeping, 50% more like to experience night sweats, and 60% more likely to experience pain with intercourse, compared with women who had not experienced any abuse.

Physical abuse was associated with 33% higher odds of night sweats, and sexual assault was associated with 41% higher odds of vaginal dryness, 42% higher odds of vaginal irritation, and 44% higher odds of pain with intercourse.

Women with clinically significant PTSD symptoms were significantly more likely to experience all the symptoms of menopause, including twofold higher odds of pain with intercourse and threefold higher odds of difficulty sleeping. When authors accounted for the effect of PTSD symptoms in the cohort, they found that only the association between emotional abuse and night sweats or pain with intercourse, and between sexual assault and vaginal dryness, remained independently significant.

Carolyn J. Gibson, PhD, MPH, of the San Francisco Veterans Affairs Health Care System, and coauthors said that the biological and hormonal changes that underpin menopausal symptoms, as well as health risk behaviors, cardiometabolic risk factors, and other chronic health conditions associated with menopause, all are impacted by trauma and its psychological effects.

“Chronic hyperarousal and hypervigilance, common in individuals who have experienced trauma and characteristic symptoms of PTSD, may affect sleep and symptom sensitivity,” they wrote.

The reverse is also true; that the symptoms of menopause can impact the symptoms of PTSD by affecting a woman’s sense of self-efficacy, interpersonal engagements, and heighten the stress associated with this period of transition.

“The clinical management of menopause symptoms may also be enhanced by trauma-informed care, including recognition of challenges that may impair efforts to address menopause-related concerns among women affected by trauma,” the authors wrote.

Clinicians also could help by providing education about the link between trauma and health, providing their patients with a safe and supportive treatment environment, and facilitating referrals for psychological or trauma-specific services when needed, they said.

The research was supported by the San Francisco Veterans Affairs Medical Center and Kaiser Permanente Northern California, and funded by the University of California San Francisco–Kaiser Permanente Grants Program for Delivery Science, the Office of Research on Women’s Health Specialized Center of Research, and grants from the National Institute of Diabetes and Digestive and Kidney Diseases.

SOURCE: Gibson C et al. JAMA Intern Med. 2018 Nov 19. doi: 10.1001/jamainternmed.2018.5233.