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VIDEO: Stem cells may reverse premature menopause, restore fertility
CHICAGO –
Neither of the women had menstruated for about 5 years; both were in premature menopause and wanted desperately to start a family. Estrogen levels began increasing soon after treatment, and night sweats and other symptoms of menopause almost disappeared. After a year, the treated ovary was almost the size of a normal premenopausal ovary. There weren’t any complications or side effects, and both women are now pursuing pregnancy.
The results are “very exciting, very encouraging,” said senior investigator Ayman Al-Hendy, MD, PhD, a gynecology professor at the University of Illinois at Chicago.
“The eggs are there, but they are not active.” Something about the stem cells seems “to activate these eggs to become fertilizable,” he said.
Far more work is planned on the project, and there’s no shortage of volunteers; premature menopause is a devastating diagnosis to young women hoping to start families.
Dr. Al-Hendy explained the procedure and the next steps in a video interview at the Endocrine Society annual meeting.
The work is supported by MD Stem Cells and the National Institutes of Health. Dr. Al-Hendy didn’t have any relevant disclosures.
SOURCE: Al-Hendy A et al. ENDO 2018, Abstract OR33-6.
CHICAGO –
Neither of the women had menstruated for about 5 years; both were in premature menopause and wanted desperately to start a family. Estrogen levels began increasing soon after treatment, and night sweats and other symptoms of menopause almost disappeared. After a year, the treated ovary was almost the size of a normal premenopausal ovary. There weren’t any complications or side effects, and both women are now pursuing pregnancy.
The results are “very exciting, very encouraging,” said senior investigator Ayman Al-Hendy, MD, PhD, a gynecology professor at the University of Illinois at Chicago.
“The eggs are there, but they are not active.” Something about the stem cells seems “to activate these eggs to become fertilizable,” he said.
Far more work is planned on the project, and there’s no shortage of volunteers; premature menopause is a devastating diagnosis to young women hoping to start families.
Dr. Al-Hendy explained the procedure and the next steps in a video interview at the Endocrine Society annual meeting.
The work is supported by MD Stem Cells and the National Institutes of Health. Dr. Al-Hendy didn’t have any relevant disclosures.
SOURCE: Al-Hendy A et al. ENDO 2018, Abstract OR33-6.
CHICAGO –
Neither of the women had menstruated for about 5 years; both were in premature menopause and wanted desperately to start a family. Estrogen levels began increasing soon after treatment, and night sweats and other symptoms of menopause almost disappeared. After a year, the treated ovary was almost the size of a normal premenopausal ovary. There weren’t any complications or side effects, and both women are now pursuing pregnancy.
The results are “very exciting, very encouraging,” said senior investigator Ayman Al-Hendy, MD, PhD, a gynecology professor at the University of Illinois at Chicago.
“The eggs are there, but they are not active.” Something about the stem cells seems “to activate these eggs to become fertilizable,” he said.
Far more work is planned on the project, and there’s no shortage of volunteers; premature menopause is a devastating diagnosis to young women hoping to start families.
Dr. Al-Hendy explained the procedure and the next steps in a video interview at the Endocrine Society annual meeting.
The work is supported by MD Stem Cells and the National Institutes of Health. Dr. Al-Hendy didn’t have any relevant disclosures.
SOURCE: Al-Hendy A et al. ENDO 2018, Abstract OR33-6.
REPORTING FROM ENDO 2018
Menopause accelerates RA functional decline
Rheumatoid arthritis gets worse after menopause, likely because of lower hormone levels, according to a review of 8,189 women in the National Data Bank for Rheumatic Diseases, published recently in Rheumatology.
The investigators compared scores on the Health Assessment Questionnaire (HAQ) between 2,005 premenopausal women with a mean age of 39.7 years; 611 women transitioning through menopause with a mean age of 50.7 years, and 5,573 postmenopausal women with a mean age of 62.3 years. As participants in the data bank, the women completed a questionnaire at regular intervals that included the HAQ, which is a 3-point measure of functional status, with 0 meaning no disability and 3 severe disability. They had all been diagnosed with rheumatoid arthritis prior to menopause.
“Women with RA have better functional status prior to menopause, even after controlling for covariates,” and after menopause, functional decline worsens and accelerates, said investigators led by Elizabeth Mollard, PhD, a nurse practitioner at the University of Nebraska Medical Center, Lincoln. The findings were “robust even after adjustment for other significant factors.”
The team also found that functional decline was less in women who had a longer reproductive life; had ever been pregnant; or had ever used hormone replacement therapy (HRT).
The findings support the notion that hormone exposure plays a role in RA severity, at least in women. It’s well known that RA activity trails off when women are pregnant, but increases after delivery, when hormone levels are returning to baseline. It’s also known that women who go through menopause early are at greater risk for developing RA. Longer reproductive life, pregnancy, and HRT use, meanwhile, all increase women’s hormonal exposure and were protective in the study.
“Women have changes in disease development and progression surrounding reproductive and hormonal events. ... Our results suggest further study on hormonal involvement in functional decline in women with RA,” the investigators said.
Menopausal stage was determined by survey response. Pregnant women and those with hysterectomies were excluded from the study, as were those who went through menopause before the age of 40 years, and those over the age of 55 who had not reported a menstruation cessation date.
There was no external funding for the work. Dr. Mollard had no disclosures.
SOURCE: Mollard E et. al. Rheumatology. 2018 Jan 29. doi: 10.1093/rheumatology/kex526
Rheumatoid arthritis gets worse after menopause, likely because of lower hormone levels, according to a review of 8,189 women in the National Data Bank for Rheumatic Diseases, published recently in Rheumatology.
The investigators compared scores on the Health Assessment Questionnaire (HAQ) between 2,005 premenopausal women with a mean age of 39.7 years; 611 women transitioning through menopause with a mean age of 50.7 years, and 5,573 postmenopausal women with a mean age of 62.3 years. As participants in the data bank, the women completed a questionnaire at regular intervals that included the HAQ, which is a 3-point measure of functional status, with 0 meaning no disability and 3 severe disability. They had all been diagnosed with rheumatoid arthritis prior to menopause.
“Women with RA have better functional status prior to menopause, even after controlling for covariates,” and after menopause, functional decline worsens and accelerates, said investigators led by Elizabeth Mollard, PhD, a nurse practitioner at the University of Nebraska Medical Center, Lincoln. The findings were “robust even after adjustment for other significant factors.”
The team also found that functional decline was less in women who had a longer reproductive life; had ever been pregnant; or had ever used hormone replacement therapy (HRT).
The findings support the notion that hormone exposure plays a role in RA severity, at least in women. It’s well known that RA activity trails off when women are pregnant, but increases after delivery, when hormone levels are returning to baseline. It’s also known that women who go through menopause early are at greater risk for developing RA. Longer reproductive life, pregnancy, and HRT use, meanwhile, all increase women’s hormonal exposure and were protective in the study.
“Women have changes in disease development and progression surrounding reproductive and hormonal events. ... Our results suggest further study on hormonal involvement in functional decline in women with RA,” the investigators said.
Menopausal stage was determined by survey response. Pregnant women and those with hysterectomies were excluded from the study, as were those who went through menopause before the age of 40 years, and those over the age of 55 who had not reported a menstruation cessation date.
There was no external funding for the work. Dr. Mollard had no disclosures.
SOURCE: Mollard E et. al. Rheumatology. 2018 Jan 29. doi: 10.1093/rheumatology/kex526
Rheumatoid arthritis gets worse after menopause, likely because of lower hormone levels, according to a review of 8,189 women in the National Data Bank for Rheumatic Diseases, published recently in Rheumatology.
The investigators compared scores on the Health Assessment Questionnaire (HAQ) between 2,005 premenopausal women with a mean age of 39.7 years; 611 women transitioning through menopause with a mean age of 50.7 years, and 5,573 postmenopausal women with a mean age of 62.3 years. As participants in the data bank, the women completed a questionnaire at regular intervals that included the HAQ, which is a 3-point measure of functional status, with 0 meaning no disability and 3 severe disability. They had all been diagnosed with rheumatoid arthritis prior to menopause.
“Women with RA have better functional status prior to menopause, even after controlling for covariates,” and after menopause, functional decline worsens and accelerates, said investigators led by Elizabeth Mollard, PhD, a nurse practitioner at the University of Nebraska Medical Center, Lincoln. The findings were “robust even after adjustment for other significant factors.”
The team also found that functional decline was less in women who had a longer reproductive life; had ever been pregnant; or had ever used hormone replacement therapy (HRT).
The findings support the notion that hormone exposure plays a role in RA severity, at least in women. It’s well known that RA activity trails off when women are pregnant, but increases after delivery, when hormone levels are returning to baseline. It’s also known that women who go through menopause early are at greater risk for developing RA. Longer reproductive life, pregnancy, and HRT use, meanwhile, all increase women’s hormonal exposure and were protective in the study.
“Women have changes in disease development and progression surrounding reproductive and hormonal events. ... Our results suggest further study on hormonal involvement in functional decline in women with RA,” the investigators said.
Menopausal stage was determined by survey response. Pregnant women and those with hysterectomies were excluded from the study, as were those who went through menopause before the age of 40 years, and those over the age of 55 who had not reported a menstruation cessation date.
There was no external funding for the work. Dr. Mollard had no disclosures.
SOURCE: Mollard E et. al. Rheumatology. 2018 Jan 29. doi: 10.1093/rheumatology/kex526
FROM RHEUMATOLOGY
Key clinical point:
Major finding: HAQ scores were 0.68 points higher in postmenopausal women, compared with premenopausal women of the same age.
Study details: Review of 8,189 women in the National Data Bank for Rheumatic Diseases.
Disclosures: There was no external funding for the work. The lead investigator had no disclosures.
Source: Mollard E et. al. Rheumatology. 2018 Jan 29. doi: 10.1093/rheumatology/kex526
Hormone therapy may reduce depressive symptoms in early menopause
Hormone therapy may reduce the likelihood of depressive symptoms during early menopause, according to data from a placebo-controlled study published online Jan. 10 in JAMA Psychiatry.
Researchers randomized 172 medically healthy women who were perimenopausal or early postmenopausal to either patches of 0.1 mg of 17 beta-estradiol or placebo patches for 12 months, as well as oral micronized progesterone or placebo every 2-3 months.
Women in the placebo arm were more than twice as likely to score at least 16 on the Center for Epidemiologic Studies–Depression Scale (CES-D) at least once during the study, compared with women in the hormone therapy arm (32.3% vs. 17.3%; odds ratio, 2.5; 95% confidence interval, 1.1-5.7; P = .03). They also scored at least 16 on the scale during more visits than did women in the intervention arm (P = .002).
Women who received placebo had a significantly higher mean CES-D score over the course of the 12-month study, compared with those in the intervention arm. At 6 months, mean unadjusted CES-D scores were 5.6 in the placebo group and 4.2 in the intervention group. At 12 months, the scores were 5.7 and 4 respectively.
“Importantly, these results were significant despite statistically adjusting for change in vasomotor symptom bother, suggesting that TE+IMP [transdermal estradiol + intermittent micronized progesterone] has direct prophylactic mood benefits that are independent from its beneficial effects on menopausal symptoms, as previously observed in women with major depressive disorder treated with TE+IMP,” wrote Jennifer L. Gordon, PhD, of the psychology department at the University of Regina, Saskatchewan, and her associates.
The effect of hormone therapy on depression scores changed significantly depending on the women’s stage of menopause. Women in the early menopause transition experienced significant mood benefits, but women in the late menopause transition and those who were postmenopausal did not.
Treatment effects also were influenced by stress, as women who reported experiencing more stressful life events in the 6 months before enrolling in the study showed greater mood benefits than did those with fewer stressful life events.
However, baseline estradiol levels, baseline vasomotor symptoms, history of depression, and history of abuse did not significantly change the effects of treatment.
, compared with the placebo group, and one woman in the treatment group experienced acute deep vein thrombosis that led her to stop treatment and receive medical care. Two cases of major depressive disorder were noted in the placebo group.
Dr. Gordon and her associates cited several limitations. For example, they said, the active and placebo patches used in the study were not identical. “However, our findings remain significant when adjusting for participants’ beliefs about their treatment condition,” they wrote.
The study was supported by the National Institutes of Health, and one author was supported by a fellowship of the Fonds de la Recherche du Québec–Santé. No conflicts of interest were declared.
SOURCE: Gordon JL et al. JAMA Psychiatry. 2018 Jan 10. doi: 1010/jamapsychiatry.2018.3998.
Hormone therapy may reduce the likelihood of depressive symptoms during early menopause, according to data from a placebo-controlled study published online Jan. 10 in JAMA Psychiatry.
Researchers randomized 172 medically healthy women who were perimenopausal or early postmenopausal to either patches of 0.1 mg of 17 beta-estradiol or placebo patches for 12 months, as well as oral micronized progesterone or placebo every 2-3 months.
Women in the placebo arm were more than twice as likely to score at least 16 on the Center for Epidemiologic Studies–Depression Scale (CES-D) at least once during the study, compared with women in the hormone therapy arm (32.3% vs. 17.3%; odds ratio, 2.5; 95% confidence interval, 1.1-5.7; P = .03). They also scored at least 16 on the scale during more visits than did women in the intervention arm (P = .002).
Women who received placebo had a significantly higher mean CES-D score over the course of the 12-month study, compared with those in the intervention arm. At 6 months, mean unadjusted CES-D scores were 5.6 in the placebo group and 4.2 in the intervention group. At 12 months, the scores were 5.7 and 4 respectively.
“Importantly, these results were significant despite statistically adjusting for change in vasomotor symptom bother, suggesting that TE+IMP [transdermal estradiol + intermittent micronized progesterone] has direct prophylactic mood benefits that are independent from its beneficial effects on menopausal symptoms, as previously observed in women with major depressive disorder treated with TE+IMP,” wrote Jennifer L. Gordon, PhD, of the psychology department at the University of Regina, Saskatchewan, and her associates.
The effect of hormone therapy on depression scores changed significantly depending on the women’s stage of menopause. Women in the early menopause transition experienced significant mood benefits, but women in the late menopause transition and those who were postmenopausal did not.
Treatment effects also were influenced by stress, as women who reported experiencing more stressful life events in the 6 months before enrolling in the study showed greater mood benefits than did those with fewer stressful life events.
However, baseline estradiol levels, baseline vasomotor symptoms, history of depression, and history of abuse did not significantly change the effects of treatment.
, compared with the placebo group, and one woman in the treatment group experienced acute deep vein thrombosis that led her to stop treatment and receive medical care. Two cases of major depressive disorder were noted in the placebo group.
Dr. Gordon and her associates cited several limitations. For example, they said, the active and placebo patches used in the study were not identical. “However, our findings remain significant when adjusting for participants’ beliefs about their treatment condition,” they wrote.
The study was supported by the National Institutes of Health, and one author was supported by a fellowship of the Fonds de la Recherche du Québec–Santé. No conflicts of interest were declared.
SOURCE: Gordon JL et al. JAMA Psychiatry. 2018 Jan 10. doi: 1010/jamapsychiatry.2018.3998.
Hormone therapy may reduce the likelihood of depressive symptoms during early menopause, according to data from a placebo-controlled study published online Jan. 10 in JAMA Psychiatry.
Researchers randomized 172 medically healthy women who were perimenopausal or early postmenopausal to either patches of 0.1 mg of 17 beta-estradiol or placebo patches for 12 months, as well as oral micronized progesterone or placebo every 2-3 months.
Women in the placebo arm were more than twice as likely to score at least 16 on the Center for Epidemiologic Studies–Depression Scale (CES-D) at least once during the study, compared with women in the hormone therapy arm (32.3% vs. 17.3%; odds ratio, 2.5; 95% confidence interval, 1.1-5.7; P = .03). They also scored at least 16 on the scale during more visits than did women in the intervention arm (P = .002).
Women who received placebo had a significantly higher mean CES-D score over the course of the 12-month study, compared with those in the intervention arm. At 6 months, mean unadjusted CES-D scores were 5.6 in the placebo group and 4.2 in the intervention group. At 12 months, the scores were 5.7 and 4 respectively.
“Importantly, these results were significant despite statistically adjusting for change in vasomotor symptom bother, suggesting that TE+IMP [transdermal estradiol + intermittent micronized progesterone] has direct prophylactic mood benefits that are independent from its beneficial effects on menopausal symptoms, as previously observed in women with major depressive disorder treated with TE+IMP,” wrote Jennifer L. Gordon, PhD, of the psychology department at the University of Regina, Saskatchewan, and her associates.
The effect of hormone therapy on depression scores changed significantly depending on the women’s stage of menopause. Women in the early menopause transition experienced significant mood benefits, but women in the late menopause transition and those who were postmenopausal did not.
Treatment effects also were influenced by stress, as women who reported experiencing more stressful life events in the 6 months before enrolling in the study showed greater mood benefits than did those with fewer stressful life events.
However, baseline estradiol levels, baseline vasomotor symptoms, history of depression, and history of abuse did not significantly change the effects of treatment.
, compared with the placebo group, and one woman in the treatment group experienced acute deep vein thrombosis that led her to stop treatment and receive medical care. Two cases of major depressive disorder were noted in the placebo group.
Dr. Gordon and her associates cited several limitations. For example, they said, the active and placebo patches used in the study were not identical. “However, our findings remain significant when adjusting for participants’ beliefs about their treatment condition,” they wrote.
The study was supported by the National Institutes of Health, and one author was supported by a fellowship of the Fonds de la Recherche du Québec–Santé. No conflicts of interest were declared.
SOURCE: Gordon JL et al. JAMA Psychiatry. 2018 Jan 10. doi: 1010/jamapsychiatry.2018.3998.
FROM JAMA PSYCHIATRY
Key clinical point: Transdermal hormone therapy may reduce the likelihood of depressive symptoms in early menopause.
Major finding: Women who did not receive hormone therapy had more than a twofold higher likelihood of high depression scores, compared with women who were treated with transdermal estradiol.
Data source: Placebo-controlled, double-blind, randomized trial of 172 perimenopausal women.
Disclosures: The study was supported by the National Institutes of Health, and one author was supported by a fellowship of the Fonds de la Recherche du Québec–Santé. No conflicts of interest were declared.
Source: Gordon JL et al. JAMA Psychiatry. 2018 Jan 10. doi: 1010/jamapsychiatry.2018.3998.
views
The authors of this study are to be commended for conducting this randomized controlled trial to investigate the efficacy of a biologically rational strategy to prevent depressive symptoms in menopausal women, Hadine Joffe, MD, and Martha Hickey, MD, wrote in an accompanying editorial (JAMA Psychiatry. 2018 Jan 10. doi: 10.1001/jamapsychiatry.2017.3945).
The mechanisms of depression in menopause are not well understood, but increased changes in estradiol concentrations, nocturnal hot flashes, and sleep disturbance have been linked to the emergence of depressive symptoms. However, this study did not report accurate measures of hot flashes and sleep disturbance, which is important because of the central role of those symptoms in menopause associated mood disturbance.
Using hormone therapy in an effort to prevent depressive symptoms throughout perimenopause must be balanced with the adverse effects associated with extended exposure to hormone therapy, such as breast cancer. The results of this trial illustrate a potential role of hormone therapy in mood regulation, but they do not support changes in clinical guidance.
Dr. Joffe is affiliated with the Connors Center for Women’s Health and Gender Biology at Brigham and Women’s Hospital, the department of psychiatry at the hospital, and Harvard Medical School, all in Boston. Dr. Hickey is affiliated with the department of obstetrics and gynaecology at The University of Melbourne. Dr. Joffe was supported by the National Institute on Aging, and she declared research funding and consultancies from private industry, including Merck and SAGE. Dr. Hickey was supported by the Australian National Health and Medical Research Council and had no conflicts of interest to declare.
Don’t choose hormones to protect postmenopausal women
Hormone therapy should not be used to prevent chronic conditions in postmenopausal women, according to updated recommendations from the U.S. Preventive Services Task Force. The recommendations were published online Dec. 12 in JAMA.
In the latest recommendation statement, the USPSTF issued D recommendations against using combination estrogen and progestin to prevent chronic conditions in postmenopausal women and against using estrogen only to prevent chronic conditions in postmenopausal women who have undergone hysterectomies (JAMA. 2017 Dec 12. doi: 10.1001/jama.2017.18261). A grade D recommendation is defined as “The USPSTF recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits.”
In response to public comments, the USPSTF team made several changes including adjusting the language to clarify that the recommendations apply only to postmenopausal women, and adding tables showing estimates of increased or decreased risk of various outcomes for postmenopausal women receiving different hormone therapies.
Approximately 40,000 women aged 53-79 years were included in an evidence report from Gerald Gartlehner, MD, of the University of North Carolina, Chapel Hill, and his colleagues that accompanied the recommendations (JAMA. 2017 Dec 12. doi: 10.1001/jama.2017.16952).
The researchers found that women taking estrogen alone had significantly lower risk of breast cancer, diabetes, and osteoporotic fractures, but significantly higher risk of gallbladder disease, stroke, urinary incontinence, and venous thromboembolism, compared with women taking placebo. In addition, women using a combination of estrogen and progestin had significantly lower risk of colorectal cancer, diabetes, and osteoporotic fractures, but significantly higher risk of breast cancer, probable dementia, gallbladder disease, stroke, urinary incontinence, and venous thromboembolism, compared with women taking placebo.
“Hormone therapy for the primary prevention of chronic conditions in menopausal women is associated with some beneficial effects but also with a substantial increase of risks for harms,” and the current evidence for the risks and benefits of hormone therapy is inconclusive, the researchers said.
The final recommendation remains consistent with the USPSTF draft statement issued earlier in 2017 and with the final recommendation statements issued in 2012.
The researchers had no relevant financial conflicts to disclose.
Twenty-five years ago, the U.S. Preventive Services Task Force advised clinicians to consider hormone therapy for the prevention of disease in all women, particularly those at risk for coronary heart disease, Deborah Grady, MD, wrote in an editorial (JAMA Intern Med. 2017 Dec 12. doi: 10.1001/jamainternmed.2017.7861). Dr. Grady was one of the coauthors of a literature review supporting the American College of Physicians’ recommendation to counsel asymptomatic postmenopausal women about hormone therapy based on data from observational studies. “No randomized trials with clinical outcomes had been conducted,” Dr. Grady said. By 2002, data from three large randomized trials told a different story, and the Task Force recommended against using estrogen alone as a strategy to prevent chronic conditions in postmenopausal women, she noted.
“I believe that the fear of hormone therapy is overblown,” Dr. Grady wrote. “When adequately informed, women with moderate to severe symptoms and without contraindications should be able to take such small risks if hormone therapy improves symptoms and quality of life,” she said.
In fact, professional societies, including the North American Menopause Society, the American College of Obstetricians and Gynecologists, and the Endocrine Society support hormone therapy for symptomatic women who are recently menopausal, said Dr. Grady. However, a key lesson learned from the ongoing research on hormone therapy is the importance of conducting clinical trials that are large enough to identify serious adverse effects, she added.
Dr. Grady is affiliated with the University of California, San Francisco. She had no financial conflicts to disclose.
Twenty-five years ago, the U.S. Preventive Services Task Force advised clinicians to consider hormone therapy for the prevention of disease in all women, particularly those at risk for coronary heart disease, Deborah Grady, MD, wrote in an editorial (JAMA Intern Med. 2017 Dec 12. doi: 10.1001/jamainternmed.2017.7861). Dr. Grady was one of the coauthors of a literature review supporting the American College of Physicians’ recommendation to counsel asymptomatic postmenopausal women about hormone therapy based on data from observational studies. “No randomized trials with clinical outcomes had been conducted,” Dr. Grady said. By 2002, data from three large randomized trials told a different story, and the Task Force recommended against using estrogen alone as a strategy to prevent chronic conditions in postmenopausal women, she noted.
“I believe that the fear of hormone therapy is overblown,” Dr. Grady wrote. “When adequately informed, women with moderate to severe symptoms and without contraindications should be able to take such small risks if hormone therapy improves symptoms and quality of life,” she said.
In fact, professional societies, including the North American Menopause Society, the American College of Obstetricians and Gynecologists, and the Endocrine Society support hormone therapy for symptomatic women who are recently menopausal, said Dr. Grady. However, a key lesson learned from the ongoing research on hormone therapy is the importance of conducting clinical trials that are large enough to identify serious adverse effects, she added.
Dr. Grady is affiliated with the University of California, San Francisco. She had no financial conflicts to disclose.
Twenty-five years ago, the U.S. Preventive Services Task Force advised clinicians to consider hormone therapy for the prevention of disease in all women, particularly those at risk for coronary heart disease, Deborah Grady, MD, wrote in an editorial (JAMA Intern Med. 2017 Dec 12. doi: 10.1001/jamainternmed.2017.7861). Dr. Grady was one of the coauthors of a literature review supporting the American College of Physicians’ recommendation to counsel asymptomatic postmenopausal women about hormone therapy based on data from observational studies. “No randomized trials with clinical outcomes had been conducted,” Dr. Grady said. By 2002, data from three large randomized trials told a different story, and the Task Force recommended against using estrogen alone as a strategy to prevent chronic conditions in postmenopausal women, she noted.
“I believe that the fear of hormone therapy is overblown,” Dr. Grady wrote. “When adequately informed, women with moderate to severe symptoms and without contraindications should be able to take such small risks if hormone therapy improves symptoms and quality of life,” she said.
In fact, professional societies, including the North American Menopause Society, the American College of Obstetricians and Gynecologists, and the Endocrine Society support hormone therapy for symptomatic women who are recently menopausal, said Dr. Grady. However, a key lesson learned from the ongoing research on hormone therapy is the importance of conducting clinical trials that are large enough to identify serious adverse effects, she added.
Dr. Grady is affiliated with the University of California, San Francisco. She had no financial conflicts to disclose.
Hormone therapy should not be used to prevent chronic conditions in postmenopausal women, according to updated recommendations from the U.S. Preventive Services Task Force. The recommendations were published online Dec. 12 in JAMA.
In the latest recommendation statement, the USPSTF issued D recommendations against using combination estrogen and progestin to prevent chronic conditions in postmenopausal women and against using estrogen only to prevent chronic conditions in postmenopausal women who have undergone hysterectomies (JAMA. 2017 Dec 12. doi: 10.1001/jama.2017.18261). A grade D recommendation is defined as “The USPSTF recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits.”
In response to public comments, the USPSTF team made several changes including adjusting the language to clarify that the recommendations apply only to postmenopausal women, and adding tables showing estimates of increased or decreased risk of various outcomes for postmenopausal women receiving different hormone therapies.
Approximately 40,000 women aged 53-79 years were included in an evidence report from Gerald Gartlehner, MD, of the University of North Carolina, Chapel Hill, and his colleagues that accompanied the recommendations (JAMA. 2017 Dec 12. doi: 10.1001/jama.2017.16952).
The researchers found that women taking estrogen alone had significantly lower risk of breast cancer, diabetes, and osteoporotic fractures, but significantly higher risk of gallbladder disease, stroke, urinary incontinence, and venous thromboembolism, compared with women taking placebo. In addition, women using a combination of estrogen and progestin had significantly lower risk of colorectal cancer, diabetes, and osteoporotic fractures, but significantly higher risk of breast cancer, probable dementia, gallbladder disease, stroke, urinary incontinence, and venous thromboembolism, compared with women taking placebo.
“Hormone therapy for the primary prevention of chronic conditions in menopausal women is associated with some beneficial effects but also with a substantial increase of risks for harms,” and the current evidence for the risks and benefits of hormone therapy is inconclusive, the researchers said.
The final recommendation remains consistent with the USPSTF draft statement issued earlier in 2017 and with the final recommendation statements issued in 2012.
The researchers had no relevant financial conflicts to disclose.
Hormone therapy should not be used to prevent chronic conditions in postmenopausal women, according to updated recommendations from the U.S. Preventive Services Task Force. The recommendations were published online Dec. 12 in JAMA.
In the latest recommendation statement, the USPSTF issued D recommendations against using combination estrogen and progestin to prevent chronic conditions in postmenopausal women and against using estrogen only to prevent chronic conditions in postmenopausal women who have undergone hysterectomies (JAMA. 2017 Dec 12. doi: 10.1001/jama.2017.18261). A grade D recommendation is defined as “The USPSTF recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits.”
In response to public comments, the USPSTF team made several changes including adjusting the language to clarify that the recommendations apply only to postmenopausal women, and adding tables showing estimates of increased or decreased risk of various outcomes for postmenopausal women receiving different hormone therapies.
Approximately 40,000 women aged 53-79 years were included in an evidence report from Gerald Gartlehner, MD, of the University of North Carolina, Chapel Hill, and his colleagues that accompanied the recommendations (JAMA. 2017 Dec 12. doi: 10.1001/jama.2017.16952).
The researchers found that women taking estrogen alone had significantly lower risk of breast cancer, diabetes, and osteoporotic fractures, but significantly higher risk of gallbladder disease, stroke, urinary incontinence, and venous thromboembolism, compared with women taking placebo. In addition, women using a combination of estrogen and progestin had significantly lower risk of colorectal cancer, diabetes, and osteoporotic fractures, but significantly higher risk of breast cancer, probable dementia, gallbladder disease, stroke, urinary incontinence, and venous thromboembolism, compared with women taking placebo.
“Hormone therapy for the primary prevention of chronic conditions in menopausal women is associated with some beneficial effects but also with a substantial increase of risks for harms,” and the current evidence for the risks and benefits of hormone therapy is inconclusive, the researchers said.
The final recommendation remains consistent with the USPSTF draft statement issued earlier in 2017 and with the final recommendation statements issued in 2012.
The researchers had no relevant financial conflicts to disclose.
FROM JAMA
How to assess a patient for a bisphosphonate drug holiday
Recorded at the 2017 meeting of the North American Menopause Society
Co-Chair, 2017 NAMS Pre-Meeting Symposium
Founding Director, Oregon Osteoporosis Center
Dr. McClung reports being a consultant to Amgen and Radius Health and a speaker for Amgen and Radius Health.
Co-Chair, 2017 NAMS Pre-Meeting Symposium
Founding Director, Oregon Osteoporosis Center
Dr. McClung reports being a consultant to Amgen and Radius Health and a speaker for Amgen and Radius Health.
Co-Chair, 2017 NAMS Pre-Meeting Symposium
Founding Director, Oregon Osteoporosis Center
Dr. McClung reports being a consultant to Amgen and Radius Health and a speaker for Amgen and Radius Health.
Recorded at the 2017 meeting of the North American Menopause Society
Recorded at the 2017 meeting of the North American Menopause Society
2017 Update on bone health
Bone health remains one of the most important health care concerns in the United States today. In 2004, the Surgeon General released a report on bone health and osteoporosis. According to the report’s introduction:
This first-ever Surgeon General’s Report on bone health and osteoporosis illustrates the large burden that bone disease places on our Nation and its citizens. Like other chronic diseases that disproportionately affect the elderly, the prevalence of bone disease and fractures is projected to increase markedly as the population ages. If these predictions come true, bone disease and fractures will have a tremendous negative impact on the future well-being of Americans. But as this report makes clear, they need not come true: by working together we can change the picture of aging in America. Osteoporosis and fractures…no longer should be thought of as an inevitable part of growing old. By focusing on prevention and lifestyle changes, including physical activity and nutrition, as well as early diagnosis and appropriate treatment, Americans can avoid much of the damaging impact of bone disease.1
Related article:
2016 Update on bone health
Although men also experience osteoporosis as they age, in women the rapid loss of bone at menopause makes their disease burden much greater. As women’s health care providers, we stand at the front line for preventing, diagnosing, and treating osteoporosis to reduce the impact of this disease. In this Update I focus on important information that has emerged in the past year.
Read about new ACP guidelines to assess fracture risk
Guidelines for therapy: How to assess fracture risk and when to treat
American College of Obstetricians and Gynecologists Committee on Practice Bulletins--Gynecology. ACOG Practice Bulletin No. 129: Osteoporosis. Obstet Gynecol. 2012;120(3):718-734.
Qaseem A, Forciea MA, McLean RM, Denberg TD; Clinical Guidelines Committee of the American College of Physicians. Treatment of low bone density or osteoporosis to prevent fractures in men and women: a clinical practice guideline update from the American College of Physicians. Ann Intern Med. 2017;166(11):818-839.
A crucial component for good bone health maintenance and osteoporotic fracture prevention is understanding the current guidelines for therapy. The most recent practice bulletin of the American College of Obstetricians and Gynecologists (ACOG) on osteoporosis was published in 2012. ACOG states that treatment be recommended for women who have a bone mineral density (BMD) T-score of -2.5 or lower.
For women in the low bone mass category (T-score between -1 and -2.5), use of the Fracture Risk Assessment Tool (FRAX) calculator can assist in making an informed treatment decision.2 Based on the FRAX calculator, women who have a 10-year risk of major osteoporotic fracture of 20% or greater, or a risk of hip fracture of 3% or greater, are candidates for pharmacologic therapy.
Women who have experienced a low-trauma fracture (especially of the vertebra or hip) also are candidates for treatment, even in the absence of osteoporosis on a dual-energy x-ray absorptiometry (DXA) report.
Related article:
Women’s Preventive Services Initiative Guidelines provide consensus for practicing ObGyns
Updated recommendations from the ACP
The 2017 guideline published by the American College of Physicians (ACP), whose target audience is "all clinicians," recommends that, for women who have known osteoporosis, clinicians offer pharmacologic treatment with alendronate, risedronate, zoledronic acid, or denosumab to reduce the risk for hip and vertebral fractures.
In addition, the ACP recommends that clinicians make the decision whether or not to treat osteopenic women 65 years of age or older who are at a high risk for fracture based on a discussion of patient preferences, fracture risk profile, and benefits, harms, and costs of medications. This may seem somewhat contradictory to ACOG's guidance vis-a-vis women younger than 65 years of age.
The ACP further states that given the limited evidence supporting the benefit of treatment, the balance of benefits and harms in treating osteopenic women is most favorable when the risk for fracture is high. Women younger than 65 years with osteopenia and women older than 65 years with mild osteopenia (T-score between -1.0 and -1.5) will benefit less than women who are 65 years of age or older with severe osteopenia (T-score <-2.0).
Risk factors and risk assessment tools
Clinicians can use their own judgment based on risk factors for fracture (lower body weight, smoking, weight loss, family history of fractures, decreased physical activity, alcohol or caffeine use, low calcium and vitamin D intake, corticosteroid use), or they can use a risk assessment tool. Several risk assessment tools, such as the FRAX calculator mentioned earlier, are available to predict fracture risk among untreated people with low bone density. Although the FRAX calculator is widely used, there is no evidence from randomized controlled trials demonstrating a benefit of fracture reduction when FRAX scores are used in treatment decision making.
Duration of therapy. The ACP recommends that clinicians treat osteoporotic women with pharmacologic therapy for 5 years. Bone density monitoring is not recommended during the 5-year treatment period for osteoporosis in women; current evidence does not show any benefit for bone density monitoring during treatment.
Moderate-quality evidence demonstrated that women treated with antiresorptive therapies (including bisphosphonates, raloxifene, and teriparatide) benefited from reduced fractures, even if no increase in BMD occurred or if BMD decreased.
As before, all women with osteoporosis or a previous low-trauma fracture should be treated. Use of the FRAX calculator should involve clinician judgment, and other risk factors should be taken into account. For most women, treatment should be continued for 5 years. There is no benefit in continued bone mass assessment (DXA testing) while a patient is on pharmacologic therapy.
Read about fracture risk after stopping HT
Another WHI update: No increase in fractures after stopping HT
Watts NB, Cauley JA, Jackson RD, et al; Women's Health Initiative Investigators. No increase in fractures after stopping hormone therapy: results from the Women's Health Initiative. J Clin Endocrinol Metab. 2017;102(1):302-308.
The analysis and reanalysis of the Women's Health Initiative (WHI) trial data seems never-ending, yet the article by Watts and colleagues is important. Although the WHI hormone therapy (HT) trials showed that treatment protects against hip and total fractures, a later observational report suggested loss of benefit and rebound increased risk after HT was discontinued.3 The purpose of the Watts' study was to examine fractures after stopping HT.
Related article:
Did long-term follow-up of WHI participants reveal any mortality increase among women who received HT?
Details of the study
Two placebo-controlled randomized trials served as the study setting. The study included WHI participants (n = 15,187) who continued to take active HT or placebo through the intervention period and who did not take HT in the postintervention period. The trial interventions included conjugated equine estrogen (CEE) plus medroxyprogesterone acetate (MPA) for women with natural menopause and CEE alone for women with prior hysterectomy. The investigators recorded total fractures and hip fractures through 5 years after HT discontinuation.
Findings on fractures. Hip fractures occurred infrequently, with approximately 2.5 per 1,000 person-years. This finding was similar between trials and in former HT users and placebo groups.
No difference was found in total fractures in the CEE plus MPA trial for former HT users compared with former placebo users (28.9 per 1,000 person-years and 29.9 per 1,000 person-years, respectively; hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.87-1.09; P = .63). In the CEE-alone trial, however, total fractures were higher in former placebo users (36.9 per 1,000 person-years) compared with the former active-treatment group (31.1 per 1,000 person-years). This finding suggests a residual benefit of CEE in reducing total fractures (HR, 0.85; 95% CI, 0.73-0.98; P = .03).
Investigators' takeaway. The authors concluded that, after discontinuing HT, there was no evidence of increased fracture risk (sustained or transient) in former HT users compared with former placebo users. In the CEE-alone trial, there was a residual benefit for total fracture reduction in former HT users compared with placebo users.
Gynecologists have long believed that on stopping HT, the loss of bone mass will follow at the same rate as it would at natural menopause. These WHI trials demonstrate, however, that through 5 years, women who stopped HT had no increase in hip or total fractures, and hysterectomized women who stopped estrogen therapy actually had fewer fractures than the placebo group. Keep in mind that this large cohort was not chosen based on risk of osteoporotic fractures. In fact, baseline bone mass was not even measured in these women, making the results even more "real world."
Read about reassessing FRAX scores
A new look at fracture risk assessment scores
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-e23.
Jiang X, Gruner M, Trémollieres F, et al. Diagnostic accuracy of FRAX in predicting the 10-year risk of osteoporotic fractures using the USA treatment thresholds: a systematic review and meta-analysis. Bone. 2017;99:20-25.
The FRAX score has become a popular form of triage for women who do not yet meet the bone mass criteria of osteoporosis. Current practice guidelines recommend use of fracture risk scores for screening and pharmacologic therapeutic decision making. Some newer data, however, may give rise to questions about its utility, especially in younger women.
Fracture risk analysis in a large postmenopausal population
Gourlay and colleagues conducted a retrospective competing risk analysis of new occurrence of treatment-level and screening-level fracture risk scores. Study participants were postmenopausal women aged 50 years and older who had not previously received pharmacologic treatment and had not had a first hip or clinical vertebral facture.
Details of the study
In 54,280 postmenopausal women aged 50 to 64 years who did not have a bone mineral density test, the time for 10% to develop a treatment-level FRAX score could not be estimated accurately because the incidence of treatment-level scores was rare.
A total of 6,096 women had FRAX scores calculated with bone mineral density testing. In this group, the estimated unadjusted time to treatment-level FRAX scores was 7.6 years (95% CI, 6.6-8.7) for those aged 65 to 69, and 5.1 years (95% CI, 3.5-7.5) for women aged 75 to 79 at baseline.
Of 17,967 women aged 50 to 64 who had a screening-level FRAX at baseline, 100 (0.6%) experienced a hip or clinical vertebral fracture by age 65 years.
Age is key factor. Gourlay and colleagues concluded that postmenopausal women who had subthreshold fracture risk scores at baseline would be unlikely to develop a treatment-level FRAX score between ages 50 and 64. The increased incidence of treatment-level fracture risk scores, osteoporosis, and major osteoporotic fracture after age 65, however, supports more frequent consideration of FRAX assessment and bone mineral density testing.
Related article:
2015 Update on osteoporosis
Meta-analysis of FRAX tool accuracy
In another study, Jiang and colleagues conducted a systematic review and meta-analysis to determine how the FRAX score performed in predicting the 10-year risk of major osteoporotic fractures and hip fractures. The investigators used the US treatment thresholds.
Details of the study
Seven studies (n = 57,027) were analyzed to assess the diagnostic accuracy of FRAX in predicting major osteoporotic fractures; 20% was used as the 10-year fracture risk threshold for intervention. The mean sensitivity and specificity, along with their 95% CIs, were 10.25% (3.76%-25.06%) and 97.02% (91.17%-99.03%), respectively.
For hip fracture prediction, 6 studies (n = 50,944) were analyzed, and 3% was used as the 10-year fracture risk threshold. The mean sensitivity and specificity, along with their 95% CIs, were 45.70% (24.88%-68.13%) and 84.70% (76.41%-90.44%), respectively.
Predictive value of FRAX. The authors concluded that, using the 10-year intervention thresholds of 20% for major osteoporotic fracture and 3% for hip fracture, FRAX performed better in identifying individuals who will not have a major osteoporotic fracture or hip fracture within 10 years than in identifying those who will experience a fracture. A substantial number of those who developed fractures, especially major osteoporotic fracture within 10 years of follow up, were missed by the baseline FRAX assessment.
Increasing age is still arguably among the most important factors for decreasing bone health. Older women are more likely to develop treatment-level FRAX scores more quickly than younger women. In addition, the FRAX tool is better in predicting which women will not develop a fracture in the next 10 years than in predicting those who will experience a fracture.
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.
- United States Office of the Surgeon General. Bone health and osteoporosis: a report of the Surgeon General. Rockville, Maryland: Office of the Surgeon General (US); 2004. https://www.ncbi.nlm.nih.gov/books/NBK45513/. Accessed November 6, 2017.
- Centre for Metabolic Bone Diseases, University of Sheffield, United Kingdom. FRAX Fracture Risk Assessment Tool website. www.sheffield.ac.uk/FRAX. Accessed November 6, 2017.
- Yates J, Barrett-Connor E, Barlas S, Chen YT, Miller PD, Siris ES. Rapid loss of hip fracture protection after estrogen cessation: evidence from the National Osteoporosis Risk Assessment. Obstet Gynecol. 2004;103(3):440–446.
Dr. Goldstein is Professor in the Department of Obstetrics and Gynecology, New York
University School of Medicine, and Director of Gynecologic Ultrasound and Co-
Director of Bone Densitometry and Body Composition at New York University Medical
Center in New York, New York. He serves on the OBG Management Board of Editors.
The author reports no financial relationships relevant to this article
Dr. Goldstein is Professor in the Department of Obstetrics and Gynecology, New York
University School of Medicine, and Director of Gynecologic Ultrasound and Co-
Director of Bone Densitometry and Body Composition at New York University Medical
Center in New York, New York. He serves on the OBG Management Board of Editors.
The author reports no financial relationships relevant to this article
Dr. Goldstein is Professor in the Department of Obstetrics and Gynecology, New York
University School of Medicine, and Director of Gynecologic Ultrasound and Co-
Director of Bone Densitometry and Body Composition at New York University Medical
Center in New York, New York. He serves on the OBG Management Board of Editors.
The author reports no financial relationships relevant to this article
Bone health remains one of the most important health care concerns in the United States today. In 2004, the Surgeon General released a report on bone health and osteoporosis. According to the report’s introduction:
This first-ever Surgeon General’s Report on bone health and osteoporosis illustrates the large burden that bone disease places on our Nation and its citizens. Like other chronic diseases that disproportionately affect the elderly, the prevalence of bone disease and fractures is projected to increase markedly as the population ages. If these predictions come true, bone disease and fractures will have a tremendous negative impact on the future well-being of Americans. But as this report makes clear, they need not come true: by working together we can change the picture of aging in America. Osteoporosis and fractures…no longer should be thought of as an inevitable part of growing old. By focusing on prevention and lifestyle changes, including physical activity and nutrition, as well as early diagnosis and appropriate treatment, Americans can avoid much of the damaging impact of bone disease.1
Related article:
2016 Update on bone health
Although men also experience osteoporosis as they age, in women the rapid loss of bone at menopause makes their disease burden much greater. As women’s health care providers, we stand at the front line for preventing, diagnosing, and treating osteoporosis to reduce the impact of this disease. In this Update I focus on important information that has emerged in the past year.
Read about new ACP guidelines to assess fracture risk
Guidelines for therapy: How to assess fracture risk and when to treat
American College of Obstetricians and Gynecologists Committee on Practice Bulletins--Gynecology. ACOG Practice Bulletin No. 129: Osteoporosis. Obstet Gynecol. 2012;120(3):718-734.
Qaseem A, Forciea MA, McLean RM, Denberg TD; Clinical Guidelines Committee of the American College of Physicians. Treatment of low bone density or osteoporosis to prevent fractures in men and women: a clinical practice guideline update from the American College of Physicians. Ann Intern Med. 2017;166(11):818-839.
A crucial component for good bone health maintenance and osteoporotic fracture prevention is understanding the current guidelines for therapy. The most recent practice bulletin of the American College of Obstetricians and Gynecologists (ACOG) on osteoporosis was published in 2012. ACOG states that treatment be recommended for women who have a bone mineral density (BMD) T-score of -2.5 or lower.
For women in the low bone mass category (T-score between -1 and -2.5), use of the Fracture Risk Assessment Tool (FRAX) calculator can assist in making an informed treatment decision.2 Based on the FRAX calculator, women who have a 10-year risk of major osteoporotic fracture of 20% or greater, or a risk of hip fracture of 3% or greater, are candidates for pharmacologic therapy.
Women who have experienced a low-trauma fracture (especially of the vertebra or hip) also are candidates for treatment, even in the absence of osteoporosis on a dual-energy x-ray absorptiometry (DXA) report.
Related article:
Women’s Preventive Services Initiative Guidelines provide consensus for practicing ObGyns
Updated recommendations from the ACP
The 2017 guideline published by the American College of Physicians (ACP), whose target audience is "all clinicians," recommends that, for women who have known osteoporosis, clinicians offer pharmacologic treatment with alendronate, risedronate, zoledronic acid, or denosumab to reduce the risk for hip and vertebral fractures.
In addition, the ACP recommends that clinicians make the decision whether or not to treat osteopenic women 65 years of age or older who are at a high risk for fracture based on a discussion of patient preferences, fracture risk profile, and benefits, harms, and costs of medications. This may seem somewhat contradictory to ACOG's guidance vis-a-vis women younger than 65 years of age.
The ACP further states that given the limited evidence supporting the benefit of treatment, the balance of benefits and harms in treating osteopenic women is most favorable when the risk for fracture is high. Women younger than 65 years with osteopenia and women older than 65 years with mild osteopenia (T-score between -1.0 and -1.5) will benefit less than women who are 65 years of age or older with severe osteopenia (T-score <-2.0).
Risk factors and risk assessment tools
Clinicians can use their own judgment based on risk factors for fracture (lower body weight, smoking, weight loss, family history of fractures, decreased physical activity, alcohol or caffeine use, low calcium and vitamin D intake, corticosteroid use), or they can use a risk assessment tool. Several risk assessment tools, such as the FRAX calculator mentioned earlier, are available to predict fracture risk among untreated people with low bone density. Although the FRAX calculator is widely used, there is no evidence from randomized controlled trials demonstrating a benefit of fracture reduction when FRAX scores are used in treatment decision making.
Duration of therapy. The ACP recommends that clinicians treat osteoporotic women with pharmacologic therapy for 5 years. Bone density monitoring is not recommended during the 5-year treatment period for osteoporosis in women; current evidence does not show any benefit for bone density monitoring during treatment.
Moderate-quality evidence demonstrated that women treated with antiresorptive therapies (including bisphosphonates, raloxifene, and teriparatide) benefited from reduced fractures, even if no increase in BMD occurred or if BMD decreased.
As before, all women with osteoporosis or a previous low-trauma fracture should be treated. Use of the FRAX calculator should involve clinician judgment, and other risk factors should be taken into account. For most women, treatment should be continued for 5 years. There is no benefit in continued bone mass assessment (DXA testing) while a patient is on pharmacologic therapy.
Read about fracture risk after stopping HT
Another WHI update: No increase in fractures after stopping HT
Watts NB, Cauley JA, Jackson RD, et al; Women's Health Initiative Investigators. No increase in fractures after stopping hormone therapy: results from the Women's Health Initiative. J Clin Endocrinol Metab. 2017;102(1):302-308.
The analysis and reanalysis of the Women's Health Initiative (WHI) trial data seems never-ending, yet the article by Watts and colleagues is important. Although the WHI hormone therapy (HT) trials showed that treatment protects against hip and total fractures, a later observational report suggested loss of benefit and rebound increased risk after HT was discontinued.3 The purpose of the Watts' study was to examine fractures after stopping HT.
Related article:
Did long-term follow-up of WHI participants reveal any mortality increase among women who received HT?
Details of the study
Two placebo-controlled randomized trials served as the study setting. The study included WHI participants (n = 15,187) who continued to take active HT or placebo through the intervention period and who did not take HT in the postintervention period. The trial interventions included conjugated equine estrogen (CEE) plus medroxyprogesterone acetate (MPA) for women with natural menopause and CEE alone for women with prior hysterectomy. The investigators recorded total fractures and hip fractures through 5 years after HT discontinuation.
Findings on fractures. Hip fractures occurred infrequently, with approximately 2.5 per 1,000 person-years. This finding was similar between trials and in former HT users and placebo groups.
No difference was found in total fractures in the CEE plus MPA trial for former HT users compared with former placebo users (28.9 per 1,000 person-years and 29.9 per 1,000 person-years, respectively; hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.87-1.09; P = .63). In the CEE-alone trial, however, total fractures were higher in former placebo users (36.9 per 1,000 person-years) compared with the former active-treatment group (31.1 per 1,000 person-years). This finding suggests a residual benefit of CEE in reducing total fractures (HR, 0.85; 95% CI, 0.73-0.98; P = .03).
Investigators' takeaway. The authors concluded that, after discontinuing HT, there was no evidence of increased fracture risk (sustained or transient) in former HT users compared with former placebo users. In the CEE-alone trial, there was a residual benefit for total fracture reduction in former HT users compared with placebo users.
Gynecologists have long believed that on stopping HT, the loss of bone mass will follow at the same rate as it would at natural menopause. These WHI trials demonstrate, however, that through 5 years, women who stopped HT had no increase in hip or total fractures, and hysterectomized women who stopped estrogen therapy actually had fewer fractures than the placebo group. Keep in mind that this large cohort was not chosen based on risk of osteoporotic fractures. In fact, baseline bone mass was not even measured in these women, making the results even more "real world."
Read about reassessing FRAX scores
A new look at fracture risk assessment scores
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-e23.
Jiang X, Gruner M, Trémollieres F, et al. Diagnostic accuracy of FRAX in predicting the 10-year risk of osteoporotic fractures using the USA treatment thresholds: a systematic review and meta-analysis. Bone. 2017;99:20-25.
The FRAX score has become a popular form of triage for women who do not yet meet the bone mass criteria of osteoporosis. Current practice guidelines recommend use of fracture risk scores for screening and pharmacologic therapeutic decision making. Some newer data, however, may give rise to questions about its utility, especially in younger women.
Fracture risk analysis in a large postmenopausal population
Gourlay and colleagues conducted a retrospective competing risk analysis of new occurrence of treatment-level and screening-level fracture risk scores. Study participants were postmenopausal women aged 50 years and older who had not previously received pharmacologic treatment and had not had a first hip or clinical vertebral facture.
Details of the study
In 54,280 postmenopausal women aged 50 to 64 years who did not have a bone mineral density test, the time for 10% to develop a treatment-level FRAX score could not be estimated accurately because the incidence of treatment-level scores was rare.
A total of 6,096 women had FRAX scores calculated with bone mineral density testing. In this group, the estimated unadjusted time to treatment-level FRAX scores was 7.6 years (95% CI, 6.6-8.7) for those aged 65 to 69, and 5.1 years (95% CI, 3.5-7.5) for women aged 75 to 79 at baseline.
Of 17,967 women aged 50 to 64 who had a screening-level FRAX at baseline, 100 (0.6%) experienced a hip or clinical vertebral fracture by age 65 years.
Age is key factor. Gourlay and colleagues concluded that postmenopausal women who had subthreshold fracture risk scores at baseline would be unlikely to develop a treatment-level FRAX score between ages 50 and 64. The increased incidence of treatment-level fracture risk scores, osteoporosis, and major osteoporotic fracture after age 65, however, supports more frequent consideration of FRAX assessment and bone mineral density testing.
Related article:
2015 Update on osteoporosis
Meta-analysis of FRAX tool accuracy
In another study, Jiang and colleagues conducted a systematic review and meta-analysis to determine how the FRAX score performed in predicting the 10-year risk of major osteoporotic fractures and hip fractures. The investigators used the US treatment thresholds.
Details of the study
Seven studies (n = 57,027) were analyzed to assess the diagnostic accuracy of FRAX in predicting major osteoporotic fractures; 20% was used as the 10-year fracture risk threshold for intervention. The mean sensitivity and specificity, along with their 95% CIs, were 10.25% (3.76%-25.06%) and 97.02% (91.17%-99.03%), respectively.
For hip fracture prediction, 6 studies (n = 50,944) were analyzed, and 3% was used as the 10-year fracture risk threshold. The mean sensitivity and specificity, along with their 95% CIs, were 45.70% (24.88%-68.13%) and 84.70% (76.41%-90.44%), respectively.
Predictive value of FRAX. The authors concluded that, using the 10-year intervention thresholds of 20% for major osteoporotic fracture and 3% for hip fracture, FRAX performed better in identifying individuals who will not have a major osteoporotic fracture or hip fracture within 10 years than in identifying those who will experience a fracture. A substantial number of those who developed fractures, especially major osteoporotic fracture within 10 years of follow up, were missed by the baseline FRAX assessment.
Increasing age is still arguably among the most important factors for decreasing bone health. Older women are more likely to develop treatment-level FRAX scores more quickly than younger women. In addition, the FRAX tool is better in predicting which women will not develop a fracture in the next 10 years than in predicting those who will experience a fracture.
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.
Bone health remains one of the most important health care concerns in the United States today. In 2004, the Surgeon General released a report on bone health and osteoporosis. According to the report’s introduction:
This first-ever Surgeon General’s Report on bone health and osteoporosis illustrates the large burden that bone disease places on our Nation and its citizens. Like other chronic diseases that disproportionately affect the elderly, the prevalence of bone disease and fractures is projected to increase markedly as the population ages. If these predictions come true, bone disease and fractures will have a tremendous negative impact on the future well-being of Americans. But as this report makes clear, they need not come true: by working together we can change the picture of aging in America. Osteoporosis and fractures…no longer should be thought of as an inevitable part of growing old. By focusing on prevention and lifestyle changes, including physical activity and nutrition, as well as early diagnosis and appropriate treatment, Americans can avoid much of the damaging impact of bone disease.1
Related article:
2016 Update on bone health
Although men also experience osteoporosis as they age, in women the rapid loss of bone at menopause makes their disease burden much greater. As women’s health care providers, we stand at the front line for preventing, diagnosing, and treating osteoporosis to reduce the impact of this disease. In this Update I focus on important information that has emerged in the past year.
Read about new ACP guidelines to assess fracture risk
Guidelines for therapy: How to assess fracture risk and when to treat
American College of Obstetricians and Gynecologists Committee on Practice Bulletins--Gynecology. ACOG Practice Bulletin No. 129: Osteoporosis. Obstet Gynecol. 2012;120(3):718-734.
Qaseem A, Forciea MA, McLean RM, Denberg TD; Clinical Guidelines Committee of the American College of Physicians. Treatment of low bone density or osteoporosis to prevent fractures in men and women: a clinical practice guideline update from the American College of Physicians. Ann Intern Med. 2017;166(11):818-839.
A crucial component for good bone health maintenance and osteoporotic fracture prevention is understanding the current guidelines for therapy. The most recent practice bulletin of the American College of Obstetricians and Gynecologists (ACOG) on osteoporosis was published in 2012. ACOG states that treatment be recommended for women who have a bone mineral density (BMD) T-score of -2.5 or lower.
For women in the low bone mass category (T-score between -1 and -2.5), use of the Fracture Risk Assessment Tool (FRAX) calculator can assist in making an informed treatment decision.2 Based on the FRAX calculator, women who have a 10-year risk of major osteoporotic fracture of 20% or greater, or a risk of hip fracture of 3% or greater, are candidates for pharmacologic therapy.
Women who have experienced a low-trauma fracture (especially of the vertebra or hip) also are candidates for treatment, even in the absence of osteoporosis on a dual-energy x-ray absorptiometry (DXA) report.
Related article:
Women’s Preventive Services Initiative Guidelines provide consensus for practicing ObGyns
Updated recommendations from the ACP
The 2017 guideline published by the American College of Physicians (ACP), whose target audience is "all clinicians," recommends that, for women who have known osteoporosis, clinicians offer pharmacologic treatment with alendronate, risedronate, zoledronic acid, or denosumab to reduce the risk for hip and vertebral fractures.
In addition, the ACP recommends that clinicians make the decision whether or not to treat osteopenic women 65 years of age or older who are at a high risk for fracture based on a discussion of patient preferences, fracture risk profile, and benefits, harms, and costs of medications. This may seem somewhat contradictory to ACOG's guidance vis-a-vis women younger than 65 years of age.
The ACP further states that given the limited evidence supporting the benefit of treatment, the balance of benefits and harms in treating osteopenic women is most favorable when the risk for fracture is high. Women younger than 65 years with osteopenia and women older than 65 years with mild osteopenia (T-score between -1.0 and -1.5) will benefit less than women who are 65 years of age or older with severe osteopenia (T-score <-2.0).
Risk factors and risk assessment tools
Clinicians can use their own judgment based on risk factors for fracture (lower body weight, smoking, weight loss, family history of fractures, decreased physical activity, alcohol or caffeine use, low calcium and vitamin D intake, corticosteroid use), or they can use a risk assessment tool. Several risk assessment tools, such as the FRAX calculator mentioned earlier, are available to predict fracture risk among untreated people with low bone density. Although the FRAX calculator is widely used, there is no evidence from randomized controlled trials demonstrating a benefit of fracture reduction when FRAX scores are used in treatment decision making.
Duration of therapy. The ACP recommends that clinicians treat osteoporotic women with pharmacologic therapy for 5 years. Bone density monitoring is not recommended during the 5-year treatment period for osteoporosis in women; current evidence does not show any benefit for bone density monitoring during treatment.
Moderate-quality evidence demonstrated that women treated with antiresorptive therapies (including bisphosphonates, raloxifene, and teriparatide) benefited from reduced fractures, even if no increase in BMD occurred or if BMD decreased.
As before, all women with osteoporosis or a previous low-trauma fracture should be treated. Use of the FRAX calculator should involve clinician judgment, and other risk factors should be taken into account. For most women, treatment should be continued for 5 years. There is no benefit in continued bone mass assessment (DXA testing) while a patient is on pharmacologic therapy.
Read about fracture risk after stopping HT
Another WHI update: No increase in fractures after stopping HT
Watts NB, Cauley JA, Jackson RD, et al; Women's Health Initiative Investigators. No increase in fractures after stopping hormone therapy: results from the Women's Health Initiative. J Clin Endocrinol Metab. 2017;102(1):302-308.
The analysis and reanalysis of the Women's Health Initiative (WHI) trial data seems never-ending, yet the article by Watts and colleagues is important. Although the WHI hormone therapy (HT) trials showed that treatment protects against hip and total fractures, a later observational report suggested loss of benefit and rebound increased risk after HT was discontinued.3 The purpose of the Watts' study was to examine fractures after stopping HT.
Related article:
Did long-term follow-up of WHI participants reveal any mortality increase among women who received HT?
Details of the study
Two placebo-controlled randomized trials served as the study setting. The study included WHI participants (n = 15,187) who continued to take active HT or placebo through the intervention period and who did not take HT in the postintervention period. The trial interventions included conjugated equine estrogen (CEE) plus medroxyprogesterone acetate (MPA) for women with natural menopause and CEE alone for women with prior hysterectomy. The investigators recorded total fractures and hip fractures through 5 years after HT discontinuation.
Findings on fractures. Hip fractures occurred infrequently, with approximately 2.5 per 1,000 person-years. This finding was similar between trials and in former HT users and placebo groups.
No difference was found in total fractures in the CEE plus MPA trial for former HT users compared with former placebo users (28.9 per 1,000 person-years and 29.9 per 1,000 person-years, respectively; hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.87-1.09; P = .63). In the CEE-alone trial, however, total fractures were higher in former placebo users (36.9 per 1,000 person-years) compared with the former active-treatment group (31.1 per 1,000 person-years). This finding suggests a residual benefit of CEE in reducing total fractures (HR, 0.85; 95% CI, 0.73-0.98; P = .03).
Investigators' takeaway. The authors concluded that, after discontinuing HT, there was no evidence of increased fracture risk (sustained or transient) in former HT users compared with former placebo users. In the CEE-alone trial, there was a residual benefit for total fracture reduction in former HT users compared with placebo users.
Gynecologists have long believed that on stopping HT, the loss of bone mass will follow at the same rate as it would at natural menopause. These WHI trials demonstrate, however, that through 5 years, women who stopped HT had no increase in hip or total fractures, and hysterectomized women who stopped estrogen therapy actually had fewer fractures than the placebo group. Keep in mind that this large cohort was not chosen based on risk of osteoporotic fractures. In fact, baseline bone mass was not even measured in these women, making the results even more "real world."
Read about reassessing FRAX scores
A new look at fracture risk assessment scores
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-e23.
Jiang X, Gruner M, Trémollieres F, et al. Diagnostic accuracy of FRAX in predicting the 10-year risk of osteoporotic fractures using the USA treatment thresholds: a systematic review and meta-analysis. Bone. 2017;99:20-25.
The FRAX score has become a popular form of triage for women who do not yet meet the bone mass criteria of osteoporosis. Current practice guidelines recommend use of fracture risk scores for screening and pharmacologic therapeutic decision making. Some newer data, however, may give rise to questions about its utility, especially in younger women.
Fracture risk analysis in a large postmenopausal population
Gourlay and colleagues conducted a retrospective competing risk analysis of new occurrence of treatment-level and screening-level fracture risk scores. Study participants were postmenopausal women aged 50 years and older who had not previously received pharmacologic treatment and had not had a first hip or clinical vertebral facture.
Details of the study
In 54,280 postmenopausal women aged 50 to 64 years who did not have a bone mineral density test, the time for 10% to develop a treatment-level FRAX score could not be estimated accurately because the incidence of treatment-level scores was rare.
A total of 6,096 women had FRAX scores calculated with bone mineral density testing. In this group, the estimated unadjusted time to treatment-level FRAX scores was 7.6 years (95% CI, 6.6-8.7) for those aged 65 to 69, and 5.1 years (95% CI, 3.5-7.5) for women aged 75 to 79 at baseline.
Of 17,967 women aged 50 to 64 who had a screening-level FRAX at baseline, 100 (0.6%) experienced a hip or clinical vertebral fracture by age 65 years.
Age is key factor. Gourlay and colleagues concluded that postmenopausal women who had subthreshold fracture risk scores at baseline would be unlikely to develop a treatment-level FRAX score between ages 50 and 64. The increased incidence of treatment-level fracture risk scores, osteoporosis, and major osteoporotic fracture after age 65, however, supports more frequent consideration of FRAX assessment and bone mineral density testing.
Related article:
2015 Update on osteoporosis
Meta-analysis of FRAX tool accuracy
In another study, Jiang and colleagues conducted a systematic review and meta-analysis to determine how the FRAX score performed in predicting the 10-year risk of major osteoporotic fractures and hip fractures. The investigators used the US treatment thresholds.
Details of the study
Seven studies (n = 57,027) were analyzed to assess the diagnostic accuracy of FRAX in predicting major osteoporotic fractures; 20% was used as the 10-year fracture risk threshold for intervention. The mean sensitivity and specificity, along with their 95% CIs, were 10.25% (3.76%-25.06%) and 97.02% (91.17%-99.03%), respectively.
For hip fracture prediction, 6 studies (n = 50,944) were analyzed, and 3% was used as the 10-year fracture risk threshold. The mean sensitivity and specificity, along with their 95% CIs, were 45.70% (24.88%-68.13%) and 84.70% (76.41%-90.44%), respectively.
Predictive value of FRAX. The authors concluded that, using the 10-year intervention thresholds of 20% for major osteoporotic fracture and 3% for hip fracture, FRAX performed better in identifying individuals who will not have a major osteoporotic fracture or hip fracture within 10 years than in identifying those who will experience a fracture. A substantial number of those who developed fractures, especially major osteoporotic fracture within 10 years of follow up, were missed by the baseline FRAX assessment.
Increasing age is still arguably among the most important factors for decreasing bone health. Older women are more likely to develop treatment-level FRAX scores more quickly than younger women. In addition, the FRAX tool is better in predicting which women will not develop a fracture in the next 10 years than in predicting those who will experience a fracture.
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.
- United States Office of the Surgeon General. Bone health and osteoporosis: a report of the Surgeon General. Rockville, Maryland: Office of the Surgeon General (US); 2004. https://www.ncbi.nlm.nih.gov/books/NBK45513/. Accessed November 6, 2017.
- Centre for Metabolic Bone Diseases, University of Sheffield, United Kingdom. FRAX Fracture Risk Assessment Tool website. www.sheffield.ac.uk/FRAX. Accessed November 6, 2017.
- Yates J, Barrett-Connor E, Barlas S, Chen YT, Miller PD, Siris ES. Rapid loss of hip fracture protection after estrogen cessation: evidence from the National Osteoporosis Risk Assessment. Obstet Gynecol. 2004;103(3):440–446.
- United States Office of the Surgeon General. Bone health and osteoporosis: a report of the Surgeon General. Rockville, Maryland: Office of the Surgeon General (US); 2004. https://www.ncbi.nlm.nih.gov/books/NBK45513/. Accessed November 6, 2017.
- Centre for Metabolic Bone Diseases, University of Sheffield, United Kingdom. FRAX Fracture Risk Assessment Tool website. www.sheffield.ac.uk/FRAX. Accessed November 6, 2017.
- Yates J, Barrett-Connor E, Barlas S, Chen YT, Miller PD, Siris ES. Rapid loss of hip fracture protection after estrogen cessation: evidence from the National Osteoporosis Risk Assessment. Obstet Gynecol. 2004;103(3):440–446.
Hypoactive sexual desire disorder: The ideal patient for treatment with flibanserin
Strategies to evaluate postmenopausal bleeding
Postmenopausal bleeding is a symptom that can announce the presence of a gynecologic malignancy. In this column, we will discuss the important considerations to make in the work-up of this symptom.
Roughly 10% of women will present for evaluation of postmenopausal bleeding.1 More than a third of these women will have benign pathology, with the incidence of endometrial cancer in this group at only about 5%.2 Other gynecologic malignancies should be considered as well, including cervical, vaginal, vulvar, and more rarely, those of the fallopian tubes or ovaries.
Use of ultrasound
Ultrasound is a commonly performed initial approach to work-up because of its noninvasive nature. Transvaginal ultrasound has a high negative predictive value of 99.4%-100% in ruling out malignancy.3 Among women with postmenopausal bleeding, the risk of cancer is 7.3% if their endometrial lining is 5 mm or greater and less than 0.07% risk if their lining is 4 mm or less. Therefore, this cutoff dimension is typically used to triage patients to additional sampling.
If ultrasound is performed on postmenopausal women who are asymptomatic (no bleeding), then an endometrial stripe of greater than 11 mm is considered justification for further work-up and is associated with a 6.7% risk of endometrial cancer.4 If the ultrasound reveals intracavitary lesions, a sonohysterogram would be preferred to characterize intrauterine pathology. In fact, sonohysterography is superior to transvaginal ultrasound (with a sensitivity of 80% vs. 49%, respectively) in detecting endometrial polypoid lesions.5 Preoperative identification of an intracavitary lesion may assist in selecting the best sampling technique (blind vs. hysteroscopy-guided approach).
Endometrial sampling
If an ultrasound reveals a thickened or unevaluable endometrial stripe or if the clinician chooses to proceed directly with diagnostic confirmation, several options for endometrial sampling exist, including office-based or operative procedures, as well as blind or visually guided ones. Endometrial pipelle biopsy, D&C without hysteroscopy, endometrial lavage, and endometrial brush biopsy all constitute “blind” sampling techniques. Targeted biopsy techniques include hysteroscopy D&C and saline infusion sonohysterography–guided biopsy.
Blind D&C
Although D&C may be considered the gold standard of diagnostic sampling techniques, it should be noted that 60% of these procedures sample less than half of the endometrium.6 When used in conjunction with hysteroscopy, the sensitivity in detecting cancer is high at 97% with a specificity of 93%-100%.7
While some patients are candidates for office-based procedures, D&C often requires regional or general anesthesia and is frequently performed in a hospital-based environment or surgical center. This may be most appropriate for patients who have had failed office attempts at sampling, have multiple medical comorbidities that limit the feasibility of office-based procedures (such as morbid obesity), or have severe cervical stenosis. D&C is associated with an increased risk for uterine perforation, compared with outpatient sampling procedures.
The need to go to the operating room rather than to an ambulatory setting also may increase the costs borne by the patient. The advantages of D&C include the potential for large-volume sampling and the potentially therapeutic nature of the procedure in cases of benign pathology.
Office-based procedures
Office-based sampling techniques include those using a pipelle, those employing an endometrial brush, and those guided by saline infusion sonohysterography. If performed in the office, they require minimal or no cervical dilation, are associated with a lower risk of perforation or adverse reaction to anesthesia, and usually have lower costs for patients.
Endometrial pipelle biopsies are a very effective diagnostic tool when there is global, endometrial pathology; they have a sensitivity of 83% in confirming cancer.8 It is an inexpensive and technically straightforward technique that can be easily performed in an office setting.
However, when the endometrial lining is atrophied, alternative tools may provide superior results. Endometrial brushes have been shown to be 33% more successful in collecting adequate samples,compared with pipelles, because they sample a larger endometrial surface area.9
There is ongoing development of sampling techniques, such as endometrial lavage or the combination of saline infusion sonohysterography and endometrial biopsy.10 However, future studies regarding accuracy, cost, and patient acceptability are needed before these techniques are translated to the clinical setting.
Targeted endometrial sampling
Targeted or visually guided sampling, such as hysteroscopy, has been shown to be very accurate in identifying benign pathology, although the sensitivity of hysteroscopic diagnosis of cancer is significantly lower at approximately 50%.11 Therefore, the benefit of hysteroscopy is in complementing the blind nature of D&C by guiding sampling of intracavitary lesions, should they exist.
Hysteroscopy is safe in endometrial cancer and is not associated with upstaging the cancer from transtubal extirpation of malignant cells.12
The addition of hysteroscopy contributes some cost and equipment to the blind D&C procedure; therefore, it might be best applied in cases where there is known intracavitary pathology or inadequate prior sampling. In well-selected patients, hysteroscopy often can be used in an office setting, which improves the practicality of the procedure. Smaller and, in some cases, disposable equipment aids in the feasibility of adding visual guidance to office sampling.
Optimizing sampling
Postmenopausal women have a higher risk for sampling failure, compared with younger women. Obesity also is a risk for failed sampling.13 Cervical ripening with misoprostol may increase access to the endometrial cavity, and ultrasound guidance may decrease the risk of uterine perforation in a stenotic cervix.
Clinicians should ensure that histology results are concordant with clinical data. Discordant results should be reevaluated. For example, if an ultrasound demonstrates a thickened endometrial stripe, but the sampling reveals “scant atrophic tissue,” then there is unexplained pathology to address. Further work-up, such as more comprehensive sampling with hysteroscopy, should be considered in such cases. Additionally, persistent postmenopausal bleeding, despite a benign endometrial biopsy, should be reevaluated over time to rule out occult disease missed during prior sampling.
Clinicians are now equipped with multiple ways of obtaining clinical data, and patients have options that may decrease barriers to their care. Hysteroscopy does not improve upon D&C in the diagnosis of endometrial cancer, although it may be helpful in distinguishing and treating nonmalignant lesions.
Dr. Cotangco is a resident in the department of obstetrics and gynecology at the University of Illinois, Chicago. Dr. Rossi is an assistant professor in the division of gynecologic oncology at the University of North Carolina, Chapel Hill. They reported having no relevant financial disclosures.
References
1. Acta Obstet Gynecol Scand. 2004 Feb;83(2):203-7.
2. Menopause Int. 2010 Mar;16(1):5-8.
3. Obstet Gynecol. 2009 Aug;114(2 Pt 1):409-11.
4. Ultrasound Obstet Gynecol. 2004 Oct;24(5):558-65.
5. Ultrasound Obstet Gynecol. 2001 Aug;18(2):157-62.
6. Am J Obstet Gynecol. 2009 Jul;201(1):5-11.
7. Obstet Gynecol Clin North Am. 2000 Jun;27(2):235-44.
8. J Reprod Med. 1995 Aug;40(8):553-5.
9. BJOG. 2008 Jul;115(8):1028-36.
10. PLoS Med. 2016 Dec. doi: 10.1371/journal.pmed.1002206.
11. Arch Gynecol Obstet. 2012 Mar;285(3):839-43.
12. Am J Obstet Gynecol. 2012 Jul;207(1):71.e1-5.
13. Gynecol Oncol. 2017 Feb;144(2):324-8.
Postmenopausal bleeding is a symptom that can announce the presence of a gynecologic malignancy. In this column, we will discuss the important considerations to make in the work-up of this symptom.
Roughly 10% of women will present for evaluation of postmenopausal bleeding.1 More than a third of these women will have benign pathology, with the incidence of endometrial cancer in this group at only about 5%.2 Other gynecologic malignancies should be considered as well, including cervical, vaginal, vulvar, and more rarely, those of the fallopian tubes or ovaries.
Use of ultrasound
Ultrasound is a commonly performed initial approach to work-up because of its noninvasive nature. Transvaginal ultrasound has a high negative predictive value of 99.4%-100% in ruling out malignancy.3 Among women with postmenopausal bleeding, the risk of cancer is 7.3% if their endometrial lining is 5 mm or greater and less than 0.07% risk if their lining is 4 mm or less. Therefore, this cutoff dimension is typically used to triage patients to additional sampling.
If ultrasound is performed on postmenopausal women who are asymptomatic (no bleeding), then an endometrial stripe of greater than 11 mm is considered justification for further work-up and is associated with a 6.7% risk of endometrial cancer.4 If the ultrasound reveals intracavitary lesions, a sonohysterogram would be preferred to characterize intrauterine pathology. In fact, sonohysterography is superior to transvaginal ultrasound (with a sensitivity of 80% vs. 49%, respectively) in detecting endometrial polypoid lesions.5 Preoperative identification of an intracavitary lesion may assist in selecting the best sampling technique (blind vs. hysteroscopy-guided approach).
Endometrial sampling
If an ultrasound reveals a thickened or unevaluable endometrial stripe or if the clinician chooses to proceed directly with diagnostic confirmation, several options for endometrial sampling exist, including office-based or operative procedures, as well as blind or visually guided ones. Endometrial pipelle biopsy, D&C without hysteroscopy, endometrial lavage, and endometrial brush biopsy all constitute “blind” sampling techniques. Targeted biopsy techniques include hysteroscopy D&C and saline infusion sonohysterography–guided biopsy.
Blind D&C
Although D&C may be considered the gold standard of diagnostic sampling techniques, it should be noted that 60% of these procedures sample less than half of the endometrium.6 When used in conjunction with hysteroscopy, the sensitivity in detecting cancer is high at 97% with a specificity of 93%-100%.7
While some patients are candidates for office-based procedures, D&C often requires regional or general anesthesia and is frequently performed in a hospital-based environment or surgical center. This may be most appropriate for patients who have had failed office attempts at sampling, have multiple medical comorbidities that limit the feasibility of office-based procedures (such as morbid obesity), or have severe cervical stenosis. D&C is associated with an increased risk for uterine perforation, compared with outpatient sampling procedures.
The need to go to the operating room rather than to an ambulatory setting also may increase the costs borne by the patient. The advantages of D&C include the potential for large-volume sampling and the potentially therapeutic nature of the procedure in cases of benign pathology.
Office-based procedures
Office-based sampling techniques include those using a pipelle, those employing an endometrial brush, and those guided by saline infusion sonohysterography. If performed in the office, they require minimal or no cervical dilation, are associated with a lower risk of perforation or adverse reaction to anesthesia, and usually have lower costs for patients.
Endometrial pipelle biopsies are a very effective diagnostic tool when there is global, endometrial pathology; they have a sensitivity of 83% in confirming cancer.8 It is an inexpensive and technically straightforward technique that can be easily performed in an office setting.
However, when the endometrial lining is atrophied, alternative tools may provide superior results. Endometrial brushes have been shown to be 33% more successful in collecting adequate samples,compared with pipelles, because they sample a larger endometrial surface area.9
There is ongoing development of sampling techniques, such as endometrial lavage or the combination of saline infusion sonohysterography and endometrial biopsy.10 However, future studies regarding accuracy, cost, and patient acceptability are needed before these techniques are translated to the clinical setting.
Targeted endometrial sampling
Targeted or visually guided sampling, such as hysteroscopy, has been shown to be very accurate in identifying benign pathology, although the sensitivity of hysteroscopic diagnosis of cancer is significantly lower at approximately 50%.11 Therefore, the benefit of hysteroscopy is in complementing the blind nature of D&C by guiding sampling of intracavitary lesions, should they exist.
Hysteroscopy is safe in endometrial cancer and is not associated with upstaging the cancer from transtubal extirpation of malignant cells.12
The addition of hysteroscopy contributes some cost and equipment to the blind D&C procedure; therefore, it might be best applied in cases where there is known intracavitary pathology or inadequate prior sampling. In well-selected patients, hysteroscopy often can be used in an office setting, which improves the practicality of the procedure. Smaller and, in some cases, disposable equipment aids in the feasibility of adding visual guidance to office sampling.
Optimizing sampling
Postmenopausal women have a higher risk for sampling failure, compared with younger women. Obesity also is a risk for failed sampling.13 Cervical ripening with misoprostol may increase access to the endometrial cavity, and ultrasound guidance may decrease the risk of uterine perforation in a stenotic cervix.
Clinicians should ensure that histology results are concordant with clinical data. Discordant results should be reevaluated. For example, if an ultrasound demonstrates a thickened endometrial stripe, but the sampling reveals “scant atrophic tissue,” then there is unexplained pathology to address. Further work-up, such as more comprehensive sampling with hysteroscopy, should be considered in such cases. Additionally, persistent postmenopausal bleeding, despite a benign endometrial biopsy, should be reevaluated over time to rule out occult disease missed during prior sampling.
Clinicians are now equipped with multiple ways of obtaining clinical data, and patients have options that may decrease barriers to their care. Hysteroscopy does not improve upon D&C in the diagnosis of endometrial cancer, although it may be helpful in distinguishing and treating nonmalignant lesions.
Dr. Cotangco is a resident in the department of obstetrics and gynecology at the University of Illinois, Chicago. Dr. Rossi is an assistant professor in the division of gynecologic oncology at the University of North Carolina, Chapel Hill. They reported having no relevant financial disclosures.
References
1. Acta Obstet Gynecol Scand. 2004 Feb;83(2):203-7.
2. Menopause Int. 2010 Mar;16(1):5-8.
3. Obstet Gynecol. 2009 Aug;114(2 Pt 1):409-11.
4. Ultrasound Obstet Gynecol. 2004 Oct;24(5):558-65.
5. Ultrasound Obstet Gynecol. 2001 Aug;18(2):157-62.
6. Am J Obstet Gynecol. 2009 Jul;201(1):5-11.
7. Obstet Gynecol Clin North Am. 2000 Jun;27(2):235-44.
8. J Reprod Med. 1995 Aug;40(8):553-5.
9. BJOG. 2008 Jul;115(8):1028-36.
10. PLoS Med. 2016 Dec. doi: 10.1371/journal.pmed.1002206.
11. Arch Gynecol Obstet. 2012 Mar;285(3):839-43.
12. Am J Obstet Gynecol. 2012 Jul;207(1):71.e1-5.
13. Gynecol Oncol. 2017 Feb;144(2):324-8.
Postmenopausal bleeding is a symptom that can announce the presence of a gynecologic malignancy. In this column, we will discuss the important considerations to make in the work-up of this symptom.
Roughly 10% of women will present for evaluation of postmenopausal bleeding.1 More than a third of these women will have benign pathology, with the incidence of endometrial cancer in this group at only about 5%.2 Other gynecologic malignancies should be considered as well, including cervical, vaginal, vulvar, and more rarely, those of the fallopian tubes or ovaries.
Use of ultrasound
Ultrasound is a commonly performed initial approach to work-up because of its noninvasive nature. Transvaginal ultrasound has a high negative predictive value of 99.4%-100% in ruling out malignancy.3 Among women with postmenopausal bleeding, the risk of cancer is 7.3% if their endometrial lining is 5 mm or greater and less than 0.07% risk if their lining is 4 mm or less. Therefore, this cutoff dimension is typically used to triage patients to additional sampling.
If ultrasound is performed on postmenopausal women who are asymptomatic (no bleeding), then an endometrial stripe of greater than 11 mm is considered justification for further work-up and is associated with a 6.7% risk of endometrial cancer.4 If the ultrasound reveals intracavitary lesions, a sonohysterogram would be preferred to characterize intrauterine pathology. In fact, sonohysterography is superior to transvaginal ultrasound (with a sensitivity of 80% vs. 49%, respectively) in detecting endometrial polypoid lesions.5 Preoperative identification of an intracavitary lesion may assist in selecting the best sampling technique (blind vs. hysteroscopy-guided approach).
Endometrial sampling
If an ultrasound reveals a thickened or unevaluable endometrial stripe or if the clinician chooses to proceed directly with diagnostic confirmation, several options for endometrial sampling exist, including office-based or operative procedures, as well as blind or visually guided ones. Endometrial pipelle biopsy, D&C without hysteroscopy, endometrial lavage, and endometrial brush biopsy all constitute “blind” sampling techniques. Targeted biopsy techniques include hysteroscopy D&C and saline infusion sonohysterography–guided biopsy.
Blind D&C
Although D&C may be considered the gold standard of diagnostic sampling techniques, it should be noted that 60% of these procedures sample less than half of the endometrium.6 When used in conjunction with hysteroscopy, the sensitivity in detecting cancer is high at 97% with a specificity of 93%-100%.7
While some patients are candidates for office-based procedures, D&C often requires regional or general anesthesia and is frequently performed in a hospital-based environment or surgical center. This may be most appropriate for patients who have had failed office attempts at sampling, have multiple medical comorbidities that limit the feasibility of office-based procedures (such as morbid obesity), or have severe cervical stenosis. D&C is associated with an increased risk for uterine perforation, compared with outpatient sampling procedures.
The need to go to the operating room rather than to an ambulatory setting also may increase the costs borne by the patient. The advantages of D&C include the potential for large-volume sampling and the potentially therapeutic nature of the procedure in cases of benign pathology.
Office-based procedures
Office-based sampling techniques include those using a pipelle, those employing an endometrial brush, and those guided by saline infusion sonohysterography. If performed in the office, they require minimal or no cervical dilation, are associated with a lower risk of perforation or adverse reaction to anesthesia, and usually have lower costs for patients.
Endometrial pipelle biopsies are a very effective diagnostic tool when there is global, endometrial pathology; they have a sensitivity of 83% in confirming cancer.8 It is an inexpensive and technically straightforward technique that can be easily performed in an office setting.
However, when the endometrial lining is atrophied, alternative tools may provide superior results. Endometrial brushes have been shown to be 33% more successful in collecting adequate samples,compared with pipelles, because they sample a larger endometrial surface area.9
There is ongoing development of sampling techniques, such as endometrial lavage or the combination of saline infusion sonohysterography and endometrial biopsy.10 However, future studies regarding accuracy, cost, and patient acceptability are needed before these techniques are translated to the clinical setting.
Targeted endometrial sampling
Targeted or visually guided sampling, such as hysteroscopy, has been shown to be very accurate in identifying benign pathology, although the sensitivity of hysteroscopic diagnosis of cancer is significantly lower at approximately 50%.11 Therefore, the benefit of hysteroscopy is in complementing the blind nature of D&C by guiding sampling of intracavitary lesions, should they exist.
Hysteroscopy is safe in endometrial cancer and is not associated with upstaging the cancer from transtubal extirpation of malignant cells.12
The addition of hysteroscopy contributes some cost and equipment to the blind D&C procedure; therefore, it might be best applied in cases where there is known intracavitary pathology or inadequate prior sampling. In well-selected patients, hysteroscopy often can be used in an office setting, which improves the practicality of the procedure. Smaller and, in some cases, disposable equipment aids in the feasibility of adding visual guidance to office sampling.
Optimizing sampling
Postmenopausal women have a higher risk for sampling failure, compared with younger women. Obesity also is a risk for failed sampling.13 Cervical ripening with misoprostol may increase access to the endometrial cavity, and ultrasound guidance may decrease the risk of uterine perforation in a stenotic cervix.
Clinicians should ensure that histology results are concordant with clinical data. Discordant results should be reevaluated. For example, if an ultrasound demonstrates a thickened endometrial stripe, but the sampling reveals “scant atrophic tissue,” then there is unexplained pathology to address. Further work-up, such as more comprehensive sampling with hysteroscopy, should be considered in such cases. Additionally, persistent postmenopausal bleeding, despite a benign endometrial biopsy, should be reevaluated over time to rule out occult disease missed during prior sampling.
Clinicians are now equipped with multiple ways of obtaining clinical data, and patients have options that may decrease barriers to their care. Hysteroscopy does not improve upon D&C in the diagnosis of endometrial cancer, although it may be helpful in distinguishing and treating nonmalignant lesions.
Dr. Cotangco is a resident in the department of obstetrics and gynecology at the University of Illinois, Chicago. Dr. Rossi is an assistant professor in the division of gynecologic oncology at the University of North Carolina, Chapel Hill. They reported having no relevant financial disclosures.
References
1. Acta Obstet Gynecol Scand. 2004 Feb;83(2):203-7.
2. Menopause Int. 2010 Mar;16(1):5-8.
3. Obstet Gynecol. 2009 Aug;114(2 Pt 1):409-11.
4. Ultrasound Obstet Gynecol. 2004 Oct;24(5):558-65.
5. Ultrasound Obstet Gynecol. 2001 Aug;18(2):157-62.
6. Am J Obstet Gynecol. 2009 Jul;201(1):5-11.
7. Obstet Gynecol Clin North Am. 2000 Jun;27(2):235-44.
8. J Reprod Med. 1995 Aug;40(8):553-5.
9. BJOG. 2008 Jul;115(8):1028-36.
10. PLoS Med. 2016 Dec. doi: 10.1371/journal.pmed.1002206.
11. Arch Gynecol Obstet. 2012 Mar;285(3):839-43.
12. Am J Obstet Gynecol. 2012 Jul;207(1):71.e1-5.
13. Gynecol Oncol. 2017 Feb;144(2):324-8.
Did long-term follow-up of WHI participants reveal any mortality increase among women who received HT?
EXPERT COMMENTARY
A 2013 report from the Women’s Health Initiative (WHI), the large National Institutes of Health–funded placebo-controlledrandomized trial of postmenopausal hormone therapy (HT) with oral estrogen (for women with hysterectomy) or estrogen-progestin (for women with an intact uterus), with 13 years of cumulative follow-up, documented the safety of systemic HT when initiated by women younger than 60 years of age or within 10 years of menopause onset.1 Now, with 18 years of cumulative follow-up data available (intervention and extended postintervention phases), the WHI investigators present all-cause and cause-specific mortality outcomes from the 2 HT trials.
Related article:
2017 Update on menopause
Details of the study
A total of 27,347 WHI participants (baseline mean age, 63.4 years; 80.6% white) used oral estrogen-progestin therapy (EPT) or placebo for a median of 5.6 years (n = 16,608) or estrogen-only therapy (ET) or placebo for a median of 7.2 years (n = 10,739). Each hazard ratio (HR) reported below refers to 18-year cumulative follow-up.
All-cause mortality. In the overall pooled cohort (EPT and ET groups), all-cause mortality was similar, with a rate of 27.1% in the HT group and 27.6% in the placebo group (HR, 0.99; 95% confidence interval [CI], 0.94–1.03). The mortality end points included deaths from all causes; cardiovascular disease (coronary heart disease, stroke, and other cardiovascular diseases); cancer (breast, colorectal, and other cancers); and other (Alzheimer disease, other dementia, chronic obstructive pulmonary disease, injuries and accidents, and other).
Stratifying by baseline participant age (comparing women aged 50–59 years with those aged 70–79 years), the HR for all-cause mortality in the pooled cohort during the intervention phase was 0.61 (95% CI, 0.43–0.87), and during the cumulative 18-year follow-up, the HR was 0.87 (95% CI, 0.76–1.00).
Cause-specific mortality. Neither cardiovascular disease mortality nor total cancer mortality was significantly impacted by HT use. In the pooled cohort, cardiovascular disease mortality was 8.9% in the HT group and 9.0% in the placebo group (HR, 1.00; 95% CI, 0.92–1.08), with no differences between the EPT and the ET trials. Cancer mortality rates in the pooled cohort also were similar, with 8.2% in the HT group and 8.0% in the placebo group (HR, 1.03; 95% CI, 0.95–1.12).
With respect to breast cancer mortality, the impact of HT diverged for EPT and ET. For the EPT group, the HR for breast cancer mortality was 1.44 (95% CI, 0.97–2.15; P = .07), while for the ET group the HR was 0.55 (95% CI, 0.33–0.92; P = .02).
Related articles:
Does the discontinuation of menopausal hormone therapy affect a woman’s cardiovascular risk?
Study strengths and weaknesses
The WHI represents the largest randomized placebo-controlled trials of HT. The current WHI trials report provides new, cumulative 18-year follow-up data on all-cause and cause-specific mortality in women treated with HT or placebo.
The authors noted, however, that the use of only one HT dose, formulation, and route of administration in each trial may limit the generalizability of the study results to other HT preparations. For example, the WHI did not examine the transdermal route of estrogen administration. Likewise, the WHI did not examine use of progestational agents other than medroxyprogesterone acetate. In addition, while almost all cohort deaths were captured through the National Death Index for the data analyses, specificity of cause of death may vary across outcomes. Further, since multiple outcomes and subgroups were examined, clinicians should interpret cause-specific mortality rates with caution.
Given the complex impact of HT, all-cause mortality represents an important summary outcome in assessing the safety of 5 to 7 years of HT use. This report's reassuring findings regarding the safety of HT support the guidance from The North American Menopause Society and the Endocrine Society, which endorse the use of HT for symptomatic recently menopausal women without contraindications.2,3
--ANDREW M. KAUNITZ, MD
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.
- Manson JE, Chlebowski RT, Stefanick ML, et al. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women's Health Initiative randomized trials. JAMA. 2013;310(13):1353-1368.
- The 2017 hormone therapy position statement of The North American Menopause Society. Menopause. 2017;24(7):728-753.
- Stuenkel CA, Davis SR, Gompel A, et al. Treatment of symptoms of the menopause: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2015;100(11):3975-4011.
EXPERT COMMENTARY
A 2013 report from the Women’s Health Initiative (WHI), the large National Institutes of Health–funded placebo-controlledrandomized trial of postmenopausal hormone therapy (HT) with oral estrogen (for women with hysterectomy) or estrogen-progestin (for women with an intact uterus), with 13 years of cumulative follow-up, documented the safety of systemic HT when initiated by women younger than 60 years of age or within 10 years of menopause onset.1 Now, with 18 years of cumulative follow-up data available (intervention and extended postintervention phases), the WHI investigators present all-cause and cause-specific mortality outcomes from the 2 HT trials.
Related article:
2017 Update on menopause
Details of the study
A total of 27,347 WHI participants (baseline mean age, 63.4 years; 80.6% white) used oral estrogen-progestin therapy (EPT) or placebo for a median of 5.6 years (n = 16,608) or estrogen-only therapy (ET) or placebo for a median of 7.2 years (n = 10,739). Each hazard ratio (HR) reported below refers to 18-year cumulative follow-up.
All-cause mortality. In the overall pooled cohort (EPT and ET groups), all-cause mortality was similar, with a rate of 27.1% in the HT group and 27.6% in the placebo group (HR, 0.99; 95% confidence interval [CI], 0.94–1.03). The mortality end points included deaths from all causes; cardiovascular disease (coronary heart disease, stroke, and other cardiovascular diseases); cancer (breast, colorectal, and other cancers); and other (Alzheimer disease, other dementia, chronic obstructive pulmonary disease, injuries and accidents, and other).
Stratifying by baseline participant age (comparing women aged 50–59 years with those aged 70–79 years), the HR for all-cause mortality in the pooled cohort during the intervention phase was 0.61 (95% CI, 0.43–0.87), and during the cumulative 18-year follow-up, the HR was 0.87 (95% CI, 0.76–1.00).
Cause-specific mortality. Neither cardiovascular disease mortality nor total cancer mortality was significantly impacted by HT use. In the pooled cohort, cardiovascular disease mortality was 8.9% in the HT group and 9.0% in the placebo group (HR, 1.00; 95% CI, 0.92–1.08), with no differences between the EPT and the ET trials. Cancer mortality rates in the pooled cohort also were similar, with 8.2% in the HT group and 8.0% in the placebo group (HR, 1.03; 95% CI, 0.95–1.12).
With respect to breast cancer mortality, the impact of HT diverged for EPT and ET. For the EPT group, the HR for breast cancer mortality was 1.44 (95% CI, 0.97–2.15; P = .07), while for the ET group the HR was 0.55 (95% CI, 0.33–0.92; P = .02).
Related articles:
Does the discontinuation of menopausal hormone therapy affect a woman’s cardiovascular risk?
Study strengths and weaknesses
The WHI represents the largest randomized placebo-controlled trials of HT. The current WHI trials report provides new, cumulative 18-year follow-up data on all-cause and cause-specific mortality in women treated with HT or placebo.
The authors noted, however, that the use of only one HT dose, formulation, and route of administration in each trial may limit the generalizability of the study results to other HT preparations. For example, the WHI did not examine the transdermal route of estrogen administration. Likewise, the WHI did not examine use of progestational agents other than medroxyprogesterone acetate. In addition, while almost all cohort deaths were captured through the National Death Index for the data analyses, specificity of cause of death may vary across outcomes. Further, since multiple outcomes and subgroups were examined, clinicians should interpret cause-specific mortality rates with caution.
Given the complex impact of HT, all-cause mortality represents an important summary outcome in assessing the safety of 5 to 7 years of HT use. This report's reassuring findings regarding the safety of HT support the guidance from The North American Menopause Society and the Endocrine Society, which endorse the use of HT for symptomatic recently menopausal women without contraindications.2,3
--ANDREW M. KAUNITZ, MD
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.
EXPERT COMMENTARY
A 2013 report from the Women’s Health Initiative (WHI), the large National Institutes of Health–funded placebo-controlledrandomized trial of postmenopausal hormone therapy (HT) with oral estrogen (for women with hysterectomy) or estrogen-progestin (for women with an intact uterus), with 13 years of cumulative follow-up, documented the safety of systemic HT when initiated by women younger than 60 years of age or within 10 years of menopause onset.1 Now, with 18 years of cumulative follow-up data available (intervention and extended postintervention phases), the WHI investigators present all-cause and cause-specific mortality outcomes from the 2 HT trials.
Related article:
2017 Update on menopause
Details of the study
A total of 27,347 WHI participants (baseline mean age, 63.4 years; 80.6% white) used oral estrogen-progestin therapy (EPT) or placebo for a median of 5.6 years (n = 16,608) or estrogen-only therapy (ET) or placebo for a median of 7.2 years (n = 10,739). Each hazard ratio (HR) reported below refers to 18-year cumulative follow-up.
All-cause mortality. In the overall pooled cohort (EPT and ET groups), all-cause mortality was similar, with a rate of 27.1% in the HT group and 27.6% in the placebo group (HR, 0.99; 95% confidence interval [CI], 0.94–1.03). The mortality end points included deaths from all causes; cardiovascular disease (coronary heart disease, stroke, and other cardiovascular diseases); cancer (breast, colorectal, and other cancers); and other (Alzheimer disease, other dementia, chronic obstructive pulmonary disease, injuries and accidents, and other).
Stratifying by baseline participant age (comparing women aged 50–59 years with those aged 70–79 years), the HR for all-cause mortality in the pooled cohort during the intervention phase was 0.61 (95% CI, 0.43–0.87), and during the cumulative 18-year follow-up, the HR was 0.87 (95% CI, 0.76–1.00).
Cause-specific mortality. Neither cardiovascular disease mortality nor total cancer mortality was significantly impacted by HT use. In the pooled cohort, cardiovascular disease mortality was 8.9% in the HT group and 9.0% in the placebo group (HR, 1.00; 95% CI, 0.92–1.08), with no differences between the EPT and the ET trials. Cancer mortality rates in the pooled cohort also were similar, with 8.2% in the HT group and 8.0% in the placebo group (HR, 1.03; 95% CI, 0.95–1.12).
With respect to breast cancer mortality, the impact of HT diverged for EPT and ET. For the EPT group, the HR for breast cancer mortality was 1.44 (95% CI, 0.97–2.15; P = .07), while for the ET group the HR was 0.55 (95% CI, 0.33–0.92; P = .02).
Related articles:
Does the discontinuation of menopausal hormone therapy affect a woman’s cardiovascular risk?
Study strengths and weaknesses
The WHI represents the largest randomized placebo-controlled trials of HT. The current WHI trials report provides new, cumulative 18-year follow-up data on all-cause and cause-specific mortality in women treated with HT or placebo.
The authors noted, however, that the use of only one HT dose, formulation, and route of administration in each trial may limit the generalizability of the study results to other HT preparations. For example, the WHI did not examine the transdermal route of estrogen administration. Likewise, the WHI did not examine use of progestational agents other than medroxyprogesterone acetate. In addition, while almost all cohort deaths were captured through the National Death Index for the data analyses, specificity of cause of death may vary across outcomes. Further, since multiple outcomes and subgroups were examined, clinicians should interpret cause-specific mortality rates with caution.
Given the complex impact of HT, all-cause mortality represents an important summary outcome in assessing the safety of 5 to 7 years of HT use. This report's reassuring findings regarding the safety of HT support the guidance from The North American Menopause Society and the Endocrine Society, which endorse the use of HT for symptomatic recently menopausal women without contraindications.2,3
--ANDREW M. KAUNITZ, MD
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.
- Manson JE, Chlebowski RT, Stefanick ML, et al. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women's Health Initiative randomized trials. JAMA. 2013;310(13):1353-1368.
- The 2017 hormone therapy position statement of The North American Menopause Society. Menopause. 2017;24(7):728-753.
- Stuenkel CA, Davis SR, Gompel A, et al. Treatment of symptoms of the menopause: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2015;100(11):3975-4011.
- Manson JE, Chlebowski RT, Stefanick ML, et al. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women's Health Initiative randomized trials. JAMA. 2013;310(13):1353-1368.
- The 2017 hormone therapy position statement of The North American Menopause Society. Menopause. 2017;24(7):728-753.
- Stuenkel CA, Davis SR, Gompel A, et al. Treatment of symptoms of the menopause: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2015;100(11):3975-4011.
Beyond the Kegel: the who, why, and how of pelvic floor PT
PHILADELPHIA – When a woman is referred for pelvic floor physical therapy, what’s involved? Is there evidence behind the treatments, and what exactly does pelvic floor therapy look like?
Denise Hartzell Leggin, a physical therapist who specializes in pelvic floor dysfunction, reviewed how the female pelvic floor can change with age, and provided the rationale for pelvic floor physical therapy (PT) at the annual meeting of the North American Menopause Society.
“Physical therapists treat musculoskeletal and neuromuscular dysfunctions,” said Ms. Hartzell Leggin. So, when a physician suspects a musculoskeletal cause for pelvic floor dysfunction, a PT referral may be appropriate, she said.
Why refer for PT?
As part of the aging process, pelvic floor dysfunction can coexist with the genitourinary syndrome of menopause (GSM), said Ms. Hartzell. Though the pathophysiology is not always clear, aging does have some effect on the pelvic floor musculature and, together with GSM, can contribute to women’s urogenital symptoms in later life.
These symptoms, she said, can be the harbingers of “a host of clinical conditions,” including urinary incontinence and fecal incontinence, constipation, and bladder-emptying problems. Also, changes in the pelvic musculature from childbirth, surgeries, and hypotonicity or hypertonicity can contribute to sexual dysfunction in later life, said Ms. Hartzell Leggin, who is affiliated with Good Shepherd Penn Partners and in private practice in the Philadelphia area.
The musculature of the pelvic floor functions as more than a bowl for carrying the pelvic organs, Ms. Hartzell Leggin said. The collective muscles and fascia form a sling that fills in the pelvic ring and functions as an integrated system with constant resting tone. But the musculature is also active and interactive.
“The diaphragm and the pelvic floor move in symmetry during respiration,” and pelvic floor tone tightens in anticipation of increased intra-abdominal pressure from a cough, a sneeze, or even a laugh. “These are active structures – the brain can talk to the pelvic floor and make it do something,” she said.
Who’s a good candidate?
Looking at risk factors for pelvic organ prolapse alone, Ms. Hartzell Leggin said these can include age, body mass index, a history of occupational or recreational heavy lifting, chronic cough, and even genetics.
However, one of the most significant risk factors for prolapse of pelvic organs is simply having had a vaginal delivery. Up to 50% of women who have delivered a child vaginally may eventually have some degree of pelvic organ prolapse, though not all women will be symptomatic, Ms. Hartzell Leggin said.
Since postsurgical pelvic organ prolapse rates may top 30% within 2 years, an initial referral for pelvic floor PT is a rational conservative approach, she said. And even if a patient progresses to surgery, PT may be a useful adjunct.
Pelvic floor dysfunction may also be considered if a diastasis recti is discovered on physical exam, or if the patient reports a linear abdominal bulge. Patients with diastasis recti are more likely to have pelvic floor dysfunction than the general population, she said, so it’s worth asking about any related symptoms.
For voiding issues, “conservative treatment is first-line,” said Ms. Hartzell Leggin, so a PT referral for pelvic floor therapy and, in some cases, some behavioral retraining can help with issues of urinary frequency and urgency. These are options that may be considered before prescribing anticholinergic medication, she said.
How does pelvic floor PT work?
When a physician refers a patient for pelvic floor PT, what’s the process? The physical therapy evaluation will begin with history taking, including the chief complaint, past medical and surgical history, and an obstetric/gynecologic/sexual history, said Ms. Hartzell Leggin. Medications are also reviewed.
The physical therapist’s examination should encompass a thorough orthopedic examination, with attention to the lumbar spine and hips, and posture and gait. An external and internal examination of the pelvic floor will look for muscle tone at rest and with strain, and for any defects or prolapse.
Pelvic floor strength is assessed according to ability to contract, with some assessment of strength available through palpation. More quantitative means may include manometry, dynamometry, or the use of progressive weighted vaginal cones.
There’s no single standardized measurement tool to assess pelvic floor strength. Palpation is a valuable tool for an experienced clinician, and it also can provide real-time feedback to the patient as she becomes more aware of her pelvic floor. The discipline is moving toward more standardized terminology, with several reporting scales now available to report pelvic floor strength, said Ms. Hartzell Leggin.
The Pelvic Floor Distress Inventory is a validated tool that captures information about the impact of pelvic floor dysfunction on a patient’s daily functioning. “I think I capture a lot when my patient comes in and completes that form,” said Ms. Hartzell Leggin. The Genitourinary Pain Index is another validated tool that measures urinary symptoms, pain, and associated quality of life impacts. Patients may be asked to keep a home therapy and symptom or voiding diary for additional information.
The pelvic floor PT treatment algorithm will vary, depending on whether there’s underlying hypertonicity or hypotonicity, but will involve pelvic floor exercises, soft tissue mobilization, and consideration of a variety of modalities including electrical stimulation and ultrasound. For hypertonicity, vaginal dilators may be used, while weighted vaginal cones may be used for hypotonicity.
Physical therapists should know when to refer a patient back to a physician and should always work as part of an interdisciplinary team, she said.
Ms. Hartzell Leggin reported that she is the president of Elite Rehabilitation Services in Audubon, Pa.
[email protected]
On Twitter @karioakes
PHILADELPHIA – When a woman is referred for pelvic floor physical therapy, what’s involved? Is there evidence behind the treatments, and what exactly does pelvic floor therapy look like?
Denise Hartzell Leggin, a physical therapist who specializes in pelvic floor dysfunction, reviewed how the female pelvic floor can change with age, and provided the rationale for pelvic floor physical therapy (PT) at the annual meeting of the North American Menopause Society.
“Physical therapists treat musculoskeletal and neuromuscular dysfunctions,” said Ms. Hartzell Leggin. So, when a physician suspects a musculoskeletal cause for pelvic floor dysfunction, a PT referral may be appropriate, she said.
Why refer for PT?
As part of the aging process, pelvic floor dysfunction can coexist with the genitourinary syndrome of menopause (GSM), said Ms. Hartzell. Though the pathophysiology is not always clear, aging does have some effect on the pelvic floor musculature and, together with GSM, can contribute to women’s urogenital symptoms in later life.
These symptoms, she said, can be the harbingers of “a host of clinical conditions,” including urinary incontinence and fecal incontinence, constipation, and bladder-emptying problems. Also, changes in the pelvic musculature from childbirth, surgeries, and hypotonicity or hypertonicity can contribute to sexual dysfunction in later life, said Ms. Hartzell Leggin, who is affiliated with Good Shepherd Penn Partners and in private practice in the Philadelphia area.
The musculature of the pelvic floor functions as more than a bowl for carrying the pelvic organs, Ms. Hartzell Leggin said. The collective muscles and fascia form a sling that fills in the pelvic ring and functions as an integrated system with constant resting tone. But the musculature is also active and interactive.
“The diaphragm and the pelvic floor move in symmetry during respiration,” and pelvic floor tone tightens in anticipation of increased intra-abdominal pressure from a cough, a sneeze, or even a laugh. “These are active structures – the brain can talk to the pelvic floor and make it do something,” she said.
Who’s a good candidate?
Looking at risk factors for pelvic organ prolapse alone, Ms. Hartzell Leggin said these can include age, body mass index, a history of occupational or recreational heavy lifting, chronic cough, and even genetics.
However, one of the most significant risk factors for prolapse of pelvic organs is simply having had a vaginal delivery. Up to 50% of women who have delivered a child vaginally may eventually have some degree of pelvic organ prolapse, though not all women will be symptomatic, Ms. Hartzell Leggin said.
Since postsurgical pelvic organ prolapse rates may top 30% within 2 years, an initial referral for pelvic floor PT is a rational conservative approach, she said. And even if a patient progresses to surgery, PT may be a useful adjunct.
Pelvic floor dysfunction may also be considered if a diastasis recti is discovered on physical exam, or if the patient reports a linear abdominal bulge. Patients with diastasis recti are more likely to have pelvic floor dysfunction than the general population, she said, so it’s worth asking about any related symptoms.
For voiding issues, “conservative treatment is first-line,” said Ms. Hartzell Leggin, so a PT referral for pelvic floor therapy and, in some cases, some behavioral retraining can help with issues of urinary frequency and urgency. These are options that may be considered before prescribing anticholinergic medication, she said.
How does pelvic floor PT work?
When a physician refers a patient for pelvic floor PT, what’s the process? The physical therapy evaluation will begin with history taking, including the chief complaint, past medical and surgical history, and an obstetric/gynecologic/sexual history, said Ms. Hartzell Leggin. Medications are also reviewed.
The physical therapist’s examination should encompass a thorough orthopedic examination, with attention to the lumbar spine and hips, and posture and gait. An external and internal examination of the pelvic floor will look for muscle tone at rest and with strain, and for any defects or prolapse.
Pelvic floor strength is assessed according to ability to contract, with some assessment of strength available through palpation. More quantitative means may include manometry, dynamometry, or the use of progressive weighted vaginal cones.
There’s no single standardized measurement tool to assess pelvic floor strength. Palpation is a valuable tool for an experienced clinician, and it also can provide real-time feedback to the patient as she becomes more aware of her pelvic floor. The discipline is moving toward more standardized terminology, with several reporting scales now available to report pelvic floor strength, said Ms. Hartzell Leggin.
The Pelvic Floor Distress Inventory is a validated tool that captures information about the impact of pelvic floor dysfunction on a patient’s daily functioning. “I think I capture a lot when my patient comes in and completes that form,” said Ms. Hartzell Leggin. The Genitourinary Pain Index is another validated tool that measures urinary symptoms, pain, and associated quality of life impacts. Patients may be asked to keep a home therapy and symptom or voiding diary for additional information.
The pelvic floor PT treatment algorithm will vary, depending on whether there’s underlying hypertonicity or hypotonicity, but will involve pelvic floor exercises, soft tissue mobilization, and consideration of a variety of modalities including electrical stimulation and ultrasound. For hypertonicity, vaginal dilators may be used, while weighted vaginal cones may be used for hypotonicity.
Physical therapists should know when to refer a patient back to a physician and should always work as part of an interdisciplinary team, she said.
Ms. Hartzell Leggin reported that she is the president of Elite Rehabilitation Services in Audubon, Pa.
[email protected]
On Twitter @karioakes
PHILADELPHIA – When a woman is referred for pelvic floor physical therapy, what’s involved? Is there evidence behind the treatments, and what exactly does pelvic floor therapy look like?
Denise Hartzell Leggin, a physical therapist who specializes in pelvic floor dysfunction, reviewed how the female pelvic floor can change with age, and provided the rationale for pelvic floor physical therapy (PT) at the annual meeting of the North American Menopause Society.
“Physical therapists treat musculoskeletal and neuromuscular dysfunctions,” said Ms. Hartzell Leggin. So, when a physician suspects a musculoskeletal cause for pelvic floor dysfunction, a PT referral may be appropriate, she said.
Why refer for PT?
As part of the aging process, pelvic floor dysfunction can coexist with the genitourinary syndrome of menopause (GSM), said Ms. Hartzell. Though the pathophysiology is not always clear, aging does have some effect on the pelvic floor musculature and, together with GSM, can contribute to women’s urogenital symptoms in later life.
These symptoms, she said, can be the harbingers of “a host of clinical conditions,” including urinary incontinence and fecal incontinence, constipation, and bladder-emptying problems. Also, changes in the pelvic musculature from childbirth, surgeries, and hypotonicity or hypertonicity can contribute to sexual dysfunction in later life, said Ms. Hartzell Leggin, who is affiliated with Good Shepherd Penn Partners and in private practice in the Philadelphia area.
The musculature of the pelvic floor functions as more than a bowl for carrying the pelvic organs, Ms. Hartzell Leggin said. The collective muscles and fascia form a sling that fills in the pelvic ring and functions as an integrated system with constant resting tone. But the musculature is also active and interactive.
“The diaphragm and the pelvic floor move in symmetry during respiration,” and pelvic floor tone tightens in anticipation of increased intra-abdominal pressure from a cough, a sneeze, or even a laugh. “These are active structures – the brain can talk to the pelvic floor and make it do something,” she said.
Who’s a good candidate?
Looking at risk factors for pelvic organ prolapse alone, Ms. Hartzell Leggin said these can include age, body mass index, a history of occupational or recreational heavy lifting, chronic cough, and even genetics.
However, one of the most significant risk factors for prolapse of pelvic organs is simply having had a vaginal delivery. Up to 50% of women who have delivered a child vaginally may eventually have some degree of pelvic organ prolapse, though not all women will be symptomatic, Ms. Hartzell Leggin said.
Since postsurgical pelvic organ prolapse rates may top 30% within 2 years, an initial referral for pelvic floor PT is a rational conservative approach, she said. And even if a patient progresses to surgery, PT may be a useful adjunct.
Pelvic floor dysfunction may also be considered if a diastasis recti is discovered on physical exam, or if the patient reports a linear abdominal bulge. Patients with diastasis recti are more likely to have pelvic floor dysfunction than the general population, she said, so it’s worth asking about any related symptoms.
For voiding issues, “conservative treatment is first-line,” said Ms. Hartzell Leggin, so a PT referral for pelvic floor therapy and, in some cases, some behavioral retraining can help with issues of urinary frequency and urgency. These are options that may be considered before prescribing anticholinergic medication, she said.
How does pelvic floor PT work?
When a physician refers a patient for pelvic floor PT, what’s the process? The physical therapy evaluation will begin with history taking, including the chief complaint, past medical and surgical history, and an obstetric/gynecologic/sexual history, said Ms. Hartzell Leggin. Medications are also reviewed.
The physical therapist’s examination should encompass a thorough orthopedic examination, with attention to the lumbar spine and hips, and posture and gait. An external and internal examination of the pelvic floor will look for muscle tone at rest and with strain, and for any defects or prolapse.
Pelvic floor strength is assessed according to ability to contract, with some assessment of strength available through palpation. More quantitative means may include manometry, dynamometry, or the use of progressive weighted vaginal cones.
There’s no single standardized measurement tool to assess pelvic floor strength. Palpation is a valuable tool for an experienced clinician, and it also can provide real-time feedback to the patient as she becomes more aware of her pelvic floor. The discipline is moving toward more standardized terminology, with several reporting scales now available to report pelvic floor strength, said Ms. Hartzell Leggin.
The Pelvic Floor Distress Inventory is a validated tool that captures information about the impact of pelvic floor dysfunction on a patient’s daily functioning. “I think I capture a lot when my patient comes in and completes that form,” said Ms. Hartzell Leggin. The Genitourinary Pain Index is another validated tool that measures urinary symptoms, pain, and associated quality of life impacts. Patients may be asked to keep a home therapy and symptom or voiding diary for additional information.
The pelvic floor PT treatment algorithm will vary, depending on whether there’s underlying hypertonicity or hypotonicity, but will involve pelvic floor exercises, soft tissue mobilization, and consideration of a variety of modalities including electrical stimulation and ultrasound. For hypertonicity, vaginal dilators may be used, while weighted vaginal cones may be used for hypotonicity.
Physical therapists should know when to refer a patient back to a physician and should always work as part of an interdisciplinary team, she said.
Ms. Hartzell Leggin reported that she is the president of Elite Rehabilitation Services in Audubon, Pa.
[email protected]
On Twitter @karioakes
EXPERT ANALYSIS FROM NAMS 2017