Menopause

Vitamin D deficiency detected at the time of multiple sclerosis (MS) diagnosis is associated with cognitive impairment and may also impact disability, according to new research that adds to the known adverse relationship between low vitamin D and MS.

“We confirmed that low vitamin D may affect not only early disability but also cognition in newly MS diagnosed patients,” said lead author Eleonora Virgilio, MD, of the MS Center, neurology unit, at the University of Eastern Piedmont, Novara, Italy.

“The possible effects of vitamin D on both cognition (in particular, information processing speed) and early disability in newly diagnosed MS patients needs to be further investigated because this association might represent a marker of future disability, supporting the need for prompt supplementation,” she said.

The findings were presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
 

Low vitamin D and MS

Previous studies have linked insufficient serum vitamin D with everything from the development of MS to activity and disease progression, but less has been reported on a specific link to the impairment of cognitive function, an important complication of MS.

“Cognitive impairment, and, in particular, slowed information processing speed, is very frequent in the MS population from the early stages of disease, and frequently underestimated,” Dr. Virgilio noted. “It has yet to be completely elucidated what the exact underlying mechanisms are.”

To evaluate the relationship, Dr. Virgilio and colleagues enrolled 60 patients in Italy with MS who were newly diagnosed and had serum vitamin D levels collected upon diagnosis. The participants were also tested at diagnosis with the Symbol Digit Modalities Test (SDMT) for information processing speed, which is a hallmark of the cognitive impairment that can occur in MS and is typically the first cognitive domain to show effects of the disease.

Among the patients, 40 were female and the mean age at diagnosis was 39.5 years; 90% had relapsing remitting MS at baseline and 10% had progressive MS. Their median Expanded Disability Status Scale score at diagnosis was 1.5.

At baseline, as many as 85% of the participants (51) had low serum vitamin D levels, defined as below 30 ng/mL, which Dr. Virgilio noted is consistent with other rates reported among people with MS in the Lombardy region of Italy, where the study was conducted.

The patients had a mean vitamin D level of 21.17 ng/mL (± 10.02), with 51.7% considered to have a deficiency (less than 20 ng/mL) and 33.3% with an insufficiency (20-30 ng/mL).

Of the patients, 16 (27%) had cognitive impairment, defined as a z score of 1.5 or less. Their mean raw SDMT score was 46.50 (± 14.73) and mean z score was –0.62 (± 1.29).

Importantly, those with cognitive impairment were significantly more likely to have severe hypovitaminosis D, compared with those with sufficient vitamin D levels, none of whom showed cognitive impairment (P = .02).

Furthermore, vitamin D levels positively correlated with SDMT raw values (P = .001) and z score (P = .008).

Over a mean follow-up of 2 years, a significant correlation was observed between serum vitamin D levels at diagnosis and early disability on the MS severity score (MSSS; P = .02) and a weak correlation with age-related MSSS (ARMSS; P = .08) at the last clinical follow-up.

Dr. Virgilio noted that factors including disease treatment effects or other factors could have played a role in the weaker results. “It is possible that the linear correlation we found was not as strong as expected [because of] an effect of treatment with disease-modifying therapies or vitamin D supplementation, or because of the short follow-up available at the moment for our population – only for a mean period of 2 years after MS diagnosis.”

The mechanisms for vitamin D deficiency in the MS population are likely multifactorial, with genetic as well as environmental links, she noted.

“The immunomodulatory effects of vitamin D are well known,” Dr. Virgilio said.

“Vitamin D was already linked to cognitive function in other neurodegenerative diseases, [including] Alzheimer’s disease, but more importantly, also in other autoimmune diseases, such as systemic lupus erythematosus,” she explained.
 

Vitamin D also linked to long-term cognitive function

The study adds to recent research showing longer-term effects of vitamin D deficiency and cognitive impairment in MS: In the longitudinal BENEFIT trial published in 2020, researchers following 278 patients with MS over the course of 11 years found that a 50 ng/L higher mean vitamin D level in the first 2 years of the study was associated with a 65% lower odds of a poor performance on Paced Auditory Serial Addition Test scores at the 11-year follow-up.

That study also looked at neurofilament light chain concentrations, which are associated with MS disease activity, and found they were 20% lower among those with higher vitamin D at baseline. Smokers also had lower cognitive scores.

“Lower vitamin D and smoking after clinical onset predicted worse long-term cognitive function and neuronal integrity in patients with MS,” the authors concluded.

The authors disclosed no relevant financial relationships.

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

Vitamin D deficiency detected at the time of multiple sclerosis (MS) diagnosis is associated with cognitive impairment and may also impact disability, according to new research that adds to the known adverse relationship between low vitamin D and MS.

“We confirmed that low vitamin D may affect not only early disability but also cognition in newly MS diagnosed patients,” said lead author Eleonora Virgilio, MD, of the MS Center, neurology unit, at the University of Eastern Piedmont, Novara, Italy.

“The possible effects of vitamin D on both cognition (in particular, information processing speed) and early disability in newly diagnosed MS patients needs to be further investigated because this association might represent a marker of future disability, supporting the need for prompt supplementation,” she said.

The findings were presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
 

Low vitamin D and MS

Previous studies have linked insufficient serum vitamin D with everything from the development of MS to activity and disease progression, but less has been reported on a specific link to the impairment of cognitive function, an important complication of MS.

“Cognitive impairment, and, in particular, slowed information processing speed, is very frequent in the MS population from the early stages of disease, and frequently underestimated,” Dr. Virgilio noted. “It has yet to be completely elucidated what the exact underlying mechanisms are.”

To evaluate the relationship, Dr. Virgilio and colleagues enrolled 60 patients in Italy with MS who were newly diagnosed and had serum vitamin D levels collected upon diagnosis. The participants were also tested at diagnosis with the Symbol Digit Modalities Test (SDMT) for information processing speed, which is a hallmark of the cognitive impairment that can occur in MS and is typically the first cognitive domain to show effects of the disease.

Among the patients, 40 were female and the mean age at diagnosis was 39.5 years; 90% had relapsing remitting MS at baseline and 10% had progressive MS. Their median Expanded Disability Status Scale score at diagnosis was 1.5.

At baseline, as many as 85% of the participants (51) had low serum vitamin D levels, defined as below 30 ng/mL, which Dr. Virgilio noted is consistent with other rates reported among people with MS in the Lombardy region of Italy, where the study was conducted.

The patients had a mean vitamin D level of 21.17 ng/mL (± 10.02), with 51.7% considered to have a deficiency (less than 20 ng/mL) and 33.3% with an insufficiency (20-30 ng/mL).

Of the patients, 16 (27%) had cognitive impairment, defined as a z score of 1.5 or less. Their mean raw SDMT score was 46.50 (± 14.73) and mean z score was –0.62 (± 1.29).

Importantly, those with cognitive impairment were significantly more likely to have severe hypovitaminosis D, compared with those with sufficient vitamin D levels, none of whom showed cognitive impairment (P = .02).

Furthermore, vitamin D levels positively correlated with SDMT raw values (P = .001) and z score (P = .008).

Over a mean follow-up of 2 years, a significant correlation was observed between serum vitamin D levels at diagnosis and early disability on the MS severity score (MSSS; P = .02) and a weak correlation with age-related MSSS (ARMSS; P = .08) at the last clinical follow-up.

Dr. Virgilio noted that factors including disease treatment effects or other factors could have played a role in the weaker results. “It is possible that the linear correlation we found was not as strong as expected [because of] an effect of treatment with disease-modifying therapies or vitamin D supplementation, or because of the short follow-up available at the moment for our population – only for a mean period of 2 years after MS diagnosis.”

The mechanisms for vitamin D deficiency in the MS population are likely multifactorial, with genetic as well as environmental links, she noted.

“The immunomodulatory effects of vitamin D are well known,” Dr. Virgilio said.

“Vitamin D was already linked to cognitive function in other neurodegenerative diseases, [including] Alzheimer’s disease, but more importantly, also in other autoimmune diseases, such as systemic lupus erythematosus,” she explained.
 

Vitamin D also linked to long-term cognitive function

The study adds to recent research showing longer-term effects of vitamin D deficiency and cognitive impairment in MS: In the longitudinal BENEFIT trial published in 2020, researchers following 278 patients with MS over the course of 11 years found that a 50 ng/L higher mean vitamin D level in the first 2 years of the study was associated with a 65% lower odds of a poor performance on Paced Auditory Serial Addition Test scores at the 11-year follow-up.

That study also looked at neurofilament light chain concentrations, which are associated with MS disease activity, and found they were 20% lower among those with higher vitamin D at baseline. Smokers also had lower cognitive scores.

“Lower vitamin D and smoking after clinical onset predicted worse long-term cognitive function and neuronal integrity in patients with MS,” the authors concluded.

The authors disclosed no relevant financial relationships.

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

Vitamin D deficiency detected at the time of multiple sclerosis (MS) diagnosis is associated with cognitive impairment and may also impact disability, according to new research that adds to the known adverse relationship between low vitamin D and MS.

“We confirmed that low vitamin D may affect not only early disability but also cognition in newly MS diagnosed patients,” said lead author Eleonora Virgilio, MD, of the MS Center, neurology unit, at the University of Eastern Piedmont, Novara, Italy.

“The possible effects of vitamin D on both cognition (in particular, information processing speed) and early disability in newly diagnosed MS patients needs to be further investigated because this association might represent a marker of future disability, supporting the need for prompt supplementation,” she said.

The findings were presented at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.
 

Low vitamin D and MS

Previous studies have linked insufficient serum vitamin D with everything from the development of MS to activity and disease progression, but less has been reported on a specific link to the impairment of cognitive function, an important complication of MS.

“Cognitive impairment, and, in particular, slowed information processing speed, is very frequent in the MS population from the early stages of disease, and frequently underestimated,” Dr. Virgilio noted. “It has yet to be completely elucidated what the exact underlying mechanisms are.”

To evaluate the relationship, Dr. Virgilio and colleagues enrolled 60 patients in Italy with MS who were newly diagnosed and had serum vitamin D levels collected upon diagnosis. The participants were also tested at diagnosis with the Symbol Digit Modalities Test (SDMT) for information processing speed, which is a hallmark of the cognitive impairment that can occur in MS and is typically the first cognitive domain to show effects of the disease.

Among the patients, 40 were female and the mean age at diagnosis was 39.5 years; 90% had relapsing remitting MS at baseline and 10% had progressive MS. Their median Expanded Disability Status Scale score at diagnosis was 1.5.

At baseline, as many as 85% of the participants (51) had low serum vitamin D levels, defined as below 30 ng/mL, which Dr. Virgilio noted is consistent with other rates reported among people with MS in the Lombardy region of Italy, where the study was conducted.

The patients had a mean vitamin D level of 21.17 ng/mL (± 10.02), with 51.7% considered to have a deficiency (less than 20 ng/mL) and 33.3% with an insufficiency (20-30 ng/mL).

Of the patients, 16 (27%) had cognitive impairment, defined as a z score of 1.5 or less. Their mean raw SDMT score was 46.50 (± 14.73) and mean z score was –0.62 (± 1.29).

Importantly, those with cognitive impairment were significantly more likely to have severe hypovitaminosis D, compared with those with sufficient vitamin D levels, none of whom showed cognitive impairment (P = .02).

Furthermore, vitamin D levels positively correlated with SDMT raw values (P = .001) and z score (P = .008).

Over a mean follow-up of 2 years, a significant correlation was observed between serum vitamin D levels at diagnosis and early disability on the MS severity score (MSSS; P = .02) and a weak correlation with age-related MSSS (ARMSS; P = .08) at the last clinical follow-up.

Dr. Virgilio noted that factors including disease treatment effects or other factors could have played a role in the weaker results. “It is possible that the linear correlation we found was not as strong as expected [because of] an effect of treatment with disease-modifying therapies or vitamin D supplementation, or because of the short follow-up available at the moment for our population – only for a mean period of 2 years after MS diagnosis.”

The mechanisms for vitamin D deficiency in the MS population are likely multifactorial, with genetic as well as environmental links, she noted.

“The immunomodulatory effects of vitamin D are well known,” Dr. Virgilio said.

“Vitamin D was already linked to cognitive function in other neurodegenerative diseases, [including] Alzheimer’s disease, but more importantly, also in other autoimmune diseases, such as systemic lupus erythematosus,” she explained.
 

Vitamin D also linked to long-term cognitive function

The study adds to recent research showing longer-term effects of vitamin D deficiency and cognitive impairment in MS: In the longitudinal BENEFIT trial published in 2020, researchers following 278 patients with MS over the course of 11 years found that a 50 ng/L higher mean vitamin D level in the first 2 years of the study was associated with a 65% lower odds of a poor performance on Paced Auditory Serial Addition Test scores at the 11-year follow-up.

That study also looked at neurofilament light chain concentrations, which are associated with MS disease activity, and found they were 20% lower among those with higher vitamin D at baseline. Smokers also had lower cognitive scores.

“Lower vitamin D and smoking after clinical onset predicted worse long-term cognitive function and neuronal integrity in patients with MS,” the authors concluded.

The authors disclosed no relevant financial relationships.

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

Menopause is a key time to monitor women for the development or increase of cardiovascular risk factors, according to a new consensus statement developed by the Task Force on Gender of the European Society of Cardiology and a multidisciplinary ESC working group on Women’s Health in Menopause.

“After menopause, traditional cardiovascular risk factors are adversely affected – particularly hypertension,” wrote Angela H.E.M. Maas, MD, of Radboud University Medical Center, Nijmegen, Netherlands, and colleagues.

“Since the first ESC consensus paper on the management of cardiovascular risk in perimenopausal women was published in 2007, we have a greater understanding on the role of female-specific risk factors for cardiovascular disease (CVD),” they said.

In a consensus statement published in the European Heart Journal, the authors presented clinical guidance for diagnosis and management of cardiovascular risk factors during the menopause transition. The transition to menopause increases a woman’s risk for developing several CVD risk factors, including central adiposity, increased insulin resistance, a proatherogenic lipid profile, and autonomic dysfunction that can contribute to increased heart rate variability, according to the statement.

Estrogen changes may affect ischemic disease

In general, obstructive coronary artery disease (CAD) strikes women later than men, but coronary vasomotor conditions are a common cause of ischemic heart disease in women with or without CAD, the authors noted.

“Lower estrogen levels after menopause are related to altered vascular function, enhanced inflammation, and up-regulation of other hormonal systems such as the renin–angiotensin–aldosterone system, the sympathetic nervous system, and reduced nitric oxide–dependent vasodilation,” they wrote. They recommended use of the coronary artery calcium score for screening middle-aged women who are symptomatic or at intermediate cardiovascular risk.

The transition to menopause causes changes in lipid profiles, and a rise in blood pressure in particular “may be both a direct effect of hormonal changes on the vasculature and metabolic changes with aging,” but hypertension in early post menopause is “often poorly managed,” the authors noted.

Compared with asymptomatic women, women who suffer from severe menopausal symptoms often have increased cardiovascular disease risk factors. For example, the Women’s Health Initiative (WHI) study showed a 48% increased risk of incident diabetes at follow-up in women with severe symptoms of hot flashes and night sweats, the authors wrote. Clinicians should also be aware of the increased immune reactivity that occurs during and after menopause and the increased CVD risk associated with autoimmune and endocrine disorders, they said.
 

Multiple strategies to reduce risk

Strategies to address the cardiovascular risk in menopause include assessing glucose, lipid levels, and blood pressure during the transition to menopause, according to the statement.

In addition, they recommended increasing employer awareness of menopause, as changes may interfere with working ability. A healthy lifestyle including healthy diet and regular exercise can help reduce cardiovascular risks and relieve symptoms. Menopausal hormone therapy (MHT) may be indicated to relieve symptoms, including symptoms of depression, and provide cardioprotection for younger women around the time of menopause, according to the statement.

However, “MHT is not recommended in women at high CV risk and after a previous CVD event,” and all women should be assessed for cardiovascular risk factors before starting MHT, they emphasized.
 

Results raise awareness of cardiovascular health and menopause link

“Over the past 20 years, our knowledge of how menopause might contribute to cardiovascular disease has dramatically evolved,” said Samar El Khoudary, MD, of the University of Pittsburg, in an interview.

“We have accumulated data that consistently point to the menopause transition as a time of change in cardiovascular health. As such, there is a compelling need to discuss the implications of the accumulating body of literature on this topic,” she said. “The goal is to raise awareness for both health care providers and women of the significant adverse cardiovascular health changes accompanying the menopause transition and to point out the importance of adopting prevention strategies early during this stage,” she explained.

The impact of the hormonal changes of menopause on CVD risk “is very complex,” Dr. El Khoudary said. “Until now, we could not prove that using estrogen therapy is cardioprotective,” she emphasized. “Studies point to the need to consider the timing of hormone use, as well as types and route of administration,” she noted. “The truth is that, although the menopause transition is associated with an acceleration in CVD risk, the exact mechanism still is not completely clear. Hormone changes contribute, but they are not the ultimate contributor,” she added.

 

Research gaps include data on lifestyle and behavioral interventions

“Irrespective of the accumulating findings showing adverse changes in multiple cardiovascular health parameters, as women transition through menopause, we do not have data documenting current status of ideal cardiovascular health components during the menopause transition among women,” said Dr. El Khoudary. “The limited data we have [suggest] that a very small proportion of women transitioning through menopause eat a healthy diet (less than 20%) or practice physical activity (about7.2%) at a level that matches the current recommendations,” she noted.

“Lifestyle and behavioral interventions are critical to maintain a healthy heart and reduce heart disease; we do not have adequate randomized clinical trials testing these interventions specifically during the menopause transition,” she said.

“Similarly, we are in need of randomized clinical trials of therapeutic interventions such as lipid-lowering medications and menopause hormone therapy in women transitioning through menopause,” said Dr. El Khoudary. “This high-risk population has not been the focus of previous clinical trials, leaving us with questions of how the results from these studies might apply to women during the menopause transition,” she said.
 

Consensus invites collaboration

“I commend the group for putting together a statement that crosses practice and specialty boundaries,” said Lubna Pal, MD, of Yale School of Medicine, New Haven, Conn., in an interview. Although the statement does not present novel information, it “has the power of unifying the various providers by bringing focus on the individual elements spanning a woman’s life that cumulatively determine her lifetime health risk,” she said. Preeclampsia may be a risk factor for cardiovascular disease later in life, and events in reproductive age may determine a woman’s trajectory during the transition to menopause and beyond, Dr. Pal noted.

“The consensus statement will likely be read by internists and family medicine providers as well as ob.gyns.; it encourages all those involved in caring for female patients to take on the responsibility of ‘passing on the baton,’ such that all women who are deemed at an enhanced risk for cardiovascular disease are assured due diligence in care through stringent surveillance and timely interventions,” said Dr. Pal. “It is a call for the various providers who care for women at distinct stages of life to work together toward a shared goal of optimizing every woman’s health across her lifespan,” she said.

“More research is needed for us to better understand the mechanisms at play” in the development of cardiovascular risk and in understanding the continuity of changes across women’s lifespans, Dr. Pal said. “We have associations, but not much information about causation,” she emphasized. However, the statement promotes the dissemination of information about women’s health and sensitizes providers to the potential and the power of preventive care. “We should be much more liberal and loud in holding conversations about risk quantification and risk reduction, and this statement is a resounding effort toward identifying and mitigating long-term cardiovascular risk, even if only through promoting a healthier lifestyle in those deemed at risk,” she added.  

The statement received no outside funding. Lead author Dr. Maas had no financial conflicts to disclose. Dr. El Khoudary had no financial conflicts to disclose. Dr. Pal had no relevant financial conflicts to disclose.

Menopause is a key time to monitor women for the development or increase of cardiovascular risk factors, according to a new consensus statement developed by the Task Force on Gender of the European Society of Cardiology and a multidisciplinary ESC working group on Women’s Health in Menopause.

“After menopause, traditional cardiovascular risk factors are adversely affected – particularly hypertension,” wrote Angela H.E.M. Maas, MD, of Radboud University Medical Center, Nijmegen, Netherlands, and colleagues.

“Since the first ESC consensus paper on the management of cardiovascular risk in perimenopausal women was published in 2007, we have a greater understanding on the role of female-specific risk factors for cardiovascular disease (CVD),” they said.

In a consensus statement published in the European Heart Journal, the authors presented clinical guidance for diagnosis and management of cardiovascular risk factors during the menopause transition. The transition to menopause increases a woman’s risk for developing several CVD risk factors, including central adiposity, increased insulin resistance, a proatherogenic lipid profile, and autonomic dysfunction that can contribute to increased heart rate variability, according to the statement.

Estrogen changes may affect ischemic disease

In general, obstructive coronary artery disease (CAD) strikes women later than men, but coronary vasomotor conditions are a common cause of ischemic heart disease in women with or without CAD, the authors noted.

“Lower estrogen levels after menopause are related to altered vascular function, enhanced inflammation, and up-regulation of other hormonal systems such as the renin–angiotensin–aldosterone system, the sympathetic nervous system, and reduced nitric oxide–dependent vasodilation,” they wrote. They recommended use of the coronary artery calcium score for screening middle-aged women who are symptomatic or at intermediate cardiovascular risk.

The transition to menopause causes changes in lipid profiles, and a rise in blood pressure in particular “may be both a direct effect of hormonal changes on the vasculature and metabolic changes with aging,” but hypertension in early post menopause is “often poorly managed,” the authors noted.

Compared with asymptomatic women, women who suffer from severe menopausal symptoms often have increased cardiovascular disease risk factors. For example, the Women’s Health Initiative (WHI) study showed a 48% increased risk of incident diabetes at follow-up in women with severe symptoms of hot flashes and night sweats, the authors wrote. Clinicians should also be aware of the increased immune reactivity that occurs during and after menopause and the increased CVD risk associated with autoimmune and endocrine disorders, they said.
 

Multiple strategies to reduce risk

Strategies to address the cardiovascular risk in menopause include assessing glucose, lipid levels, and blood pressure during the transition to menopause, according to the statement.

In addition, they recommended increasing employer awareness of menopause, as changes may interfere with working ability. A healthy lifestyle including healthy diet and regular exercise can help reduce cardiovascular risks and relieve symptoms. Menopausal hormone therapy (MHT) may be indicated to relieve symptoms, including symptoms of depression, and provide cardioprotection for younger women around the time of menopause, according to the statement.

However, “MHT is not recommended in women at high CV risk and after a previous CVD event,” and all women should be assessed for cardiovascular risk factors before starting MHT, they emphasized.
 

Results raise awareness of cardiovascular health and menopause link

“Over the past 20 years, our knowledge of how menopause might contribute to cardiovascular disease has dramatically evolved,” said Samar El Khoudary, MD, of the University of Pittsburg, in an interview.

“We have accumulated data that consistently point to the menopause transition as a time of change in cardiovascular health. As such, there is a compelling need to discuss the implications of the accumulating body of literature on this topic,” she said. “The goal is to raise awareness for both health care providers and women of the significant adverse cardiovascular health changes accompanying the menopause transition and to point out the importance of adopting prevention strategies early during this stage,” she explained.

The impact of the hormonal changes of menopause on CVD risk “is very complex,” Dr. El Khoudary said. “Until now, we could not prove that using estrogen therapy is cardioprotective,” she emphasized. “Studies point to the need to consider the timing of hormone use, as well as types and route of administration,” she noted. “The truth is that, although the menopause transition is associated with an acceleration in CVD risk, the exact mechanism still is not completely clear. Hormone changes contribute, but they are not the ultimate contributor,” she added.

 

Research gaps include data on lifestyle and behavioral interventions

“Irrespective of the accumulating findings showing adverse changes in multiple cardiovascular health parameters, as women transition through menopause, we do not have data documenting current status of ideal cardiovascular health components during the menopause transition among women,” said Dr. El Khoudary. “The limited data we have [suggest] that a very small proportion of women transitioning through menopause eat a healthy diet (less than 20%) or practice physical activity (about7.2%) at a level that matches the current recommendations,” she noted.

“Lifestyle and behavioral interventions are critical to maintain a healthy heart and reduce heart disease; we do not have adequate randomized clinical trials testing these interventions specifically during the menopause transition,” she said.

“Similarly, we are in need of randomized clinical trials of therapeutic interventions such as lipid-lowering medications and menopause hormone therapy in women transitioning through menopause,” said Dr. El Khoudary. “This high-risk population has not been the focus of previous clinical trials, leaving us with questions of how the results from these studies might apply to women during the menopause transition,” she said.
 

Consensus invites collaboration

“I commend the group for putting together a statement that crosses practice and specialty boundaries,” said Lubna Pal, MD, of Yale School of Medicine, New Haven, Conn., in an interview. Although the statement does not present novel information, it “has the power of unifying the various providers by bringing focus on the individual elements spanning a woman’s life that cumulatively determine her lifetime health risk,” she said. Preeclampsia may be a risk factor for cardiovascular disease later in life, and events in reproductive age may determine a woman’s trajectory during the transition to menopause and beyond, Dr. Pal noted.

“The consensus statement will likely be read by internists and family medicine providers as well as ob.gyns.; it encourages all those involved in caring for female patients to take on the responsibility of ‘passing on the baton,’ such that all women who are deemed at an enhanced risk for cardiovascular disease are assured due diligence in care through stringent surveillance and timely interventions,” said Dr. Pal. “It is a call for the various providers who care for women at distinct stages of life to work together toward a shared goal of optimizing every woman’s health across her lifespan,” she said.

“More research is needed for us to better understand the mechanisms at play” in the development of cardiovascular risk and in understanding the continuity of changes across women’s lifespans, Dr. Pal said. “We have associations, but not much information about causation,” she emphasized. However, the statement promotes the dissemination of information about women’s health and sensitizes providers to the potential and the power of preventive care. “We should be much more liberal and loud in holding conversations about risk quantification and risk reduction, and this statement is a resounding effort toward identifying and mitigating long-term cardiovascular risk, even if only through promoting a healthier lifestyle in those deemed at risk,” she added.  

The statement received no outside funding. Lead author Dr. Maas had no financial conflicts to disclose. Dr. El Khoudary had no financial conflicts to disclose. Dr. Pal had no relevant financial conflicts to disclose.

Menopause is a key time to monitor women for the development or increase of cardiovascular risk factors, according to a new consensus statement developed by the Task Force on Gender of the European Society of Cardiology and a multidisciplinary ESC working group on Women’s Health in Menopause.

“After menopause, traditional cardiovascular risk factors are adversely affected – particularly hypertension,” wrote Angela H.E.M. Maas, MD, of Radboud University Medical Center, Nijmegen, Netherlands, and colleagues.

“Since the first ESC consensus paper on the management of cardiovascular risk in perimenopausal women was published in 2007, we have a greater understanding on the role of female-specific risk factors for cardiovascular disease (CVD),” they said.

In a consensus statement published in the European Heart Journal, the authors presented clinical guidance for diagnosis and management of cardiovascular risk factors during the menopause transition. The transition to menopause increases a woman’s risk for developing several CVD risk factors, including central adiposity, increased insulin resistance, a proatherogenic lipid profile, and autonomic dysfunction that can contribute to increased heart rate variability, according to the statement.

Estrogen changes may affect ischemic disease

In general, obstructive coronary artery disease (CAD) strikes women later than men, but coronary vasomotor conditions are a common cause of ischemic heart disease in women with or without CAD, the authors noted.

“Lower estrogen levels after menopause are related to altered vascular function, enhanced inflammation, and up-regulation of other hormonal systems such as the renin–angiotensin–aldosterone system, the sympathetic nervous system, and reduced nitric oxide–dependent vasodilation,” they wrote. They recommended use of the coronary artery calcium score for screening middle-aged women who are symptomatic or at intermediate cardiovascular risk.

The transition to menopause causes changes in lipid profiles, and a rise in blood pressure in particular “may be both a direct effect of hormonal changes on the vasculature and metabolic changes with aging,” but hypertension in early post menopause is “often poorly managed,” the authors noted.

Compared with asymptomatic women, women who suffer from severe menopausal symptoms often have increased cardiovascular disease risk factors. For example, the Women’s Health Initiative (WHI) study showed a 48% increased risk of incident diabetes at follow-up in women with severe symptoms of hot flashes and night sweats, the authors wrote. Clinicians should also be aware of the increased immune reactivity that occurs during and after menopause and the increased CVD risk associated with autoimmune and endocrine disorders, they said.
 

Multiple strategies to reduce risk

Strategies to address the cardiovascular risk in menopause include assessing glucose, lipid levels, and blood pressure during the transition to menopause, according to the statement.

In addition, they recommended increasing employer awareness of menopause, as changes may interfere with working ability. A healthy lifestyle including healthy diet and regular exercise can help reduce cardiovascular risks and relieve symptoms. Menopausal hormone therapy (MHT) may be indicated to relieve symptoms, including symptoms of depression, and provide cardioprotection for younger women around the time of menopause, according to the statement.

However, “MHT is not recommended in women at high CV risk and after a previous CVD event,” and all women should be assessed for cardiovascular risk factors before starting MHT, they emphasized.
 

Results raise awareness of cardiovascular health and menopause link

“Over the past 20 years, our knowledge of how menopause might contribute to cardiovascular disease has dramatically evolved,” said Samar El Khoudary, MD, of the University of Pittsburg, in an interview.

“We have accumulated data that consistently point to the menopause transition as a time of change in cardiovascular health. As such, there is a compelling need to discuss the implications of the accumulating body of literature on this topic,” she said. “The goal is to raise awareness for both health care providers and women of the significant adverse cardiovascular health changes accompanying the menopause transition and to point out the importance of adopting prevention strategies early during this stage,” she explained.

The impact of the hormonal changes of menopause on CVD risk “is very complex,” Dr. El Khoudary said. “Until now, we could not prove that using estrogen therapy is cardioprotective,” she emphasized. “Studies point to the need to consider the timing of hormone use, as well as types and route of administration,” she noted. “The truth is that, although the menopause transition is associated with an acceleration in CVD risk, the exact mechanism still is not completely clear. Hormone changes contribute, but they are not the ultimate contributor,” she added.

 

Research gaps include data on lifestyle and behavioral interventions

“Irrespective of the accumulating findings showing adverse changes in multiple cardiovascular health parameters, as women transition through menopause, we do not have data documenting current status of ideal cardiovascular health components during the menopause transition among women,” said Dr. El Khoudary. “The limited data we have [suggest] that a very small proportion of women transitioning through menopause eat a healthy diet (less than 20%) or practice physical activity (about7.2%) at a level that matches the current recommendations,” she noted.

“Lifestyle and behavioral interventions are critical to maintain a healthy heart and reduce heart disease; we do not have adequate randomized clinical trials testing these interventions specifically during the menopause transition,” she said.

“Similarly, we are in need of randomized clinical trials of therapeutic interventions such as lipid-lowering medications and menopause hormone therapy in women transitioning through menopause,” said Dr. El Khoudary. “This high-risk population has not been the focus of previous clinical trials, leaving us with questions of how the results from these studies might apply to women during the menopause transition,” she said.
 

Consensus invites collaboration

“I commend the group for putting together a statement that crosses practice and specialty boundaries,” said Lubna Pal, MD, of Yale School of Medicine, New Haven, Conn., in an interview. Although the statement does not present novel information, it “has the power of unifying the various providers by bringing focus on the individual elements spanning a woman’s life that cumulatively determine her lifetime health risk,” she said. Preeclampsia may be a risk factor for cardiovascular disease later in life, and events in reproductive age may determine a woman’s trajectory during the transition to menopause and beyond, Dr. Pal noted.

“The consensus statement will likely be read by internists and family medicine providers as well as ob.gyns.; it encourages all those involved in caring for female patients to take on the responsibility of ‘passing on the baton,’ such that all women who are deemed at an enhanced risk for cardiovascular disease are assured due diligence in care through stringent surveillance and timely interventions,” said Dr. Pal. “It is a call for the various providers who care for women at distinct stages of life to work together toward a shared goal of optimizing every woman’s health across her lifespan,” she said.

“More research is needed for us to better understand the mechanisms at play” in the development of cardiovascular risk and in understanding the continuity of changes across women’s lifespans, Dr. Pal said. “We have associations, but not much information about causation,” she emphasized. However, the statement promotes the dissemination of information about women’s health and sensitizes providers to the potential and the power of preventive care. “We should be much more liberal and loud in holding conversations about risk quantification and risk reduction, and this statement is a resounding effort toward identifying and mitigating long-term cardiovascular risk, even if only through promoting a healthier lifestyle in those deemed at risk,” she added.  

The statement received no outside funding. Lead author Dr. Maas had no financial conflicts to disclose. Dr. El Khoudary had no financial conflicts to disclose. Dr. Pal had no relevant financial conflicts to disclose.

Postmenopausal women not only have larger brain volume than women who are premenopausal, but they also experience larger reductions in brain volume over time, reported Ananthan Ambikairajah of the Centre for Research on Ageing, Health and Wellbeing, Australian National University, Canberra, and associates. Their report was published in Menopause.

In this large population-based cohort of 5,072 women aged 37-73 years, the goal of the study was to look at links between brain volume and measures of menstruation history, such as menopausal status, age at menopause, age at menarche, and the duration of a woman’s reproductive stage, but to do so within the context of how it relates to dementia prevalence. Citing a study in The Lancet Neurology, the authors noted that the age-standardized prevalence for dementia is 17% higher in women than in men, and they speculated that it may be important to look beyond age for answers.
 

What about menstrual history and Alzheimer’s disease?

According to the Framingham Study in Neurology, the remaining lifetime risk of Alzheimer’s disease (AD) is nearly double for a 65-year-old woman (12%) compared with a 65-year-old man (6.3%), leading Mr. Ambikairajah and associates to conclude that “menstruation history may also be particularly relevant, given that it is unique to female aging.” They further speculated, citing several related studies, that because AD pathology is initiated decades prior to the onset of clinical signs, menstruation history and its effects on brain health may, in fact, be reflected in brain volume.

Postmenopausal women had 0.82% and 1.33% larger total brain and hippocampal volume, respectively, compared with premenopausal women. Postmenopausal women had a 23% greater decrease in total brain volume but not in hippocampal volume over time, compared with premenopausal women.

As Braak and Braak illustrated in Acta Neuropathologica, chronic inflammation has been linked to brain shrinkage “consistent with the pattern of results in the present study,” Mr. Ambikairajah and colleagues noted, adding that longitudinal neuroimaging/biomarker studies are needed to explore this further.

What made this study unique was its ability to match pre- and postmenopausal women for age, a critically important attribute “given that aging and menopause both progress concurrently, which can make it difficult to determine the individual contribution of each for measures of brain health,” the authors explained.

In an interview, Constance Bohon, MD, an ob.gyn. in private practice and assistant clinical professor, George Washington University, Washington, observed: “The conclusion [in this study] is that an early age of menarche, delayed age of menopause and increased duration of the reproductive stage is negatively associated with brain volume.”
 

What of the neuroprotective effects of endogenous estrogen?

“Their findings are not consistent with a neuroprotective effect of endogenous estrogen exposure on brain volume,” she noted, adding that the study “did not assess the effect of exogenous estrogen on brain volume. Neither was the effect of exogenous or endogenous estrogen on cerebral blood flow assessed. In a study published in Obstetrics & Gynecology, the conclusion was that oophorectomy before the age of natural menopause is associated with a decrease in cognitive impairment and dementia. There was no assessment of brain volume or cerebral blood flow. Likewise in a report published in Neurobiology of Aging, Maki P and Resnick S M. concluded that estrogen helps maintain hippocampal and prefrontal function as women age,” observed Dr. Bohon, noting that the study did not assess brain volume.

“It is unclear whether the most predictive assessment for worsening cognition and dementia is the finding of decreased total brain volume, decreased hippocampal volume, or decreased cerebral blood flow. The effect of both endogenous and exogenous estrogen on the risk for dementia needs further evaluation,” she cautioned.

Mr. Ambikairajah cited one financial disclosure; the remaining contributors had no relevant disclosures.

Postmenopausal women not only have larger brain volume than women who are premenopausal, but they also experience larger reductions in brain volume over time, reported Ananthan Ambikairajah of the Centre for Research on Ageing, Health and Wellbeing, Australian National University, Canberra, and associates. Their report was published in Menopause.

In this large population-based cohort of 5,072 women aged 37-73 years, the goal of the study was to look at links between brain volume and measures of menstruation history, such as menopausal status, age at menopause, age at menarche, and the duration of a woman’s reproductive stage, but to do so within the context of how it relates to dementia prevalence. Citing a study in The Lancet Neurology, the authors noted that the age-standardized prevalence for dementia is 17% higher in women than in men, and they speculated that it may be important to look beyond age for answers.
 

What about menstrual history and Alzheimer’s disease?

According to the Framingham Study in Neurology, the remaining lifetime risk of Alzheimer’s disease (AD) is nearly double for a 65-year-old woman (12%) compared with a 65-year-old man (6.3%), leading Mr. Ambikairajah and associates to conclude that “menstruation history may also be particularly relevant, given that it is unique to female aging.” They further speculated, citing several related studies, that because AD pathology is initiated decades prior to the onset of clinical signs, menstruation history and its effects on brain health may, in fact, be reflected in brain volume.

Postmenopausal women had 0.82% and 1.33% larger total brain and hippocampal volume, respectively, compared with premenopausal women. Postmenopausal women had a 23% greater decrease in total brain volume but not in hippocampal volume over time, compared with premenopausal women.

As Braak and Braak illustrated in Acta Neuropathologica, chronic inflammation has been linked to brain shrinkage “consistent with the pattern of results in the present study,” Mr. Ambikairajah and colleagues noted, adding that longitudinal neuroimaging/biomarker studies are needed to explore this further.

What made this study unique was its ability to match pre- and postmenopausal women for age, a critically important attribute “given that aging and menopause both progress concurrently, which can make it difficult to determine the individual contribution of each for measures of brain health,” the authors explained.

In an interview, Constance Bohon, MD, an ob.gyn. in private practice and assistant clinical professor, George Washington University, Washington, observed: “The conclusion [in this study] is that an early age of menarche, delayed age of menopause and increased duration of the reproductive stage is negatively associated with brain volume.”
 

What of the neuroprotective effects of endogenous estrogen?

“Their findings are not consistent with a neuroprotective effect of endogenous estrogen exposure on brain volume,” she noted, adding that the study “did not assess the effect of exogenous estrogen on brain volume. Neither was the effect of exogenous or endogenous estrogen on cerebral blood flow assessed. In a study published in Obstetrics & Gynecology, the conclusion was that oophorectomy before the age of natural menopause is associated with a decrease in cognitive impairment and dementia. There was no assessment of brain volume or cerebral blood flow. Likewise in a report published in Neurobiology of Aging, Maki P and Resnick S M. concluded that estrogen helps maintain hippocampal and prefrontal function as women age,” observed Dr. Bohon, noting that the study did not assess brain volume.

“It is unclear whether the most predictive assessment for worsening cognition and dementia is the finding of decreased total brain volume, decreased hippocampal volume, or decreased cerebral blood flow. The effect of both endogenous and exogenous estrogen on the risk for dementia needs further evaluation,” she cautioned.

Mr. Ambikairajah cited one financial disclosure; the remaining contributors had no relevant disclosures.

Postmenopausal women not only have larger brain volume than women who are premenopausal, but they also experience larger reductions in brain volume over time, reported Ananthan Ambikairajah of the Centre for Research on Ageing, Health and Wellbeing, Australian National University, Canberra, and associates. Their report was published in Menopause.

In this large population-based cohort of 5,072 women aged 37-73 years, the goal of the study was to look at links between brain volume and measures of menstruation history, such as menopausal status, age at menopause, age at menarche, and the duration of a woman’s reproductive stage, but to do so within the context of how it relates to dementia prevalence. Citing a study in The Lancet Neurology, the authors noted that the age-standardized prevalence for dementia is 17% higher in women than in men, and they speculated that it may be important to look beyond age for answers.
 

What about menstrual history and Alzheimer’s disease?

According to the Framingham Study in Neurology, the remaining lifetime risk of Alzheimer’s disease (AD) is nearly double for a 65-year-old woman (12%) compared with a 65-year-old man (6.3%), leading Mr. Ambikairajah and associates to conclude that “menstruation history may also be particularly relevant, given that it is unique to female aging.” They further speculated, citing several related studies, that because AD pathology is initiated decades prior to the onset of clinical signs, menstruation history and its effects on brain health may, in fact, be reflected in brain volume.

Postmenopausal women had 0.82% and 1.33% larger total brain and hippocampal volume, respectively, compared with premenopausal women. Postmenopausal women had a 23% greater decrease in total brain volume but not in hippocampal volume over time, compared with premenopausal women.

As Braak and Braak illustrated in Acta Neuropathologica, chronic inflammation has been linked to brain shrinkage “consistent with the pattern of results in the present study,” Mr. Ambikairajah and colleagues noted, adding that longitudinal neuroimaging/biomarker studies are needed to explore this further.

What made this study unique was its ability to match pre- and postmenopausal women for age, a critically important attribute “given that aging and menopause both progress concurrently, which can make it difficult to determine the individual contribution of each for measures of brain health,” the authors explained.

In an interview, Constance Bohon, MD, an ob.gyn. in private practice and assistant clinical professor, George Washington University, Washington, observed: “The conclusion [in this study] is that an early age of menarche, delayed age of menopause and increased duration of the reproductive stage is negatively associated with brain volume.”
 

What of the neuroprotective effects of endogenous estrogen?

“Their findings are not consistent with a neuroprotective effect of endogenous estrogen exposure on brain volume,” she noted, adding that the study “did not assess the effect of exogenous estrogen on brain volume. Neither was the effect of exogenous or endogenous estrogen on cerebral blood flow assessed. In a study published in Obstetrics & Gynecology, the conclusion was that oophorectomy before the age of natural menopause is associated with a decrease in cognitive impairment and dementia. There was no assessment of brain volume or cerebral blood flow. Likewise in a report published in Neurobiology of Aging, Maki P and Resnick S M. concluded that estrogen helps maintain hippocampal and prefrontal function as women age,” observed Dr. Bohon, noting that the study did not assess brain volume.

“It is unclear whether the most predictive assessment for worsening cognition and dementia is the finding of decreased total brain volume, decreased hippocampal volume, or decreased cerebral blood flow. The effect of both endogenous and exogenous estrogen on the risk for dementia needs further evaluation,” she cautioned.

Mr. Ambikairajah cited one financial disclosure; the remaining contributors had no relevant disclosures.

It wasn’t until I (Dr. Leistikow) finished my psychiatry residency that I realized the training I had received in women’s mental health was unusual. It was simply a required experience for PGY-3 residents at Johns Hopkins University, Baltimore.

Rawpixel/Getty Images

All of us, regardless of interest, spent 1 afternoon a week over 6 months caring for patients in a specialty psychiatric clinic for women (run by Dr. Payne and Dr. Osborne). We discussed cases and received didactics on such topics as risk factors for postpartum depression; the risks of untreated mental illness in pregnancy, compared with the risks of various psychiatric medications; how to choose and dose medications for bipolar disorder as blood levels change across pregnancy; which resources to consult to determine the amounts and risks of various medications passed on in breast milk; and how to diagnose and treat premenstrual dysphoric disorder, to name a few lecture subjects.

By the time we were done, all residents had received more than 20 hours of teaching about how to treat mental illness in women across the reproductive life cycle. This was 20 hours more than is currently required by the American College of Graduate Medical Education, the accrediting body for all residencies, including psychiatry.¹ It is time for that to change.

Women’s need for psychiatric treatment that addresses reproductive transitions is not new; it is as old as time. Not only do women who previously needed psychiatric treatment continue to need treatment when they get pregnant or are breastfeeding, but it is now well recognized that times of reproductive transition or flux – whether premenstrual, post partum, or perimenopausal – confer increased risk for both new-onset and exacerbations of prior mental illnesses.

What has changed is psychiatry’s ability to finally meet that need. Previously, despite the fact that women make up the majority of patients presenting for treatment, that nearly all women will menstruate and go through menopause, and that more than 80% of American women will have at least one pregnancy during their lifetime,psychiatrists practice as if these reproductive transitions were unfortunate blips getting in the doctor’s way.² We mostly threw up our hands when our patients became pregnant, reflexively stopped all medications, and expected women to suffer for the sake of their babies.

Over the last 20-30 years, however, a grassroots movement has established what is now an international reproductive psychiatry community with a large and growing research base, with both agreed-upon best practices and evolving standards of care informed by and responsive to the scientific literature. We now know that untreated maternal psychiatric illness carries its own risks for infants both before and after delivery; that many maternal pharmacologic treatments are lower risk for infants than previously thought; that protecting and treating women’s mental health in pregnancy has benefits for women, their babies, and the families that depend on them; and that there is now a growing evidence base informing both new and older treatments and enabling women and their doctors to make complex decisions balancing risk and benefit across the life cycle.

Many psychiatrists-in-training are hungry for this knowledge. At last count, in the United States alone, there were 16 women’s mental health fellowships available, up from just 3 in 2008.³ The problem is that none of them are accredited or funded by the ACGME, because reproductive psychiatry (here used interchangeably with the term women’s mental health) has not been officially recognized as a subspecialty. This means that current funding frequently rests on philanthropy, which often cannot be sustained, and clinical billing, which gives fellows in some programs such heavy clinical responsibilities that little time is left for scholarly work. Lack of subspecialty status also blocks numerous important downstream effects that would flow from this recognition.

Reproductive psychiatry clearly already meets criteria laid out by the American Board of Medical Specialties for defining a subspecialty field. As argued elsewhere, it has a distinct patient population with definable care needs and a standalone body of scientific medical knowledge as well as a national (and international) community of experts that has already done much to improve women’s access to care they desperately need.⁴ It also meets the ACGME’s criteria for a new subspecialty except for approval by the American Board of Psychiatry and Neurology.⁵ Finally, it also meets the requirements of the ABPN except for having 25 fellowship programs with 50 fellowship positions and 50 trainees per year completing fellowships, a challenging Catch-22 without the necessary funding that would accrue from accreditation.⁶

Despite growing awareness and demand, there remains a shortage of psychiatrists trained to treat women during times of reproductive transition and to pass their recommendations and knowledge on to their primary care and ob.gyn. colleagues. What official recognition would bring, in addition to funding for fellowships post residency, is a guaranteed seat at the table in psychiatry residencies, in terms of a required number of hours devoted to these topics for trainees, ensuring that all graduating psychiatrists have at least some exposure to the knowledge and practices so material to their patients.

It isn’t enough to wait for residencies to see the writing on the wall and voluntarily carve out a slice of pie devoted to women’s mental health from the limited time and resources available to train residents. A 2017 survey of psychiatry residency program training directors found that 23%, or almost a quarter of programs that responded, offered no reproductive psychiatry training at all, that 49% required 5 hours or less across all 4 years of training, and that 75% of programs had no required clinical exposure to reproductive psychiatry patients.⁷ Despite the fact that 87% of training directors surveyed agreed either that reproductive psychiatry was “an important area of education” or a subject general residents should be competent in, ACGME-recognized specialties take precedence.

A system so patchy and insufficient won’t do. It’s not good enough for the trainees who frequently have to look outside of their own institutions for the training they know they need. It’s not good enough for the pregnant or postpartum patient looking for evidence-based advice, who is currently left on her own to determine, prior to booking an appointment, whether a specific psychiatrist has received any training relevant to treating her. Adding reproductive psychiatry to the topics a graduating psychiatrist must have some proficiency in also signals to recent graduates and experienced attendings, as well as the relevant examining boards and producers of continuing medical education content, that women’s mental health is no longer a fringe topic but rather foundational to all practicing psychiatrists.

The oil needed to prime this pump is official recognition of the subspecialty that reproductive psychiatry already is. The women’s mental health community is ready. The research base is well established and growing exponentially. The number of women’s mental health fellowships is healthy and would increase significantly with ACGME funding. Psychiatry residency training programs can turn to recent graduates of these fellowships as well as their own faculty with reproductive psychiatry experience to teach trainees. In addition, the National Curriculum in Reproductive Psychiatry, over the last 4 years, has created a repository of free online modules dedicated to facilitating this type of training, with case discussions across numerous topics for use by both educators and trainees. The American Psychiatric Association recently formed the Committee on Women’s Mental Health in 2020 and will be publishing a textbook based on work done by the NCRP within the coming year.

Imagine the changed world that would open to all psychiatrists if reproductive psychiatry were given the credentials it deserves. When writing prescriptions, we would view pregnancy as the potential outcome it is in any woman of reproductive age, given that 50% of pregnancies are unplanned, and let women know ahead of time how to think about possible fetal effects rather than waiting for their panicked phone messages or hearing that they have stopped their medications abruptly. We would work to identify our patient’s individual risk factors for postpartum depression predelivery to reduce that risk and prevent or limit illness. We would plan ahead for close follow-up post partum during the window of greatest risk, rather than expecting women to drop out of care while taking care of their infants or languish on scheduling waiting lists. We would feel confident in giving evidence-based advice to our patients around times of reproductive transition across the life cycle, but especially in pregnancy and lactation, empowering women to make healthy decisions for themselves and their families, no longer abandoning them just when they need us most.

 

References

1. ACGME Program Requirements for Graduate Medical Education in Psychiatry. Accreditation Counsel for Graduate Medical Education. 2020 Jul 1.

2. Livingston G. “They’re waiting longer, but U.S. women today more likely to have children than a decade ago.” Pew Research Center’s Social & Demographic Trends Project. pewsocialtrends.org. 2018 Jan 18.

3. Nagle-Yang S et al. Acad Psychiatry. 2018 Apr;42(2):202-6.

4. Payne JL. Int Rev Psychiatry. 2019 May;31(3):207-9.

5. Accreditation Council for Graduate Medical Education Policies and Procedures. 2020 Sep 26.

6. American Board of Psychiatry and Neurology. Requirements for Subspecialty Recognition, Attachment A. 2008.

7. Osborne LM et al. Acad Psychiatry. 2018 Apr;42(2):197-201.
 

Dr. Leistikow is a reproductive psychiatrist and clinical assistant professor in the department of psychiatry at the University of Maryland, Baltimore, where she sees patients and helps train residents and fellows. She is on the education committee of the National Curriculum in Reproductive Psychiatry (NCRPtraining.org) and has written about women’s mental health for textbooks, scientific journals and on her private practice blog at www.womenspsychiatrybaltimore.com. Dr. Leistikow has no conflicts of interest.

Dr. Payne is associate professor of psychiatry and behavioral sciences and director of the Women’s Mood Disorders Center at Johns Hopkins University, Baltimore. In addition to providing outstanding clinical care for women with mood disorders, she conducts research into the genetic, biological, and environmental factors involved in postpartum depression. She and her colleagues have recently identified two epigenetic biomarkers of postpartum depression and are working hard to replicate this work with National Institutes of Health funding. Most recently, she was appointed to the American Psychiatric Association’s committee on women’s mental health and is serving as president-elect for both the Marcé of North America and the International Marcé Perinatal Mental Health Societies. She disclosed the following relevant financial relationships: serve(d) as a director, officer, partner, employee, adviser, consultant, or trustee for Sage Therapeutics and Janssen Pharmaceuticals.
 

Dr. Osborne is associate professor of psychiatry and behavioral sciences and of gynecology and obstetrics at Johns Hopkins University, where she directs a postdoctoral fellowship program in reproductive psychiatry. She is an expert on the diagnosis and treatment of mood and anxiety disorders during pregnancy, the post partum, the premenstrual period, and perimenopause. Her work is supported by the Brain and Behavior Foundation, the Doris Duke Foundation, the American Board of Psychiatry and Neurology, and the National Institute of Mental Health. She has no conflicts of interest.

It wasn’t until I (Dr. Leistikow) finished my psychiatry residency that I realized the training I had received in women’s mental health was unusual. It was simply a required experience for PGY-3 residents at Johns Hopkins University, Baltimore.

Rawpixel/Getty Images

All of us, regardless of interest, spent 1 afternoon a week over 6 months caring for patients in a specialty psychiatric clinic for women (run by Dr. Payne and Dr. Osborne). We discussed cases and received didactics on such topics as risk factors for postpartum depression; the risks of untreated mental illness in pregnancy, compared with the risks of various psychiatric medications; how to choose and dose medications for bipolar disorder as blood levels change across pregnancy; which resources to consult to determine the amounts and risks of various medications passed on in breast milk; and how to diagnose and treat premenstrual dysphoric disorder, to name a few lecture subjects.

By the time we were done, all residents had received more than 20 hours of teaching about how to treat mental illness in women across the reproductive life cycle. This was 20 hours more than is currently required by the American College of Graduate Medical Education, the accrediting body for all residencies, including psychiatry.¹ It is time for that to change.

Women’s need for psychiatric treatment that addresses reproductive transitions is not new; it is as old as time. Not only do women who previously needed psychiatric treatment continue to need treatment when they get pregnant or are breastfeeding, but it is now well recognized that times of reproductive transition or flux – whether premenstrual, post partum, or perimenopausal – confer increased risk for both new-onset and exacerbations of prior mental illnesses.

What has changed is psychiatry’s ability to finally meet that need. Previously, despite the fact that women make up the majority of patients presenting for treatment, that nearly all women will menstruate and go through menopause, and that more than 80% of American women will have at least one pregnancy during their lifetime,psychiatrists practice as if these reproductive transitions were unfortunate blips getting in the doctor’s way.² We mostly threw up our hands when our patients became pregnant, reflexively stopped all medications, and expected women to suffer for the sake of their babies.

Over the last 20-30 years, however, a grassroots movement has established what is now an international reproductive psychiatry community with a large and growing research base, with both agreed-upon best practices and evolving standards of care informed by and responsive to the scientific literature. We now know that untreated maternal psychiatric illness carries its own risks for infants both before and after delivery; that many maternal pharmacologic treatments are lower risk for infants than previously thought; that protecting and treating women’s mental health in pregnancy has benefits for women, their babies, and the families that depend on them; and that there is now a growing evidence base informing both new and older treatments and enabling women and their doctors to make complex decisions balancing risk and benefit across the life cycle.

Many psychiatrists-in-training are hungry for this knowledge. At last count, in the United States alone, there were 16 women’s mental health fellowships available, up from just 3 in 2008.³ The problem is that none of them are accredited or funded by the ACGME, because reproductive psychiatry (here used interchangeably with the term women’s mental health) has not been officially recognized as a subspecialty. This means that current funding frequently rests on philanthropy, which often cannot be sustained, and clinical billing, which gives fellows in some programs such heavy clinical responsibilities that little time is left for scholarly work. Lack of subspecialty status also blocks numerous important downstream effects that would flow from this recognition.

Reproductive psychiatry clearly already meets criteria laid out by the American Board of Medical Specialties for defining a subspecialty field. As argued elsewhere, it has a distinct patient population with definable care needs and a standalone body of scientific medical knowledge as well as a national (and international) community of experts that has already done much to improve women’s access to care they desperately need.⁴ It also meets the ACGME’s criteria for a new subspecialty except for approval by the American Board of Psychiatry and Neurology.⁵ Finally, it also meets the requirements of the ABPN except for having 25 fellowship programs with 50 fellowship positions and 50 trainees per year completing fellowships, a challenging Catch-22 without the necessary funding that would accrue from accreditation.⁶

Despite growing awareness and demand, there remains a shortage of psychiatrists trained to treat women during times of reproductive transition and to pass their recommendations and knowledge on to their primary care and ob.gyn. colleagues. What official recognition would bring, in addition to funding for fellowships post residency, is a guaranteed seat at the table in psychiatry residencies, in terms of a required number of hours devoted to these topics for trainees, ensuring that all graduating psychiatrists have at least some exposure to the knowledge and practices so material to their patients.

It isn’t enough to wait for residencies to see the writing on the wall and voluntarily carve out a slice of pie devoted to women’s mental health from the limited time and resources available to train residents. A 2017 survey of psychiatry residency program training directors found that 23%, or almost a quarter of programs that responded, offered no reproductive psychiatry training at all, that 49% required 5 hours or less across all 4 years of training, and that 75% of programs had no required clinical exposure to reproductive psychiatry patients.⁷ Despite the fact that 87% of training directors surveyed agreed either that reproductive psychiatry was “an important area of education” or a subject general residents should be competent in, ACGME-recognized specialties take precedence.

A system so patchy and insufficient won’t do. It’s not good enough for the trainees who frequently have to look outside of their own institutions for the training they know they need. It’s not good enough for the pregnant or postpartum patient looking for evidence-based advice, who is currently left on her own to determine, prior to booking an appointment, whether a specific psychiatrist has received any training relevant to treating her. Adding reproductive psychiatry to the topics a graduating psychiatrist must have some proficiency in also signals to recent graduates and experienced attendings, as well as the relevant examining boards and producers of continuing medical education content, that women’s mental health is no longer a fringe topic but rather foundational to all practicing psychiatrists.

The oil needed to prime this pump is official recognition of the subspecialty that reproductive psychiatry already is. The women’s mental health community is ready. The research base is well established and growing exponentially. The number of women’s mental health fellowships is healthy and would increase significantly with ACGME funding. Psychiatry residency training programs can turn to recent graduates of these fellowships as well as their own faculty with reproductive psychiatry experience to teach trainees. In addition, the National Curriculum in Reproductive Psychiatry, over the last 4 years, has created a repository of free online modules dedicated to facilitating this type of training, with case discussions across numerous topics for use by both educators and trainees. The American Psychiatric Association recently formed the Committee on Women’s Mental Health in 2020 and will be publishing a textbook based on work done by the NCRP within the coming year.

Imagine the changed world that would open to all psychiatrists if reproductive psychiatry were given the credentials it deserves. When writing prescriptions, we would view pregnancy as the potential outcome it is in any woman of reproductive age, given that 50% of pregnancies are unplanned, and let women know ahead of time how to think about possible fetal effects rather than waiting for their panicked phone messages or hearing that they have stopped their medications abruptly. We would work to identify our patient’s individual risk factors for postpartum depression predelivery to reduce that risk and prevent or limit illness. We would plan ahead for close follow-up post partum during the window of greatest risk, rather than expecting women to drop out of care while taking care of their infants or languish on scheduling waiting lists. We would feel confident in giving evidence-based advice to our patients around times of reproductive transition across the life cycle, but especially in pregnancy and lactation, empowering women to make healthy decisions for themselves and their families, no longer abandoning them just when they need us most.

 

References

1. ACGME Program Requirements for Graduate Medical Education in Psychiatry. Accreditation Counsel for Graduate Medical Education. 2020 Jul 1.

2. Livingston G. “They’re waiting longer, but U.S. women today more likely to have children than a decade ago.” Pew Research Center’s Social & Demographic Trends Project. pewsocialtrends.org. 2018 Jan 18.

3. Nagle-Yang S et al. Acad Psychiatry. 2018 Apr;42(2):202-6.

4. Payne JL. Int Rev Psychiatry. 2019 May;31(3):207-9.

5. Accreditation Council for Graduate Medical Education Policies and Procedures. 2020 Sep 26.

6. American Board of Psychiatry and Neurology. Requirements for Subspecialty Recognition, Attachment A. 2008.

7. Osborne LM et al. Acad Psychiatry. 2018 Apr;42(2):197-201.
 

Dr. Leistikow is a reproductive psychiatrist and clinical assistant professor in the department of psychiatry at the University of Maryland, Baltimore, where she sees patients and helps train residents and fellows. She is on the education committee of the National Curriculum in Reproductive Psychiatry (NCRPtraining.org) and has written about women’s mental health for textbooks, scientific journals and on her private practice blog at www.womenspsychiatrybaltimore.com. Dr. Leistikow has no conflicts of interest.

Dr. Payne is associate professor of psychiatry and behavioral sciences and director of the Women’s Mood Disorders Center at Johns Hopkins University, Baltimore. In addition to providing outstanding clinical care for women with mood disorders, she conducts research into the genetic, biological, and environmental factors involved in postpartum depression. She and her colleagues have recently identified two epigenetic biomarkers of postpartum depression and are working hard to replicate this work with National Institutes of Health funding. Most recently, she was appointed to the American Psychiatric Association’s committee on women’s mental health and is serving as president-elect for both the Marcé of North America and the International Marcé Perinatal Mental Health Societies. She disclosed the following relevant financial relationships: serve(d) as a director, officer, partner, employee, adviser, consultant, or trustee for Sage Therapeutics and Janssen Pharmaceuticals.
 

Dr. Osborne is associate professor of psychiatry and behavioral sciences and of gynecology and obstetrics at Johns Hopkins University, where she directs a postdoctoral fellowship program in reproductive psychiatry. She is an expert on the diagnosis and treatment of mood and anxiety disorders during pregnancy, the post partum, the premenstrual period, and perimenopause. Her work is supported by the Brain and Behavior Foundation, the Doris Duke Foundation, the American Board of Psychiatry and Neurology, and the National Institute of Mental Health. She has no conflicts of interest.

It wasn’t until I (Dr. Leistikow) finished my psychiatry residency that I realized the training I had received in women’s mental health was unusual. It was simply a required experience for PGY-3 residents at Johns Hopkins University, Baltimore.

Rawpixel/Getty Images

All of us, regardless of interest, spent 1 afternoon a week over 6 months caring for patients in a specialty psychiatric clinic for women (run by Dr. Payne and Dr. Osborne). We discussed cases and received didactics on such topics as risk factors for postpartum depression; the risks of untreated mental illness in pregnancy, compared with the risks of various psychiatric medications; how to choose and dose medications for bipolar disorder as blood levels change across pregnancy; which resources to consult to determine the amounts and risks of various medications passed on in breast milk; and how to diagnose and treat premenstrual dysphoric disorder, to name a few lecture subjects.

By the time we were done, all residents had received more than 20 hours of teaching about how to treat mental illness in women across the reproductive life cycle. This was 20 hours more than is currently required by the American College of Graduate Medical Education, the accrediting body for all residencies, including psychiatry.¹ It is time for that to change.

Women’s need for psychiatric treatment that addresses reproductive transitions is not new; it is as old as time. Not only do women who previously needed psychiatric treatment continue to need treatment when they get pregnant or are breastfeeding, but it is now well recognized that times of reproductive transition or flux – whether premenstrual, post partum, or perimenopausal – confer increased risk for both new-onset and exacerbations of prior mental illnesses.

What has changed is psychiatry’s ability to finally meet that need. Previously, despite the fact that women make up the majority of patients presenting for treatment, that nearly all women will menstruate and go through menopause, and that more than 80% of American women will have at least one pregnancy during their lifetime,psychiatrists practice as if these reproductive transitions were unfortunate blips getting in the doctor’s way.² We mostly threw up our hands when our patients became pregnant, reflexively stopped all medications, and expected women to suffer for the sake of their babies.

Over the last 20-30 years, however, a grassroots movement has established what is now an international reproductive psychiatry community with a large and growing research base, with both agreed-upon best practices and evolving standards of care informed by and responsive to the scientific literature. We now know that untreated maternal psychiatric illness carries its own risks for infants both before and after delivery; that many maternal pharmacologic treatments are lower risk for infants than previously thought; that protecting and treating women’s mental health in pregnancy has benefits for women, their babies, and the families that depend on them; and that there is now a growing evidence base informing both new and older treatments and enabling women and their doctors to make complex decisions balancing risk and benefit across the life cycle.

Many psychiatrists-in-training are hungry for this knowledge. At last count, in the United States alone, there were 16 women’s mental health fellowships available, up from just 3 in 2008.³ The problem is that none of them are accredited or funded by the ACGME, because reproductive psychiatry (here used interchangeably with the term women’s mental health) has not been officially recognized as a subspecialty. This means that current funding frequently rests on philanthropy, which often cannot be sustained, and clinical billing, which gives fellows in some programs such heavy clinical responsibilities that little time is left for scholarly work. Lack of subspecialty status also blocks numerous important downstream effects that would flow from this recognition.

Reproductive psychiatry clearly already meets criteria laid out by the American Board of Medical Specialties for defining a subspecialty field. As argued elsewhere, it has a distinct patient population with definable care needs and a standalone body of scientific medical knowledge as well as a national (and international) community of experts that has already done much to improve women’s access to care they desperately need.⁴ It also meets the ACGME’s criteria for a new subspecialty except for approval by the American Board of Psychiatry and Neurology.⁵ Finally, it also meets the requirements of the ABPN except for having 25 fellowship programs with 50 fellowship positions and 50 trainees per year completing fellowships, a challenging Catch-22 without the necessary funding that would accrue from accreditation.⁶

Despite growing awareness and demand, there remains a shortage of psychiatrists trained to treat women during times of reproductive transition and to pass their recommendations and knowledge on to their primary care and ob.gyn. colleagues. What official recognition would bring, in addition to funding for fellowships post residency, is a guaranteed seat at the table in psychiatry residencies, in terms of a required number of hours devoted to these topics for trainees, ensuring that all graduating psychiatrists have at least some exposure to the knowledge and practices so material to their patients.

It isn’t enough to wait for residencies to see the writing on the wall and voluntarily carve out a slice of pie devoted to women’s mental health from the limited time and resources available to train residents. A 2017 survey of psychiatry residency program training directors found that 23%, or almost a quarter of programs that responded, offered no reproductive psychiatry training at all, that 49% required 5 hours or less across all 4 years of training, and that 75% of programs had no required clinical exposure to reproductive psychiatry patients.⁷ Despite the fact that 87% of training directors surveyed agreed either that reproductive psychiatry was “an important area of education” or a subject general residents should be competent in, ACGME-recognized specialties take precedence.

A system so patchy and insufficient won’t do. It’s not good enough for the trainees who frequently have to look outside of their own institutions for the training they know they need. It’s not good enough for the pregnant or postpartum patient looking for evidence-based advice, who is currently left on her own to determine, prior to booking an appointment, whether a specific psychiatrist has received any training relevant to treating her. Adding reproductive psychiatry to the topics a graduating psychiatrist must have some proficiency in also signals to recent graduates and experienced attendings, as well as the relevant examining boards and producers of continuing medical education content, that women’s mental health is no longer a fringe topic but rather foundational to all practicing psychiatrists.

The oil needed to prime this pump is official recognition of the subspecialty that reproductive psychiatry already is. The women’s mental health community is ready. The research base is well established and growing exponentially. The number of women’s mental health fellowships is healthy and would increase significantly with ACGME funding. Psychiatry residency training programs can turn to recent graduates of these fellowships as well as their own faculty with reproductive psychiatry experience to teach trainees. In addition, the National Curriculum in Reproductive Psychiatry, over the last 4 years, has created a repository of free online modules dedicated to facilitating this type of training, with case discussions across numerous topics for use by both educators and trainees. The American Psychiatric Association recently formed the Committee on Women’s Mental Health in 2020 and will be publishing a textbook based on work done by the NCRP within the coming year.

Imagine the changed world that would open to all psychiatrists if reproductive psychiatry were given the credentials it deserves. When writing prescriptions, we would view pregnancy as the potential outcome it is in any woman of reproductive age, given that 50% of pregnancies are unplanned, and let women know ahead of time how to think about possible fetal effects rather than waiting for their panicked phone messages or hearing that they have stopped their medications abruptly. We would work to identify our patient’s individual risk factors for postpartum depression predelivery to reduce that risk and prevent or limit illness. We would plan ahead for close follow-up post partum during the window of greatest risk, rather than expecting women to drop out of care while taking care of their infants or languish on scheduling waiting lists. We would feel confident in giving evidence-based advice to our patients around times of reproductive transition across the life cycle, but especially in pregnancy and lactation, empowering women to make healthy decisions for themselves and their families, no longer abandoning them just when they need us most.

 

References

1. ACGME Program Requirements for Graduate Medical Education in Psychiatry. Accreditation Counsel for Graduate Medical Education. 2020 Jul 1.

2. Livingston G. “They’re waiting longer, but U.S. women today more likely to have children than a decade ago.” Pew Research Center’s Social & Demographic Trends Project. pewsocialtrends.org. 2018 Jan 18.

3. Nagle-Yang S et al. Acad Psychiatry. 2018 Apr;42(2):202-6.

4. Payne JL. Int Rev Psychiatry. 2019 May;31(3):207-9.

5. Accreditation Council for Graduate Medical Education Policies and Procedures. 2020 Sep 26.

6. American Board of Psychiatry and Neurology. Requirements for Subspecialty Recognition, Attachment A. 2008.

7. Osborne LM et al. Acad Psychiatry. 2018 Apr;42(2):197-201.
 

Dr. Leistikow is a reproductive psychiatrist and clinical assistant professor in the department of psychiatry at the University of Maryland, Baltimore, where she sees patients and helps train residents and fellows. She is on the education committee of the National Curriculum in Reproductive Psychiatry (NCRPtraining.org) and has written about women’s mental health for textbooks, scientific journals and on her private practice blog at www.womenspsychiatrybaltimore.com. Dr. Leistikow has no conflicts of interest.

Dr. Payne is associate professor of psychiatry and behavioral sciences and director of the Women’s Mood Disorders Center at Johns Hopkins University, Baltimore. In addition to providing outstanding clinical care for women with mood disorders, she conducts research into the genetic, biological, and environmental factors involved in postpartum depression. She and her colleagues have recently identified two epigenetic biomarkers of postpartum depression and are working hard to replicate this work with National Institutes of Health funding. Most recently, she was appointed to the American Psychiatric Association’s committee on women’s mental health and is serving as president-elect for both the Marcé of North America and the International Marcé Perinatal Mental Health Societies. She disclosed the following relevant financial relationships: serve(d) as a director, officer, partner, employee, adviser, consultant, or trustee for Sage Therapeutics and Janssen Pharmaceuticals.
 

Dr. Osborne is associate professor of psychiatry and behavioral sciences and of gynecology and obstetrics at Johns Hopkins University, where she directs a postdoctoral fellowship program in reproductive psychiatry. She is an expert on the diagnosis and treatment of mood and anxiety disorders during pregnancy, the post partum, the premenstrual period, and perimenopause. Her work is supported by the Brain and Behavior Foundation, the Doris Duke Foundation, the American Board of Psychiatry and Neurology, and the National Institute of Mental Health. She has no conflicts of interest.

“Increases in age at menarche are significantly associated with increases in cardiovascular health among women,” reported Yi Zheng, MPH, and colleagues at the University of Florida, Gainesville.

Mr. Zheng and colleagues conducted a cross-sectional analysis of 20,447 women aged 18 or older using data from a nationally representative sample of the 1999-2016 National Health and Nutrition Examinations Survey (NHANES). In all, 2,292 (11.2%) were determined to have ideal cardiovascular health (CVH).

Early menarche was confirmed to be related to increases in body mass index and greater incidence of type 2 diabetes, consistent with earlier studies, the authors confirmed. Those with nonideal CVH were more likely to have reported early menarche; those with ideal CVH were not only younger, but they also had college or graduate level education or above and higher poverty income ratio. Those with ideal CVH were also less likely to be to be of non-Hispanic Black heritage or to have been previously married.
 

BMI may be the missing link between early menarche and CVH

Unlike previous studies, the researchers found no significant link between early menarche and blood pressure, total cholesterol, smoking, physical activity, or diet using fully adjusted model data, leading them to conclude that “the associations between early menarche and CVH might be mainly driven by its associations with BMI.”

Mr. Zheng and colleagues suggested that future studies should evaluate the causal relationships between age at menarche and BMI and whether genetic factors and childhood lifestyle predispose women to early menarche and obesity.

“Our findings further highlighted that age at menarche may be used to identify high-risk population[s] and to guide targeted preventions to maintain and improve CVH,” the authors noted. Although they cited several strengths and limitations of the study, they emphasized that the wide use of Life’s Simple 7 factors (blood pressure, total cholesterol, glucose levels, smoking, BMI, physical activity, and diet) to measure CVH should “only be regarded as a surrogate construct, and future efforts are needed to better characterize CVH,” they cautioned.
 

The findings offer an opportunity to more closely track CVH in racial and ethnic groups

In a separate editorial, Ewa M. Gross-Sawicka, MD, PhD, and Eiran Z. Gorodeski, MD, MPH, both of the Harrington Heart and Vascular Institute, Cleveland, observed: “That the authors found African American women had the lowest overall CVH scores, even after adjusting for differences, highlights the importance of beginning cardiovascular health education earlier, especially for those in certain racial and ethnic groups.”

Dr. Gross-Sawicka and Dr. Gorodeski also raised several key questions that warrant further research: “1) Why do women who experience late menarche have improved cardiovascular health while those who experience early menarche have reduced cardiovascular health? 2) Why do the ‘beneficial’ effects of late menarche on CVH last 10 years longer than the ‘detrimental’ effects of early menarche? 3) Since both early and late menarche are associated with increased risk of cardiovascular disease, are women who experience menarche at an older age more cognizant of the cardiovascular risks compared with younger women and adjust their CVH accordingly?”

A key point also worth further consideration: “It is unclear whether age at menarche is directly associated with CVH, or if this relationship is mediated by the association of age at menarche and BMI and/or hyperglycemia,” said Dr. Gross-Sawicka and Dr. Gorodeski.

In an interview, Jan Shifren, MD, director, Midlife Women’s Health Center, Massachusetts General Hospital, Boston, noted, “The principal finding is that early menarche is associated with worse cardiovascular health, which may reflect the adverse impact of obesity and glucose intolerance on CVH, as obesity also is a risk factor for early menarche. The association between early menarche and worse CVH was significant only in women aged 25-34 years, but not in older women, possibly as other risk factors become more important as women age. One of the most concerning findings in this study ... is that only 11% had ideal CVH based on a combination of behavioral and health factors. As cardiovascular disease is the leading cause of death for women, we must do a better job of optimizing [their] cardiovascular health. Clinicians need to focus on optimizing cardiovascular health for all of their midlife patients, whether or not they experienced early menarche!”

Mr. Zheng and colleagues, as well as Dr. Shifren and Dr. Grodeski, had no conflicts of interest to report. Dr. Gross-Sawicka has received funding from Abbott and Novartis.

“Increases in age at menarche are significantly associated with increases in cardiovascular health among women,” reported Yi Zheng, MPH, and colleagues at the University of Florida, Gainesville.

Mr. Zheng and colleagues conducted a cross-sectional analysis of 20,447 women aged 18 or older using data from a nationally representative sample of the 1999-2016 National Health and Nutrition Examinations Survey (NHANES). In all, 2,292 (11.2%) were determined to have ideal cardiovascular health (CVH).

Early menarche was confirmed to be related to increases in body mass index and greater incidence of type 2 diabetes, consistent with earlier studies, the authors confirmed. Those with nonideal CVH were more likely to have reported early menarche; those with ideal CVH were not only younger, but they also had college or graduate level education or above and higher poverty income ratio. Those with ideal CVH were also less likely to be to be of non-Hispanic Black heritage or to have been previously married.
 

BMI may be the missing link between early menarche and CVH

Unlike previous studies, the researchers found no significant link between early menarche and blood pressure, total cholesterol, smoking, physical activity, or diet using fully adjusted model data, leading them to conclude that “the associations between early menarche and CVH might be mainly driven by its associations with BMI.”

Mr. Zheng and colleagues suggested that future studies should evaluate the causal relationships between age at menarche and BMI and whether genetic factors and childhood lifestyle predispose women to early menarche and obesity.

“Our findings further highlighted that age at menarche may be used to identify high-risk population[s] and to guide targeted preventions to maintain and improve CVH,” the authors noted. Although they cited several strengths and limitations of the study, they emphasized that the wide use of Life’s Simple 7 factors (blood pressure, total cholesterol, glucose levels, smoking, BMI, physical activity, and diet) to measure CVH should “only be regarded as a surrogate construct, and future efforts are needed to better characterize CVH,” they cautioned.
 

The findings offer an opportunity to more closely track CVH in racial and ethnic groups

In a separate editorial, Ewa M. Gross-Sawicka, MD, PhD, and Eiran Z. Gorodeski, MD, MPH, both of the Harrington Heart and Vascular Institute, Cleveland, observed: “That the authors found African American women had the lowest overall CVH scores, even after adjusting for differences, highlights the importance of beginning cardiovascular health education earlier, especially for those in certain racial and ethnic groups.”

Dr. Gross-Sawicka and Dr. Gorodeski also raised several key questions that warrant further research: “1) Why do women who experience late menarche have improved cardiovascular health while those who experience early menarche have reduced cardiovascular health? 2) Why do the ‘beneficial’ effects of late menarche on CVH last 10 years longer than the ‘detrimental’ effects of early menarche? 3) Since both early and late menarche are associated with increased risk of cardiovascular disease, are women who experience menarche at an older age more cognizant of the cardiovascular risks compared with younger women and adjust their CVH accordingly?”

A key point also worth further consideration: “It is unclear whether age at menarche is directly associated with CVH, or if this relationship is mediated by the association of age at menarche and BMI and/or hyperglycemia,” said Dr. Gross-Sawicka and Dr. Gorodeski.

In an interview, Jan Shifren, MD, director, Midlife Women’s Health Center, Massachusetts General Hospital, Boston, noted, “The principal finding is that early menarche is associated with worse cardiovascular health, which may reflect the adverse impact of obesity and glucose intolerance on CVH, as obesity also is a risk factor for early menarche. The association between early menarche and worse CVH was significant only in women aged 25-34 years, but not in older women, possibly as other risk factors become more important as women age. One of the most concerning findings in this study ... is that only 11% had ideal CVH based on a combination of behavioral and health factors. As cardiovascular disease is the leading cause of death for women, we must do a better job of optimizing [their] cardiovascular health. Clinicians need to focus on optimizing cardiovascular health for all of their midlife patients, whether or not they experienced early menarche!”

Mr. Zheng and colleagues, as well as Dr. Shifren and Dr. Grodeski, had no conflicts of interest to report. Dr. Gross-Sawicka has received funding from Abbott and Novartis.

“Increases in age at menarche are significantly associated with increases in cardiovascular health among women,” reported Yi Zheng, MPH, and colleagues at the University of Florida, Gainesville.

Mr. Zheng and colleagues conducted a cross-sectional analysis of 20,447 women aged 18 or older using data from a nationally representative sample of the 1999-2016 National Health and Nutrition Examinations Survey (NHANES). In all, 2,292 (11.2%) were determined to have ideal cardiovascular health (CVH).

Early menarche was confirmed to be related to increases in body mass index and greater incidence of type 2 diabetes, consistent with earlier studies, the authors confirmed. Those with nonideal CVH were more likely to have reported early menarche; those with ideal CVH were not only younger, but they also had college or graduate level education or above and higher poverty income ratio. Those with ideal CVH were also less likely to be to be of non-Hispanic Black heritage or to have been previously married.
 

BMI may be the missing link between early menarche and CVH

Unlike previous studies, the researchers found no significant link between early menarche and blood pressure, total cholesterol, smoking, physical activity, or diet using fully adjusted model data, leading them to conclude that “the associations between early menarche and CVH might be mainly driven by its associations with BMI.”

Mr. Zheng and colleagues suggested that future studies should evaluate the causal relationships between age at menarche and BMI and whether genetic factors and childhood lifestyle predispose women to early menarche and obesity.

“Our findings further highlighted that age at menarche may be used to identify high-risk population[s] and to guide targeted preventions to maintain and improve CVH,” the authors noted. Although they cited several strengths and limitations of the study, they emphasized that the wide use of Life’s Simple 7 factors (blood pressure, total cholesterol, glucose levels, smoking, BMI, physical activity, and diet) to measure CVH should “only be regarded as a surrogate construct, and future efforts are needed to better characterize CVH,” they cautioned.
 

The findings offer an opportunity to more closely track CVH in racial and ethnic groups

In a separate editorial, Ewa M. Gross-Sawicka, MD, PhD, and Eiran Z. Gorodeski, MD, MPH, both of the Harrington Heart and Vascular Institute, Cleveland, observed: “That the authors found African American women had the lowest overall CVH scores, even after adjusting for differences, highlights the importance of beginning cardiovascular health education earlier, especially for those in certain racial and ethnic groups.”

Dr. Gross-Sawicka and Dr. Gorodeski also raised several key questions that warrant further research: “1) Why do women who experience late menarche have improved cardiovascular health while those who experience early menarche have reduced cardiovascular health? 2) Why do the ‘beneficial’ effects of late menarche on CVH last 10 years longer than the ‘detrimental’ effects of early menarche? 3) Since both early and late menarche are associated with increased risk of cardiovascular disease, are women who experience menarche at an older age more cognizant of the cardiovascular risks compared with younger women and adjust their CVH accordingly?”

A key point also worth further consideration: “It is unclear whether age at menarche is directly associated with CVH, or if this relationship is mediated by the association of age at menarche and BMI and/or hyperglycemia,” said Dr. Gross-Sawicka and Dr. Gorodeski.

In an interview, Jan Shifren, MD, director, Midlife Women’s Health Center, Massachusetts General Hospital, Boston, noted, “The principal finding is that early menarche is associated with worse cardiovascular health, which may reflect the adverse impact of obesity and glucose intolerance on CVH, as obesity also is a risk factor for early menarche. The association between early menarche and worse CVH was significant only in women aged 25-34 years, but not in older women, possibly as other risk factors become more important as women age. One of the most concerning findings in this study ... is that only 11% had ideal CVH based on a combination of behavioral and health factors. As cardiovascular disease is the leading cause of death for women, we must do a better job of optimizing [their] cardiovascular health. Clinicians need to focus on optimizing cardiovascular health for all of their midlife patients, whether or not they experienced early menarche!”

Mr. Zheng and colleagues, as well as Dr. Shifren and Dr. Grodeski, had no conflicts of interest to report. Dr. Gross-Sawicka has received funding from Abbott and Novartis.

Endometrial cancer is the most common gynecologic ma­lignancy, with approximately 59,000 cases diagnosed annually,¹ and a lifetime risk of approximately 3.1% in the United States.² Type I endometrial cancer includes tumors with endometrioid histology that are grade 1 or 2. Type II endometrial cancer includes tumors that have grade 3 endometrioid or nonendometrioid histology, including serous, clear cell, mucinous, squamous transitional cell, mesonephric, and undifferentiated tumors.³ Type I endometrial cancer is hormone sensitive, generally stimulated by estrogen and suppressed by progestins.

Endometrial cancer is diagnosed at a mean age of 63 years,⁴ and only 15% of cases occur before age 50.⁵ Women with an elevated body mass index (BMI) have a markedly increased risk of both Types I and II endometrial cancer (TABLE).⁶ Hence, endometrial cancer is highly prevalent in obese postmenopausal women. For these women health interventions that may reduce the risk of developing endometrial cancer include dieting, physical activity, bariatric surgery, and progestin therapy.

Educating patients is a priority

Many women do not know that postmenopausal bleeding is a sign of endometrial cancer. All postmenopausal women should be advised that if they develop vaginal bleeding they need to be evaluated by a clinician.⁷ Women who are knowledgeable about the link between postmenopausal vaginal bleeding and endometrial cancer can be encouraged to share this information with their postmenopausal friends in order to reach more people with this important information. All obese postmenopausal women should be advised that weight loss and increased physical activity can reduce the risk of developing endometrial cancer.

How weight loss and physical activity affect risk

Intentional weight loss has been reported to reduce the risk of endometrial cancer in postmenopausal women. As part of the Women’s Health Initiative observational study, 36,794 postmenopausal women aged 50 to 79 years with a uterus had their body weight and height measured at entry into the study and after 3 years of follow-up.⁸ During the 11 years following study entry, there were 566 incident cases of endometrial cancer. Compared with women who had a stable weight, intentional weight loss of ≥5% was associated with a 40% reduction in the risk of endometrial cancer (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.42–0.86). Compared with women who had a stable weight, women who had weight gain ≥10% had an increased risk of endometrial cancer (HR, 1.26; 95% CI, 1.00–1.57).

High levels of physical activity may be associated with a decreased risk of endometrial cancer. In one study, compared with a sedentary lifestyle, higher levels of physical activity were reported to be associated with a decreased risk of endometrial cancer.⁹

Continue to: How bariatric surgery affects risk...

Many cancers are associated with obesity, including endometrial, breast, colon, pancreas, gallbladder, and renal. Obesity is associated with increased conversion of androgens to estrogens in fat tissue, stimulating excessive endometrial proliferation and increasing the risk of endometrial hyperplasia and cancer. Bariatric surgery reliably causes sustained weight reduction. Multiple studies have reported that bariatric surgery reduces the risk of endometrial cancer.

Schauer and colleagues used data from the Kaiser Permanente health system to identify 22,198 obese people who had undergone bariatric surgery and 66,427 matched controls who were obese but did not have surgery.¹⁰ The study population was 81% female, with a mean age of 45 years and a mean BMI of 45 kg/m². After an average 3.5 years of follow-up there were 2,542 incident cases of cancer, including 322 cases of endometrial cancer. Compared with conventional weight loss treatment, bariatric surgery reduced the risk of endometrial cancer by 50% (HR, 0.50; 95% CI, 0.37–0.67; P<.001).¹⁰ In addition, bariatric surgery reduced the risk of colon and pancreatic cancer by 41% and 54%, respectively.¹⁰

In the Swedish Obese Subjects (SOS) study, 1,420 women who underwent bariatric surgery and 1,447 matched controls who received conventional obesity treatment were followed for 18 years.¹¹ At study entry, the mean age of the women was approximately 48 years, and the mean BMI was approximately 42 kg/m². In follow-up there were 76 incident cases of endometrial cancer. Compared with women receiving conventional obesity treatment, women who had bariatric surgery had a non–statistically significant 49% decrease in the risk of developing endometrial cancer (HR, 0.51; 95% CI, 0.24–1.10)

In a systematic review of 5 additional studies (not including publications 10 or 11) of the impact of bariatric surgery on the risk of developing endometrial cancer, the surgery was associated with a 68% risk reduction (odds ratio [OR], 0.32; 95% CI, 0.16–0.63) compared with matched obese women that did not have surgery.¹²

Although there are no randomized prospective studies showing that bariatric surgery reduces the risk of endometrial cancer, the weight of the observation evidence is strong. In addition, bariatric surgery was reported to reduce all-cause mortality in the SOS study.¹³ Hence, for obese postmenopausal women, if lifestyle changes do not result in sustained weight loss, bariatric surgery may be an optimal approach to improving health outcomes.

Continue to: Progestin treatment and endometrial cancer risk...

Estrogen stimulates endometrial cell proliferation. Hence, unopposed chronic exposure to estrogen is a major risk factor for developing endometrial hyperplasia and cancer. Progestins block the proliferative effect of estrogen and cause cell differentiation, resulting in stromal decidualization. Progestins also reduce the concentration of estrogen and progesterone receptors and increase the activity of enzymes that convert estradiol to estrone, blocking estrogen-induced endometrial proliferation.¹⁴

In women with endometrial hyperplasia, progestins have been shown to be effective in resolving the hyperplasia in approximately 80% of cases. Both oral progestins and the 52-mg levonorgestrel-containing intrauterine device (LNG-IUD) have been reported to be effective in the treatment of endometrial hyperplasia. In a Cochrane systematic review and meta-analysis, the 52-mg LNG-IUD was reported to be somewhat more effective in resolving endometrial hyperplasia than cyclic oral progestins (89% vs 72%, respectively).¹⁵

Other studies have also reported that the 52 mg LNG-IUD was more effective than oral progestin therapy for women with complex atypical endometrial hyperplasia.¹⁶ There are no large randomized clinical trials of progestin therapy on prevention for future development of endometrial cancer in obese postmenopausal women who have a normal endometrial histology. However, for an obese perimenopausal woman, insertion of a 52-mg LNG-IUD may help to minimize excessive uterine bleeding during the menopause transition and reduce the risk of developing endometrial hyperplasia during the early postmenopause.

We can help our patients reduce their risk of endometrial cancer

Obese postmenopausal women are at increased risk for developing endometrial cancer. Gynecologists play an important role in the prevention and early detection of endometrial cancer. We can make a difference and improve the health of our obese peri- and postmenopausal women by recommending interventions that reduce the risk of endometrial cancer, thereby improving the health of our patients. ●

Endometrial cancer is the most common gynecologic ma­lignancy, with approximately 59,000 cases diagnosed annually,¹ and a lifetime risk of approximately 3.1% in the United States.² Type I endometrial cancer includes tumors with endometrioid histology that are grade 1 or 2. Type II endometrial cancer includes tumors that have grade 3 endometrioid or nonendometrioid histology, including serous, clear cell, mucinous, squamous transitional cell, mesonephric, and undifferentiated tumors.³ Type I endometrial cancer is hormone sensitive, generally stimulated by estrogen and suppressed by progestins.

Endometrial cancer is diagnosed at a mean age of 63 years,⁴ and only 15% of cases occur before age 50.⁵ Women with an elevated body mass index (BMI) have a markedly increased risk of both Types I and II endometrial cancer (TABLE).⁶ Hence, endometrial cancer is highly prevalent in obese postmenopausal women. For these women health interventions that may reduce the risk of developing endometrial cancer include dieting, physical activity, bariatric surgery, and progestin therapy.

Educating patients is a priority

Many women do not know that postmenopausal bleeding is a sign of endometrial cancer. All postmenopausal women should be advised that if they develop vaginal bleeding they need to be evaluated by a clinician.⁷ Women who are knowledgeable about the link between postmenopausal vaginal bleeding and endometrial cancer can be encouraged to share this information with their postmenopausal friends in order to reach more people with this important information. All obese postmenopausal women should be advised that weight loss and increased physical activity can reduce the risk of developing endometrial cancer.

How weight loss and physical activity affect risk

Intentional weight loss has been reported to reduce the risk of endometrial cancer in postmenopausal women. As part of the Women’s Health Initiative observational study, 36,794 postmenopausal women aged 50 to 79 years with a uterus had their body weight and height measured at entry into the study and after 3 years of follow-up.⁸ During the 11 years following study entry, there were 566 incident cases of endometrial cancer. Compared with women who had a stable weight, intentional weight loss of ≥5% was associated with a 40% reduction in the risk of endometrial cancer (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.42–0.86). Compared with women who had a stable weight, women who had weight gain ≥10% had an increased risk of endometrial cancer (HR, 1.26; 95% CI, 1.00–1.57).

High levels of physical activity may be associated with a decreased risk of endometrial cancer. In one study, compared with a sedentary lifestyle, higher levels of physical activity were reported to be associated with a decreased risk of endometrial cancer.⁹

Continue to: How bariatric surgery affects risk...

Many cancers are associated with obesity, including endometrial, breast, colon, pancreas, gallbladder, and renal. Obesity is associated with increased conversion of androgens to estrogens in fat tissue, stimulating excessive endometrial proliferation and increasing the risk of endometrial hyperplasia and cancer. Bariatric surgery reliably causes sustained weight reduction. Multiple studies have reported that bariatric surgery reduces the risk of endometrial cancer.

Schauer and colleagues used data from the Kaiser Permanente health system to identify 22,198 obese people who had undergone bariatric surgery and 66,427 matched controls who were obese but did not have surgery.¹⁰ The study population was 81% female, with a mean age of 45 years and a mean BMI of 45 kg/m². After an average 3.5 years of follow-up there were 2,542 incident cases of cancer, including 322 cases of endometrial cancer. Compared with conventional weight loss treatment, bariatric surgery reduced the risk of endometrial cancer by 50% (HR, 0.50; 95% CI, 0.37–0.67; P<.001).¹⁰ In addition, bariatric surgery reduced the risk of colon and pancreatic cancer by 41% and 54%, respectively.¹⁰

In the Swedish Obese Subjects (SOS) study, 1,420 women who underwent bariatric surgery and 1,447 matched controls who received conventional obesity treatment were followed for 18 years.¹¹ At study entry, the mean age of the women was approximately 48 years, and the mean BMI was approximately 42 kg/m². In follow-up there were 76 incident cases of endometrial cancer. Compared with women receiving conventional obesity treatment, women who had bariatric surgery had a non–statistically significant 49% decrease in the risk of developing endometrial cancer (HR, 0.51; 95% CI, 0.24–1.10)

In a systematic review of 5 additional studies (not including publications 10 or 11) of the impact of bariatric surgery on the risk of developing endometrial cancer, the surgery was associated with a 68% risk reduction (odds ratio [OR], 0.32; 95% CI, 0.16–0.63) compared with matched obese women that did not have surgery.¹²

Although there are no randomized prospective studies showing that bariatric surgery reduces the risk of endometrial cancer, the weight of the observation evidence is strong. In addition, bariatric surgery was reported to reduce all-cause mortality in the SOS study.¹³ Hence, for obese postmenopausal women, if lifestyle changes do not result in sustained weight loss, bariatric surgery may be an optimal approach to improving health outcomes.

Continue to: Progestin treatment and endometrial cancer risk...

Estrogen stimulates endometrial cell proliferation. Hence, unopposed chronic exposure to estrogen is a major risk factor for developing endometrial hyperplasia and cancer. Progestins block the proliferative effect of estrogen and cause cell differentiation, resulting in stromal decidualization. Progestins also reduce the concentration of estrogen and progesterone receptors and increase the activity of enzymes that convert estradiol to estrone, blocking estrogen-induced endometrial proliferation.¹⁴

In women with endometrial hyperplasia, progestins have been shown to be effective in resolving the hyperplasia in approximately 80% of cases. Both oral progestins and the 52-mg levonorgestrel-containing intrauterine device (LNG-IUD) have been reported to be effective in the treatment of endometrial hyperplasia. In a Cochrane systematic review and meta-analysis, the 52-mg LNG-IUD was reported to be somewhat more effective in resolving endometrial hyperplasia than cyclic oral progestins (89% vs 72%, respectively).¹⁵

Other studies have also reported that the 52 mg LNG-IUD was more effective than oral progestin therapy for women with complex atypical endometrial hyperplasia.¹⁶ There are no large randomized clinical trials of progestin therapy on prevention for future development of endometrial cancer in obese postmenopausal women who have a normal endometrial histology. However, for an obese perimenopausal woman, insertion of a 52-mg LNG-IUD may help to minimize excessive uterine bleeding during the menopause transition and reduce the risk of developing endometrial hyperplasia during the early postmenopause.

We can help our patients reduce their risk of endometrial cancer

Obese postmenopausal women are at increased risk for developing endometrial cancer. Gynecologists play an important role in the prevention and early detection of endometrial cancer. We can make a difference and improve the health of our obese peri- and postmenopausal women by recommending interventions that reduce the risk of endometrial cancer, thereby improving the health of our patients. ●

Endometrial cancer is the most common gynecologic ma­lignancy, with approximately 59,000 cases diagnosed annually,¹ and a lifetime risk of approximately 3.1% in the United States.² Type I endometrial cancer includes tumors with endometrioid histology that are grade 1 or 2. Type II endometrial cancer includes tumors that have grade 3 endometrioid or nonendometrioid histology, including serous, clear cell, mucinous, squamous transitional cell, mesonephric, and undifferentiated tumors.³ Type I endometrial cancer is hormone sensitive, generally stimulated by estrogen and suppressed by progestins.

Endometrial cancer is diagnosed at a mean age of 63 years,⁴ and only 15% of cases occur before age 50.⁵ Women with an elevated body mass index (BMI) have a markedly increased risk of both Types I and II endometrial cancer (TABLE).⁶ Hence, endometrial cancer is highly prevalent in obese postmenopausal women. For these women health interventions that may reduce the risk of developing endometrial cancer include dieting, physical activity, bariatric surgery, and progestin therapy.

Educating patients is a priority

Many women do not know that postmenopausal bleeding is a sign of endometrial cancer. All postmenopausal women should be advised that if they develop vaginal bleeding they need to be evaluated by a clinician.⁷ Women who are knowledgeable about the link between postmenopausal vaginal bleeding and endometrial cancer can be encouraged to share this information with their postmenopausal friends in order to reach more people with this important information. All obese postmenopausal women should be advised that weight loss and increased physical activity can reduce the risk of developing endometrial cancer.

How weight loss and physical activity affect risk

Intentional weight loss has been reported to reduce the risk of endometrial cancer in postmenopausal women. As part of the Women’s Health Initiative observational study, 36,794 postmenopausal women aged 50 to 79 years with a uterus had their body weight and height measured at entry into the study and after 3 years of follow-up.⁸ During the 11 years following study entry, there were 566 incident cases of endometrial cancer. Compared with women who had a stable weight, intentional weight loss of ≥5% was associated with a 40% reduction in the risk of endometrial cancer (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.42–0.86). Compared with women who had a stable weight, women who had weight gain ≥10% had an increased risk of endometrial cancer (HR, 1.26; 95% CI, 1.00–1.57).

High levels of physical activity may be associated with a decreased risk of endometrial cancer. In one study, compared with a sedentary lifestyle, higher levels of physical activity were reported to be associated with a decreased risk of endometrial cancer.⁹

Continue to: How bariatric surgery affects risk...

Many cancers are associated with obesity, including endometrial, breast, colon, pancreas, gallbladder, and renal. Obesity is associated with increased conversion of androgens to estrogens in fat tissue, stimulating excessive endometrial proliferation and increasing the risk of endometrial hyperplasia and cancer. Bariatric surgery reliably causes sustained weight reduction. Multiple studies have reported that bariatric surgery reduces the risk of endometrial cancer.

Schauer and colleagues used data from the Kaiser Permanente health system to identify 22,198 obese people who had undergone bariatric surgery and 66,427 matched controls who were obese but did not have surgery.¹⁰ The study population was 81% female, with a mean age of 45 years and a mean BMI of 45 kg/m². After an average 3.5 years of follow-up there were 2,542 incident cases of cancer, including 322 cases of endometrial cancer. Compared with conventional weight loss treatment, bariatric surgery reduced the risk of endometrial cancer by 50% (HR, 0.50; 95% CI, 0.37–0.67; P<.001).¹⁰ In addition, bariatric surgery reduced the risk of colon and pancreatic cancer by 41% and 54%, respectively.¹⁰

In the Swedish Obese Subjects (SOS) study, 1,420 women who underwent bariatric surgery and 1,447 matched controls who received conventional obesity treatment were followed for 18 years.¹¹ At study entry, the mean age of the women was approximately 48 years, and the mean BMI was approximately 42 kg/m². In follow-up there were 76 incident cases of endometrial cancer. Compared with women receiving conventional obesity treatment, women who had bariatric surgery had a non–statistically significant 49% decrease in the risk of developing endometrial cancer (HR, 0.51; 95% CI, 0.24–1.10)

In a systematic review of 5 additional studies (not including publications 10 or 11) of the impact of bariatric surgery on the risk of developing endometrial cancer, the surgery was associated with a 68% risk reduction (odds ratio [OR], 0.32; 95% CI, 0.16–0.63) compared with matched obese women that did not have surgery.¹²

Although there are no randomized prospective studies showing that bariatric surgery reduces the risk of endometrial cancer, the weight of the observation evidence is strong. In addition, bariatric surgery was reported to reduce all-cause mortality in the SOS study.¹³ Hence, for obese postmenopausal women, if lifestyle changes do not result in sustained weight loss, bariatric surgery may be an optimal approach to improving health outcomes.

Continue to: Progestin treatment and endometrial cancer risk...

Estrogen stimulates endometrial cell proliferation. Hence, unopposed chronic exposure to estrogen is a major risk factor for developing endometrial hyperplasia and cancer. Progestins block the proliferative effect of estrogen and cause cell differentiation, resulting in stromal decidualization. Progestins also reduce the concentration of estrogen and progesterone receptors and increase the activity of enzymes that convert estradiol to estrone, blocking estrogen-induced endometrial proliferation.¹⁴

In women with endometrial hyperplasia, progestins have been shown to be effective in resolving the hyperplasia in approximately 80% of cases. Both oral progestins and the 52-mg levonorgestrel-containing intrauterine device (LNG-IUD) have been reported to be effective in the treatment of endometrial hyperplasia. In a Cochrane systematic review and meta-analysis, the 52-mg LNG-IUD was reported to be somewhat more effective in resolving endometrial hyperplasia than cyclic oral progestins (89% vs 72%, respectively).¹⁵

Other studies have also reported that the 52 mg LNG-IUD was more effective than oral progestin therapy for women with complex atypical endometrial hyperplasia.¹⁶ There are no large randomized clinical trials of progestin therapy on prevention for future development of endometrial cancer in obese postmenopausal women who have a normal endometrial histology. However, for an obese perimenopausal woman, insertion of a 52-mg LNG-IUD may help to minimize excessive uterine bleeding during the menopause transition and reduce the risk of developing endometrial hyperplasia during the early postmenopause.

We can help our patients reduce their risk of endometrial cancer

Obese postmenopausal women are at increased risk for developing endometrial cancer. Gynecologists play an important role in the prevention and early detection of endometrial cancer. We can make a difference and improve the health of our obese peri- and postmenopausal women by recommending interventions that reduce the risk of endometrial cancer, thereby improving the health of our patients. ●

Changes in hormones, body composition, lipids, and vascular health during the menopause transition can increase a woman’s chance of developing cardiovascular disease (CVD) after menopause, the American Heart Association said in a scientific statement.

“This statement aims to raise awareness of both healthcare providers and women about the menopause transition as a time of increasing heart disease risk,” Samar R. El Khoudary, PhD, MPH, who chaired the writing group, said in an interview.

“As such, it emphasizes the importance of monitoring women’s health during midlife and targeting this stage as a critical window for applying early intervention strategies that aim to maintain a healthy heart and reduce the risk of heart disease,” said Dr. El Khoudary, of the University of Pittsburgh.

The statement was published online Nov. 30 in Circulation.
 

Evolution in knowledge

During the past 20 years, knowledge of how menopause might contribute to CVD has evolved “dramatically,” Dr. El Khoudary noted. The accumulated data consistently point to the menopause transition as a time of change in heart health.

“Importantly,” she said, the latest AHA guidelines for CVD prevention in women, published in 2011, do not include data now available on the menopause transition as a time of increased CVD risk.

“As such, there is a compelling need to discuss the implications of the accumulating body of literature on this topic,” said Dr. El Khoudary.

The statement provides a contemporary synthesis of the existing data on menopause and how it relates to CVD, the leading cause of death of U.S. women.

Earlier age at natural menopause has generally been found to be a marker of greater CVD risk. Iatrogenically induced menopause (bilateral oophorectomy) during the premenopausal period is also associated with higher CVD risk, the data suggest.

Vasomotor symptoms are associated with worse levels of CVD risk factors and measures of subclinical atherosclerosis. Sleep disturbance has also been linked to greater risk for subclinical CVD and worse CV health indexes in women during midlife.

Increases in central/visceral fat and decreases in lean muscle mass are more pronounced during the menopause transition. This increased central adiposity is associated with increased risk for mortality, even among those with normal body mass index, the writing group found.

Increases in lipid levels (LDL cholesterol and apolipoprotein B), metabolic syndrome risk, and vascular remodeling at midlife are driven by the menopause transition more than aging, whereas increases in blood pressure, insulin level, and glucose level are likely more influenced by chronological aging, they reported.
 

Lifestyle interventions

The writing group noted that, because of the increase in overall life expectancy in the United States, a significant proportion of women will spend up to 40% of their lives after menopause.

Yet data suggest that only 7.2% of women transitioning to menopause are meeting physical activity guidelines and that fewer than 20% of those women are consistently maintaining a healthy diet.

Limited data from randomized, controlled trials suggest that a multidimensional lifestyle intervention during the menopause transition can prevent weight gain and reduce blood pressure and levels of triglycerides, blood glucose, and insulin and reduce the incidence of subclinical carotid atherosclerosis, they pointed out.

“Novel data” indicate a reversal in the associations of HDL cholesterol with CVD risk over the menopause transition, suggesting that higher HDL cholesterol levels may not consistently reflect good cardiovascular health in middle-aged women, the group noted.

There are also data suggesting that starting menopause hormone therapy when younger than 60 years or within 10 years of menopause is associated with reduced CVD risk.

The group said further research is needed into the cardiometabolic effects of menopause hormone therapy, including effects associated with form, route, and duration of administration, in women traversing menopause.

They also noted that data for the primary and secondary prevention of atherosclerotic CVD and improved survival with lipid-lowering interventions “remain elusive” for women and that further study is needed to develop evidence-based recommendations tailored specifically to women.

The research had no commercial funding. Dr. El Khoudary has disclosed no relevant financial relationships.

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

Changes in hormones, body composition, lipids, and vascular health during the menopause transition can increase a woman’s chance of developing cardiovascular disease (CVD) after menopause, the American Heart Association said in a scientific statement.

“This statement aims to raise awareness of both healthcare providers and women about the menopause transition as a time of increasing heart disease risk,” Samar R. El Khoudary, PhD, MPH, who chaired the writing group, said in an interview.

“As such, it emphasizes the importance of monitoring women’s health during midlife and targeting this stage as a critical window for applying early intervention strategies that aim to maintain a healthy heart and reduce the risk of heart disease,” said Dr. El Khoudary, of the University of Pittsburgh.

The statement was published online Nov. 30 in Circulation.
 

Evolution in knowledge

During the past 20 years, knowledge of how menopause might contribute to CVD has evolved “dramatically,” Dr. El Khoudary noted. The accumulated data consistently point to the menopause transition as a time of change in heart health.

“Importantly,” she said, the latest AHA guidelines for CVD prevention in women, published in 2011, do not include data now available on the menopause transition as a time of increased CVD risk.

“As such, there is a compelling need to discuss the implications of the accumulating body of literature on this topic,” said Dr. El Khoudary.

The statement provides a contemporary synthesis of the existing data on menopause and how it relates to CVD, the leading cause of death of U.S. women.

Earlier age at natural menopause has generally been found to be a marker of greater CVD risk. Iatrogenically induced menopause (bilateral oophorectomy) during the premenopausal period is also associated with higher CVD risk, the data suggest.

Vasomotor symptoms are associated with worse levels of CVD risk factors and measures of subclinical atherosclerosis. Sleep disturbance has also been linked to greater risk for subclinical CVD and worse CV health indexes in women during midlife.

Increases in central/visceral fat and decreases in lean muscle mass are more pronounced during the menopause transition. This increased central adiposity is associated with increased risk for mortality, even among those with normal body mass index, the writing group found.

Increases in lipid levels (LDL cholesterol and apolipoprotein B), metabolic syndrome risk, and vascular remodeling at midlife are driven by the menopause transition more than aging, whereas increases in blood pressure, insulin level, and glucose level are likely more influenced by chronological aging, they reported.
 

Lifestyle interventions

The writing group noted that, because of the increase in overall life expectancy in the United States, a significant proportion of women will spend up to 40% of their lives after menopause.

Yet data suggest that only 7.2% of women transitioning to menopause are meeting physical activity guidelines and that fewer than 20% of those women are consistently maintaining a healthy diet.

Limited data from randomized, controlled trials suggest that a multidimensional lifestyle intervention during the menopause transition can prevent weight gain and reduce blood pressure and levels of triglycerides, blood glucose, and insulin and reduce the incidence of subclinical carotid atherosclerosis, they pointed out.

“Novel data” indicate a reversal in the associations of HDL cholesterol with CVD risk over the menopause transition, suggesting that higher HDL cholesterol levels may not consistently reflect good cardiovascular health in middle-aged women, the group noted.

There are also data suggesting that starting menopause hormone therapy when younger than 60 years or within 10 years of menopause is associated with reduced CVD risk.

The group said further research is needed into the cardiometabolic effects of menopause hormone therapy, including effects associated with form, route, and duration of administration, in women traversing menopause.

They also noted that data for the primary and secondary prevention of atherosclerotic CVD and improved survival with lipid-lowering interventions “remain elusive” for women and that further study is needed to develop evidence-based recommendations tailored specifically to women.

The research had no commercial funding. Dr. El Khoudary has disclosed no relevant financial relationships.

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

Changes in hormones, body composition, lipids, and vascular health during the menopause transition can increase a woman’s chance of developing cardiovascular disease (CVD) after menopause, the American Heart Association said in a scientific statement.

“This statement aims to raise awareness of both healthcare providers and women about the menopause transition as a time of increasing heart disease risk,” Samar R. El Khoudary, PhD, MPH, who chaired the writing group, said in an interview.

“As such, it emphasizes the importance of monitoring women’s health during midlife and targeting this stage as a critical window for applying early intervention strategies that aim to maintain a healthy heart and reduce the risk of heart disease,” said Dr. El Khoudary, of the University of Pittsburgh.

The statement was published online Nov. 30 in Circulation.
 

Evolution in knowledge

During the past 20 years, knowledge of how menopause might contribute to CVD has evolved “dramatically,” Dr. El Khoudary noted. The accumulated data consistently point to the menopause transition as a time of change in heart health.

“Importantly,” she said, the latest AHA guidelines for CVD prevention in women, published in 2011, do not include data now available on the menopause transition as a time of increased CVD risk.

“As such, there is a compelling need to discuss the implications of the accumulating body of literature on this topic,” said Dr. El Khoudary.

The statement provides a contemporary synthesis of the existing data on menopause and how it relates to CVD, the leading cause of death of U.S. women.

Earlier age at natural menopause has generally been found to be a marker of greater CVD risk. Iatrogenically induced menopause (bilateral oophorectomy) during the premenopausal period is also associated with higher CVD risk, the data suggest.

Vasomotor symptoms are associated with worse levels of CVD risk factors and measures of subclinical atherosclerosis. Sleep disturbance has also been linked to greater risk for subclinical CVD and worse CV health indexes in women during midlife.

Increases in central/visceral fat and decreases in lean muscle mass are more pronounced during the menopause transition. This increased central adiposity is associated with increased risk for mortality, even among those with normal body mass index, the writing group found.

Increases in lipid levels (LDL cholesterol and apolipoprotein B), metabolic syndrome risk, and vascular remodeling at midlife are driven by the menopause transition more than aging, whereas increases in blood pressure, insulin level, and glucose level are likely more influenced by chronological aging, they reported.
 

Lifestyle interventions

The writing group noted that, because of the increase in overall life expectancy in the United States, a significant proportion of women will spend up to 40% of their lives after menopause.

Yet data suggest that only 7.2% of women transitioning to menopause are meeting physical activity guidelines and that fewer than 20% of those women are consistently maintaining a healthy diet.

Limited data from randomized, controlled trials suggest that a multidimensional lifestyle intervention during the menopause transition can prevent weight gain and reduce blood pressure and levels of triglycerides, blood glucose, and insulin and reduce the incidence of subclinical carotid atherosclerosis, they pointed out.

“Novel data” indicate a reversal in the associations of HDL cholesterol with CVD risk over the menopause transition, suggesting that higher HDL cholesterol levels may not consistently reflect good cardiovascular health in middle-aged women, the group noted.

There are also data suggesting that starting menopause hormone therapy when younger than 60 years or within 10 years of menopause is associated with reduced CVD risk.

The group said further research is needed into the cardiometabolic effects of menopause hormone therapy, including effects associated with form, route, and duration of administration, in women traversing menopause.

They also noted that data for the primary and secondary prevention of atherosclerotic CVD and improved survival with lipid-lowering interventions “remain elusive” for women and that further study is needed to develop evidence-based recommendations tailored specifically to women.

The research had no commercial funding. Dr. El Khoudary has disclosed no relevant financial relationships.

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

Endocrine diseases of any type – not just diabetes – can represent a cardiovascular risk and patients with those disorders should be screened for high cholesterol, according to a new clinical practice guideline from the Endocrine Society.

“The simple recommendation to check a lipid panel in patients with endocrine diseases and calculate cardiovascular risk may be practice changing because that is not done routinely,” Connie Newman, MD, chair of the Endocrine Society committee that developed the guideline, said in an interview.

“Usually the focus is on assessment and treatment of the endocrine disease, rather than on assessment and treatment of atherosclerotic cardiovascular disease risk,” said Newman, an adjunct professor of medicine in the department of medicine, division of endocrinology, diabetes & metabolism, at New York University.

Whereas diabetes, well-known for its increased cardiovascular risk profile, is commonly addressed in other cardiovascular and cholesterol practice management guidelines, the array of other endocrine diseases are not typically included.

“This guideline is the first of its kind,” Dr. Newman said. “The Endocrine Society has not previously issued a guideline on lipid management in endocrine disorders [and] other organizations have not written guidelines on this topic. 

“Rather, guidelines have been written on cholesterol management, but these do not describe cholesterol management in patients with endocrine diseases such as thyroid disease [hypothyroidism and hyperthyroidism], Cushing’s syndrome, acromegaly, growth hormone deficiency, menopause, male hypogonadism, and obesity,” she noted.

But these conditions carry a host of cardiovascular risk factors that may require careful monitoring and management.

“Although endocrine hormones, such as thyroid hormone, cortisol, estrogen, testosterone, growth hormone, and insulin, affect pathways for lipid metabolism, physicians lack guidance on lipid abnormalities, cardiovascular risk, and treatment to reduce lipids and cardiovascular risk in patients with endocrine diseases,” she explained.

Vinaya Simha, MD, an internal medicine specialist at the Mayo Clinic in Rochester, Minn., agrees that the guideline is notable in addressing an unmet need.

Recommendations that stand out to Dr. Simha include the suggestion of adding eicosapentaenoic acid (EPA) ethyl ester to reduce the risk of cardiovascular disease in adults with diabetes or atherosclerotic cardiovascular disease who have elevated triglyceride levels despite statin treatment.

James L. Rosenzweig, MD, an endocrinologist at Hebrew SeniorLife in Boston, agreed that this is an important addition to an area that needs more guidance.

“Many of these clinical situations can exacerbate dyslipidemia and some also increase the cardiovascular risk to a greater extent in combination with elevated cholesterol and/or triglycerides,” he said in an interview. 

“In many cases, treatment of the underlying disorder appropriately can have an important impact in resolving the lipid disorder. In others, more aggressive pharmacological treatment is indicated,” he said.

“I think that this will be a valuable resource, especially for endocrinologists, but it can be used as well by providers in other disciplines.”
 

Key recommendations for different endocrine conditions

The guideline, published in the Journal of Clinical Endocrinology & Metabolism, details those risks and provides evidence-based recommendations on their management and treatment.

Key recommendations include:

• Obtain a lipid panel and evaluate cardiovascular risk factors in all adults with endocrine disorders.
• In patients with  and risk factors for cardiovascular disease, start statin therapy in addition to lifestyle modification to reduce cardiovascular risk. “This could mean earlier treatment because other guidelines recommend consideration of therapy at age 40,” Dr. Newman said.
• Statin therapy is also recommended for adults over 40 with  with a duration of diabetes of more than 20 years and/or microvascular complications, regardless of their cardiovascular risk score. “This means earlier treatment of patients with type 1 diabetes with statins in order to reduce cardiovascular disease risk,” Dr. Newman noted.
• In patients with hyperlipidemia, rule out  as the cause before treating with lipid-lowering medications. And among patients who are found to have hypothyroidism, reevaluate the lipid profile when the patient has thyroid hormone levels in the normal range.
• Adults with persistent endogenous Cushing’s syndrome should have their lipid profile monitored. Statin therapy should be considered in addition to lifestyle modifications, irrespective of the cardiovascular risk score.
• In postmenopausal women, high cholesterol or triglycerides should be treated with statins rather than hormone therapy.
• Evaluate and treat lipids and other cardiovascular risk factors in women who enter menopause early (before the age of 40-45 years).

Nice summary of ‘risk-enhancing’ endocrine disorders

Dr. Simha said in an interview that the new guideline is “probably the first comprehensive statement addressing lipid treatment in patients with a broad range of endocrine disorders besides diabetes.”

“Most of the treatment recommendations are congruent with other current guidelines such as the American College of Cardiology/American Heart Association [guidelines], but there is specific mention of which endocrine disorders represent enhanced cardiovascular risk,” she explained.

The new recommendations are notable for including “a nice summary of how different endocrine disorders affect lipid values, and also which endocrine disorders need to be considered as ‘risk-enhancing factors,’ ” Dr. Simha noted.

“The use of EPA in patients with hypertriglyceridemia is novel, compared to the ACC/AHA recommendation. This reflects new data which is now available,” she added.

The American Association of Clinical Endocrinologists also just issued a new algorithm on lipid management and prevention of cardiovascular disease in which treatment of hypertriglyceridemia is emphasized.

In addition, the new Endocrine Society guideline “also mentions an LDL [cholesterol] treatment threshold of 70 mg/dL, and 55 mg/dL in some patient categories, which previous guidelines have not,” Dr. Simha noted.

Overall, Dr. Newman added that the goal of the guideline is to increase awareness of key issues with endocrine diseases that may not necessarily be on clinicians’ radars.

“We hope that it will make a lipid panel and cardiovascular risk evaluation routine in adults with endocrine diseases and cause a greater focus on therapies to reduce heart disease and stroke,” she said.

Dr. Newman, Dr. Simha, and Dr. Rosenzweig reported no relevant financial relationships.

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

Endocrine diseases of any type – not just diabetes – can represent a cardiovascular risk and patients with those disorders should be screened for high cholesterol, according to a new clinical practice guideline from the Endocrine Society.

“The simple recommendation to check a lipid panel in patients with endocrine diseases and calculate cardiovascular risk may be practice changing because that is not done routinely,” Connie Newman, MD, chair of the Endocrine Society committee that developed the guideline, said in an interview.

“Usually the focus is on assessment and treatment of the endocrine disease, rather than on assessment and treatment of atherosclerotic cardiovascular disease risk,” said Newman, an adjunct professor of medicine in the department of medicine, division of endocrinology, diabetes & metabolism, at New York University.

Whereas diabetes, well-known for its increased cardiovascular risk profile, is commonly addressed in other cardiovascular and cholesterol practice management guidelines, the array of other endocrine diseases are not typically included.

“This guideline is the first of its kind,” Dr. Newman said. “The Endocrine Society has not previously issued a guideline on lipid management in endocrine disorders [and] other organizations have not written guidelines on this topic. 

“Rather, guidelines have been written on cholesterol management, but these do not describe cholesterol management in patients with endocrine diseases such as thyroid disease [hypothyroidism and hyperthyroidism], Cushing’s syndrome, acromegaly, growth hormone deficiency, menopause, male hypogonadism, and obesity,” she noted.

But these conditions carry a host of cardiovascular risk factors that may require careful monitoring and management.

“Although endocrine hormones, such as thyroid hormone, cortisol, estrogen, testosterone, growth hormone, and insulin, affect pathways for lipid metabolism, physicians lack guidance on lipid abnormalities, cardiovascular risk, and treatment to reduce lipids and cardiovascular risk in patients with endocrine diseases,” she explained.

Vinaya Simha, MD, an internal medicine specialist at the Mayo Clinic in Rochester, Minn., agrees that the guideline is notable in addressing an unmet need.

Recommendations that stand out to Dr. Simha include the suggestion of adding eicosapentaenoic acid (EPA) ethyl ester to reduce the risk of cardiovascular disease in adults with diabetes or atherosclerotic cardiovascular disease who have elevated triglyceride levels despite statin treatment.

James L. Rosenzweig, MD, an endocrinologist at Hebrew SeniorLife in Boston, agreed that this is an important addition to an area that needs more guidance.

“Many of these clinical situations can exacerbate dyslipidemia and some also increase the cardiovascular risk to a greater extent in combination with elevated cholesterol and/or triglycerides,” he said in an interview. 

“In many cases, treatment of the underlying disorder appropriately can have an important impact in resolving the lipid disorder. In others, more aggressive pharmacological treatment is indicated,” he said.

“I think that this will be a valuable resource, especially for endocrinologists, but it can be used as well by providers in other disciplines.”
 

Key recommendations for different endocrine conditions

The guideline, published in the Journal of Clinical Endocrinology & Metabolism, details those risks and provides evidence-based recommendations on their management and treatment.

Key recommendations include:

• Obtain a lipid panel and evaluate cardiovascular risk factors in all adults with endocrine disorders.
• In patients with  and risk factors for cardiovascular disease, start statin therapy in addition to lifestyle modification to reduce cardiovascular risk. “This could mean earlier treatment because other guidelines recommend consideration of therapy at age 40,” Dr. Newman said.
• Statin therapy is also recommended for adults over 40 with  with a duration of diabetes of more than 20 years and/or microvascular complications, regardless of their cardiovascular risk score. “This means earlier treatment of patients with type 1 diabetes with statins in order to reduce cardiovascular disease risk,” Dr. Newman noted.
• In patients with hyperlipidemia, rule out  as the cause before treating with lipid-lowering medications. And among patients who are found to have hypothyroidism, reevaluate the lipid profile when the patient has thyroid hormone levels in the normal range.
• Adults with persistent endogenous Cushing’s syndrome should have their lipid profile monitored. Statin therapy should be considered in addition to lifestyle modifications, irrespective of the cardiovascular risk score.
• In postmenopausal women, high cholesterol or triglycerides should be treated with statins rather than hormone therapy.
• Evaluate and treat lipids and other cardiovascular risk factors in women who enter menopause early (before the age of 40-45 years).

Nice summary of ‘risk-enhancing’ endocrine disorders

Dr. Simha said in an interview that the new guideline is “probably the first comprehensive statement addressing lipid treatment in patients with a broad range of endocrine disorders besides diabetes.”

“Most of the treatment recommendations are congruent with other current guidelines such as the American College of Cardiology/American Heart Association [guidelines], but there is specific mention of which endocrine disorders represent enhanced cardiovascular risk,” she explained.

The new recommendations are notable for including “a nice summary of how different endocrine disorders affect lipid values, and also which endocrine disorders need to be considered as ‘risk-enhancing factors,’ ” Dr. Simha noted.

“The use of EPA in patients with hypertriglyceridemia is novel, compared to the ACC/AHA recommendation. This reflects new data which is now available,” she added.

The American Association of Clinical Endocrinologists also just issued a new algorithm on lipid management and prevention of cardiovascular disease in which treatment of hypertriglyceridemia is emphasized.

In addition, the new Endocrine Society guideline “also mentions an LDL [cholesterol] treatment threshold of 70 mg/dL, and 55 mg/dL in some patient categories, which previous guidelines have not,” Dr. Simha noted.

Overall, Dr. Newman added that the goal of the guideline is to increase awareness of key issues with endocrine diseases that may not necessarily be on clinicians’ radars.

“We hope that it will make a lipid panel and cardiovascular risk evaluation routine in adults with endocrine diseases and cause a greater focus on therapies to reduce heart disease and stroke,” she said.

Dr. Newman, Dr. Simha, and Dr. Rosenzweig reported no relevant financial relationships.

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

Endocrine diseases of any type – not just diabetes – can represent a cardiovascular risk and patients with those disorders should be screened for high cholesterol, according to a new clinical practice guideline from the Endocrine Society.

“The simple recommendation to check a lipid panel in patients with endocrine diseases and calculate cardiovascular risk may be practice changing because that is not done routinely,” Connie Newman, MD, chair of the Endocrine Society committee that developed the guideline, said in an interview.

“Usually the focus is on assessment and treatment of the endocrine disease, rather than on assessment and treatment of atherosclerotic cardiovascular disease risk,” said Newman, an adjunct professor of medicine in the department of medicine, division of endocrinology, diabetes & metabolism, at New York University.

Whereas diabetes, well-known for its increased cardiovascular risk profile, is commonly addressed in other cardiovascular and cholesterol practice management guidelines, the array of other endocrine diseases are not typically included.

“This guideline is the first of its kind,” Dr. Newman said. “The Endocrine Society has not previously issued a guideline on lipid management in endocrine disorders [and] other organizations have not written guidelines on this topic. 

“Rather, guidelines have been written on cholesterol management, but these do not describe cholesterol management in patients with endocrine diseases such as thyroid disease [hypothyroidism and hyperthyroidism], Cushing’s syndrome, acromegaly, growth hormone deficiency, menopause, male hypogonadism, and obesity,” she noted.

But these conditions carry a host of cardiovascular risk factors that may require careful monitoring and management.

“Although endocrine hormones, such as thyroid hormone, cortisol, estrogen, testosterone, growth hormone, and insulin, affect pathways for lipid metabolism, physicians lack guidance on lipid abnormalities, cardiovascular risk, and treatment to reduce lipids and cardiovascular risk in patients with endocrine diseases,” she explained.

Vinaya Simha, MD, an internal medicine specialist at the Mayo Clinic in Rochester, Minn., agrees that the guideline is notable in addressing an unmet need.

Recommendations that stand out to Dr. Simha include the suggestion of adding eicosapentaenoic acid (EPA) ethyl ester to reduce the risk of cardiovascular disease in adults with diabetes or atherosclerotic cardiovascular disease who have elevated triglyceride levels despite statin treatment.

James L. Rosenzweig, MD, an endocrinologist at Hebrew SeniorLife in Boston, agreed that this is an important addition to an area that needs more guidance.

“Many of these clinical situations can exacerbate dyslipidemia and some also increase the cardiovascular risk to a greater extent in combination with elevated cholesterol and/or triglycerides,” he said in an interview. 

“In many cases, treatment of the underlying disorder appropriately can have an important impact in resolving the lipid disorder. In others, more aggressive pharmacological treatment is indicated,” he said.

“I think that this will be a valuable resource, especially for endocrinologists, but it can be used as well by providers in other disciplines.”
 

Key recommendations for different endocrine conditions

The guideline, published in the Journal of Clinical Endocrinology & Metabolism, details those risks and provides evidence-based recommendations on their management and treatment.

Key recommendations include:

• Obtain a lipid panel and evaluate cardiovascular risk factors in all adults with endocrine disorders.
• In patients with  and risk factors for cardiovascular disease, start statin therapy in addition to lifestyle modification to reduce cardiovascular risk. “This could mean earlier treatment because other guidelines recommend consideration of therapy at age 40,” Dr. Newman said.
• Statin therapy is also recommended for adults over 40 with  with a duration of diabetes of more than 20 years and/or microvascular complications, regardless of their cardiovascular risk score. “This means earlier treatment of patients with type 1 diabetes with statins in order to reduce cardiovascular disease risk,” Dr. Newman noted.
• In patients with hyperlipidemia, rule out  as the cause before treating with lipid-lowering medications. And among patients who are found to have hypothyroidism, reevaluate the lipid profile when the patient has thyroid hormone levels in the normal range.
• Adults with persistent endogenous Cushing’s syndrome should have their lipid profile monitored. Statin therapy should be considered in addition to lifestyle modifications, irrespective of the cardiovascular risk score.
• In postmenopausal women, high cholesterol or triglycerides should be treated with statins rather than hormone therapy.
• Evaluate and treat lipids and other cardiovascular risk factors in women who enter menopause early (before the age of 40-45 years).

Nice summary of ‘risk-enhancing’ endocrine disorders

Dr. Simha said in an interview that the new guideline is “probably the first comprehensive statement addressing lipid treatment in patients with a broad range of endocrine disorders besides diabetes.”

“Most of the treatment recommendations are congruent with other current guidelines such as the American College of Cardiology/American Heart Association [guidelines], but there is specific mention of which endocrine disorders represent enhanced cardiovascular risk,” she explained.

The new recommendations are notable for including “a nice summary of how different endocrine disorders affect lipid values, and also which endocrine disorders need to be considered as ‘risk-enhancing factors,’ ” Dr. Simha noted.

“The use of EPA in patients with hypertriglyceridemia is novel, compared to the ACC/AHA recommendation. This reflects new data which is now available,” she added.

The American Association of Clinical Endocrinologists also just issued a new algorithm on lipid management and prevention of cardiovascular disease in which treatment of hypertriglyceridemia is emphasized.

In addition, the new Endocrine Society guideline “also mentions an LDL [cholesterol] treatment threshold of 70 mg/dL, and 55 mg/dL in some patient categories, which previous guidelines have not,” Dr. Simha noted.

Overall, Dr. Newman added that the goal of the guideline is to increase awareness of key issues with endocrine diseases that may not necessarily be on clinicians’ radars.

“We hope that it will make a lipid panel and cardiovascular risk evaluation routine in adults with endocrine diseases and cause a greater focus on therapies to reduce heart disease and stroke,” she said.

Dr. Newman, Dr. Simha, and Dr. Rosenzweig reported no relevant financial relationships.

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

A new, large study has confirmed that different types of hormone replacement therapy (HRT) are associated with an increased risk for breast cancer and has provided additional information on factors associated with that increased risk.

The study was published online on October 28 in The BMJ.

“The study confirms increased risk of breast cancer in patients taking HRT but shows that the magnitude of risk depends on a number of factors,” first author Yana Vinogradova, PhD, said in an interview. Dr. Vinogradova is a medical statistician at the University of Nottingham (England).

The study also suggests the risk may be lower than was estimated in a large meta-analysis of 24 trials that was published in 2019 in The Lancet. In that study, researchers suggested the risk for breast cancer with HRT was higher and persisted longer than had been thought.

This conclusion from the meta-analysis was widely reported in the lay press and led to the UK Medicine and Healthcare Products Regulatory Agency issuing a safety alert for HRT regarding breast cancer. Experts in the field questioned the alert and said it caused undue anxiety. The European Medicines Agency also issued a safety alert because of the study.

This new study was begun before publication of the meta-analysis. Although the results are broadly similar in suggesting increased risk for breast cancer with HRT use, findings from the new study suggest the risk is lower than had been estimated in the meta-analysis and that the risk diminishes more rapidly after stopping HRT than was suggested by the meta-analysis.

“The publicity surrounding publication of the meta-analysis highlighted unexpectedly high risks and led to a heightened level of concern in some quarters,” Dr. Vinogradova commented. “Our study, based on general population data, has not confirmed any such findings. In general, it showed lower levels of risk and clarified the variability of magnitude within them.”

Dr. Vinogradova said the discrepancy could be related to the fact that the studies were designed differently. The meta-analysis relied on results from 24 studies that were conducted around the world at different periods and included women of different ages and backgrounds. The studies in the meta-analysis used different methods, including questionnaires that relied on women’s memories and therefore could have been biased, she said.

In contrast, the new study analyzed EMR data collected prospectively by general practices in the United Kingdom. The data came from the QResearch and from the Clinical Practice Research Datalink (CPRD) databases, the two largest primary care databases in the United Kingdom, which were linked to hospital, mortality, and cancer registries.

Because this study used a “consistent design” and “consistent data sources,” these new results “are likely to be more accurate and reliable for assessing risks among HRT users,” Dr. Vinogradova commented.

This study used an observational design, so it cannot prove that HRT causes breast cancer. These results may better represent women in the general U.K. population, compared with the earlier meta-analysis, she added.

Commenting on the new study, Michael Jones, PhD, senior staff scientist in genetics and epidemiology at the Institute of Cancer Research, London, also emphasized that it was large and its data came from general practitioner medical records, “so the strong statistical associations are unlikely to be due to chance.

“The results of this study generally confirm what has been seen before and is well established – that the use of combined estrogen plus progestogen HRT is associated with increased risk of breast cancer, and this risk increases with duration of use. But reassuringly, after stopping HRT, the raised risk of breast cancer mostly returns to that seen in nonusers of HRT,” he said.

“It’s important to note that no one study should be considered in isolation,” he added. “Even though some risks were found to be slightly smaller than those reported in another meta-analysis of the worldwide epidemiological evidence recently published in 2019, women considering use of HRT should still follow advice given to them by their [general practitioners].”
 

Study details

In the study, researchers evaluated all types of HRT commonly prescribed in the United Kingdom over the past 20 years, including topical estrogen, vaginal pessaries, and creams. They grouped HRT use by recent (within the past 5 years) and past (5 or more years ago) and HRT duration as short term (less than 5 years) and long term (5 years or longer). Results were adjusted for a range of factors that could affect breast cancer risk, including lifestyle, smoking, alcohol consumption, other medical conditions, family history, and use of other prescribed drugs.

The analysis included 98,611 women aged 50-79 years who were first diagnosed with breast cancer between 1998 and 2019. These women were matched by age and general practice to 457,498 women who were not diagnosed with breast cancer over these years. HRT use was reported in 34% (33,703) of women with breast cancer and in 31% (134,391) of women without breast cancer.

Overall, the risk for breast cancer was increased with use of most HRT drugs (adjusted odds ratio, 1.21; 95% confidence, 1.19-1.23), compared with not using HRT drugs. The highest risk was tied to combined estrogen/progestogen HRT (adjusted OR, 1.26; 95% CI, 1.24-1.29). The lowest risk was tied to estrogen-only HRT (adjusted OR, 1.06; 95% CI, 1.03-1.10). Estrogen cream and vaginal estrogen were not associated with increased breast cancer risk.

In general, breast cancer risk was higher among recent HRT users and those receiving long-term therapy. HRT-associated breast cancer risk increased with age and declined after discontinuing treatment. Therapy of less than 1 year was not associated with increased breast cancer risk.

Women who had recently been receiving long-term combined estrogen/progestogen HRT had a 79% increased risk for breast cancer (adjusted OR, 1.79; 95% CI, 1.73-1.85), compared with never-users. Among recent long-term users of combined HRT, breast cancer risk was highest for norethisterone (adjusted OR, 1.88; 95% CI, 1.79-1.99) and lowest for dydrogesterone (adjusted OR, 1.24; 95% CI, 1.03-1.48). Women who had recently been receiving long-term estrogen-only HRT had a 15% increased risk for breast cancer compared to never-users (adjusted OR, 1.15; 95% CI, 1.09-1.21).

Among women who discontinued HRT 5 or more years ago, risk for breast cancer was no longer increased for long-term estrogen-only therapy and short-term estrogen/progestogen therapy. However, breast cancer risk remained elevated 5 years after discontinuing long-term estrogen/progestogen (adjusted OR, 1.16; 95% CI, 1.11-1.21).

HRT-associated risk for breast cancer increased with age across all durations of therapy.

Compared with never-use, recent long-term estrogen-only therapy was associated with zero extra breast cancer cases per 10,000 women-years among women aged 50-59 years and eight extra cases per 10,000 women-years among women aged 70-79.

Recent long-term estrogen/progestogen use was associated with 15 extra breast cancer cases among women aged 50-59 and 36 extra cases among women aged 70-79 per 10,000 women-years.

Past long-term estrogen/progestogen use was associated with zero extra breast cancer cases among women aged 50-59 and eight extra cases among women aged 70-79 per 10,000 women-years.

Summarizing, Dr. Vinogradova said the increased risk for breast cancer with HRT appears to be “relatively small, particularly for younger women and for any women who use HRT only for a restricted period.”

Decisions about whether to use HRT and which type to use should depend on symptom severity, patient factors, and suitability of other treatment options, she commented.

“Particularly for those women who our study has shown to be most at risk, these decisions should be made through discussions between the patient and her doctor,” she concluded. “We hope that the new and more detailed information provided by our study will facilitate such prescribing decisions.”

The study was partially funded by the School for Primary Care Research of the National Institute for Health Research, by Cancer Research UK, and by the Cancer Research UK Oxford Center. Dr. Vinogradova has disclosed no relevant financial relationships. Senior author Julia Hippisley-Cox is an unpaid director of QResearch and was a paid director of ClinRisk until 2019. The other authors have disclosed no relevant financial relationships.
 

A version of this story originally appeared on Medscape.com.

A new, large study has confirmed that different types of hormone replacement therapy (HRT) are associated with an increased risk for breast cancer and has provided additional information on factors associated with that increased risk.

The study was published online on October 28 in The BMJ.

“The study confirms increased risk of breast cancer in patients taking HRT but shows that the magnitude of risk depends on a number of factors,” first author Yana Vinogradova, PhD, said in an interview. Dr. Vinogradova is a medical statistician at the University of Nottingham (England).

The study also suggests the risk may be lower than was estimated in a large meta-analysis of 24 trials that was published in 2019 in The Lancet. In that study, researchers suggested the risk for breast cancer with HRT was higher and persisted longer than had been thought.

This conclusion from the meta-analysis was widely reported in the lay press and led to the UK Medicine and Healthcare Products Regulatory Agency issuing a safety alert for HRT regarding breast cancer. Experts in the field questioned the alert and said it caused undue anxiety. The European Medicines Agency also issued a safety alert because of the study.

This new study was begun before publication of the meta-analysis. Although the results are broadly similar in suggesting increased risk for breast cancer with HRT use, findings from the new study suggest the risk is lower than had been estimated in the meta-analysis and that the risk diminishes more rapidly after stopping HRT than was suggested by the meta-analysis.

“The publicity surrounding publication of the meta-analysis highlighted unexpectedly high risks and led to a heightened level of concern in some quarters,” Dr. Vinogradova commented. “Our study, based on general population data, has not confirmed any such findings. In general, it showed lower levels of risk and clarified the variability of magnitude within them.”

Dr. Vinogradova said the discrepancy could be related to the fact that the studies were designed differently. The meta-analysis relied on results from 24 studies that were conducted around the world at different periods and included women of different ages and backgrounds. The studies in the meta-analysis used different methods, including questionnaires that relied on women’s memories and therefore could have been biased, she said.

In contrast, the new study analyzed EMR data collected prospectively by general practices in the United Kingdom. The data came from the QResearch and from the Clinical Practice Research Datalink (CPRD) databases, the two largest primary care databases in the United Kingdom, which were linked to hospital, mortality, and cancer registries.

Because this study used a “consistent design” and “consistent data sources,” these new results “are likely to be more accurate and reliable for assessing risks among HRT users,” Dr. Vinogradova commented.

This study used an observational design, so it cannot prove that HRT causes breast cancer. These results may better represent women in the general U.K. population, compared with the earlier meta-analysis, she added.

Commenting on the new study, Michael Jones, PhD, senior staff scientist in genetics and epidemiology at the Institute of Cancer Research, London, also emphasized that it was large and its data came from general practitioner medical records, “so the strong statistical associations are unlikely to be due to chance.

“The results of this study generally confirm what has been seen before and is well established – that the use of combined estrogen plus progestogen HRT is associated with increased risk of breast cancer, and this risk increases with duration of use. But reassuringly, after stopping HRT, the raised risk of breast cancer mostly returns to that seen in nonusers of HRT,” he said.

“It’s important to note that no one study should be considered in isolation,” he added. “Even though some risks were found to be slightly smaller than those reported in another meta-analysis of the worldwide epidemiological evidence recently published in 2019, women considering use of HRT should still follow advice given to them by their [general practitioners].”
 

Study details

In the study, researchers evaluated all types of HRT commonly prescribed in the United Kingdom over the past 20 years, including topical estrogen, vaginal pessaries, and creams. They grouped HRT use by recent (within the past 5 years) and past (5 or more years ago) and HRT duration as short term (less than 5 years) and long term (5 years or longer). Results were adjusted for a range of factors that could affect breast cancer risk, including lifestyle, smoking, alcohol consumption, other medical conditions, family history, and use of other prescribed drugs.

The analysis included 98,611 women aged 50-79 years who were first diagnosed with breast cancer between 1998 and 2019. These women were matched by age and general practice to 457,498 women who were not diagnosed with breast cancer over these years. HRT use was reported in 34% (33,703) of women with breast cancer and in 31% (134,391) of women without breast cancer.

Overall, the risk for breast cancer was increased with use of most HRT drugs (adjusted odds ratio, 1.21; 95% confidence, 1.19-1.23), compared with not using HRT drugs. The highest risk was tied to combined estrogen/progestogen HRT (adjusted OR, 1.26; 95% CI, 1.24-1.29). The lowest risk was tied to estrogen-only HRT (adjusted OR, 1.06; 95% CI, 1.03-1.10). Estrogen cream and vaginal estrogen were not associated with increased breast cancer risk.

In general, breast cancer risk was higher among recent HRT users and those receiving long-term therapy. HRT-associated breast cancer risk increased with age and declined after discontinuing treatment. Therapy of less than 1 year was not associated with increased breast cancer risk.

Women who had recently been receiving long-term combined estrogen/progestogen HRT had a 79% increased risk for breast cancer (adjusted OR, 1.79; 95% CI, 1.73-1.85), compared with never-users. Among recent long-term users of combined HRT, breast cancer risk was highest for norethisterone (adjusted OR, 1.88; 95% CI, 1.79-1.99) and lowest for dydrogesterone (adjusted OR, 1.24; 95% CI, 1.03-1.48). Women who had recently been receiving long-term estrogen-only HRT had a 15% increased risk for breast cancer compared to never-users (adjusted OR, 1.15; 95% CI, 1.09-1.21).

Among women who discontinued HRT 5 or more years ago, risk for breast cancer was no longer increased for long-term estrogen-only therapy and short-term estrogen/progestogen therapy. However, breast cancer risk remained elevated 5 years after discontinuing long-term estrogen/progestogen (adjusted OR, 1.16; 95% CI, 1.11-1.21).

HRT-associated risk for breast cancer increased with age across all durations of therapy.

Compared with never-use, recent long-term estrogen-only therapy was associated with zero extra breast cancer cases per 10,000 women-years among women aged 50-59 years and eight extra cases per 10,000 women-years among women aged 70-79.

Recent long-term estrogen/progestogen use was associated with 15 extra breast cancer cases among women aged 50-59 and 36 extra cases among women aged 70-79 per 10,000 women-years.

Past long-term estrogen/progestogen use was associated with zero extra breast cancer cases among women aged 50-59 and eight extra cases among women aged 70-79 per 10,000 women-years.

Summarizing, Dr. Vinogradova said the increased risk for breast cancer with HRT appears to be “relatively small, particularly for younger women and for any women who use HRT only for a restricted period.”

Decisions about whether to use HRT and which type to use should depend on symptom severity, patient factors, and suitability of other treatment options, she commented.

“Particularly for those women who our study has shown to be most at risk, these decisions should be made through discussions between the patient and her doctor,” she concluded. “We hope that the new and more detailed information provided by our study will facilitate such prescribing decisions.”

The study was partially funded by the School for Primary Care Research of the National Institute for Health Research, by Cancer Research UK, and by the Cancer Research UK Oxford Center. Dr. Vinogradova has disclosed no relevant financial relationships. Senior author Julia Hippisley-Cox is an unpaid director of QResearch and was a paid director of ClinRisk until 2019. The other authors have disclosed no relevant financial relationships.
 

A version of this story originally appeared on Medscape.com.

A new, large study has confirmed that different types of hormone replacement therapy (HRT) are associated with an increased risk for breast cancer and has provided additional information on factors associated with that increased risk.

The study was published online on October 28 in The BMJ.

“The study confirms increased risk of breast cancer in patients taking HRT but shows that the magnitude of risk depends on a number of factors,” first author Yana Vinogradova, PhD, said in an interview. Dr. Vinogradova is a medical statistician at the University of Nottingham (England).

The study also suggests the risk may be lower than was estimated in a large meta-analysis of 24 trials that was published in 2019 in The Lancet. In that study, researchers suggested the risk for breast cancer with HRT was higher and persisted longer than had been thought.

This conclusion from the meta-analysis was widely reported in the lay press and led to the UK Medicine and Healthcare Products Regulatory Agency issuing a safety alert for HRT regarding breast cancer. Experts in the field questioned the alert and said it caused undue anxiety. The European Medicines Agency also issued a safety alert because of the study.

This new study was begun before publication of the meta-analysis. Although the results are broadly similar in suggesting increased risk for breast cancer with HRT use, findings from the new study suggest the risk is lower than had been estimated in the meta-analysis and that the risk diminishes more rapidly after stopping HRT than was suggested by the meta-analysis.

“The publicity surrounding publication of the meta-analysis highlighted unexpectedly high risks and led to a heightened level of concern in some quarters,” Dr. Vinogradova commented. “Our study, based on general population data, has not confirmed any such findings. In general, it showed lower levels of risk and clarified the variability of magnitude within them.”

Dr. Vinogradova said the discrepancy could be related to the fact that the studies were designed differently. The meta-analysis relied on results from 24 studies that were conducted around the world at different periods and included women of different ages and backgrounds. The studies in the meta-analysis used different methods, including questionnaires that relied on women’s memories and therefore could have been biased, she said.

In contrast, the new study analyzed EMR data collected prospectively by general practices in the United Kingdom. The data came from the QResearch and from the Clinical Practice Research Datalink (CPRD) databases, the two largest primary care databases in the United Kingdom, which were linked to hospital, mortality, and cancer registries.

Because this study used a “consistent design” and “consistent data sources,” these new results “are likely to be more accurate and reliable for assessing risks among HRT users,” Dr. Vinogradova commented.

This study used an observational design, so it cannot prove that HRT causes breast cancer. These results may better represent women in the general U.K. population, compared with the earlier meta-analysis, she added.

Commenting on the new study, Michael Jones, PhD, senior staff scientist in genetics and epidemiology at the Institute of Cancer Research, London, also emphasized that it was large and its data came from general practitioner medical records, “so the strong statistical associations are unlikely to be due to chance.

“The results of this study generally confirm what has been seen before and is well established – that the use of combined estrogen plus progestogen HRT is associated with increased risk of breast cancer, and this risk increases with duration of use. But reassuringly, after stopping HRT, the raised risk of breast cancer mostly returns to that seen in nonusers of HRT,” he said.

“It’s important to note that no one study should be considered in isolation,” he added. “Even though some risks were found to be slightly smaller than those reported in another meta-analysis of the worldwide epidemiological evidence recently published in 2019, women considering use of HRT should still follow advice given to them by their [general practitioners].”
 

Study details

In the study, researchers evaluated all types of HRT commonly prescribed in the United Kingdom over the past 20 years, including topical estrogen, vaginal pessaries, and creams. They grouped HRT use by recent (within the past 5 years) and past (5 or more years ago) and HRT duration as short term (less than 5 years) and long term (5 years or longer). Results were adjusted for a range of factors that could affect breast cancer risk, including lifestyle, smoking, alcohol consumption, other medical conditions, family history, and use of other prescribed drugs.

The analysis included 98,611 women aged 50-79 years who were first diagnosed with breast cancer between 1998 and 2019. These women were matched by age and general practice to 457,498 women who were not diagnosed with breast cancer over these years. HRT use was reported in 34% (33,703) of women with breast cancer and in 31% (134,391) of women without breast cancer.

Overall, the risk for breast cancer was increased with use of most HRT drugs (adjusted odds ratio, 1.21; 95% confidence, 1.19-1.23), compared with not using HRT drugs. The highest risk was tied to combined estrogen/progestogen HRT (adjusted OR, 1.26; 95% CI, 1.24-1.29). The lowest risk was tied to estrogen-only HRT (adjusted OR, 1.06; 95% CI, 1.03-1.10). Estrogen cream and vaginal estrogen were not associated with increased breast cancer risk.

In general, breast cancer risk was higher among recent HRT users and those receiving long-term therapy. HRT-associated breast cancer risk increased with age and declined after discontinuing treatment. Therapy of less than 1 year was not associated with increased breast cancer risk.

Women who had recently been receiving long-term combined estrogen/progestogen HRT had a 79% increased risk for breast cancer (adjusted OR, 1.79; 95% CI, 1.73-1.85), compared with never-users. Among recent long-term users of combined HRT, breast cancer risk was highest for norethisterone (adjusted OR, 1.88; 95% CI, 1.79-1.99) and lowest for dydrogesterone (adjusted OR, 1.24; 95% CI, 1.03-1.48). Women who had recently been receiving long-term estrogen-only HRT had a 15% increased risk for breast cancer compared to never-users (adjusted OR, 1.15; 95% CI, 1.09-1.21).

Among women who discontinued HRT 5 or more years ago, risk for breast cancer was no longer increased for long-term estrogen-only therapy and short-term estrogen/progestogen therapy. However, breast cancer risk remained elevated 5 years after discontinuing long-term estrogen/progestogen (adjusted OR, 1.16; 95% CI, 1.11-1.21).

HRT-associated risk for breast cancer increased with age across all durations of therapy.

Compared with never-use, recent long-term estrogen-only therapy was associated with zero extra breast cancer cases per 10,000 women-years among women aged 50-59 years and eight extra cases per 10,000 women-years among women aged 70-79.

Recent long-term estrogen/progestogen use was associated with 15 extra breast cancer cases among women aged 50-59 and 36 extra cases among women aged 70-79 per 10,000 women-years.

Past long-term estrogen/progestogen use was associated with zero extra breast cancer cases among women aged 50-59 and eight extra cases among women aged 70-79 per 10,000 women-years.

Summarizing, Dr. Vinogradova said the increased risk for breast cancer with HRT appears to be “relatively small, particularly for younger women and for any women who use HRT only for a restricted period.”

Decisions about whether to use HRT and which type to use should depend on symptom severity, patient factors, and suitability of other treatment options, she commented.

“Particularly for those women who our study has shown to be most at risk, these decisions should be made through discussions between the patient and her doctor,” she concluded. “We hope that the new and more detailed information provided by our study will facilitate such prescribing decisions.”

The study was partially funded by the School for Primary Care Research of the National Institute for Health Research, by Cancer Research UK, and by the Cancer Research UK Oxford Center. Dr. Vinogradova has disclosed no relevant financial relationships. Senior author Julia Hippisley-Cox is an unpaid director of QResearch and was a paid director of ClinRisk until 2019. The other authors have disclosed no relevant financial relationships.
 

A version of this story originally appeared on Medscape.com.

Women with polycystic ovarian syndrome (PCOS) before menopause appear to have a greater risk of stroke, heart attack, and other cardiovascular events after menopause, according to findings presented at the virtual American Society for Reproductive Medicine (ASRM) 2020 Scientific Congress.

“We found a PCOS diagnosis prior to menopause was associated with a 64% increased risk of cardiovascular disease after menopause independent of age at enrollment, race, body mass index, and smoking status,” presenter Jacob Christ, MD, a resident at the University of Washington in Seattle, told attendees. “Taken together, our results suggest that women with PCOS have more risk factors for future cardiovascular disease at baseline, and a present PCOS diagnosis prior to menopause is associated with an increased risk of cardiovascular disease after menopause.”

The results are important to consider in women seeking care related to fertility, according to Amanda N. Kallen, MD, assistant professor of reproductive endocrinology and infertility at Yale Medicine in New Haven, Conn.

“As fertility specialists, we often see women with PCOS visit us when they are having trouble conceiving, but often [they] do not return to our care once they’ve built their family,” said Dr. Kallen, who was not involved in the research.

“This excellent talk emphasized how critical it is for us as reproductive endocrinologists to have ongoing discussions with PCOS patients about long-term cardiovascular risks at every opportunity, and to emphasize that these risks persist long after the reproductive years have ended,” Dr. Kallen said in an interview.
 

Identifying women at higher risk

Characteristics of PCOS in adolescence are already understood, including hyperandrogenism, acne, irregular bleeding, and variable ages of menarche, Dr. Christ explained. Similarly, in women’s reproductive years, PCOS is linked to abnormal uterine bleeding, hirsutism, dyslipidemia, infertility, impaired glucose tolerance, gestational diabetes, and preeclampsia.

“What is less clear is if baseline cardiometabolic dysfunction during reproductive years translates into cardiovascular disease after menopause,” Dr. Christ said. “Menopausal changes may reduce risk of cardiovascular disease among PCOS women, as it is known that overall, androgen levels decline during menopause. Furthermore, ovarian aging may be delayed in PCOS women, which may be protective against cardiovascular disease.”

To learn more, the researchers completed a secondary analysis of data from the Study of Women’s Health Across the Nation (SWAN), a prospective cohort study. Women enrolled in the study were aged 42-52 years at baseline, had a uterus and at least one ovary, and menstruated within the previous 3 months. Women were considered to have PCOS if they had both biochemical hyperandrogenism and a history of irregular menses.

The researchers included participants in the secondary analysis if they had complete data on the women’s baseline menstrual status and total testosterone and if the women had at least one follow-up visit after menopause. Menopause was approximated as 51 years old if not otherwise reported (or 1 year after study entry if age 51 at entry). At the follow-up visit, women self-reported any cardiovascular disease events since menopause.

The study’s primary outcome was the first postmenopausal cardiovascular event. These included any of the following: myocardial infarction, cerebrovascular accident or stroke, angina, percutaneous coronary intervention or angioplasty, coronary artery bypass graft, heart failure, carotid artery procedure, peripheral artery disease or lower extremity procedure, renal artery procedure, deep vein thrombosis, pulmonary embolism, and abdominal aortic aneurysm.

Among 1,340 women included in the analysis, 174 (13%) women had PCOS and 1,166 did not. The average age at screening and at menopause were not significantly different between the groups, but they did differ based on other baseline characteristics.

More women with PCOS frequently smoked cigarettes (22%) vs. those without PCOS (12.7%), and women with PCOS had an average body mass index of 31.3, vs. 26.7 among those without PCOS. Women with PCOS also had higher systolic blood pressure (120.7 vs. 115.8 mm Hg), higher total cholesterol (202 vs. 192 mg/dL), and higher fasting blood glucose (103.7 vs. 89.2 mg/dL; P < .01 for all).

After the researchers controlled for age at enrollment, race, BMI, and smoking status, women with PCOS had 1.6 times greater odds of a cardiovascular event after menopause compared with women without PCOS (odds ratio [OR], 1.6; P = .029). Those with PCOS also had a significantly higher Atherosclerotic Cardiovascular Disease risk scores (P = .024), but their Framingham 10-year risk score was not significantly different from those without PCOS.

Although the findings are not necessarily surprising, the study’s value particularly lay in its size, prospective data collection, and rigorous methods, said Ginny Ryan, MD, MA, professor and division chief of reproductive endocrinology and infertility at the University of Washington in Seattle.

“While this study’s criteria used to identify subjects with PCOS selected a population with a particularly severe phenotype of PCOS and thus a higher risk population for cardiovascular disease, it is vital for women’s health providers to truly understand the medium- and long-term life-threatening associations found more commonly in many with PCOS,” Dr. Ryan, who attended the talk and was not involved in the research, said in an interview.

“This study emphasizes the importance of identifying PCOS before menopause, not just for the patient’s immediate well-being, but also so that appropriate counseling and referral can take place to optimize primary, secondary, and tertiary prevention efforts against CVD and related morbidity and mortality,” Dr. Ryan said. “Providers who focus on reproductive health and reproductive-aged women have the opportunity to play a vital role in optimizing the long-term health of their patients.”

Aside from being a prospective cohort with more than 2 decades of follow-up, the study’s other strengths included the definition of PCOS before menopause and use of multiple markers of postmenopausal cardiovascular disease, Dr. Christ said. The study’s main weaknesses were the exclusion of mild PCOS, the self-reporting of cardiovascular events, and the multiple ways of defining menopause.

Dr. Kallen is a consultant for Gynaesight and a reviewer for Healthline. Dr. Christ and Dr. Ryan have disclosed no relevant financial relationships.

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

Women with polycystic ovarian syndrome (PCOS) before menopause appear to have a greater risk of stroke, heart attack, and other cardiovascular events after menopause, according to findings presented at the virtual American Society for Reproductive Medicine (ASRM) 2020 Scientific Congress.

“We found a PCOS diagnosis prior to menopause was associated with a 64% increased risk of cardiovascular disease after menopause independent of age at enrollment, race, body mass index, and smoking status,” presenter Jacob Christ, MD, a resident at the University of Washington in Seattle, told attendees. “Taken together, our results suggest that women with PCOS have more risk factors for future cardiovascular disease at baseline, and a present PCOS diagnosis prior to menopause is associated with an increased risk of cardiovascular disease after menopause.”

The results are important to consider in women seeking care related to fertility, according to Amanda N. Kallen, MD, assistant professor of reproductive endocrinology and infertility at Yale Medicine in New Haven, Conn.

“As fertility specialists, we often see women with PCOS visit us when they are having trouble conceiving, but often [they] do not return to our care once they’ve built their family,” said Dr. Kallen, who was not involved in the research.

“This excellent talk emphasized how critical it is for us as reproductive endocrinologists to have ongoing discussions with PCOS patients about long-term cardiovascular risks at every opportunity, and to emphasize that these risks persist long after the reproductive years have ended,” Dr. Kallen said in an interview.
 

Identifying women at higher risk

Characteristics of PCOS in adolescence are already understood, including hyperandrogenism, acne, irregular bleeding, and variable ages of menarche, Dr. Christ explained. Similarly, in women’s reproductive years, PCOS is linked to abnormal uterine bleeding, hirsutism, dyslipidemia, infertility, impaired glucose tolerance, gestational diabetes, and preeclampsia.

“What is less clear is if baseline cardiometabolic dysfunction during reproductive years translates into cardiovascular disease after menopause,” Dr. Christ said. “Menopausal changes may reduce risk of cardiovascular disease among PCOS women, as it is known that overall, androgen levels decline during menopause. Furthermore, ovarian aging may be delayed in PCOS women, which may be protective against cardiovascular disease.”

To learn more, the researchers completed a secondary analysis of data from the Study of Women’s Health Across the Nation (SWAN), a prospective cohort study. Women enrolled in the study were aged 42-52 years at baseline, had a uterus and at least one ovary, and menstruated within the previous 3 months. Women were considered to have PCOS if they had both biochemical hyperandrogenism and a history of irregular menses.

The researchers included participants in the secondary analysis if they had complete data on the women’s baseline menstrual status and total testosterone and if the women had at least one follow-up visit after menopause. Menopause was approximated as 51 years old if not otherwise reported (or 1 year after study entry if age 51 at entry). At the follow-up visit, women self-reported any cardiovascular disease events since menopause.

The study’s primary outcome was the first postmenopausal cardiovascular event. These included any of the following: myocardial infarction, cerebrovascular accident or stroke, angina, percutaneous coronary intervention or angioplasty, coronary artery bypass graft, heart failure, carotid artery procedure, peripheral artery disease or lower extremity procedure, renal artery procedure, deep vein thrombosis, pulmonary embolism, and abdominal aortic aneurysm.

Among 1,340 women included in the analysis, 174 (13%) women had PCOS and 1,166 did not. The average age at screening and at menopause were not significantly different between the groups, but they did differ based on other baseline characteristics.

More women with PCOS frequently smoked cigarettes (22%) vs. those without PCOS (12.7%), and women with PCOS had an average body mass index of 31.3, vs. 26.7 among those without PCOS. Women with PCOS also had higher systolic blood pressure (120.7 vs. 115.8 mm Hg), higher total cholesterol (202 vs. 192 mg/dL), and higher fasting blood glucose (103.7 vs. 89.2 mg/dL; P < .01 for all).

After the researchers controlled for age at enrollment, race, BMI, and smoking status, women with PCOS had 1.6 times greater odds of a cardiovascular event after menopause compared with women without PCOS (odds ratio [OR], 1.6; P = .029). Those with PCOS also had a significantly higher Atherosclerotic Cardiovascular Disease risk scores (P = .024), but their Framingham 10-year risk score was not significantly different from those without PCOS.

Although the findings are not necessarily surprising, the study’s value particularly lay in its size, prospective data collection, and rigorous methods, said Ginny Ryan, MD, MA, professor and division chief of reproductive endocrinology and infertility at the University of Washington in Seattle.

“While this study’s criteria used to identify subjects with PCOS selected a population with a particularly severe phenotype of PCOS and thus a higher risk population for cardiovascular disease, it is vital for women’s health providers to truly understand the medium- and long-term life-threatening associations found more commonly in many with PCOS,” Dr. Ryan, who attended the talk and was not involved in the research, said in an interview.

“This study emphasizes the importance of identifying PCOS before menopause, not just for the patient’s immediate well-being, but also so that appropriate counseling and referral can take place to optimize primary, secondary, and tertiary prevention efforts against CVD and related morbidity and mortality,” Dr. Ryan said. “Providers who focus on reproductive health and reproductive-aged women have the opportunity to play a vital role in optimizing the long-term health of their patients.”

Aside from being a prospective cohort with more than 2 decades of follow-up, the study’s other strengths included the definition of PCOS before menopause and use of multiple markers of postmenopausal cardiovascular disease, Dr. Christ said. The study’s main weaknesses were the exclusion of mild PCOS, the self-reporting of cardiovascular events, and the multiple ways of defining menopause.

Dr. Kallen is a consultant for Gynaesight and a reviewer for Healthline. Dr. Christ and Dr. Ryan have disclosed no relevant financial relationships.

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

Women with polycystic ovarian syndrome (PCOS) before menopause appear to have a greater risk of stroke, heart attack, and other cardiovascular events after menopause, according to findings presented at the virtual American Society for Reproductive Medicine (ASRM) 2020 Scientific Congress.

“We found a PCOS diagnosis prior to menopause was associated with a 64% increased risk of cardiovascular disease after menopause independent of age at enrollment, race, body mass index, and smoking status,” presenter Jacob Christ, MD, a resident at the University of Washington in Seattle, told attendees. “Taken together, our results suggest that women with PCOS have more risk factors for future cardiovascular disease at baseline, and a present PCOS diagnosis prior to menopause is associated with an increased risk of cardiovascular disease after menopause.”

The results are important to consider in women seeking care related to fertility, according to Amanda N. Kallen, MD, assistant professor of reproductive endocrinology and infertility at Yale Medicine in New Haven, Conn.

“As fertility specialists, we often see women with PCOS visit us when they are having trouble conceiving, but often [they] do not return to our care once they’ve built their family,” said Dr. Kallen, who was not involved in the research.

“This excellent talk emphasized how critical it is for us as reproductive endocrinologists to have ongoing discussions with PCOS patients about long-term cardiovascular risks at every opportunity, and to emphasize that these risks persist long after the reproductive years have ended,” Dr. Kallen said in an interview.
 

Identifying women at higher risk

Characteristics of PCOS in adolescence are already understood, including hyperandrogenism, acne, irregular bleeding, and variable ages of menarche, Dr. Christ explained. Similarly, in women’s reproductive years, PCOS is linked to abnormal uterine bleeding, hirsutism, dyslipidemia, infertility, impaired glucose tolerance, gestational diabetes, and preeclampsia.

“What is less clear is if baseline cardiometabolic dysfunction during reproductive years translates into cardiovascular disease after menopause,” Dr. Christ said. “Menopausal changes may reduce risk of cardiovascular disease among PCOS women, as it is known that overall, androgen levels decline during menopause. Furthermore, ovarian aging may be delayed in PCOS women, which may be protective against cardiovascular disease.”

To learn more, the researchers completed a secondary analysis of data from the Study of Women’s Health Across the Nation (SWAN), a prospective cohort study. Women enrolled in the study were aged 42-52 years at baseline, had a uterus and at least one ovary, and menstruated within the previous 3 months. Women were considered to have PCOS if they had both biochemical hyperandrogenism and a history of irregular menses.

The researchers included participants in the secondary analysis if they had complete data on the women’s baseline menstrual status and total testosterone and if the women had at least one follow-up visit after menopause. Menopause was approximated as 51 years old if not otherwise reported (or 1 year after study entry if age 51 at entry). At the follow-up visit, women self-reported any cardiovascular disease events since menopause.

The study’s primary outcome was the first postmenopausal cardiovascular event. These included any of the following: myocardial infarction, cerebrovascular accident or stroke, angina, percutaneous coronary intervention or angioplasty, coronary artery bypass graft, heart failure, carotid artery procedure, peripheral artery disease or lower extremity procedure, renal artery procedure, deep vein thrombosis, pulmonary embolism, and abdominal aortic aneurysm.

Among 1,340 women included in the analysis, 174 (13%) women had PCOS and 1,166 did not. The average age at screening and at menopause were not significantly different between the groups, but they did differ based on other baseline characteristics.

More women with PCOS frequently smoked cigarettes (22%) vs. those without PCOS (12.7%), and women with PCOS had an average body mass index of 31.3, vs. 26.7 among those without PCOS. Women with PCOS also had higher systolic blood pressure (120.7 vs. 115.8 mm Hg), higher total cholesterol (202 vs. 192 mg/dL), and higher fasting blood glucose (103.7 vs. 89.2 mg/dL; P < .01 for all).

After the researchers controlled for age at enrollment, race, BMI, and smoking status, women with PCOS had 1.6 times greater odds of a cardiovascular event after menopause compared with women without PCOS (odds ratio [OR], 1.6; P = .029). Those with PCOS also had a significantly higher Atherosclerotic Cardiovascular Disease risk scores (P = .024), but their Framingham 10-year risk score was not significantly different from those without PCOS.

Although the findings are not necessarily surprising, the study’s value particularly lay in its size, prospective data collection, and rigorous methods, said Ginny Ryan, MD, MA, professor and division chief of reproductive endocrinology and infertility at the University of Washington in Seattle.

“While this study’s criteria used to identify subjects with PCOS selected a population with a particularly severe phenotype of PCOS and thus a higher risk population for cardiovascular disease, it is vital for women’s health providers to truly understand the medium- and long-term life-threatening associations found more commonly in many with PCOS,” Dr. Ryan, who attended the talk and was not involved in the research, said in an interview.

“This study emphasizes the importance of identifying PCOS before menopause, not just for the patient’s immediate well-being, but also so that appropriate counseling and referral can take place to optimize primary, secondary, and tertiary prevention efforts against CVD and related morbidity and mortality,” Dr. Ryan said. “Providers who focus on reproductive health and reproductive-aged women have the opportunity to play a vital role in optimizing the long-term health of their patients.”

Aside from being a prospective cohort with more than 2 decades of follow-up, the study’s other strengths included the definition of PCOS before menopause and use of multiple markers of postmenopausal cardiovascular disease, Dr. Christ said. The study’s main weaknesses were the exclusion of mild PCOS, the self-reporting of cardiovascular events, and the multiple ways of defining menopause.

Dr. Kallen is a consultant for Gynaesight and a reviewer for Healthline. Dr. Christ and Dr. Ryan have disclosed no relevant financial relationships.

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