Menopause

MADRID – Because of the hormone changes that occur throughout their lives, women experience sleep problems that differ significantly from those experienced by men. Indeed, 75%-84% of pregnant women don’t sleep well during the third trimester, and up to 80% of women in menopause have symptoms that prevent them from getting a good night’s rest. For those seeking a precision medicine approach, the challenge is to identify the relationship between the different sex-related phenotypes and the sleep conditions.

Irene Cano, MD, PhD, is the coordinator of the sleep department at the Spanish Society of Pulmonology and Thoracic Surgery. She spoke with this news organization about the significant impact of hormones on sleep disorders in women.

“Reproductive hormones like estrogen and progesterone play a meaningful role in brain functions – not only those linked to the regulation of reproduction but also other physiological processes related to the regulation of circadian rhythms, cognitive performance, mood, and sleep. In addition, other hormones – for example, prolactin, growth hormone, cortisol, and melatonin – have sex-dependent effects on sleep,” Dr. Cano said.

Girls start puberty at a younger age than boys. As girls enter adolescence, they go to bed later and waking up earlier. So, girls are getting less than the 10 hours of sleep that they should be getting at this stage of life. The result is sleep debt, which gives rise to various problems: poor academic performance, ADHD, obesity, and metabolic problems, to name a few. As Ariadna Farré, RN, a sleep unit nurse, noted at SEPAR’s Joint Winter Meeting, “schools would have to start morning classes later to get adolescents to perform well academically. As the situation is now, half of the kids are falling asleep at their desks.”
 

Influencing sleep quality

Dr. Cano explained the issue as follows: “In adolescence, along with changes in young women’s hormone levels, we begin to see differences between the sexes. The changes in levels of estrogens and progesterone are what’s responsible for the changes that, to some extent, cause those disturbances in the quality of our sleep and in the stages of our sleep.”

Thus, sleep can be affected by the changes in hormone level that occur during a menstrual cycle. Estrogens, which increase during the follicular phase, are associated with REM sleep, while progesterone, which increases during the luteal phase, increases non-REM sleep. “In the 3-6 days prior to menstruation, it’s quite common for a woman to report difficulties falling asleep and staying asleep, in connection with a decline in the percentage of time she spends in REM sleep, in the context of premenstrual syndrome. In addition,” Dr. Cano pointed out, “menstrual bleeding, that loss of blood, is associated with a drop in iron levels, making it more likely that the woman will experience restless legs syndrome.”
 

Cardiovascular system

This news organization also spoke with Milagros Merino, MD, PhD, president of the Spanish Sleep Society. “The consequences that lack of sleep have on the cardiovascular system – we’re essentially talking about certain arrhythmias, high blood pressure, thrombosis in some cases, stroke, and heart attack. Lack of sleep also gives rise to endocrine and metabolic issues, like overweight and being at a greater risk of developing diabetes. And as for mental health, we see, among other things, attention and memory problems, emotional lability, and irascibility. Numerous studies have confirmed all of this.”

Sleep apnea also deserves mention, Dr. Merino added. “Although this disorder is more common in men, we’re seeing it more and more now in women, along with the cardiovascular issues that it brings about.”

Another cardiovascular risk factor is insomnia, said Dr. Merino. “This sleep disorder is more prevalent in women. As hormones constantly change, the ways women sleep constantly change, from one stage of life to the next. They sleep one way in childhood, another way in adolescence, and yet another way in menopause.”
 

Sleep in pregnancy

During pregnancy, hormone changes are much more pronounced. During the first trimester, progesterone levels increase, making the woman drowsy. On top of that, her sleep is interrupted by more frequent visits to the bathroom as well as greater general discomfort.

In the second trimester, sleep interruptions persist but are not as bad as they were during the first 3 months. In the third trimester, 75%-84% of pregnant women find it difficult to sleep because of aches and pains, the need to urinate during the night, cramps, and heartburn.

“Major physical changes are happening. When the bladder gets compressed, the woman has to get up and go to the bathroom. There’s an interruption in her sleep,” Ms. Farré explained. In addition, as the pregnancy progresses, the woman gains weight and her body mass index (BMI) increases, which can bring on obstructive sleep apnea, high blood pressure, preeclampsia, and diabetes, if not closely monitored.

Other factors include concomitant treatments, such as contraceptives, and the stages of life, such as pregnancy and lactation. “When a woman of childbearing age has restless legs syndrome, more often than not, this means that she has an iron deficiency that needs to be treated with oral iron supplements,” said Dr. Merino. “However, there are few medications that can be given to a pregnant woman – and RLS is relatively common during pregnancy. So, we have to turn to oral or intravenous iron supplements. Yet another matter is narcolepsy. In these cases, all medications have to be stopped during pregnancy and lactation, as they can be harmful to the baby.”
 

Sleep apnea

While one in five menopausal women are asymptomatic, the others experience mild to severe symptoms of apnea that frequently interrupt their sleep. In this stage of life, which begins around age 50 years, the hormones that had provided protection against sleep disruptions start to decrease. As a result, there is a rise in sleep problems, especially insomnia, breathing-related sleep disorders (for example, apnea), and restless legs syndrome.

The prevalence of breathing-related sleep disorders during menopause is attributable to weight gain, the drop in levels of estrogens, and the redistribution of adipose tissue in the body. Other factors also increase a woman’s risk of experiencing apnea. They range from stress, depression, and other psychological and psychiatric conditions to health status, medication use, and simply the fact of getting older. “Sleep apnea is more common in men than in premenopausal women. The numbers even out, though, when we compare men against menopausal women,” Dr. Cano noted.

In women, symptoms of sleep apnea are frequently attributed to menopause. There is some overlap: insomnia, headache, irritability, low mood, decreased libido, fatigue during the day, and feeling sleepy. Only much later is the woman’s condition correctly diagnosed as sleep apnea. So, even though presenting with the same complaints, a man will be diagnosed with sleep apnea sooner than a woman will – in some cases, around 10 years sooner.

“On the other hand, we’d always thought that, in menopause, insomnia was characterized by awakenings occurring throughout the second half of the night. But perhaps what happens more often is that women are regularly waking up repeatedly over the course of the entire night, as opposed to experiencing a wakefulness that starts early and lasts throughout the night or having a problem falling asleep to begin with,” said Dr. Merino. “The good news is that hormone replacement therapy can get things back to the way they were. And getting better sleep will help to overcome insomnia.”
 

Socioeconomic status

Insomnia is the most common sleep disorder. It affects 10%-20% of people, mostly women. “The fact that sleep problems are more prevalent in women can be explained by the fact that among women, there is a higher incidence of conditions that disrupt sleep, such as depression,” said Dr. Cano.

“Insomnia is much more common in adult women than adult men. And at menopause, women find that the insomnia only gets worse,” Dr. Merino added. “But around that same age, 50 years old, what we start to see more frequently in men is REM sleep behavior disorder, a type of parasomnia that’s a risk marker of degenerative nerve diseases.”

Dr. Cano emphasized one finding that, though basic, is not well known. “After adjusting for socioeconomic characteristics, the difference between the sexes in reporting sleep problems is cut in half. This suggests that an important factor that explains why there are differences in sleep problems between the sexes is that women’s socioeconomic status is generally lower than men’s.

“As for sleep apnea in particular,” Dr. Cano continued, “the kinds of symptoms that women have can be different from the classic ones seen in men – snoring, pauses in breathing, and daytime sleepiness; women are being underdiagnosed, and when they are diagnosed, that’s happening at a later age and at a higher BMI.”

So, it’s alarming that, as reported by SEPAR, 90% of women with obstructive sleep apnea are not being diagnosed.
 

Precision medicine approach

“The majority of research studies on sleep apnea have focused on men – given the prevalence of cases – and the results have been extrapolated to women. This is why there’s still a lot of work to be done in terms of better defining the characteristics specific to each sleep disorder and how they relate to each sex,” said Dr. Cano. “Being able to identify the relationship between the different sex-related phenotypes and each condition will allow us to take a precision medicine approach tailored to a patient’s particular characteristics.”

As Dr. Merino put it: “The approach to sleep disorders is always personalized. The patient’s sex, in and of itself, doesn’t have that great of an impact on this approach. What does have a great impact are women’s life stages. There are some subtle differences here and there, such as types of continuous positive airway pressure machines. The ones that are designed for women have masks that are better suited to their facial features, which differ from men’s.”

A precision medicine approach can be taken to treat any sleep disorder. For insomnia, the approach allows healthcare professionals to employ an appropriate cognitive-behavioral therapy plan or to determine which drugs would be more effective – all on the basis of symptoms and the characteristics of the particular case. Regarding sleep apnea, Dr. Cano explained, “taking into account the different anatomical characteristics or the higher prevalence of positional apnea will also allow us to offer different therapeutic alternatives to continuous positive airway pressure, such as mandibular advancement devices or positional therapy devices.”

Women should be encouraged to develop good sleep habits. These include taking circadian rhythms into account and aligning lifestyles accordingly. It also means going to bed earlier than the men in the household. For menopausal women, recommended sleep habits range from keeping their bedroom at an ideal temperature, following a diet rich in vegetables to avoid becoming overweight, and exercising daily. While this advice may be more applicable to teenagers, adults can benefit from it as well: Electronic devices should be turned off well before bedtime. Whether from a phone screen, a tablet screen, or a TV screen, the light emitted can keep one awake, which can be harmful to one’s health.

Dr. Cano and Dr. Merino disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com. This article was translated from the Medscape Spanish edition.

MADRID – Because of the hormone changes that occur throughout their lives, women experience sleep problems that differ significantly from those experienced by men. Indeed, 75%-84% of pregnant women don’t sleep well during the third trimester, and up to 80% of women in menopause have symptoms that prevent them from getting a good night’s rest. For those seeking a precision medicine approach, the challenge is to identify the relationship between the different sex-related phenotypes and the sleep conditions.

Irene Cano, MD, PhD, is the coordinator of the sleep department at the Spanish Society of Pulmonology and Thoracic Surgery. She spoke with this news organization about the significant impact of hormones on sleep disorders in women.

“Reproductive hormones like estrogen and progesterone play a meaningful role in brain functions – not only those linked to the regulation of reproduction but also other physiological processes related to the regulation of circadian rhythms, cognitive performance, mood, and sleep. In addition, other hormones – for example, prolactin, growth hormone, cortisol, and melatonin – have sex-dependent effects on sleep,” Dr. Cano said.

Girls start puberty at a younger age than boys. As girls enter adolescence, they go to bed later and waking up earlier. So, girls are getting less than the 10 hours of sleep that they should be getting at this stage of life. The result is sleep debt, which gives rise to various problems: poor academic performance, ADHD, obesity, and metabolic problems, to name a few. As Ariadna Farré, RN, a sleep unit nurse, noted at SEPAR’s Joint Winter Meeting, “schools would have to start morning classes later to get adolescents to perform well academically. As the situation is now, half of the kids are falling asleep at their desks.”
 

Influencing sleep quality

Dr. Cano explained the issue as follows: “In adolescence, along with changes in young women’s hormone levels, we begin to see differences between the sexes. The changes in levels of estrogens and progesterone are what’s responsible for the changes that, to some extent, cause those disturbances in the quality of our sleep and in the stages of our sleep.”

Thus, sleep can be affected by the changes in hormone level that occur during a menstrual cycle. Estrogens, which increase during the follicular phase, are associated with REM sleep, while progesterone, which increases during the luteal phase, increases non-REM sleep. “In the 3-6 days prior to menstruation, it’s quite common for a woman to report difficulties falling asleep and staying asleep, in connection with a decline in the percentage of time she spends in REM sleep, in the context of premenstrual syndrome. In addition,” Dr. Cano pointed out, “menstrual bleeding, that loss of blood, is associated with a drop in iron levels, making it more likely that the woman will experience restless legs syndrome.”
 

Cardiovascular system

This news organization also spoke with Milagros Merino, MD, PhD, president of the Spanish Sleep Society. “The consequences that lack of sleep have on the cardiovascular system – we’re essentially talking about certain arrhythmias, high blood pressure, thrombosis in some cases, stroke, and heart attack. Lack of sleep also gives rise to endocrine and metabolic issues, like overweight and being at a greater risk of developing diabetes. And as for mental health, we see, among other things, attention and memory problems, emotional lability, and irascibility. Numerous studies have confirmed all of this.”

Sleep apnea also deserves mention, Dr. Merino added. “Although this disorder is more common in men, we’re seeing it more and more now in women, along with the cardiovascular issues that it brings about.”

Another cardiovascular risk factor is insomnia, said Dr. Merino. “This sleep disorder is more prevalent in women. As hormones constantly change, the ways women sleep constantly change, from one stage of life to the next. They sleep one way in childhood, another way in adolescence, and yet another way in menopause.”
 

Sleep in pregnancy

During pregnancy, hormone changes are much more pronounced. During the first trimester, progesterone levels increase, making the woman drowsy. On top of that, her sleep is interrupted by more frequent visits to the bathroom as well as greater general discomfort.

In the second trimester, sleep interruptions persist but are not as bad as they were during the first 3 months. In the third trimester, 75%-84% of pregnant women find it difficult to sleep because of aches and pains, the need to urinate during the night, cramps, and heartburn.

“Major physical changes are happening. When the bladder gets compressed, the woman has to get up and go to the bathroom. There’s an interruption in her sleep,” Ms. Farré explained. In addition, as the pregnancy progresses, the woman gains weight and her body mass index (BMI) increases, which can bring on obstructive sleep apnea, high blood pressure, preeclampsia, and diabetes, if not closely monitored.

Other factors include concomitant treatments, such as contraceptives, and the stages of life, such as pregnancy and lactation. “When a woman of childbearing age has restless legs syndrome, more often than not, this means that she has an iron deficiency that needs to be treated with oral iron supplements,” said Dr. Merino. “However, there are few medications that can be given to a pregnant woman – and RLS is relatively common during pregnancy. So, we have to turn to oral or intravenous iron supplements. Yet another matter is narcolepsy. In these cases, all medications have to be stopped during pregnancy and lactation, as they can be harmful to the baby.”
 

Sleep apnea

While one in five menopausal women are asymptomatic, the others experience mild to severe symptoms of apnea that frequently interrupt their sleep. In this stage of life, which begins around age 50 years, the hormones that had provided protection against sleep disruptions start to decrease. As a result, there is a rise in sleep problems, especially insomnia, breathing-related sleep disorders (for example, apnea), and restless legs syndrome.

The prevalence of breathing-related sleep disorders during menopause is attributable to weight gain, the drop in levels of estrogens, and the redistribution of adipose tissue in the body. Other factors also increase a woman’s risk of experiencing apnea. They range from stress, depression, and other psychological and psychiatric conditions to health status, medication use, and simply the fact of getting older. “Sleep apnea is more common in men than in premenopausal women. The numbers even out, though, when we compare men against menopausal women,” Dr. Cano noted.

In women, symptoms of sleep apnea are frequently attributed to menopause. There is some overlap: insomnia, headache, irritability, low mood, decreased libido, fatigue during the day, and feeling sleepy. Only much later is the woman’s condition correctly diagnosed as sleep apnea. So, even though presenting with the same complaints, a man will be diagnosed with sleep apnea sooner than a woman will – in some cases, around 10 years sooner.

“On the other hand, we’d always thought that, in menopause, insomnia was characterized by awakenings occurring throughout the second half of the night. But perhaps what happens more often is that women are regularly waking up repeatedly over the course of the entire night, as opposed to experiencing a wakefulness that starts early and lasts throughout the night or having a problem falling asleep to begin with,” said Dr. Merino. “The good news is that hormone replacement therapy can get things back to the way they were. And getting better sleep will help to overcome insomnia.”
 

Socioeconomic status

Insomnia is the most common sleep disorder. It affects 10%-20% of people, mostly women. “The fact that sleep problems are more prevalent in women can be explained by the fact that among women, there is a higher incidence of conditions that disrupt sleep, such as depression,” said Dr. Cano.

“Insomnia is much more common in adult women than adult men. And at menopause, women find that the insomnia only gets worse,” Dr. Merino added. “But around that same age, 50 years old, what we start to see more frequently in men is REM sleep behavior disorder, a type of parasomnia that’s a risk marker of degenerative nerve diseases.”

Dr. Cano emphasized one finding that, though basic, is not well known. “After adjusting for socioeconomic characteristics, the difference between the sexes in reporting sleep problems is cut in half. This suggests that an important factor that explains why there are differences in sleep problems between the sexes is that women’s socioeconomic status is generally lower than men’s.

“As for sleep apnea in particular,” Dr. Cano continued, “the kinds of symptoms that women have can be different from the classic ones seen in men – snoring, pauses in breathing, and daytime sleepiness; women are being underdiagnosed, and when they are diagnosed, that’s happening at a later age and at a higher BMI.”

So, it’s alarming that, as reported by SEPAR, 90% of women with obstructive sleep apnea are not being diagnosed.
 

Precision medicine approach

“The majority of research studies on sleep apnea have focused on men – given the prevalence of cases – and the results have been extrapolated to women. This is why there’s still a lot of work to be done in terms of better defining the characteristics specific to each sleep disorder and how they relate to each sex,” said Dr. Cano. “Being able to identify the relationship between the different sex-related phenotypes and each condition will allow us to take a precision medicine approach tailored to a patient’s particular characteristics.”

As Dr. Merino put it: “The approach to sleep disorders is always personalized. The patient’s sex, in and of itself, doesn’t have that great of an impact on this approach. What does have a great impact are women’s life stages. There are some subtle differences here and there, such as types of continuous positive airway pressure machines. The ones that are designed for women have masks that are better suited to their facial features, which differ from men’s.”

A precision medicine approach can be taken to treat any sleep disorder. For insomnia, the approach allows healthcare professionals to employ an appropriate cognitive-behavioral therapy plan or to determine which drugs would be more effective – all on the basis of symptoms and the characteristics of the particular case. Regarding sleep apnea, Dr. Cano explained, “taking into account the different anatomical characteristics or the higher prevalence of positional apnea will also allow us to offer different therapeutic alternatives to continuous positive airway pressure, such as mandibular advancement devices or positional therapy devices.”

Women should be encouraged to develop good sleep habits. These include taking circadian rhythms into account and aligning lifestyles accordingly. It also means going to bed earlier than the men in the household. For menopausal women, recommended sleep habits range from keeping their bedroom at an ideal temperature, following a diet rich in vegetables to avoid becoming overweight, and exercising daily. While this advice may be more applicable to teenagers, adults can benefit from it as well: Electronic devices should be turned off well before bedtime. Whether from a phone screen, a tablet screen, or a TV screen, the light emitted can keep one awake, which can be harmful to one’s health.

Dr. Cano and Dr. Merino disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com. This article was translated from the Medscape Spanish edition.

MADRID – Because of the hormone changes that occur throughout their lives, women experience sleep problems that differ significantly from those experienced by men. Indeed, 75%-84% of pregnant women don’t sleep well during the third trimester, and up to 80% of women in menopause have symptoms that prevent them from getting a good night’s rest. For those seeking a precision medicine approach, the challenge is to identify the relationship between the different sex-related phenotypes and the sleep conditions.

Irene Cano, MD, PhD, is the coordinator of the sleep department at the Spanish Society of Pulmonology and Thoracic Surgery. She spoke with this news organization about the significant impact of hormones on sleep disorders in women.

“Reproductive hormones like estrogen and progesterone play a meaningful role in brain functions – not only those linked to the regulation of reproduction but also other physiological processes related to the regulation of circadian rhythms, cognitive performance, mood, and sleep. In addition, other hormones – for example, prolactin, growth hormone, cortisol, and melatonin – have sex-dependent effects on sleep,” Dr. Cano said.

Girls start puberty at a younger age than boys. As girls enter adolescence, they go to bed later and waking up earlier. So, girls are getting less than the 10 hours of sleep that they should be getting at this stage of life. The result is sleep debt, which gives rise to various problems: poor academic performance, ADHD, obesity, and metabolic problems, to name a few. As Ariadna Farré, RN, a sleep unit nurse, noted at SEPAR’s Joint Winter Meeting, “schools would have to start morning classes later to get adolescents to perform well academically. As the situation is now, half of the kids are falling asleep at their desks.”
 

Influencing sleep quality

Dr. Cano explained the issue as follows: “In adolescence, along with changes in young women’s hormone levels, we begin to see differences between the sexes. The changes in levels of estrogens and progesterone are what’s responsible for the changes that, to some extent, cause those disturbances in the quality of our sleep and in the stages of our sleep.”

Thus, sleep can be affected by the changes in hormone level that occur during a menstrual cycle. Estrogens, which increase during the follicular phase, are associated with REM sleep, while progesterone, which increases during the luteal phase, increases non-REM sleep. “In the 3-6 days prior to menstruation, it’s quite common for a woman to report difficulties falling asleep and staying asleep, in connection with a decline in the percentage of time she spends in REM sleep, in the context of premenstrual syndrome. In addition,” Dr. Cano pointed out, “menstrual bleeding, that loss of blood, is associated with a drop in iron levels, making it more likely that the woman will experience restless legs syndrome.”
 

Cardiovascular system

This news organization also spoke with Milagros Merino, MD, PhD, president of the Spanish Sleep Society. “The consequences that lack of sleep have on the cardiovascular system – we’re essentially talking about certain arrhythmias, high blood pressure, thrombosis in some cases, stroke, and heart attack. Lack of sleep also gives rise to endocrine and metabolic issues, like overweight and being at a greater risk of developing diabetes. And as for mental health, we see, among other things, attention and memory problems, emotional lability, and irascibility. Numerous studies have confirmed all of this.”

Sleep apnea also deserves mention, Dr. Merino added. “Although this disorder is more common in men, we’re seeing it more and more now in women, along with the cardiovascular issues that it brings about.”

Another cardiovascular risk factor is insomnia, said Dr. Merino. “This sleep disorder is more prevalent in women. As hormones constantly change, the ways women sleep constantly change, from one stage of life to the next. They sleep one way in childhood, another way in adolescence, and yet another way in menopause.”
 

Sleep in pregnancy

During pregnancy, hormone changes are much more pronounced. During the first trimester, progesterone levels increase, making the woman drowsy. On top of that, her sleep is interrupted by more frequent visits to the bathroom as well as greater general discomfort.

In the second trimester, sleep interruptions persist but are not as bad as they were during the first 3 months. In the third trimester, 75%-84% of pregnant women find it difficult to sleep because of aches and pains, the need to urinate during the night, cramps, and heartburn.

“Major physical changes are happening. When the bladder gets compressed, the woman has to get up and go to the bathroom. There’s an interruption in her sleep,” Ms. Farré explained. In addition, as the pregnancy progresses, the woman gains weight and her body mass index (BMI) increases, which can bring on obstructive sleep apnea, high blood pressure, preeclampsia, and diabetes, if not closely monitored.

Other factors include concomitant treatments, such as contraceptives, and the stages of life, such as pregnancy and lactation. “When a woman of childbearing age has restless legs syndrome, more often than not, this means that she has an iron deficiency that needs to be treated with oral iron supplements,” said Dr. Merino. “However, there are few medications that can be given to a pregnant woman – and RLS is relatively common during pregnancy. So, we have to turn to oral or intravenous iron supplements. Yet another matter is narcolepsy. In these cases, all medications have to be stopped during pregnancy and lactation, as they can be harmful to the baby.”
 

Sleep apnea

While one in five menopausal women are asymptomatic, the others experience mild to severe symptoms of apnea that frequently interrupt their sleep. In this stage of life, which begins around age 50 years, the hormones that had provided protection against sleep disruptions start to decrease. As a result, there is a rise in sleep problems, especially insomnia, breathing-related sleep disorders (for example, apnea), and restless legs syndrome.

The prevalence of breathing-related sleep disorders during menopause is attributable to weight gain, the drop in levels of estrogens, and the redistribution of adipose tissue in the body. Other factors also increase a woman’s risk of experiencing apnea. They range from stress, depression, and other psychological and psychiatric conditions to health status, medication use, and simply the fact of getting older. “Sleep apnea is more common in men than in premenopausal women. The numbers even out, though, when we compare men against menopausal women,” Dr. Cano noted.

In women, symptoms of sleep apnea are frequently attributed to menopause. There is some overlap: insomnia, headache, irritability, low mood, decreased libido, fatigue during the day, and feeling sleepy. Only much later is the woman’s condition correctly diagnosed as sleep apnea. So, even though presenting with the same complaints, a man will be diagnosed with sleep apnea sooner than a woman will – in some cases, around 10 years sooner.

“On the other hand, we’d always thought that, in menopause, insomnia was characterized by awakenings occurring throughout the second half of the night. But perhaps what happens more often is that women are regularly waking up repeatedly over the course of the entire night, as opposed to experiencing a wakefulness that starts early and lasts throughout the night or having a problem falling asleep to begin with,” said Dr. Merino. “The good news is that hormone replacement therapy can get things back to the way they were. And getting better sleep will help to overcome insomnia.”
 

Socioeconomic status

Insomnia is the most common sleep disorder. It affects 10%-20% of people, mostly women. “The fact that sleep problems are more prevalent in women can be explained by the fact that among women, there is a higher incidence of conditions that disrupt sleep, such as depression,” said Dr. Cano.

“Insomnia is much more common in adult women than adult men. And at menopause, women find that the insomnia only gets worse,” Dr. Merino added. “But around that same age, 50 years old, what we start to see more frequently in men is REM sleep behavior disorder, a type of parasomnia that’s a risk marker of degenerative nerve diseases.”

Dr. Cano emphasized one finding that, though basic, is not well known. “After adjusting for socioeconomic characteristics, the difference between the sexes in reporting sleep problems is cut in half. This suggests that an important factor that explains why there are differences in sleep problems between the sexes is that women’s socioeconomic status is generally lower than men’s.

“As for sleep apnea in particular,” Dr. Cano continued, “the kinds of symptoms that women have can be different from the classic ones seen in men – snoring, pauses in breathing, and daytime sleepiness; women are being underdiagnosed, and when they are diagnosed, that’s happening at a later age and at a higher BMI.”

So, it’s alarming that, as reported by SEPAR, 90% of women with obstructive sleep apnea are not being diagnosed.
 

Precision medicine approach

“The majority of research studies on sleep apnea have focused on men – given the prevalence of cases – and the results have been extrapolated to women. This is why there’s still a lot of work to be done in terms of better defining the characteristics specific to each sleep disorder and how they relate to each sex,” said Dr. Cano. “Being able to identify the relationship between the different sex-related phenotypes and each condition will allow us to take a precision medicine approach tailored to a patient’s particular characteristics.”

As Dr. Merino put it: “The approach to sleep disorders is always personalized. The patient’s sex, in and of itself, doesn’t have that great of an impact on this approach. What does have a great impact are women’s life stages. There are some subtle differences here and there, such as types of continuous positive airway pressure machines. The ones that are designed for women have masks that are better suited to their facial features, which differ from men’s.”

A precision medicine approach can be taken to treat any sleep disorder. For insomnia, the approach allows healthcare professionals to employ an appropriate cognitive-behavioral therapy plan or to determine which drugs would be more effective – all on the basis of symptoms and the characteristics of the particular case. Regarding sleep apnea, Dr. Cano explained, “taking into account the different anatomical characteristics or the higher prevalence of positional apnea will also allow us to offer different therapeutic alternatives to continuous positive airway pressure, such as mandibular advancement devices or positional therapy devices.”

Women should be encouraged to develop good sleep habits. These include taking circadian rhythms into account and aligning lifestyles accordingly. It also means going to bed earlier than the men in the household. For menopausal women, recommended sleep habits range from keeping their bedroom at an ideal temperature, following a diet rich in vegetables to avoid becoming overweight, and exercising daily. While this advice may be more applicable to teenagers, adults can benefit from it as well: Electronic devices should be turned off well before bedtime. Whether from a phone screen, a tablet screen, or a TV screen, the light emitted can keep one awake, which can be harmful to one’s health.

Dr. Cano and Dr. Merino disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com. This article was translated from the Medscape Spanish edition.

Takeaway

• Early or delayed menopause and a history of irregular menstrual cycles were significantly associated with a greater risk of new-onset atrial fibrillation (AF) in women.
• Women with nulliparity and multiparity had a greater risk of new-onset AF compared with those with one to two live births.

Why this matters

• Findings highlight the significance of considering the reproductive history of women while developing tailored screening and prevention strategies for AF.

Study design

• A population-based cohort study of 235,191 women (age, 40-69 years) without AF and a history of hysterectomy and/or bilateral oophorectomy, identified from the UK Biobank (2006-2010).
• Funding: Gender and Prevention Grant from ZonMw and other.

Key results

• During a median follow-up of 11.6 years, 4,629 (2.0%) women were diagnosed with new-onset AF.
• A history of irregular menstrual cycle was associated with higher risk of new-onset AF (adjusted HR, 1.34; 95% confidence interval, 1.01-1.79; P = .04).
• Compared with women who experienced menarche at the age of 12 years, the risk of new-onset AF was significantly higher in those who experienced menarche:
• –Earlier between the ages of 7 and 11 years (aHR, 1.10; 95% CI, 1.00-1.21; P = .04) and
• –Later between the ages of 13 and 18 years (aHR, 1.08; 95% CI, 1.00-1.17; P = .05).

• The risk of new-onset AF was significantly higher in women who experienced menopause:
• –At the age of < 35 years (aHR, 2.25; 95% CI, 1.48-3.43; P < .001);
• –Between the ages of 35 and 44 years (aHR, 1.24; 95% CI, 1.10-1.39; P < .001); and
• –At the age of ≥ 60 years (aHR, 1.34; 95% CI, 1.10-1.78; P = .04).
• Women with no live births (aHR, 1.13; 95% CI, 1.04-1.24; P < .01), four to six live births (aHR, 1.12; 95% CI, 1.01-1.24; P = .04), and ≥ seven live births (aHR, 1.67; 95% CI, 1.03-2.70; P = .03) vs. those with one to two live births had a significantly higher risk of new-onset AF.

Limitations

• Observational design.

A version of this article first appeared on Medscape UK.

Reference

Lu Z, Aribas E, Geurts S, Roeters van Lennep JE, Ikram MA, Bos MM, de Groot NMS, Kavousi M. Association Between Sex-Specific Risk Factors and Risk of New-Onset Atrial Fibrillation Among Women. JAMA Netw Open. 2022;5(9):e2229716. doi: 10.1001/jamanetworkopen.2022.29716. PMID: 36048441.

Takeaway

• Early or delayed menopause and a history of irregular menstrual cycles were significantly associated with a greater risk of new-onset atrial fibrillation (AF) in women.
• Women with nulliparity and multiparity had a greater risk of new-onset AF compared with those with one to two live births.

Why this matters

• Findings highlight the significance of considering the reproductive history of women while developing tailored screening and prevention strategies for AF.

Study design

• A population-based cohort study of 235,191 women (age, 40-69 years) without AF and a history of hysterectomy and/or bilateral oophorectomy, identified from the UK Biobank (2006-2010).
• Funding: Gender and Prevention Grant from ZonMw and other.

Key results

• During a median follow-up of 11.6 years, 4,629 (2.0%) women were diagnosed with new-onset AF.
• A history of irregular menstrual cycle was associated with higher risk of new-onset AF (adjusted HR, 1.34; 95% confidence interval, 1.01-1.79; P = .04).
• Compared with women who experienced menarche at the age of 12 years, the risk of new-onset AF was significantly higher in those who experienced menarche:
• –Earlier between the ages of 7 and 11 years (aHR, 1.10; 95% CI, 1.00-1.21; P = .04) and
• –Later between the ages of 13 and 18 years (aHR, 1.08; 95% CI, 1.00-1.17; P = .05).

• The risk of new-onset AF was significantly higher in women who experienced menopause:
• –At the age of < 35 years (aHR, 2.25; 95% CI, 1.48-3.43; P < .001);
• –Between the ages of 35 and 44 years (aHR, 1.24; 95% CI, 1.10-1.39; P < .001); and
• –At the age of ≥ 60 years (aHR, 1.34; 95% CI, 1.10-1.78; P = .04).
• Women with no live births (aHR, 1.13; 95% CI, 1.04-1.24; P < .01), four to six live births (aHR, 1.12; 95% CI, 1.01-1.24; P = .04), and ≥ seven live births (aHR, 1.67; 95% CI, 1.03-2.70; P = .03) vs. those with one to two live births had a significantly higher risk of new-onset AF.

Limitations

• Observational design.

A version of this article first appeared on Medscape UK.

Reference

Lu Z, Aribas E, Geurts S, Roeters van Lennep JE, Ikram MA, Bos MM, de Groot NMS, Kavousi M. Association Between Sex-Specific Risk Factors and Risk of New-Onset Atrial Fibrillation Among Women. JAMA Netw Open. 2022;5(9):e2229716. doi: 10.1001/jamanetworkopen.2022.29716. PMID: 36048441.

Takeaway

• Early or delayed menopause and a history of irregular menstrual cycles were significantly associated with a greater risk of new-onset atrial fibrillation (AF) in women.
• Women with nulliparity and multiparity had a greater risk of new-onset AF compared with those with one to two live births.

Why this matters

• Findings highlight the significance of considering the reproductive history of women while developing tailored screening and prevention strategies for AF.

Study design

• A population-based cohort study of 235,191 women (age, 40-69 years) without AF and a history of hysterectomy and/or bilateral oophorectomy, identified from the UK Biobank (2006-2010).
• Funding: Gender and Prevention Grant from ZonMw and other.

Key results

• During a median follow-up of 11.6 years, 4,629 (2.0%) women were diagnosed with new-onset AF.
• A history of irregular menstrual cycle was associated with higher risk of new-onset AF (adjusted HR, 1.34; 95% confidence interval, 1.01-1.79; P = .04).
• Compared with women who experienced menarche at the age of 12 years, the risk of new-onset AF was significantly higher in those who experienced menarche:
• –Earlier between the ages of 7 and 11 years (aHR, 1.10; 95% CI, 1.00-1.21; P = .04) and
• –Later between the ages of 13 and 18 years (aHR, 1.08; 95% CI, 1.00-1.17; P = .05).

• The risk of new-onset AF was significantly higher in women who experienced menopause:
• –At the age of < 35 years (aHR, 2.25; 95% CI, 1.48-3.43; P < .001);
• –Between the ages of 35 and 44 years (aHR, 1.24; 95% CI, 1.10-1.39; P < .001); and
• –At the age of ≥ 60 years (aHR, 1.34; 95% CI, 1.10-1.78; P = .04).
• Women with no live births (aHR, 1.13; 95% CI, 1.04-1.24; P < .01), four to six live births (aHR, 1.12; 95% CI, 1.01-1.24; P = .04), and ≥ seven live births (aHR, 1.67; 95% CI, 1.03-2.70; P = .03) vs. those with one to two live births had a significantly higher risk of new-onset AF.

Limitations

• Observational design.

A version of this article first appeared on Medscape UK.

Reference

Lu Z, Aribas E, Geurts S, Roeters van Lennep JE, Ikram MA, Bos MM, de Groot NMS, Kavousi M. Association Between Sex-Specific Risk Factors and Risk of New-Onset Atrial Fibrillation Among Women. JAMA Netw Open. 2022;5(9):e2229716. doi: 10.1001/jamanetworkopen.2022.29716. PMID: 36048441.

The first major revision in the systematic description of ovulatory disorders in nearly 50 years has been proposed by a consensus of experts organized by the International Federation of Gynecology and Obstetrics.

“The FIGO HyPO-P system for the classification of ovulatory disorders is submitted for consideration as a worldwide standard,” according to the writing committee, who published their methodology and their proposed applications in the International Journal of Gynecology and Obstetrics.

The classification system was created to replace the much-modified World Health Organization system first described in 1973. Since that time, many modifications have been proposed to accommodate advances in imaging and new information about underlying pathologies, but there has been no subsequent authoritative reference with these modifications or any other newer organizing system.

The new system “provides a different structure for determining the diagnosis. Blood tests are not a necessary first step,” explained Malcolm G. Munro, MD, clinical professor, department of obstetrics and gynecology, University of California, Los Angeles. Dr. Munro was the first author of the publication.

The classification system “is not as focused on the specific steps for investigation of ovulatory dysfunction as much as it explains how to structure an investigation of the girl or woman with an ovulatory disorder and then how to characterize the underlying cause,” Dr. Munro said in an interview. “It is designed to allow everyone, whether clinicians, researchers, or patients, to speak the same language.”
 

New system employs four categories

The four primary categories provide just the first level of classification. The next step is encapsulated in the GAIN-FIT-PIE acronym, which frames the presumed or documented categories of etiologies for the primary categories. GAIN stands for genetic, autoimmune, iatrogenic, or neoplasm etiologies. FIT stands for functional, infectious/inflammatory, or trauma and vascular etiologies. PIE stands for physiological, idiopathic, and endocrine etiologies.

By this methodology, a patient with irregular menses, galactorrhea, and elevated prolactin and an MRI showing a pituitary tumor would be identified a type 2-N, signifying pituitary (type 2) involvement with a neoplasm (N).

A third level of classification permits specific diagnostic entities to be named, allowing the patient in the example above to receive a diagnosis of a prolactin-secreting adenoma.

Not all etiologies can be identified with current diagnostic studies, even assuming clinicians have access to the resources, such as advanced imaging, that will increase diagnostic yield. As a result, the authors acknowledged that the classification system will be “aspirational” in at least some patients, but the structure of this system is expected to lead to greater precision in understanding the causes and defining features of ovulatory disorders, which, in turn, might facilitate new research initiatives.

In the published report, diagnostic protocols based on symptoms were described as being “beyond the spectrum” of this initial description. Rather, Dr. Munro explained that the most important contribution of this new classification system are standardization and communication. The system will be amenable for educating trainees and patients, for communicating between clinicians, and as a framework for research where investigators focus on more homogeneous populations of patients.

“There are many causes of ovulatory disorders that are not related to ovarian function. This is one message. Another is that ovulatory disorders are not binary. They occur on a spectrum. These range from transient instances of delayed or failed ovulation to chronic anovulation,” he said.

The new system is “ a welcome update,” according to Mark P. Trolice, MD, director of the IVF Center and professor of obstetrics and gynecology at the University of Central Florida, both in Orlando.

Dr. Trolice pointed to the clinical value of placing PCOS in a separate category. He noted that it affects 8%-13% of women, making it the most common single cause of ovulatory dysfunction.

“Another area that required clarification from prior WHO classifications was hyperprolactinemia, which is now placed in the type II category,” Dr. Trolice said in an interview.

Better terminology can help address a complex set of disorders with multiple causes and variable manifestations.

“In the evaluation of ovulation dysfunction, it is important to remember that regular menstrual intervals do not ensure ovulation,” Dr. Trolice pointed out. Even though a serum progesterone level of higher than 3 ng/mL is one of the simplest laboratory markers for ovulation, this level, he noted, “can vary through the luteal phase and even throughout the day.”

The proposed classification system, while providing a framework for describing ovulatory disorders, is designed to be adaptable, permitting advances in the understanding of the causes of ovulatory dysfunction, in the diagnosis of the causes, and in the treatments to be incorporated.

“No system should be considered permanent,” according to Dr. Munro and his coauthors. “Review and careful modification and revision should be carried out regularly.”

Dr. Munro reports financial relationships with AbbVie, American Regent, Daiichi Sankyo, Hologic, Myovant, and Pharmacosmos. Dr. Trolice reports no potential conflicts of interest.
 

The first major revision in the systematic description of ovulatory disorders in nearly 50 years has been proposed by a consensus of experts organized by the International Federation of Gynecology and Obstetrics.

“The FIGO HyPO-P system for the classification of ovulatory disorders is submitted for consideration as a worldwide standard,” according to the writing committee, who published their methodology and their proposed applications in the International Journal of Gynecology and Obstetrics.

The classification system was created to replace the much-modified World Health Organization system first described in 1973. Since that time, many modifications have been proposed to accommodate advances in imaging and new information about underlying pathologies, but there has been no subsequent authoritative reference with these modifications or any other newer organizing system.

The new system “provides a different structure for determining the diagnosis. Blood tests are not a necessary first step,” explained Malcolm G. Munro, MD, clinical professor, department of obstetrics and gynecology, University of California, Los Angeles. Dr. Munro was the first author of the publication.

The classification system “is not as focused on the specific steps for investigation of ovulatory dysfunction as much as it explains how to structure an investigation of the girl or woman with an ovulatory disorder and then how to characterize the underlying cause,” Dr. Munro said in an interview. “It is designed to allow everyone, whether clinicians, researchers, or patients, to speak the same language.”
 

New system employs four categories

The four primary categories provide just the first level of classification. The next step is encapsulated in the GAIN-FIT-PIE acronym, which frames the presumed or documented categories of etiologies for the primary categories. GAIN stands for genetic, autoimmune, iatrogenic, or neoplasm etiologies. FIT stands for functional, infectious/inflammatory, or trauma and vascular etiologies. PIE stands for physiological, idiopathic, and endocrine etiologies.

By this methodology, a patient with irregular menses, galactorrhea, and elevated prolactin and an MRI showing a pituitary tumor would be identified a type 2-N, signifying pituitary (type 2) involvement with a neoplasm (N).

A third level of classification permits specific diagnostic entities to be named, allowing the patient in the example above to receive a diagnosis of a prolactin-secreting adenoma.

Not all etiologies can be identified with current diagnostic studies, even assuming clinicians have access to the resources, such as advanced imaging, that will increase diagnostic yield. As a result, the authors acknowledged that the classification system will be “aspirational” in at least some patients, but the structure of this system is expected to lead to greater precision in understanding the causes and defining features of ovulatory disorders, which, in turn, might facilitate new research initiatives.

In the published report, diagnostic protocols based on symptoms were described as being “beyond the spectrum” of this initial description. Rather, Dr. Munro explained that the most important contribution of this new classification system are standardization and communication. The system will be amenable for educating trainees and patients, for communicating between clinicians, and as a framework for research where investigators focus on more homogeneous populations of patients.

“There are many causes of ovulatory disorders that are not related to ovarian function. This is one message. Another is that ovulatory disorders are not binary. They occur on a spectrum. These range from transient instances of delayed or failed ovulation to chronic anovulation,” he said.

The new system is “ a welcome update,” according to Mark P. Trolice, MD, director of the IVF Center and professor of obstetrics and gynecology at the University of Central Florida, both in Orlando.

Dr. Trolice pointed to the clinical value of placing PCOS in a separate category. He noted that it affects 8%-13% of women, making it the most common single cause of ovulatory dysfunction.

“Another area that required clarification from prior WHO classifications was hyperprolactinemia, which is now placed in the type II category,” Dr. Trolice said in an interview.

Better terminology can help address a complex set of disorders with multiple causes and variable manifestations.

“In the evaluation of ovulation dysfunction, it is important to remember that regular menstrual intervals do not ensure ovulation,” Dr. Trolice pointed out. Even though a serum progesterone level of higher than 3 ng/mL is one of the simplest laboratory markers for ovulation, this level, he noted, “can vary through the luteal phase and even throughout the day.”

The proposed classification system, while providing a framework for describing ovulatory disorders, is designed to be adaptable, permitting advances in the understanding of the causes of ovulatory dysfunction, in the diagnosis of the causes, and in the treatments to be incorporated.

“No system should be considered permanent,” according to Dr. Munro and his coauthors. “Review and careful modification and revision should be carried out regularly.”

Dr. Munro reports financial relationships with AbbVie, American Regent, Daiichi Sankyo, Hologic, Myovant, and Pharmacosmos. Dr. Trolice reports no potential conflicts of interest.
 

The first major revision in the systematic description of ovulatory disorders in nearly 50 years has been proposed by a consensus of experts organized by the International Federation of Gynecology and Obstetrics.

“The FIGO HyPO-P system for the classification of ovulatory disorders is submitted for consideration as a worldwide standard,” according to the writing committee, who published their methodology and their proposed applications in the International Journal of Gynecology and Obstetrics.

The classification system was created to replace the much-modified World Health Organization system first described in 1973. Since that time, many modifications have been proposed to accommodate advances in imaging and new information about underlying pathologies, but there has been no subsequent authoritative reference with these modifications or any other newer organizing system.

The new system “provides a different structure for determining the diagnosis. Blood tests are not a necessary first step,” explained Malcolm G. Munro, MD, clinical professor, department of obstetrics and gynecology, University of California, Los Angeles. Dr. Munro was the first author of the publication.

The classification system “is not as focused on the specific steps for investigation of ovulatory dysfunction as much as it explains how to structure an investigation of the girl or woman with an ovulatory disorder and then how to characterize the underlying cause,” Dr. Munro said in an interview. “It is designed to allow everyone, whether clinicians, researchers, or patients, to speak the same language.”
 

New system employs four categories

The four primary categories provide just the first level of classification. The next step is encapsulated in the GAIN-FIT-PIE acronym, which frames the presumed or documented categories of etiologies for the primary categories. GAIN stands for genetic, autoimmune, iatrogenic, or neoplasm etiologies. FIT stands for functional, infectious/inflammatory, or trauma and vascular etiologies. PIE stands for physiological, idiopathic, and endocrine etiologies.

By this methodology, a patient with irregular menses, galactorrhea, and elevated prolactin and an MRI showing a pituitary tumor would be identified a type 2-N, signifying pituitary (type 2) involvement with a neoplasm (N).

A third level of classification permits specific diagnostic entities to be named, allowing the patient in the example above to receive a diagnosis of a prolactin-secreting adenoma.

Not all etiologies can be identified with current diagnostic studies, even assuming clinicians have access to the resources, such as advanced imaging, that will increase diagnostic yield. As a result, the authors acknowledged that the classification system will be “aspirational” in at least some patients, but the structure of this system is expected to lead to greater precision in understanding the causes and defining features of ovulatory disorders, which, in turn, might facilitate new research initiatives.

In the published report, diagnostic protocols based on symptoms were described as being “beyond the spectrum” of this initial description. Rather, Dr. Munro explained that the most important contribution of this new classification system are standardization and communication. The system will be amenable for educating trainees and patients, for communicating between clinicians, and as a framework for research where investigators focus on more homogeneous populations of patients.

“There are many causes of ovulatory disorders that are not related to ovarian function. This is one message. Another is that ovulatory disorders are not binary. They occur on a spectrum. These range from transient instances of delayed or failed ovulation to chronic anovulation,” he said.

The new system is “ a welcome update,” according to Mark P. Trolice, MD, director of the IVF Center and professor of obstetrics and gynecology at the University of Central Florida, both in Orlando.

Dr. Trolice pointed to the clinical value of placing PCOS in a separate category. He noted that it affects 8%-13% of women, making it the most common single cause of ovulatory dysfunction.

“Another area that required clarification from prior WHO classifications was hyperprolactinemia, which is now placed in the type II category,” Dr. Trolice said in an interview.

Better terminology can help address a complex set of disorders with multiple causes and variable manifestations.

“In the evaluation of ovulation dysfunction, it is important to remember that regular menstrual intervals do not ensure ovulation,” Dr. Trolice pointed out. Even though a serum progesterone level of higher than 3 ng/mL is one of the simplest laboratory markers for ovulation, this level, he noted, “can vary through the luteal phase and even throughout the day.”

The proposed classification system, while providing a framework for describing ovulatory disorders, is designed to be adaptable, permitting advances in the understanding of the causes of ovulatory dysfunction, in the diagnosis of the causes, and in the treatments to be incorporated.

“No system should be considered permanent,” according to Dr. Munro and his coauthors. “Review and careful modification and revision should be carried out regularly.”

Dr. Munro reports financial relationships with AbbVie, American Regent, Daiichi Sankyo, Hologic, Myovant, and Pharmacosmos. Dr. Trolice reports no potential conflicts of interest.
 

SEOUL, South Korea – Menopause before age 40 is associated with elevated risk of heart failure and atrial fibrillation, according to a study published in European Heart Journal, from the European Society of Cardiology (ESC). The study of more than 1.4 million women revealed that the younger the age at menopause, the higher the risk of heart failure and atrial fibrillation.

“Women with premature menopause should be aware that they may be more likely to develop heart failure or atrial fibrillation than their peers,” said study author Ga Eun Nam, MD, PhD, of Korea University College of Medicine, Seoul. “This may be good motivation to improve lifestyle habits known to be linked with heart disease, such as quitting smoking and exercising.”

Cardiovascular disease typically occurs up to 10 years later in women than men. Premenopausal women are thought to benefit from estrogen’s protective effect on the cardiovascular system. The cessation of menstruation and subsequent decline of estrogen levels may make women more vulnerable to cardiovascular disease.
 

A national population

Premature menopause affects 1% of women younger than 40 years, the ESC press release stated. Prior studies have found a link between premature (before age 40 years) and early (before age 45 years) menopause and cardiovascular disease overall, but the evidence for heart failure or atrial fibrillation alone is limited. This study examined the associations between premature menopause, age at menopause, and incident heart failure and atrial fibrillation. Data were obtained from the Korean National Health Insurance System (NHIS), which provides health screening at least every 2 years and includes 97% of the population.

The study included 1,401,175 postmenopausal women aged 30 years and older who completed the NHIS health checkup in 2009. Participants were monitored until the end of 2018 for new-onset heart failure and atrial fibrillation. Information was collected on demographics, health behaviors, and reproductive factors, including age at menopause and use of hormone replacement therapy (HRT). Age at menopause was split into four categories: younger than 40 years, 40-44 years, 45-49 years, and 50 years or older. Premature menopause was defined as having the final menstrual period before age 40 years.

Some 28,111 (2%) participants had a history of premature menopause. For these women, the average age at menopause was 36.7 years. The average age at study enrollment for women with and for those without a history of premature menopause was 60 and 61.5 years, respectively. During an average follow-up of 9.1 years, 42,699 (3.0%) developed heart failure, and 44,834 (3.2%) developed atrial fibrillation.

The researchers analyzed the association between history of premature menopause and incident heart failure and atrial fibrillation after adjusting for age, smoking, alcohol use, physical activity, income, body mass index, hypertension, type 2 diabetes, dyslipidemia, chronic kidney disease, coronary heart disease, HRT, and age at menarche. Women who experienced premature menopause had a 33% higher risk for heart failure and 9% higher risk for atrial fibrillation, compared with those who did not.
 

Reproductive history

The researchers then analyzed the associations between age at menopause and incidence of heart failure and atrial fibrillation after adjusting for the same factors as in the previous analyses. The risk for incident heart failure increased as the age at menopause decreased. Compared with women aged 50 years and older at menopause, those aged 45-49 years, 40-44 years, and younger than 40 years at menopause had 11%, 23%, and 39% greater risk for incident heart failure, respectively. Similarly, the risk for incident atrial fibrillation increased as the age at menopause decreased; the risk was 4%, 10%, and 11% higher for those aged 45-49 years, 40-44 years, and younger than 40 years at menopause, respectively, compared with women aged 50 years and older at menopause.

The authors said that several factors may explain the associations between menopausal age, heart failure, and atrial fibrillation, such as the drop in estrogen levels and changes in body fat distribution.

Dr. Nam concluded, “The misconception that heart disease primarily affects men has meant that sex-specific risk factors have been largely ignored. Evidence is growing that undergoing menopause before the age of 40 years may increase the likelihood of heart disease later in life. Our study indicates that reproductive history should be routinely considered in addition to traditional risk factors such as smoking when evaluating the future likelihood of heart failure and atrial fibrillation.”

A version of this article appeared on Medscape.com. This article was translated from the Medscape French edition.

SEOUL, South Korea – Menopause before age 40 is associated with elevated risk of heart failure and atrial fibrillation, according to a study published in European Heart Journal, from the European Society of Cardiology (ESC). The study of more than 1.4 million women revealed that the younger the age at menopause, the higher the risk of heart failure and atrial fibrillation.

“Women with premature menopause should be aware that they may be more likely to develop heart failure or atrial fibrillation than their peers,” said study author Ga Eun Nam, MD, PhD, of Korea University College of Medicine, Seoul. “This may be good motivation to improve lifestyle habits known to be linked with heart disease, such as quitting smoking and exercising.”

Cardiovascular disease typically occurs up to 10 years later in women than men. Premenopausal women are thought to benefit from estrogen’s protective effect on the cardiovascular system. The cessation of menstruation and subsequent decline of estrogen levels may make women more vulnerable to cardiovascular disease.
 

A national population

Premature menopause affects 1% of women younger than 40 years, the ESC press release stated. Prior studies have found a link between premature (before age 40 years) and early (before age 45 years) menopause and cardiovascular disease overall, but the evidence for heart failure or atrial fibrillation alone is limited. This study examined the associations between premature menopause, age at menopause, and incident heart failure and atrial fibrillation. Data were obtained from the Korean National Health Insurance System (NHIS), which provides health screening at least every 2 years and includes 97% of the population.

The study included 1,401,175 postmenopausal women aged 30 years and older who completed the NHIS health checkup in 2009. Participants were monitored until the end of 2018 for new-onset heart failure and atrial fibrillation. Information was collected on demographics, health behaviors, and reproductive factors, including age at menopause and use of hormone replacement therapy (HRT). Age at menopause was split into four categories: younger than 40 years, 40-44 years, 45-49 years, and 50 years or older. Premature menopause was defined as having the final menstrual period before age 40 years.

Some 28,111 (2%) participants had a history of premature menopause. For these women, the average age at menopause was 36.7 years. The average age at study enrollment for women with and for those without a history of premature menopause was 60 and 61.5 years, respectively. During an average follow-up of 9.1 years, 42,699 (3.0%) developed heart failure, and 44,834 (3.2%) developed atrial fibrillation.

The researchers analyzed the association between history of premature menopause and incident heart failure and atrial fibrillation after adjusting for age, smoking, alcohol use, physical activity, income, body mass index, hypertension, type 2 diabetes, dyslipidemia, chronic kidney disease, coronary heart disease, HRT, and age at menarche. Women who experienced premature menopause had a 33% higher risk for heart failure and 9% higher risk for atrial fibrillation, compared with those who did not.
 

Reproductive history

The researchers then analyzed the associations between age at menopause and incidence of heart failure and atrial fibrillation after adjusting for the same factors as in the previous analyses. The risk for incident heart failure increased as the age at menopause decreased. Compared with women aged 50 years and older at menopause, those aged 45-49 years, 40-44 years, and younger than 40 years at menopause had 11%, 23%, and 39% greater risk for incident heart failure, respectively. Similarly, the risk for incident atrial fibrillation increased as the age at menopause decreased; the risk was 4%, 10%, and 11% higher for those aged 45-49 years, 40-44 years, and younger than 40 years at menopause, respectively, compared with women aged 50 years and older at menopause.

The authors said that several factors may explain the associations between menopausal age, heart failure, and atrial fibrillation, such as the drop in estrogen levels and changes in body fat distribution.

Dr. Nam concluded, “The misconception that heart disease primarily affects men has meant that sex-specific risk factors have been largely ignored. Evidence is growing that undergoing menopause before the age of 40 years may increase the likelihood of heart disease later in life. Our study indicates that reproductive history should be routinely considered in addition to traditional risk factors such as smoking when evaluating the future likelihood of heart failure and atrial fibrillation.”

A version of this article appeared on Medscape.com. This article was translated from the Medscape French edition.

SEOUL, South Korea – Menopause before age 40 is associated with elevated risk of heart failure and atrial fibrillation, according to a study published in European Heart Journal, from the European Society of Cardiology (ESC). The study of more than 1.4 million women revealed that the younger the age at menopause, the higher the risk of heart failure and atrial fibrillation.

“Women with premature menopause should be aware that they may be more likely to develop heart failure or atrial fibrillation than their peers,” said study author Ga Eun Nam, MD, PhD, of Korea University College of Medicine, Seoul. “This may be good motivation to improve lifestyle habits known to be linked with heart disease, such as quitting smoking and exercising.”

Cardiovascular disease typically occurs up to 10 years later in women than men. Premenopausal women are thought to benefit from estrogen’s protective effect on the cardiovascular system. The cessation of menstruation and subsequent decline of estrogen levels may make women more vulnerable to cardiovascular disease.
 

A national population

Premature menopause affects 1% of women younger than 40 years, the ESC press release stated. Prior studies have found a link between premature (before age 40 years) and early (before age 45 years) menopause and cardiovascular disease overall, but the evidence for heart failure or atrial fibrillation alone is limited. This study examined the associations between premature menopause, age at menopause, and incident heart failure and atrial fibrillation. Data were obtained from the Korean National Health Insurance System (NHIS), which provides health screening at least every 2 years and includes 97% of the population.

The study included 1,401,175 postmenopausal women aged 30 years and older who completed the NHIS health checkup in 2009. Participants were monitored until the end of 2018 for new-onset heart failure and atrial fibrillation. Information was collected on demographics, health behaviors, and reproductive factors, including age at menopause and use of hormone replacement therapy (HRT). Age at menopause was split into four categories: younger than 40 years, 40-44 years, 45-49 years, and 50 years or older. Premature menopause was defined as having the final menstrual period before age 40 years.

Some 28,111 (2%) participants had a history of premature menopause. For these women, the average age at menopause was 36.7 years. The average age at study enrollment for women with and for those without a history of premature menopause was 60 and 61.5 years, respectively. During an average follow-up of 9.1 years, 42,699 (3.0%) developed heart failure, and 44,834 (3.2%) developed atrial fibrillation.

The researchers analyzed the association between history of premature menopause and incident heart failure and atrial fibrillation after adjusting for age, smoking, alcohol use, physical activity, income, body mass index, hypertension, type 2 diabetes, dyslipidemia, chronic kidney disease, coronary heart disease, HRT, and age at menarche. Women who experienced premature menopause had a 33% higher risk for heart failure and 9% higher risk for atrial fibrillation, compared with those who did not.
 

Reproductive history

The researchers then analyzed the associations between age at menopause and incidence of heart failure and atrial fibrillation after adjusting for the same factors as in the previous analyses. The risk for incident heart failure increased as the age at menopause decreased. Compared with women aged 50 years and older at menopause, those aged 45-49 years, 40-44 years, and younger than 40 years at menopause had 11%, 23%, and 39% greater risk for incident heart failure, respectively. Similarly, the risk for incident atrial fibrillation increased as the age at menopause decreased; the risk was 4%, 10%, and 11% higher for those aged 45-49 years, 40-44 years, and younger than 40 years at menopause, respectively, compared with women aged 50 years and older at menopause.

The authors said that several factors may explain the associations between menopausal age, heart failure, and atrial fibrillation, such as the drop in estrogen levels and changes in body fat distribution.

Dr. Nam concluded, “The misconception that heart disease primarily affects men has meant that sex-specific risk factors have been largely ignored. Evidence is growing that undergoing menopause before the age of 40 years may increase the likelihood of heart disease later in life. Our study indicates that reproductive history should be routinely considered in addition to traditional risk factors such as smoking when evaluating the future likelihood of heart failure and atrial fibrillation.”

A version of this article appeared on Medscape.com. This article was translated from the Medscape French edition.

CASE Healthy woman with hot flashes inquires about HT

A 54-year-old healthy woman with a history of hypothyroidism taking thyroid replacement medication comes in for her annual visit. Her last menstrual period was over 2 years ago and she reports severe hot flashes. They have greatly affected her quality of life and she must take frequent breaks at work. She wakes up frequently at night due to night sweats, which is impacting her sleep and, subsequently, her energy level. She has noted increased vaginal dryness so has been abstaining from sexual intercourse due to the discomfort. She has an intact uterus. Her family history is significant for heart disease, diagnosed in her mother at age 75.

On physical examination, she is normotensive and well-appearing. Her body mass index (BMI) is 21 kg/m². Labs obtained prior to her visit show normal renal and liver function. Her high-density lipid (HDL) level is 55 mg/dL, her low-density lipid (LDL) level is 80 mg/dL, and her triglyceride level is 100 mg/dL; HbA_1c is 5.5 mmol/mol.
 

She is interested in learning more about menopausal hormone therapy (HT) and whether or not she would be a candidate.

What information do you need to know to counsel and manage this patient?

Menopausal HT prescribing practices have changed over the last few decades as a better understanding of the risks and benefits of treatment have emerged. Prior to 2002, HT was commonly used for treatment of symptoms associated with menopause and was thought to have beneficial effects for chronic disease prevention.^1-4 After data from the Women’s Health Initiative (WHI) was released, concerns arose around the effect of HT on cardiovascular health and risk of breast cancer. As a result, HT prescriptions fell precipitously after around 2002.⁵ Since then, postintervention analysis and cumulative 18-year follow-up of WHI data, along with results from subsequent randomized controlled trials, including the Kronos Early Estrogen Prevention Study (KEEPS) and the Early Versus Late Intervention Trial with Estradiol (ELITE), have demonstrated a favorable safety profile for healthy women starting HT early in menopause (less than age 60, or within 10 years from their final menstrual period).^5-11

There are many types, formulations, and routes of HT, and the effects and risks differ for each (TABLE). For example, oral estrogen therapy, such as conjugated equine estrogens, portend a higher risk of adverse effects compared with transdermal formulations. Topical and transdermal estrogens bypass first-pass hepatic metabolism and thus are associated with a lower risk of venous thromboembolism (VTE) compared with oral formulations.^12-14 A progestogen such as micronized progesterone is used in postmenopausal women with a uterus to protect the endometrium from unopposed estrogen therapy (ET). While it comes in oral and transdermal forms, the oral formulation is most widely used and studied in the United States; transdermal forms do not provide adequate endometrial protection and should not be used in combination therapy.^15,16

Risks and benefits

Cardiovascular risk

Over time, the benefits and risks of HT use in menopausal patients have been further elucidated and defined, although they remain complex and dependent on patient clinical characteristics. HT remains the most effective treatment for vasomotor symptoms (VMS) and the genitourinary syndrome of menopause.^17,18 In 2002, concerns for increased cardiovascular disease (CVD) and breast cancer risk resulted in early cessation of the WHI trial. Since that time the risk of CVD in postmenopausal women taking HT has been found to be more nuanced. In fact, updates in the literature have shown that HT results in a reduction of coronary heart disease if started in healthy women younger than age 60 years within 10 years of menopause.^7,9-11 With this updated information, the North American Menopause society (NAMS), American College of Obstetricians and Gynecologists and the Endocrine Society have published guidelines supporting the initiation of HT for symptomatic healthy women: under the age of 60, within 10 years of menopause, and without contraindications. After age 60 years and further from menopause, the benefits and risks become less known.^18-20

Risk stratification allows for more comprehensive counseling in use of HT for treatment of bothersome VMS. From a cardiovascular health standpoint, calculating an atherosclerotic CVD (ASCVD) risk score helps to evaluate appropriateness of HT prescribing:

• For those with low 10-year CVD risk (<5%), either oral or transdermal HT is appropriate.
• For those with moderate 10-year CVD risk (5%-10%), transdermal HT is recommended over oral HT.
• For those with high 10-year CVD risk (>10%), HT is not recommended.^19,21

Breast cancer risk

Follow up since the initial WHI publication have shown that breast cancer risk is largely dependent on the formulation and route of HT used. Oral estrogen combined with a progestogen has been shown to increase the risk of invasive breast cancer, though very rarely.²² To put it into context, the absolute risk of breast cancer based on follow-up studies from WHI showed less than 1 additional case per 1,000 person years of use; less risk than associated with drinking 2 glasses of wine per day and similar to that of obesity and/or sedentary lifestyle.^23,24 Studies have shown estrogen treatment alone for postmenopausal women does not appear to increase the risk of breast cancer. In fact, follow-up data from WHI showed a nonsignificant reduction in breast cancer risk for those taking ET alone.²⁵

Breast cancer risk stratification is helpful when determining appropriateness of HT in postmenopausal women. Generally, if using risk stratification models for breast cancer (ie, Gail Risk model or international breast cancer intervention study [IBIS] tool), a patient who is average to moderate risk, HT can be offered with appropriate counseling. By contrast, a patient who is high risk should have a more detailed discussion about their risk (surveillance and risk-reducing treatments), and they may consider nonhormonal options for treatment of VMS. Women with a history of breast cancer should not be prescribed systemic HT.

Continue to: Additional HT benefits...

Additional HT benefits

The benefits of HT in postmenopausal women include improved bone health and reduction of fractures; reduction of risk for type 2 diabetes mellitus (T2DM); improvement of insulin sensitivity; improvement of lipid profiles with increased HDL and decreased LDL levels; and reduction of colon cancer risk.²⁵ For women aged younger than 60 years who start HT within 10 years of their last menstrual period, HT has been shown to cause a reduction in all-cause mortality. Important risks to counsel patients on when starting HT include the low risk of stroke and venous thromboembolism (VTE) when using oral formulations.²⁶

CASE Resolved

Her ASCVD risk score, based on her history, estimates her 10-year CVD risk to be low (<5%). Thus, from a cardiovascular standpoint, either oral or transdermal HT would be an appropriate option. Her IBIS 10-year score is 1.5%, placing her in a low-risk category for breast cancer based on her personal and family history. Given that she is less than 60 years of age and within 10 years of menopause, along with her low-risk stratification for CVD and breast cancer, she would be an appropriate patient to begin combined HT with an estrogen plus an oral progesterone, such as an estradiol patch 0.0375 mg twice weekly, along with oral micronized progesterone 100 mg nightly. The dose could be increased over time based on symptoms and tolerability of the treatment.

ALTERNATE CASE 1 The patient has additional risk factors

Consider the patient case with the following additions to her history: the patient has a BMI of 34 kg/m², a history of well-controlled hypertension while taking amlodipine 5 mg, and an ASCVD risk score of 7.5%. She reports severe VMS that are greatly impacting her quality of life. How would your recommendations or counseling change?

Focus on healthy lifestyle

Obesity and hypertension, both common chronic conditions, pose additional risks to be accounted for when counseling on and approaching HT prescribing. Her alternate ASCVD risk score places her at moderate risk for CVD within 10 years, based on guidelines as discussed above. It would still be appropriate to offer her combined HT after a shared decision-making discussion that includes a focus on healthy lifestyle habits.

Consider transdermal HT in obese women

Longitudinal studies have found that weight gain is more a consequence of aging, regardless of menopausal status. Fat distribution and body composition changes are a menopause-related phenomenon driven by estrogen deficiency. HT has been shown to preserve lean body mass and reduce visceral adiposity, resulting in favorable effects of body composition. Still, obesity results in increased risk of CVD, VTE, and certain hormone-sensitive cancers.²⁷ When considering HT in obese patients, a transdermal estrogen route is preferred to reduce risks.

For women with hypertension, prescribe transdermal HT

Overall, studies have found that HT has a neutral effect on blood pressure.²⁵ When considering formulation of HT, micronized progesterone, dydrogesterone, and drospirenone seem to be most neutral and possibly even beneficial on blood pressure compared with synthetic progestins.²⁶ Oral estrogen is associated with increased vasoconstriction and/or increased sodium retention with resultant worsened regulation of blood pressure in women with hypertension, so transdermal estrogen is preferred for women with hypertension.²⁶ Hypertension is a component of the ASCVD risk score; factoring this into a patient’s clinical picture is important when discussing appropriateness of HT prescribing. To minimize risks, the transdermal route of estrogen is preferred for those with hypertension.

Continue to: ALTERNATE CASE 1 Resolved...

ALTERNATE CASE 1 Resolved

She has a moderate ASCVD risk score, is obese, and has a history of hypertension. Through shared decision making, you ultimately start her on transdermal estrogen and micronized progesterone to treat her quality-of-life-impacting VMS, a formulation that is most likely to mitigate the possible risks in her clinical case. You see her back in the clinic every 3-6 months to monitor her blood pressure.

ALTERNATE CASE 2 The patient has a high risk for breast cancer

The patient reveals further her significant family history of breast cancer in her maternal grandmother and mother, both diagnosed in their 50s. You calculate her risk of breast cancer with a model that incorporates family history. Her Tyrer Cuzick-IBIS 10-year risk score is >5% and lifetime risk is >20%, putting her at high risk for breast cancer. Since she has a uterus and would need concomitant progesterone therapy, her risk for breast cancer is higher than if she was taking ET alone. Ultimately, together you and the patient decide to trial nonhormonal options for her VMS.

What are nonhormonal options for treatment of VMS?

While HT remains the most effective treatment for VMS, there are multiple nonhormonal treatments for women who are either at too high a risk for HT or who favor other options, which are outlined in the NAMS 2015 nonhormonal management position statement.²⁷ Cognitive behavioral therapy (CBT) has been shown to decrease bother related to VMS but not frequency. Clinical hypnosis has been shown to reduce hot flash frequency and improve sleep. Paroxetine salt (7.5 mg/day) remains the only FDA nonhormonal-approved medication for treatment of moderate to severe vasomotor symptoms. Off label use of other selective serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors have been shown in studies to reduce VMS including paroxetine at slightly higher doses (10 mg/day–20 mg/day), citalopram (10 mg/day–20 mg/day), escitalopram (10 mg/day–20 mg/day), venlafaxine (37.5 mg/day–150 mg/day), and desvenlafaxine (50 mg/day–100 mg/day). Other treatments that could be considered include off-label use of gabapentin (900 mg/day–2,400 mg/day), oxybutynin (2.5–5 mg twice daily) or clonidine (0.1 mg/day–1 mg/day divided in doses) since they all have data demonstrating they are beneficial at reducing VMS.

Nonhormonal options that may be helpful but are recommended with caution due to lack of data include weight loss, mindfulness-based stress reduction, s-equol derivatives of soy isoflavones and a stellate ganglion block. Further evidence and studies are needed for the aforementioned options.²⁷

ALTERNATE CASE 2 Resolved

She may consider any of the nonhormonal options discussed. If she meets with a medical breast specialist to discuss her elevated risk of breast cancer and considers starting risk-reducing medications, particularly tamoxifen, you will want to avoid medications that have significant CPY 2D6 inhibition, such as paroxetine and fluoxetine. Safer choices would include venlafaxine, escitalopram, or citalopram.

The bottom line

In summary, the benefits and risks of HT in the treatment of VMS remain nuanced. For healthy women younger than 60 years of age and within 10 years from their last menstrual period, the benefits of HT largely outweigh the risks. Shared decision making, along with individualized and appropriate risk stratification specific for women, can guide appropriateness of HT prescribing. For those women who cannot take HT or choose not to, there are many nonhormonal options that will help manage their bothersome VMS. ●

CASE Healthy woman with hot flashes inquires about HT

A 54-year-old healthy woman with a history of hypothyroidism taking thyroid replacement medication comes in for her annual visit. Her last menstrual period was over 2 years ago and she reports severe hot flashes. They have greatly affected her quality of life and she must take frequent breaks at work. She wakes up frequently at night due to night sweats, which is impacting her sleep and, subsequently, her energy level. She has noted increased vaginal dryness so has been abstaining from sexual intercourse due to the discomfort. She has an intact uterus. Her family history is significant for heart disease, diagnosed in her mother at age 75.

On physical examination, she is normotensive and well-appearing. Her body mass index (BMI) is 21 kg/m². Labs obtained prior to her visit show normal renal and liver function. Her high-density lipid (HDL) level is 55 mg/dL, her low-density lipid (LDL) level is 80 mg/dL, and her triglyceride level is 100 mg/dL; HbA_1c is 5.5 mmol/mol.
 

She is interested in learning more about menopausal hormone therapy (HT) and whether or not she would be a candidate.

What information do you need to know to counsel and manage this patient?

Menopausal HT prescribing practices have changed over the last few decades as a better understanding of the risks and benefits of treatment have emerged. Prior to 2002, HT was commonly used for treatment of symptoms associated with menopause and was thought to have beneficial effects for chronic disease prevention.^1-4 After data from the Women’s Health Initiative (WHI) was released, concerns arose around the effect of HT on cardiovascular health and risk of breast cancer. As a result, HT prescriptions fell precipitously after around 2002.⁵ Since then, postintervention analysis and cumulative 18-year follow-up of WHI data, along with results from subsequent randomized controlled trials, including the Kronos Early Estrogen Prevention Study (KEEPS) and the Early Versus Late Intervention Trial with Estradiol (ELITE), have demonstrated a favorable safety profile for healthy women starting HT early in menopause (less than age 60, or within 10 years from their final menstrual period).^5-11

There are many types, formulations, and routes of HT, and the effects and risks differ for each (TABLE). For example, oral estrogen therapy, such as conjugated equine estrogens, portend a higher risk of adverse effects compared with transdermal formulations. Topical and transdermal estrogens bypass first-pass hepatic metabolism and thus are associated with a lower risk of venous thromboembolism (VTE) compared with oral formulations.^12-14 A progestogen such as micronized progesterone is used in postmenopausal women with a uterus to protect the endometrium from unopposed estrogen therapy (ET). While it comes in oral and transdermal forms, the oral formulation is most widely used and studied in the United States; transdermal forms do not provide adequate endometrial protection and should not be used in combination therapy.^15,16

Risks and benefits

Cardiovascular risk

Over time, the benefits and risks of HT use in menopausal patients have been further elucidated and defined, although they remain complex and dependent on patient clinical characteristics. HT remains the most effective treatment for vasomotor symptoms (VMS) and the genitourinary syndrome of menopause.^17,18 In 2002, concerns for increased cardiovascular disease (CVD) and breast cancer risk resulted in early cessation of the WHI trial. Since that time the risk of CVD in postmenopausal women taking HT has been found to be more nuanced. In fact, updates in the literature have shown that HT results in a reduction of coronary heart disease if started in healthy women younger than age 60 years within 10 years of menopause.^7,9-11 With this updated information, the North American Menopause society (NAMS), American College of Obstetricians and Gynecologists and the Endocrine Society have published guidelines supporting the initiation of HT for symptomatic healthy women: under the age of 60, within 10 years of menopause, and without contraindications. After age 60 years and further from menopause, the benefits and risks become less known.^18-20

Risk stratification allows for more comprehensive counseling in use of HT for treatment of bothersome VMS. From a cardiovascular health standpoint, calculating an atherosclerotic CVD (ASCVD) risk score helps to evaluate appropriateness of HT prescribing:

• For those with low 10-year CVD risk (<5%), either oral or transdermal HT is appropriate.
• For those with moderate 10-year CVD risk (5%-10%), transdermal HT is recommended over oral HT.
• For those with high 10-year CVD risk (>10%), HT is not recommended.^19,21

Breast cancer risk

Follow up since the initial WHI publication have shown that breast cancer risk is largely dependent on the formulation and route of HT used. Oral estrogen combined with a progestogen has been shown to increase the risk of invasive breast cancer, though very rarely.²² To put it into context, the absolute risk of breast cancer based on follow-up studies from WHI showed less than 1 additional case per 1,000 person years of use; less risk than associated with drinking 2 glasses of wine per day and similar to that of obesity and/or sedentary lifestyle.^23,24 Studies have shown estrogen treatment alone for postmenopausal women does not appear to increase the risk of breast cancer. In fact, follow-up data from WHI showed a nonsignificant reduction in breast cancer risk for those taking ET alone.²⁵

Breast cancer risk stratification is helpful when determining appropriateness of HT in postmenopausal women. Generally, if using risk stratification models for breast cancer (ie, Gail Risk model or international breast cancer intervention study [IBIS] tool), a patient who is average to moderate risk, HT can be offered with appropriate counseling. By contrast, a patient who is high risk should have a more detailed discussion about their risk (surveillance and risk-reducing treatments), and they may consider nonhormonal options for treatment of VMS. Women with a history of breast cancer should not be prescribed systemic HT.

Continue to: Additional HT benefits...

Additional HT benefits

The benefits of HT in postmenopausal women include improved bone health and reduction of fractures; reduction of risk for type 2 diabetes mellitus (T2DM); improvement of insulin sensitivity; improvement of lipid profiles with increased HDL and decreased LDL levels; and reduction of colon cancer risk.²⁵ For women aged younger than 60 years who start HT within 10 years of their last menstrual period, HT has been shown to cause a reduction in all-cause mortality. Important risks to counsel patients on when starting HT include the low risk of stroke and venous thromboembolism (VTE) when using oral formulations.²⁶

CASE Resolved

Her ASCVD risk score, based on her history, estimates her 10-year CVD risk to be low (<5%). Thus, from a cardiovascular standpoint, either oral or transdermal HT would be an appropriate option. Her IBIS 10-year score is 1.5%, placing her in a low-risk category for breast cancer based on her personal and family history. Given that she is less than 60 years of age and within 10 years of menopause, along with her low-risk stratification for CVD and breast cancer, she would be an appropriate patient to begin combined HT with an estrogen plus an oral progesterone, such as an estradiol patch 0.0375 mg twice weekly, along with oral micronized progesterone 100 mg nightly. The dose could be increased over time based on symptoms and tolerability of the treatment.

ALTERNATE CASE 1 The patient has additional risk factors

Consider the patient case with the following additions to her history: the patient has a BMI of 34 kg/m², a history of well-controlled hypertension while taking amlodipine 5 mg, and an ASCVD risk score of 7.5%. She reports severe VMS that are greatly impacting her quality of life. How would your recommendations or counseling change?

Focus on healthy lifestyle

Obesity and hypertension, both common chronic conditions, pose additional risks to be accounted for when counseling on and approaching HT prescribing. Her alternate ASCVD risk score places her at moderate risk for CVD within 10 years, based on guidelines as discussed above. It would still be appropriate to offer her combined HT after a shared decision-making discussion that includes a focus on healthy lifestyle habits.

Consider transdermal HT in obese women

Longitudinal studies have found that weight gain is more a consequence of aging, regardless of menopausal status. Fat distribution and body composition changes are a menopause-related phenomenon driven by estrogen deficiency. HT has been shown to preserve lean body mass and reduce visceral adiposity, resulting in favorable effects of body composition. Still, obesity results in increased risk of CVD, VTE, and certain hormone-sensitive cancers.²⁷ When considering HT in obese patients, a transdermal estrogen route is preferred to reduce risks.

For women with hypertension, prescribe transdermal HT

Overall, studies have found that HT has a neutral effect on blood pressure.²⁵ When considering formulation of HT, micronized progesterone, dydrogesterone, and drospirenone seem to be most neutral and possibly even beneficial on blood pressure compared with synthetic progestins.²⁶ Oral estrogen is associated with increased vasoconstriction and/or increased sodium retention with resultant worsened regulation of blood pressure in women with hypertension, so transdermal estrogen is preferred for women with hypertension.²⁶ Hypertension is a component of the ASCVD risk score; factoring this into a patient’s clinical picture is important when discussing appropriateness of HT prescribing. To minimize risks, the transdermal route of estrogen is preferred for those with hypertension.

Continue to: ALTERNATE CASE 1 Resolved...

ALTERNATE CASE 1 Resolved

She has a moderate ASCVD risk score, is obese, and has a history of hypertension. Through shared decision making, you ultimately start her on transdermal estrogen and micronized progesterone to treat her quality-of-life-impacting VMS, a formulation that is most likely to mitigate the possible risks in her clinical case. You see her back in the clinic every 3-6 months to monitor her blood pressure.

ALTERNATE CASE 2 The patient has a high risk for breast cancer

The patient reveals further her significant family history of breast cancer in her maternal grandmother and mother, both diagnosed in their 50s. You calculate her risk of breast cancer with a model that incorporates family history. Her Tyrer Cuzick-IBIS 10-year risk score is >5% and lifetime risk is >20%, putting her at high risk for breast cancer. Since she has a uterus and would need concomitant progesterone therapy, her risk for breast cancer is higher than if she was taking ET alone. Ultimately, together you and the patient decide to trial nonhormonal options for her VMS.

What are nonhormonal options for treatment of VMS?

While HT remains the most effective treatment for VMS, there are multiple nonhormonal treatments for women who are either at too high a risk for HT or who favor other options, which are outlined in the NAMS 2015 nonhormonal management position statement.²⁷ Cognitive behavioral therapy (CBT) has been shown to decrease bother related to VMS but not frequency. Clinical hypnosis has been shown to reduce hot flash frequency and improve sleep. Paroxetine salt (7.5 mg/day) remains the only FDA nonhormonal-approved medication for treatment of moderate to severe vasomotor symptoms. Off label use of other selective serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors have been shown in studies to reduce VMS including paroxetine at slightly higher doses (10 mg/day–20 mg/day), citalopram (10 mg/day–20 mg/day), escitalopram (10 mg/day–20 mg/day), venlafaxine (37.5 mg/day–150 mg/day), and desvenlafaxine (50 mg/day–100 mg/day). Other treatments that could be considered include off-label use of gabapentin (900 mg/day–2,400 mg/day), oxybutynin (2.5–5 mg twice daily) or clonidine (0.1 mg/day–1 mg/day divided in doses) since they all have data demonstrating they are beneficial at reducing VMS.

Nonhormonal options that may be helpful but are recommended with caution due to lack of data include weight loss, mindfulness-based stress reduction, s-equol derivatives of soy isoflavones and a stellate ganglion block. Further evidence and studies are needed for the aforementioned options.²⁷

ALTERNATE CASE 2 Resolved

She may consider any of the nonhormonal options discussed. If she meets with a medical breast specialist to discuss her elevated risk of breast cancer and considers starting risk-reducing medications, particularly tamoxifen, you will want to avoid medications that have significant CPY 2D6 inhibition, such as paroxetine and fluoxetine. Safer choices would include venlafaxine, escitalopram, or citalopram.

The bottom line

In summary, the benefits and risks of HT in the treatment of VMS remain nuanced. For healthy women younger than 60 years of age and within 10 years from their last menstrual period, the benefits of HT largely outweigh the risks. Shared decision making, along with individualized and appropriate risk stratification specific for women, can guide appropriateness of HT prescribing. For those women who cannot take HT or choose not to, there are many nonhormonal options that will help manage their bothersome VMS. ●

CASE Healthy woman with hot flashes inquires about HT

A 54-year-old healthy woman with a history of hypothyroidism taking thyroid replacement medication comes in for her annual visit. Her last menstrual period was over 2 years ago and she reports severe hot flashes. They have greatly affected her quality of life and she must take frequent breaks at work. She wakes up frequently at night due to night sweats, which is impacting her sleep and, subsequently, her energy level. She has noted increased vaginal dryness so has been abstaining from sexual intercourse due to the discomfort. She has an intact uterus. Her family history is significant for heart disease, diagnosed in her mother at age 75.

On physical examination, she is normotensive and well-appearing. Her body mass index (BMI) is 21 kg/m². Labs obtained prior to her visit show normal renal and liver function. Her high-density lipid (HDL) level is 55 mg/dL, her low-density lipid (LDL) level is 80 mg/dL, and her triglyceride level is 100 mg/dL; HbA_1c is 5.5 mmol/mol.
 

She is interested in learning more about menopausal hormone therapy (HT) and whether or not she would be a candidate.

What information do you need to know to counsel and manage this patient?

Menopausal HT prescribing practices have changed over the last few decades as a better understanding of the risks and benefits of treatment have emerged. Prior to 2002, HT was commonly used for treatment of symptoms associated with menopause and was thought to have beneficial effects for chronic disease prevention.^1-4 After data from the Women’s Health Initiative (WHI) was released, concerns arose around the effect of HT on cardiovascular health and risk of breast cancer. As a result, HT prescriptions fell precipitously after around 2002.⁵ Since then, postintervention analysis and cumulative 18-year follow-up of WHI data, along with results from subsequent randomized controlled trials, including the Kronos Early Estrogen Prevention Study (KEEPS) and the Early Versus Late Intervention Trial with Estradiol (ELITE), have demonstrated a favorable safety profile for healthy women starting HT early in menopause (less than age 60, or within 10 years from their final menstrual period).^5-11

There are many types, formulations, and routes of HT, and the effects and risks differ for each (TABLE). For example, oral estrogen therapy, such as conjugated equine estrogens, portend a higher risk of adverse effects compared with transdermal formulations. Topical and transdermal estrogens bypass first-pass hepatic metabolism and thus are associated with a lower risk of venous thromboembolism (VTE) compared with oral formulations.^12-14 A progestogen such as micronized progesterone is used in postmenopausal women with a uterus to protect the endometrium from unopposed estrogen therapy (ET). While it comes in oral and transdermal forms, the oral formulation is most widely used and studied in the United States; transdermal forms do not provide adequate endometrial protection and should not be used in combination therapy.^15,16

Risks and benefits

Cardiovascular risk

Over time, the benefits and risks of HT use in menopausal patients have been further elucidated and defined, although they remain complex and dependent on patient clinical characteristics. HT remains the most effective treatment for vasomotor symptoms (VMS) and the genitourinary syndrome of menopause.^17,18 In 2002, concerns for increased cardiovascular disease (CVD) and breast cancer risk resulted in early cessation of the WHI trial. Since that time the risk of CVD in postmenopausal women taking HT has been found to be more nuanced. In fact, updates in the literature have shown that HT results in a reduction of coronary heart disease if started in healthy women younger than age 60 years within 10 years of menopause.^7,9-11 With this updated information, the North American Menopause society (NAMS), American College of Obstetricians and Gynecologists and the Endocrine Society have published guidelines supporting the initiation of HT for symptomatic healthy women: under the age of 60, within 10 years of menopause, and without contraindications. After age 60 years and further from menopause, the benefits and risks become less known.^18-20

Risk stratification allows for more comprehensive counseling in use of HT for treatment of bothersome VMS. From a cardiovascular health standpoint, calculating an atherosclerotic CVD (ASCVD) risk score helps to evaluate appropriateness of HT prescribing:

• For those with low 10-year CVD risk (<5%), either oral or transdermal HT is appropriate.
• For those with moderate 10-year CVD risk (5%-10%), transdermal HT is recommended over oral HT.
• For those with high 10-year CVD risk (>10%), HT is not recommended.^19,21

Breast cancer risk

Follow up since the initial WHI publication have shown that breast cancer risk is largely dependent on the formulation and route of HT used. Oral estrogen combined with a progestogen has been shown to increase the risk of invasive breast cancer, though very rarely.²² To put it into context, the absolute risk of breast cancer based on follow-up studies from WHI showed less than 1 additional case per 1,000 person years of use; less risk than associated with drinking 2 glasses of wine per day and similar to that of obesity and/or sedentary lifestyle.^23,24 Studies have shown estrogen treatment alone for postmenopausal women does not appear to increase the risk of breast cancer. In fact, follow-up data from WHI showed a nonsignificant reduction in breast cancer risk for those taking ET alone.²⁵

Breast cancer risk stratification is helpful when determining appropriateness of HT in postmenopausal women. Generally, if using risk stratification models for breast cancer (ie, Gail Risk model or international breast cancer intervention study [IBIS] tool), a patient who is average to moderate risk, HT can be offered with appropriate counseling. By contrast, a patient who is high risk should have a more detailed discussion about their risk (surveillance and risk-reducing treatments), and they may consider nonhormonal options for treatment of VMS. Women with a history of breast cancer should not be prescribed systemic HT.

Continue to: Additional HT benefits...

Additional HT benefits

The benefits of HT in postmenopausal women include improved bone health and reduction of fractures; reduction of risk for type 2 diabetes mellitus (T2DM); improvement of insulin sensitivity; improvement of lipid profiles with increased HDL and decreased LDL levels; and reduction of colon cancer risk.²⁵ For women aged younger than 60 years who start HT within 10 years of their last menstrual period, HT has been shown to cause a reduction in all-cause mortality. Important risks to counsel patients on when starting HT include the low risk of stroke and venous thromboembolism (VTE) when using oral formulations.²⁶

CASE Resolved

Her ASCVD risk score, based on her history, estimates her 10-year CVD risk to be low (<5%). Thus, from a cardiovascular standpoint, either oral or transdermal HT would be an appropriate option. Her IBIS 10-year score is 1.5%, placing her in a low-risk category for breast cancer based on her personal and family history. Given that she is less than 60 years of age and within 10 years of menopause, along with her low-risk stratification for CVD and breast cancer, she would be an appropriate patient to begin combined HT with an estrogen plus an oral progesterone, such as an estradiol patch 0.0375 mg twice weekly, along with oral micronized progesterone 100 mg nightly. The dose could be increased over time based on symptoms and tolerability of the treatment.

ALTERNATE CASE 1 The patient has additional risk factors

Consider the patient case with the following additions to her history: the patient has a BMI of 34 kg/m², a history of well-controlled hypertension while taking amlodipine 5 mg, and an ASCVD risk score of 7.5%. She reports severe VMS that are greatly impacting her quality of life. How would your recommendations or counseling change?

Focus on healthy lifestyle

Obesity and hypertension, both common chronic conditions, pose additional risks to be accounted for when counseling on and approaching HT prescribing. Her alternate ASCVD risk score places her at moderate risk for CVD within 10 years, based on guidelines as discussed above. It would still be appropriate to offer her combined HT after a shared decision-making discussion that includes a focus on healthy lifestyle habits.

Consider transdermal HT in obese women

Longitudinal studies have found that weight gain is more a consequence of aging, regardless of menopausal status. Fat distribution and body composition changes are a menopause-related phenomenon driven by estrogen deficiency. HT has been shown to preserve lean body mass and reduce visceral adiposity, resulting in favorable effects of body composition. Still, obesity results in increased risk of CVD, VTE, and certain hormone-sensitive cancers.²⁷ When considering HT in obese patients, a transdermal estrogen route is preferred to reduce risks.

For women with hypertension, prescribe transdermal HT

Overall, studies have found that HT has a neutral effect on blood pressure.²⁵ When considering formulation of HT, micronized progesterone, dydrogesterone, and drospirenone seem to be most neutral and possibly even beneficial on blood pressure compared with synthetic progestins.²⁶ Oral estrogen is associated with increased vasoconstriction and/or increased sodium retention with resultant worsened regulation of blood pressure in women with hypertension, so transdermal estrogen is preferred for women with hypertension.²⁶ Hypertension is a component of the ASCVD risk score; factoring this into a patient’s clinical picture is important when discussing appropriateness of HT prescribing. To minimize risks, the transdermal route of estrogen is preferred for those with hypertension.

Continue to: ALTERNATE CASE 1 Resolved...

ALTERNATE CASE 1 Resolved

She has a moderate ASCVD risk score, is obese, and has a history of hypertension. Through shared decision making, you ultimately start her on transdermal estrogen and micronized progesterone to treat her quality-of-life-impacting VMS, a formulation that is most likely to mitigate the possible risks in her clinical case. You see her back in the clinic every 3-6 months to monitor her blood pressure.

ALTERNATE CASE 2 The patient has a high risk for breast cancer

The patient reveals further her significant family history of breast cancer in her maternal grandmother and mother, both diagnosed in their 50s. You calculate her risk of breast cancer with a model that incorporates family history. Her Tyrer Cuzick-IBIS 10-year risk score is >5% and lifetime risk is >20%, putting her at high risk for breast cancer. Since she has a uterus and would need concomitant progesterone therapy, her risk for breast cancer is higher than if she was taking ET alone. Ultimately, together you and the patient decide to trial nonhormonal options for her VMS.

What are nonhormonal options for treatment of VMS?

While HT remains the most effective treatment for VMS, there are multiple nonhormonal treatments for women who are either at too high a risk for HT or who favor other options, which are outlined in the NAMS 2015 nonhormonal management position statement.²⁷ Cognitive behavioral therapy (CBT) has been shown to decrease bother related to VMS but not frequency. Clinical hypnosis has been shown to reduce hot flash frequency and improve sleep. Paroxetine salt (7.5 mg/day) remains the only FDA nonhormonal-approved medication for treatment of moderate to severe vasomotor symptoms. Off label use of other selective serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors have been shown in studies to reduce VMS including paroxetine at slightly higher doses (10 mg/day–20 mg/day), citalopram (10 mg/day–20 mg/day), escitalopram (10 mg/day–20 mg/day), venlafaxine (37.5 mg/day–150 mg/day), and desvenlafaxine (50 mg/day–100 mg/day). Other treatments that could be considered include off-label use of gabapentin (900 mg/day–2,400 mg/day), oxybutynin (2.5–5 mg twice daily) or clonidine (0.1 mg/day–1 mg/day divided in doses) since they all have data demonstrating they are beneficial at reducing VMS.

Nonhormonal options that may be helpful but are recommended with caution due to lack of data include weight loss, mindfulness-based stress reduction, s-equol derivatives of soy isoflavones and a stellate ganglion block. Further evidence and studies are needed for the aforementioned options.²⁷

ALTERNATE CASE 2 Resolved

She may consider any of the nonhormonal options discussed. If she meets with a medical breast specialist to discuss her elevated risk of breast cancer and considers starting risk-reducing medications, particularly tamoxifen, you will want to avoid medications that have significant CPY 2D6 inhibition, such as paroxetine and fluoxetine. Safer choices would include venlafaxine, escitalopram, or citalopram.

The bottom line

In summary, the benefits and risks of HT in the treatment of VMS remain nuanced. For healthy women younger than 60 years of age and within 10 years from their last menstrual period, the benefits of HT largely outweigh the risks. Shared decision making, along with individualized and appropriate risk stratification specific for women, can guide appropriateness of HT prescribing. For those women who cannot take HT or choose not to, there are many nonhormonal options that will help manage their bothersome VMS. ●

Many women with symptoms of menopause are turning to cannabis for help, researchers have found, despite a lack of evidence that the drug works for these issues. 

In a survey of perimenopausal and menopausal women who said they’ve used cannabis, nearly 80% said they use medical marijuana to alleviate symptoms such as sleep disturbances, hot flashes, and mood swings. 

“Increasingly, we see greater numbers of individuals exploiting the use of cannabis and cannabinoids for lots of conditions. We realized there was no long-term data on how women were treating themselves for conditions like menopause,” said Staci Gruber, PhD, director of the Marijuana Investigations for Neuroscientific Discovery (MIND) program at McLean Hospital, an affiliate of Harvard Medical School, Boston, who led the study.

Dr. Gruber and her colleagues surveyed 131 perimenopausal and 127 postmenopausal women about their use of cannabis, identifying them through targeted advertising and social media platforms such as Twitter, Facebook, and Reddit.

The survey, published in Menopause, found 83.5% reported habitual cannabis use and 86% said they were current users. Around half of the women reported mixed medical/recreational use; 30.8% reported recreational use only and 17.7% said they only used medical forms of the drug.

The three most common modes of cannabis use were smoking a joint, bowl, or bong (84.3%); using edibles (78.3%);, and vaping oils (52.6%).

The researchers found that women in perimenopause reported markedly worse symptoms than did those in menopause, and these women tended to use a wider variety of cannabis products.

Dr. Gruber said clinicians should be asking their menopausal patients if they use cannabis to alleviate their symptoms. 

Stephanie Faubion, MD, MBA, a women’s health expert at Mayo Clinic in Rochester, Minn., and Jacksonville, Fla., said the looming question is whether cannabis in fact works in these patients. 

“What we need is to figure out whether it works for women, and that hasn’t been studied yet,” she said. 

Dr. Faubion, medical director for the North American Menopause Society, said the society is now conducting a review of worldwide data on nonhormonal treatments for symptoms of menopause. The report, which will examine the most current research on the effects of cannabis, hypnosis, diet, exercise, acupuncture, yoga, and meditation, will be released in 2023, she said.

Dr. Gruber said she hopes her group’s research will open the doors to more detailed explorations of how strains of cannabis and their levels of cannabidiol, a chemical compound in cannabis plants, and tetrahydrocannabinol, the main psychoactive component in cannabis, affect the symptoms women experience from menopause. Clinical trials for products aimed at specific symptoms also will be important, she added.

“We have a paucity of data from primary care clinicians,” Dr. Gruber said. “We, as researchers and clinicians, should be providing women with the research to make informed choices.”

The study was supported by private donations to the MIND program at McLean Hospital. No funding sources were involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Dr. Gruber reported grants from the National Institute on Drug Abuse, Foria/Praxis Ventures, and Charlotte’s Web. She reported personal fees from the Coalition for Cannabis Policy, Education and Regulation; Beth Israel Deaconess; Fenway Health; Greenwich Biosciences Cannabis Education Working Group; and National Academy of Neuropsychology outside the submitted work. Dr. Faubion reported no relevant financial relationships.

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

Many women with symptoms of menopause are turning to cannabis for help, researchers have found, despite a lack of evidence that the drug works for these issues. 

In a survey of perimenopausal and menopausal women who said they’ve used cannabis, nearly 80% said they use medical marijuana to alleviate symptoms such as sleep disturbances, hot flashes, and mood swings. 

“Increasingly, we see greater numbers of individuals exploiting the use of cannabis and cannabinoids for lots of conditions. We realized there was no long-term data on how women were treating themselves for conditions like menopause,” said Staci Gruber, PhD, director of the Marijuana Investigations for Neuroscientific Discovery (MIND) program at McLean Hospital, an affiliate of Harvard Medical School, Boston, who led the study.

Dr. Gruber and her colleagues surveyed 131 perimenopausal and 127 postmenopausal women about their use of cannabis, identifying them through targeted advertising and social media platforms such as Twitter, Facebook, and Reddit.

The survey, published in Menopause, found 83.5% reported habitual cannabis use and 86% said they were current users. Around half of the women reported mixed medical/recreational use; 30.8% reported recreational use only and 17.7% said they only used medical forms of the drug.

The three most common modes of cannabis use were smoking a joint, bowl, or bong (84.3%); using edibles (78.3%);, and vaping oils (52.6%).

The researchers found that women in perimenopause reported markedly worse symptoms than did those in menopause, and these women tended to use a wider variety of cannabis products.

Dr. Gruber said clinicians should be asking their menopausal patients if they use cannabis to alleviate their symptoms. 

Stephanie Faubion, MD, MBA, a women’s health expert at Mayo Clinic in Rochester, Minn., and Jacksonville, Fla., said the looming question is whether cannabis in fact works in these patients. 

“What we need is to figure out whether it works for women, and that hasn’t been studied yet,” she said. 

Dr. Faubion, medical director for the North American Menopause Society, said the society is now conducting a review of worldwide data on nonhormonal treatments for symptoms of menopause. The report, which will examine the most current research on the effects of cannabis, hypnosis, diet, exercise, acupuncture, yoga, and meditation, will be released in 2023, she said.

Dr. Gruber said she hopes her group’s research will open the doors to more detailed explorations of how strains of cannabis and their levels of cannabidiol, a chemical compound in cannabis plants, and tetrahydrocannabinol, the main psychoactive component in cannabis, affect the symptoms women experience from menopause. Clinical trials for products aimed at specific symptoms also will be important, she added.

“We have a paucity of data from primary care clinicians,” Dr. Gruber said. “We, as researchers and clinicians, should be providing women with the research to make informed choices.”

The study was supported by private donations to the MIND program at McLean Hospital. No funding sources were involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Dr. Gruber reported grants from the National Institute on Drug Abuse, Foria/Praxis Ventures, and Charlotte’s Web. She reported personal fees from the Coalition for Cannabis Policy, Education and Regulation; Beth Israel Deaconess; Fenway Health; Greenwich Biosciences Cannabis Education Working Group; and National Academy of Neuropsychology outside the submitted work. Dr. Faubion reported no relevant financial relationships.

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

Many women with symptoms of menopause are turning to cannabis for help, researchers have found, despite a lack of evidence that the drug works for these issues. 

In a survey of perimenopausal and menopausal women who said they’ve used cannabis, nearly 80% said they use medical marijuana to alleviate symptoms such as sleep disturbances, hot flashes, and mood swings. 

“Increasingly, we see greater numbers of individuals exploiting the use of cannabis and cannabinoids for lots of conditions. We realized there was no long-term data on how women were treating themselves for conditions like menopause,” said Staci Gruber, PhD, director of the Marijuana Investigations for Neuroscientific Discovery (MIND) program at McLean Hospital, an affiliate of Harvard Medical School, Boston, who led the study.

Dr. Gruber and her colleagues surveyed 131 perimenopausal and 127 postmenopausal women about their use of cannabis, identifying them through targeted advertising and social media platforms such as Twitter, Facebook, and Reddit.

The survey, published in Menopause, found 83.5% reported habitual cannabis use and 86% said they were current users. Around half of the women reported mixed medical/recreational use; 30.8% reported recreational use only and 17.7% said they only used medical forms of the drug.

The three most common modes of cannabis use were smoking a joint, bowl, or bong (84.3%); using edibles (78.3%);, and vaping oils (52.6%).

The researchers found that women in perimenopause reported markedly worse symptoms than did those in menopause, and these women tended to use a wider variety of cannabis products.

Dr. Gruber said clinicians should be asking their menopausal patients if they use cannabis to alleviate their symptoms. 

Stephanie Faubion, MD, MBA, a women’s health expert at Mayo Clinic in Rochester, Minn., and Jacksonville, Fla., said the looming question is whether cannabis in fact works in these patients. 

“What we need is to figure out whether it works for women, and that hasn’t been studied yet,” she said. 

Dr. Faubion, medical director for the North American Menopause Society, said the society is now conducting a review of worldwide data on nonhormonal treatments for symptoms of menopause. The report, which will examine the most current research on the effects of cannabis, hypnosis, diet, exercise, acupuncture, yoga, and meditation, will be released in 2023, she said.

Dr. Gruber said she hopes her group’s research will open the doors to more detailed explorations of how strains of cannabis and their levels of cannabidiol, a chemical compound in cannabis plants, and tetrahydrocannabinol, the main psychoactive component in cannabis, affect the symptoms women experience from menopause. Clinical trials for products aimed at specific symptoms also will be important, she added.

“We have a paucity of data from primary care clinicians,” Dr. Gruber said. “We, as researchers and clinicians, should be providing women with the research to make informed choices.”

The study was supported by private donations to the MIND program at McLean Hospital. No funding sources were involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Dr. Gruber reported grants from the National Institute on Drug Abuse, Foria/Praxis Ventures, and Charlotte’s Web. She reported personal fees from the Coalition for Cannabis Policy, Education and Regulation; Beth Israel Deaconess; Fenway Health; Greenwich Biosciences Cannabis Education Working Group; and National Academy of Neuropsychology outside the submitted work. Dr. Faubion reported no relevant financial relationships.

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

Hormone therapy remains a topic for debate, but a constant in the 2 decades since the Women’s Health Initiative has been the demonstrated effectiveness for relief of vasomotor symptoms and reduction of fracture risk in menopausal women, according to the latest hormone therapy position statement of the North American Menopause Society.

“Healthcare professionals caring for menopausal women should understand the basic concepts of relative risk and absolute risk,” wrote Stephanie S. Faubion, MD, director of the Mayo Clinic Center for Women’s Health and medical director of NAMS, and members of the NAMS 2022 Hormone Therapy Position Statement Advisory Panel in Menopause.

The authors noted that the risks of hormone therapy vary considerably based on type, dose, duration, route of administration, timing of the start of therapy, and whether or not a progestogen is included.

The 2022 statement was commissioned to review new literature and identify the strength of recommendations and quality of evidence since the previous statement in 2017.

The current statement represents not so much a practice-changing update, “but rather that the literature has filled out in some areas,” Dr. Faubion said in an interview. “The recommendations overall haven’t changed,” she said. “The position statement reiterates that hormone therapy, which is significantly underutilized, remains a safe and effective treatment for menopause symptoms, which remain undertreated, with the benefits outweighing the risks for most healthy women who are within 10 years of menopause onset and under the age of 60 years,” she emphasized. “Individualizing therapy is key to maximizing benefits and minimizing risks,” she added.

Overall, the authors confirmed that hormone therapy remains the most effective treatment for vasomotor symptoms (VMS) and the genitourinary syndrome of menopause (GSM), and has been shown to prevent bone loss and fracture. The risks of hormone therapy differ depending on type, dose, duration of use, route of administration, timing of initiation, and whether a progestogen is used.

Risks and benefits should be stratified by age and time since the start of menopause, according to the statement.

For women younger than 60 years or within 10 years of the onset of menopause who have no contraindications, the potential benefits outweigh the risks in most cases for use of hormone therapy to manage vasomotor symptoms and to help prevent bone loss and reduce fracture risk.

For women who begin hormone therapy more than 10 or 20 years from the start of menopause, or who are aged 60 years and older, the risk-benefit ratio may be less favorable because of the increased absolute risk of coronary heart disease, stroke, venous thromboembolism, and dementia. However, strategies such as lower doses and transdermal administration may reduce this risk, according to the statement.

The authors continue to recommend that longer durations of hormone therapy be for documented indications, such as VMS relief, and that patients on longer duration of therapy be reassessed periodically as part of a shared decision-making process. Women with persistent VMS or quality of life issues, or those at risk for osteoporosis, may continue hormone therapy beyond age 60 or 65 years after appropriate evaluation and risk-benefit counseling.

Women with ongoing GSM without indications for systemic therapy whose GSM persists after over-the-counter therapies may try low-dose vaginal estrogen or other nonestrogen therapies regardless of age and for an extended duration if needed, according to the statement.
 

Challenges, research gaps, and goals

“Barriers to the use of hormone therapy include lack of access to high quality care,” Dr. Faubion said in an interview. The NAMS website, menopause.org, features an option to search for a NAMS-certified provider by ZIP code, she noted.

“Coverage of hormone therapy is highly variable and depends on the insurance company, but most women have access to one form or another with insurance coverage,” she said. “We need to continue to advocate for adequate coverage of menopause symptom treatments, including hormone therapy, so that women’s symptoms – which can significantly affect quality of life – are adequately managed.

“Additional research is needed on the thrombotic risk (venous thromboembolism, pulmonary embolism, and stroke) of oral versus transdermal therapies (including different formulations, doses, and durations of therapy),” Dr. Faubion told this news organization. “More clinical trial data are needed to confirm or refute the potential beneficial effects of hormone therapy on coronary heart disease and all-cause mortality when initiated in perimenopause or early postmenopause,” she said.

Other areas for research include “the breast effects of different estrogen preparations, including the role for selective estrogen receptor modulator (SERM) and tissue selective estrogen complex therapies, optimal progestogen or SERM regimens to prevent endometrial hyperplasia, the relationship between vasomotor symptoms and the risk for heart disease and cognitive changes, and the risks of premature ovarian insufficiency,” Dr. Faubion emphasized.

Looking ahead, “Studies are needed on the effects of longer use of low-dose vaginal estrogen therapy after breast or endometrial cancer, extended use of hormone therapy in women who are early initiators, improved tools to personalize or individualize benefits and risks of hormone therapy, and the role of aging and genetics,” said Dr. Faubion. Other areas for further research include “the long-term benefits and risks on women’s health of lifestyle modification or complementary or nonhormone therapies, if chosen in addition to or over hormone therapy for vasomotor symptoms, bone health, and cardiovascular disease risk reduction,” she added.

The complete statement was published in Menopause: The Journal of the North American Menopause Society.

The position statement received no outside funding. The authors had no financial conflicts to disclose.

Hormone therapy remains a topic for debate, but a constant in the 2 decades since the Women’s Health Initiative has been the demonstrated effectiveness for relief of vasomotor symptoms and reduction of fracture risk in menopausal women, according to the latest hormone therapy position statement of the North American Menopause Society.

“Healthcare professionals caring for menopausal women should understand the basic concepts of relative risk and absolute risk,” wrote Stephanie S. Faubion, MD, director of the Mayo Clinic Center for Women’s Health and medical director of NAMS, and members of the NAMS 2022 Hormone Therapy Position Statement Advisory Panel in Menopause.

The authors noted that the risks of hormone therapy vary considerably based on type, dose, duration, route of administration, timing of the start of therapy, and whether or not a progestogen is included.

The 2022 statement was commissioned to review new literature and identify the strength of recommendations and quality of evidence since the previous statement in 2017.

The current statement represents not so much a practice-changing update, “but rather that the literature has filled out in some areas,” Dr. Faubion said in an interview. “The recommendations overall haven’t changed,” she said. “The position statement reiterates that hormone therapy, which is significantly underutilized, remains a safe and effective treatment for menopause symptoms, which remain undertreated, with the benefits outweighing the risks for most healthy women who are within 10 years of menopause onset and under the age of 60 years,” she emphasized. “Individualizing therapy is key to maximizing benefits and minimizing risks,” she added.

Overall, the authors confirmed that hormone therapy remains the most effective treatment for vasomotor symptoms (VMS) and the genitourinary syndrome of menopause (GSM), and has been shown to prevent bone loss and fracture. The risks of hormone therapy differ depending on type, dose, duration of use, route of administration, timing of initiation, and whether a progestogen is used.

Risks and benefits should be stratified by age and time since the start of menopause, according to the statement.

For women younger than 60 years or within 10 years of the onset of menopause who have no contraindications, the potential benefits outweigh the risks in most cases for use of hormone therapy to manage vasomotor symptoms and to help prevent bone loss and reduce fracture risk.

For women who begin hormone therapy more than 10 or 20 years from the start of menopause, or who are aged 60 years and older, the risk-benefit ratio may be less favorable because of the increased absolute risk of coronary heart disease, stroke, venous thromboembolism, and dementia. However, strategies such as lower doses and transdermal administration may reduce this risk, according to the statement.

The authors continue to recommend that longer durations of hormone therapy be for documented indications, such as VMS relief, and that patients on longer duration of therapy be reassessed periodically as part of a shared decision-making process. Women with persistent VMS or quality of life issues, or those at risk for osteoporosis, may continue hormone therapy beyond age 60 or 65 years after appropriate evaluation and risk-benefit counseling.

Women with ongoing GSM without indications for systemic therapy whose GSM persists after over-the-counter therapies may try low-dose vaginal estrogen or other nonestrogen therapies regardless of age and for an extended duration if needed, according to the statement.
 

Challenges, research gaps, and goals

“Barriers to the use of hormone therapy include lack of access to high quality care,” Dr. Faubion said in an interview. The NAMS website, menopause.org, features an option to search for a NAMS-certified provider by ZIP code, she noted.

“Coverage of hormone therapy is highly variable and depends on the insurance company, but most women have access to one form or another with insurance coverage,” she said. “We need to continue to advocate for adequate coverage of menopause symptom treatments, including hormone therapy, so that women’s symptoms – which can significantly affect quality of life – are adequately managed.

“Additional research is needed on the thrombotic risk (venous thromboembolism, pulmonary embolism, and stroke) of oral versus transdermal therapies (including different formulations, doses, and durations of therapy),” Dr. Faubion told this news organization. “More clinical trial data are needed to confirm or refute the potential beneficial effects of hormone therapy on coronary heart disease and all-cause mortality when initiated in perimenopause or early postmenopause,” she said.

Other areas for research include “the breast effects of different estrogen preparations, including the role for selective estrogen receptor modulator (SERM) and tissue selective estrogen complex therapies, optimal progestogen or SERM regimens to prevent endometrial hyperplasia, the relationship between vasomotor symptoms and the risk for heart disease and cognitive changes, and the risks of premature ovarian insufficiency,” Dr. Faubion emphasized.

Looking ahead, “Studies are needed on the effects of longer use of low-dose vaginal estrogen therapy after breast or endometrial cancer, extended use of hormone therapy in women who are early initiators, improved tools to personalize or individualize benefits and risks of hormone therapy, and the role of aging and genetics,” said Dr. Faubion. Other areas for further research include “the long-term benefits and risks on women’s health of lifestyle modification or complementary or nonhormone therapies, if chosen in addition to or over hormone therapy for vasomotor symptoms, bone health, and cardiovascular disease risk reduction,” she added.

The complete statement was published in Menopause: The Journal of the North American Menopause Society.

The position statement received no outside funding. The authors had no financial conflicts to disclose.

Hormone therapy remains a topic for debate, but a constant in the 2 decades since the Women’s Health Initiative has been the demonstrated effectiveness for relief of vasomotor symptoms and reduction of fracture risk in menopausal women, according to the latest hormone therapy position statement of the North American Menopause Society.

“Healthcare professionals caring for menopausal women should understand the basic concepts of relative risk and absolute risk,” wrote Stephanie S. Faubion, MD, director of the Mayo Clinic Center for Women’s Health and medical director of NAMS, and members of the NAMS 2022 Hormone Therapy Position Statement Advisory Panel in Menopause.

The authors noted that the risks of hormone therapy vary considerably based on type, dose, duration, route of administration, timing of the start of therapy, and whether or not a progestogen is included.

The 2022 statement was commissioned to review new literature and identify the strength of recommendations and quality of evidence since the previous statement in 2017.

The current statement represents not so much a practice-changing update, “but rather that the literature has filled out in some areas,” Dr. Faubion said in an interview. “The recommendations overall haven’t changed,” she said. “The position statement reiterates that hormone therapy, which is significantly underutilized, remains a safe and effective treatment for menopause symptoms, which remain undertreated, with the benefits outweighing the risks for most healthy women who are within 10 years of menopause onset and under the age of 60 years,” she emphasized. “Individualizing therapy is key to maximizing benefits and minimizing risks,” she added.

Overall, the authors confirmed that hormone therapy remains the most effective treatment for vasomotor symptoms (VMS) and the genitourinary syndrome of menopause (GSM), and has been shown to prevent bone loss and fracture. The risks of hormone therapy differ depending on type, dose, duration of use, route of administration, timing of initiation, and whether a progestogen is used.

Risks and benefits should be stratified by age and time since the start of menopause, according to the statement.

For women younger than 60 years or within 10 years of the onset of menopause who have no contraindications, the potential benefits outweigh the risks in most cases for use of hormone therapy to manage vasomotor symptoms and to help prevent bone loss and reduce fracture risk.

For women who begin hormone therapy more than 10 or 20 years from the start of menopause, or who are aged 60 years and older, the risk-benefit ratio may be less favorable because of the increased absolute risk of coronary heart disease, stroke, venous thromboembolism, and dementia. However, strategies such as lower doses and transdermal administration may reduce this risk, according to the statement.

The authors continue to recommend that longer durations of hormone therapy be for documented indications, such as VMS relief, and that patients on longer duration of therapy be reassessed periodically as part of a shared decision-making process. Women with persistent VMS or quality of life issues, or those at risk for osteoporosis, may continue hormone therapy beyond age 60 or 65 years after appropriate evaluation and risk-benefit counseling.

Women with ongoing GSM without indications for systemic therapy whose GSM persists after over-the-counter therapies may try low-dose vaginal estrogen or other nonestrogen therapies regardless of age and for an extended duration if needed, according to the statement.
 

Challenges, research gaps, and goals

“Barriers to the use of hormone therapy include lack of access to high quality care,” Dr. Faubion said in an interview. The NAMS website, menopause.org, features an option to search for a NAMS-certified provider by ZIP code, she noted.

“Coverage of hormone therapy is highly variable and depends on the insurance company, but most women have access to one form or another with insurance coverage,” she said. “We need to continue to advocate for adequate coverage of menopause symptom treatments, including hormone therapy, so that women’s symptoms – which can significantly affect quality of life – are adequately managed.

“Additional research is needed on the thrombotic risk (venous thromboembolism, pulmonary embolism, and stroke) of oral versus transdermal therapies (including different formulations, doses, and durations of therapy),” Dr. Faubion told this news organization. “More clinical trial data are needed to confirm or refute the potential beneficial effects of hormone therapy on coronary heart disease and all-cause mortality when initiated in perimenopause or early postmenopause,” she said.

Other areas for research include “the breast effects of different estrogen preparations, including the role for selective estrogen receptor modulator (SERM) and tissue selective estrogen complex therapies, optimal progestogen or SERM regimens to prevent endometrial hyperplasia, the relationship between vasomotor symptoms and the risk for heart disease and cognitive changes, and the risks of premature ovarian insufficiency,” Dr. Faubion emphasized.

Looking ahead, “Studies are needed on the effects of longer use of low-dose vaginal estrogen therapy after breast or endometrial cancer, extended use of hormone therapy in women who are early initiators, improved tools to personalize or individualize benefits and risks of hormone therapy, and the role of aging and genetics,” said Dr. Faubion. Other areas for further research include “the long-term benefits and risks on women’s health of lifestyle modification or complementary or nonhormone therapies, if chosen in addition to or over hormone therapy for vasomotor symptoms, bone health, and cardiovascular disease risk reduction,” she added.

The complete statement was published in Menopause: The Journal of the North American Menopause Society.

The position statement received no outside funding. The authors had no financial conflicts to disclose.

Midlife women who are of normal weight or are overweight should routinely receive counseling aimed at limiting weight gain and preventing obesity and its associated health risks, a new clinical guideline states.

The recommendation, issued by the Women’s Preventive Services Initiative (WPSI) of the American College of Obstetricians and Gynecologists (ACOG), supports regular lifestyle counseling for women aged 40-60 years with normal or overweight body mass index of 18.5-29.9 kg/m². Counseling could include individualized discussion of healthy eating and physical activity initiated by health professionals involved in preventive care.

Published online in Annals of Internal Medicine, the guideline addresses the prevalence and health burdens of obesity in U.S. women of middle age and seeks to reduce the known harms of obesity with an intervention of minimal anticipated harms. High BMI increases the risk for many chronic conditions including hypertension, dyslipidemia, type 2 diabetes, coronary artery disease, stroke, and all-cause mortality.

The best way to counsel, however, remains unclear. “Although the optimal approach could not be discerned from existing trials, a range of interventions of varying duration, frequency, and intensity showed benefit with potential clinical significance,” wrote the WPSI guideline panel, led by David P. Chelmow, MD, chair of the department of obstetrics and gynecology at Virginia Commonwealth University in Richmond.

The guideline rests on a systematic literature review led by family doctor Amy G. Cantor, MD, MPH, of the Pacific Northwest Evidence-based Practice Center, at Oregon Health & Science University in Portland, suggesting moderate reductions in weight could be achieved by offering advice to this age group.

The federally supported WPSI was launched by ACOG in 2016. The guideline fills a gap in current recommendations in that it targets a specific risk group and specifies individual counseling based on its effectiveness and applicability in primary care settings.

In another benefit of routine counseling, the panel stated, “Normalizing counseling about healthy diet and physical activity by providing it to all midlife women may also mitigate concerns about weight stigma resulting from only counseling women with obesity.”

The panelists noted that during 2017-2018, the prevalence of obesity (BMI ≥ 30.0 kg/m²) was 43.3% among U.S. women aged 40-59 years, while the prevalence of severe obesity (BMI ≥ 40.0 kg/m²) was highest in this age group at 11.5%. “Midlife women gain weight at an average of approximately 1.5 pounds per year, which increases their risk for transitioning from normal or overweight to obese BMI,” the panelists wrote.

The review

Dr. Cantor’s group analyzed seven randomized controlled trials (RCTs) published up to October 2021 from 12 publications involving 51,638 participants. Although the trials were largely small and heterogeneous, they suggested that counseling may result in modest differences in weight change without causing important harms.

Four RCTs showed significant favorable weight changes for counseling over no-counseling control groups, with a mean difference of 0.87 to 2.5 kg, whereas one trial of counseling and two trials of exercise showed no differences. One of two RCTs reported improved quality-of-life measures.

As for harms, while interventions did not increase measures of depression or stress in one trial, self-reported falls (37% vs. 29%, P < .001) and injuries (19% vs. 14%, P = .03) were more frequent with exercise counseling in one trial.

“More research is needed to determine optimal content, frequency, length, and number of sessions required and should include additional patient populations,” Dr. Cantor and associates wrote.

In terms of limitations, the authors acknowledged that trials of behavioral interventions in maintaining or reducing weight in midlife women demonstrate small magnitudes of effect.

Offering a nonparticipant’s perspective on the WPSI guideline for this news organization, JoAnn E. Manson, MD, DrPH, MACP, chief of the division of preventive medicine at Brigham and Women’s Hospital in Boston, said its message is of prime importance for women of middle age and it goes beyond concern about pounds lost or gained.

“Midlife and the transition to menopause are high-risk periods for women in terms of typical changes in body composition that increase the risk of adverse cardiometabolic outcomes,” said Dr. Manson, professor of women’s health at Harvard Medical School, Boston. “Counseling women should be a priority for physicians in clinical practice. And it’s not just whether weight gain is reflected on the scales or not but whether there’s an increase in central abdominal fat, a decrease in lean muscle mass, and an increase in adverse glucose tolerance.”

It is essential for women to be vigilant at this time, she added, and their exercise regimens should include strength and resistance training to preserve lean muscle mass and boost metabolic rate. Dr. Manson’s group has issued several statements stressing how important it is for clinicians to take decisive action on the counseling front and how they can do this in very little time during routine practice.

Also in full support of the guideline is Mary L. Rosser, MD, PhD, assistant professor of women’s health in obstetrics and gynecology at Columbia University Irving Medical Center in New York. “Midlife is a wonderful opportunity to encourage patients to assess their overall health status and make changes to impact their future health. Women in middle age tend to experience weight gain due to a variety of factors including aging and lifestyle,” said Dr. Rosser, who was not involved in the writing of the review or guideline.

While aging and genetics cannot be altered, behaviors can, and in her view, favorable behaviors would also include stress reduction and adequate sleep.

“The importance of reducing obesity with early intervention and prevention must focus on all women,” Dr. Rosser said. “We must narrow the inequities gap in care especially for high-risk minority groups and underserved populations. This will reduce disease and death and provide women the gift of active living and feeling better.”

The WPSI authors have made available a summary of the review and guideline for patients.

The systematic review and clinical guideline were funded by the federal Health Resources and Services Administration through ACOG. The authors of the guideline and the review authors disclosed no relevant financial conflicts of interest. Dr. Manson and Dr. Rosser disclosed no relevant competing interests with regard to their comments.

Midlife women who are of normal weight or are overweight should routinely receive counseling aimed at limiting weight gain and preventing obesity and its associated health risks, a new clinical guideline states.

The recommendation, issued by the Women’s Preventive Services Initiative (WPSI) of the American College of Obstetricians and Gynecologists (ACOG), supports regular lifestyle counseling for women aged 40-60 years with normal or overweight body mass index of 18.5-29.9 kg/m². Counseling could include individualized discussion of healthy eating and physical activity initiated by health professionals involved in preventive care.

Published online in Annals of Internal Medicine, the guideline addresses the prevalence and health burdens of obesity in U.S. women of middle age and seeks to reduce the known harms of obesity with an intervention of minimal anticipated harms. High BMI increases the risk for many chronic conditions including hypertension, dyslipidemia, type 2 diabetes, coronary artery disease, stroke, and all-cause mortality.

The best way to counsel, however, remains unclear. “Although the optimal approach could not be discerned from existing trials, a range of interventions of varying duration, frequency, and intensity showed benefit with potential clinical significance,” wrote the WPSI guideline panel, led by David P. Chelmow, MD, chair of the department of obstetrics and gynecology at Virginia Commonwealth University in Richmond.

The guideline rests on a systematic literature review led by family doctor Amy G. Cantor, MD, MPH, of the Pacific Northwest Evidence-based Practice Center, at Oregon Health & Science University in Portland, suggesting moderate reductions in weight could be achieved by offering advice to this age group.

The federally supported WPSI was launched by ACOG in 2016. The guideline fills a gap in current recommendations in that it targets a specific risk group and specifies individual counseling based on its effectiveness and applicability in primary care settings.

In another benefit of routine counseling, the panel stated, “Normalizing counseling about healthy diet and physical activity by providing it to all midlife women may also mitigate concerns about weight stigma resulting from only counseling women with obesity.”

The panelists noted that during 2017-2018, the prevalence of obesity (BMI ≥ 30.0 kg/m²) was 43.3% among U.S. women aged 40-59 years, while the prevalence of severe obesity (BMI ≥ 40.0 kg/m²) was highest in this age group at 11.5%. “Midlife women gain weight at an average of approximately 1.5 pounds per year, which increases their risk for transitioning from normal or overweight to obese BMI,” the panelists wrote.

The review

Dr. Cantor’s group analyzed seven randomized controlled trials (RCTs) published up to October 2021 from 12 publications involving 51,638 participants. Although the trials were largely small and heterogeneous, they suggested that counseling may result in modest differences in weight change without causing important harms.

Four RCTs showed significant favorable weight changes for counseling over no-counseling control groups, with a mean difference of 0.87 to 2.5 kg, whereas one trial of counseling and two trials of exercise showed no differences. One of two RCTs reported improved quality-of-life measures.

As for harms, while interventions did not increase measures of depression or stress in one trial, self-reported falls (37% vs. 29%, P < .001) and injuries (19% vs. 14%, P = .03) were more frequent with exercise counseling in one trial.

“More research is needed to determine optimal content, frequency, length, and number of sessions required and should include additional patient populations,” Dr. Cantor and associates wrote.

In terms of limitations, the authors acknowledged that trials of behavioral interventions in maintaining or reducing weight in midlife women demonstrate small magnitudes of effect.

Offering a nonparticipant’s perspective on the WPSI guideline for this news organization, JoAnn E. Manson, MD, DrPH, MACP, chief of the division of preventive medicine at Brigham and Women’s Hospital in Boston, said its message is of prime importance for women of middle age and it goes beyond concern about pounds lost or gained.

“Midlife and the transition to menopause are high-risk periods for women in terms of typical changes in body composition that increase the risk of adverse cardiometabolic outcomes,” said Dr. Manson, professor of women’s health at Harvard Medical School, Boston. “Counseling women should be a priority for physicians in clinical practice. And it’s not just whether weight gain is reflected on the scales or not but whether there’s an increase in central abdominal fat, a decrease in lean muscle mass, and an increase in adverse glucose tolerance.”

It is essential for women to be vigilant at this time, she added, and their exercise regimens should include strength and resistance training to preserve lean muscle mass and boost metabolic rate. Dr. Manson’s group has issued several statements stressing how important it is for clinicians to take decisive action on the counseling front and how they can do this in very little time during routine practice.

Also in full support of the guideline is Mary L. Rosser, MD, PhD, assistant professor of women’s health in obstetrics and gynecology at Columbia University Irving Medical Center in New York. “Midlife is a wonderful opportunity to encourage patients to assess their overall health status and make changes to impact their future health. Women in middle age tend to experience weight gain due to a variety of factors including aging and lifestyle,” said Dr. Rosser, who was not involved in the writing of the review or guideline.

While aging and genetics cannot be altered, behaviors can, and in her view, favorable behaviors would also include stress reduction and adequate sleep.

“The importance of reducing obesity with early intervention and prevention must focus on all women,” Dr. Rosser said. “We must narrow the inequities gap in care especially for high-risk minority groups and underserved populations. This will reduce disease and death and provide women the gift of active living and feeling better.”

The WPSI authors have made available a summary of the review and guideline for patients.

The systematic review and clinical guideline were funded by the federal Health Resources and Services Administration through ACOG. The authors of the guideline and the review authors disclosed no relevant financial conflicts of interest. Dr. Manson and Dr. Rosser disclosed no relevant competing interests with regard to their comments.

Midlife women who are of normal weight or are overweight should routinely receive counseling aimed at limiting weight gain and preventing obesity and its associated health risks, a new clinical guideline states.

The recommendation, issued by the Women’s Preventive Services Initiative (WPSI) of the American College of Obstetricians and Gynecologists (ACOG), supports regular lifestyle counseling for women aged 40-60 years with normal or overweight body mass index of 18.5-29.9 kg/m². Counseling could include individualized discussion of healthy eating and physical activity initiated by health professionals involved in preventive care.

Published online in Annals of Internal Medicine, the guideline addresses the prevalence and health burdens of obesity in U.S. women of middle age and seeks to reduce the known harms of obesity with an intervention of minimal anticipated harms. High BMI increases the risk for many chronic conditions including hypertension, dyslipidemia, type 2 diabetes, coronary artery disease, stroke, and all-cause mortality.

The best way to counsel, however, remains unclear. “Although the optimal approach could not be discerned from existing trials, a range of interventions of varying duration, frequency, and intensity showed benefit with potential clinical significance,” wrote the WPSI guideline panel, led by David P. Chelmow, MD, chair of the department of obstetrics and gynecology at Virginia Commonwealth University in Richmond.

The guideline rests on a systematic literature review led by family doctor Amy G. Cantor, MD, MPH, of the Pacific Northwest Evidence-based Practice Center, at Oregon Health & Science University in Portland, suggesting moderate reductions in weight could be achieved by offering advice to this age group.

The federally supported WPSI was launched by ACOG in 2016. The guideline fills a gap in current recommendations in that it targets a specific risk group and specifies individual counseling based on its effectiveness and applicability in primary care settings.

In another benefit of routine counseling, the panel stated, “Normalizing counseling about healthy diet and physical activity by providing it to all midlife women may also mitigate concerns about weight stigma resulting from only counseling women with obesity.”

The panelists noted that during 2017-2018, the prevalence of obesity (BMI ≥ 30.0 kg/m²) was 43.3% among U.S. women aged 40-59 years, while the prevalence of severe obesity (BMI ≥ 40.0 kg/m²) was highest in this age group at 11.5%. “Midlife women gain weight at an average of approximately 1.5 pounds per year, which increases their risk for transitioning from normal or overweight to obese BMI,” the panelists wrote.

The review

Dr. Cantor’s group analyzed seven randomized controlled trials (RCTs) published up to October 2021 from 12 publications involving 51,638 participants. Although the trials were largely small and heterogeneous, they suggested that counseling may result in modest differences in weight change without causing important harms.

Four RCTs showed significant favorable weight changes for counseling over no-counseling control groups, with a mean difference of 0.87 to 2.5 kg, whereas one trial of counseling and two trials of exercise showed no differences. One of two RCTs reported improved quality-of-life measures.

As for harms, while interventions did not increase measures of depression or stress in one trial, self-reported falls (37% vs. 29%, P < .001) and injuries (19% vs. 14%, P = .03) were more frequent with exercise counseling in one trial.

“More research is needed to determine optimal content, frequency, length, and number of sessions required and should include additional patient populations,” Dr. Cantor and associates wrote.

In terms of limitations, the authors acknowledged that trials of behavioral interventions in maintaining or reducing weight in midlife women demonstrate small magnitudes of effect.

Offering a nonparticipant’s perspective on the WPSI guideline for this news organization, JoAnn E. Manson, MD, DrPH, MACP, chief of the division of preventive medicine at Brigham and Women’s Hospital in Boston, said its message is of prime importance for women of middle age and it goes beyond concern about pounds lost or gained.

“Midlife and the transition to menopause are high-risk periods for women in terms of typical changes in body composition that increase the risk of adverse cardiometabolic outcomes,” said Dr. Manson, professor of women’s health at Harvard Medical School, Boston. “Counseling women should be a priority for physicians in clinical practice. And it’s not just whether weight gain is reflected on the scales or not but whether there’s an increase in central abdominal fat, a decrease in lean muscle mass, and an increase in adverse glucose tolerance.”

It is essential for women to be vigilant at this time, she added, and their exercise regimens should include strength and resistance training to preserve lean muscle mass and boost metabolic rate. Dr. Manson’s group has issued several statements stressing how important it is for clinicians to take decisive action on the counseling front and how they can do this in very little time during routine practice.

Also in full support of the guideline is Mary L. Rosser, MD, PhD, assistant professor of women’s health in obstetrics and gynecology at Columbia University Irving Medical Center in New York. “Midlife is a wonderful opportunity to encourage patients to assess their overall health status and make changes to impact their future health. Women in middle age tend to experience weight gain due to a variety of factors including aging and lifestyle,” said Dr. Rosser, who was not involved in the writing of the review or guideline.

While aging and genetics cannot be altered, behaviors can, and in her view, favorable behaviors would also include stress reduction and adequate sleep.

“The importance of reducing obesity with early intervention and prevention must focus on all women,” Dr. Rosser said. “We must narrow the inequities gap in care especially for high-risk minority groups and underserved populations. This will reduce disease and death and provide women the gift of active living and feeling better.”

The WPSI authors have made available a summary of the review and guideline for patients.

The systematic review and clinical guideline were funded by the federal Health Resources and Services Administration through ACOG. The authors of the guideline and the review authors disclosed no relevant financial conflicts of interest. Dr. Manson and Dr. Rosser disclosed no relevant competing interests with regard to their comments.

Hormone therapy did not increase mortality in postmenopausal women treated for early-stage estrogen receptor–positive breast cancer, but, in longitudinal data from Denmark, there was a recurrence risk with vaginal estrogen therapy among those treated with aromatase inhibitors.

Genitourinary syndrome of menopause (GSM) – including vaginal dryness, burning, and urinary incontinence – is common in women treated for breast cancer. Adjuvant endocrine therapy, particularly aromatase inhibitors, can aggravate these symptoms. Both local and systemic estrogen therapy are recommended for alleviating GSM symptoms in healthy women, but concerns have been raised about their use in women with breast cancer. Previous studies examining this have suggested possible risks for breast cancer recurrence, but those studies have had several limitations including small samples and short follow-up, particularly for vaginal estrogen therapy.

In the new study, from a national Danish cohort of 8,461 postmenopausal women diagnosed between 1997 and 2004 and treated for early-stage invasive estrogen receptor–positive nonmetastatic breast cancer, neither systemic menopausal hormone therapy (MHT) nor local vaginal estrogen therapy (VET) were associated with an overall increased risk for either breast cancer recurrence or mortality. However, in the subset who had received an aromatase inhibitor – with or without tamoxifen – there was a statistically significant increased risk for breast cancer recurrence, but not mortality.

The results were published in the Journal of the National Cancer Institute.

“The data are reassuring for the majority of women with no adjuvant therapy or tamoxifen. But for those using adjuvant aromatase inhibitors, there might be a small risk,” study lead author Søren Cold, MD, PhD, senior oncologist in the department of oncology at Odense (Denmark) University Hospital, Odense, said in an interview.

Moreover, Dr. Cold noted, while this study didn’t find an increased recurrence risk with MHT for women taking aromatase inhibitors, other studies have. One in particular was stopped because of harm. The reason for the difference here is likely that the previous sample was small – just 133 women.

“Our study is mainly focusing on the use of vaginal estrogen. We had so few patients using systemic menopausal hormone therapy, those data don’t mean much. ... The risk with systemic therapy has been established. The vaginal use hasn’t been thoroughly studied before,” he noted.
 

Breast cancer recurrence elevated with VET and aromatase inhibitors

The study pool was 9,710 women who underwent complete resection for estrogen-positive breast cancer and were all allocated to 5 years of adjuvant endocrine treatment or no adjuvant treatment, according to guidelines. Overall, 3,112 received no adjuvant endocrine treatment, 2,007 were treated with tamoxifen only, 403 with an aromatase inhibitor, and 2,939 with a sequence of tamoxifen and an aromatase inhibitor.

After exclusion of 1,249 who had received VET or MHT prior to breast cancer diagnosis, there were 6,391 not prescribed any estrogen hormonal treatment, 1,957 prescribed VET, and 133 prescribed MHT with or without VET.

During an estimated median 9.8 years’ follow-up, 1,333 women (16%) had a breast cancer recurrence. Of those, 111 had received VET, 16 MHT, and 1,206 neither. Compared with those receiving no hormonal treatment, the adjusted risk of recurrence was similar for the VET users (hazard ratio, 1.08; 95% confidence interval, 0.89-1.32).

However, there was an increased risk for recurrence associated with initiating VET during aromatase inhibitor treatment (HR, 1.39, 95% CI, 1.04-1.85). For women receiving MHT, the adjusted relative risk of recurrence with aromatase inhibitors wasn’t significant (HR, 1.05; 95% CI, 0.62-1.78).

Overall, compared with women who never used hormonal treatment, the absolute 10-year breast cancer recurrence risk was 19.2% for never-users of VET or MHT, 15.4% in VET users, and 17.1% in MHT users.
 

No differences found for mortality

Of the 8,461 women in the study, 40% (3,370) died during an estimated median follow-up of 15.2 years. Of those, 497 had received VET, 47 MHT, and 2,826 neither. Compared with the never-users of estrogen therapy, the adjusted HR for overall survival in VET users was 0.78 (95% CI, 0.71-0.87). The analysis stratified by adjuvant endocrine therapy didn’t show an increase in VET users by use of aromatase inhibitors (aHR, 0.94, 95% CI, 0.70-1.26). The same was found for women prescribed MHT, compared with never-users (aHR, 0.94; 95% CI, 0.70-1.26).

Never-users of VET or MHT had an absolute 10-year overall survival of 73.8% versus 79.5% and 80.5% among the women who used VET or MHT, respectively.

Asked to comment, Nanette Santoro, MD, professor and E. Stewart Taylor Chair of Obstetrics & Gynecology at the University of Colorado at Denver, Aurora, said in an interview: “It is important to look at this issue. These findings raise but don’t answer the question that vaginal estradiol may not be as safe as we hope it is for women with breast cancer using an aromatase inhibitor.”

However, she also pointed out that “the overall increase in risk is not enormous; mortality risk was not increased. Women need to consider that there may be some risk associated with this option in their decision making about taking it. Having a satisfying sex life is also important for many women! It is really compassionate use for quality of life, so there is always that unknown element of risk in the discussion. That unknown risk has to be balanced against the benefit that the estrogen provides.”

And, Dr. Santoro also noted that the use of prescription data poses limitations. “It cannot tell us what was going on in the minds of the patient and the prescriber. There may be differences in the prescriber’s impression of the patient’s risk of recurrence that influenced the decision to provide a prescription. ... Women using AIs [aromatase inhibitors] often get pretty severe vaginal dryness symptoms and may need more estrogen to be comfortable with intercourse, but we really cannot tell this from what is in this paper.”

Indeed, Dr. Cold said: “We admit it’s not a randomized study, but we’ve done what was possible to take [confounding] factors into account, including age, tumor size, nodal status, histology, and comorbidities.”

He suggested that a potential therapeutic approach to reducing the recurrence risk might be to switch VET-treated women to tamoxifen after 2-3 years of aromatase inhibitors.

This work was supported by Breast Friends, a part of the Danish Cancer Society. Dr. Cold received support from Breast Friends for the current study. Some of the other coauthors have pharmaceutical company disclosures. Dr. Santoro is a member of the scientific advisory boards for Astellas, Menogenix, Que Oncology, and Amazon Ember, and is a consultant for Ansh Labs.

Hormone therapy did not increase mortality in postmenopausal women treated for early-stage estrogen receptor–positive breast cancer, but, in longitudinal data from Denmark, there was a recurrence risk with vaginal estrogen therapy among those treated with aromatase inhibitors.

Genitourinary syndrome of menopause (GSM) – including vaginal dryness, burning, and urinary incontinence – is common in women treated for breast cancer. Adjuvant endocrine therapy, particularly aromatase inhibitors, can aggravate these symptoms. Both local and systemic estrogen therapy are recommended for alleviating GSM symptoms in healthy women, but concerns have been raised about their use in women with breast cancer. Previous studies examining this have suggested possible risks for breast cancer recurrence, but those studies have had several limitations including small samples and short follow-up, particularly for vaginal estrogen therapy.

In the new study, from a national Danish cohort of 8,461 postmenopausal women diagnosed between 1997 and 2004 and treated for early-stage invasive estrogen receptor–positive nonmetastatic breast cancer, neither systemic menopausal hormone therapy (MHT) nor local vaginal estrogen therapy (VET) were associated with an overall increased risk for either breast cancer recurrence or mortality. However, in the subset who had received an aromatase inhibitor – with or without tamoxifen – there was a statistically significant increased risk for breast cancer recurrence, but not mortality.

The results were published in the Journal of the National Cancer Institute.

“The data are reassuring for the majority of women with no adjuvant therapy or tamoxifen. But for those using adjuvant aromatase inhibitors, there might be a small risk,” study lead author Søren Cold, MD, PhD, senior oncologist in the department of oncology at Odense (Denmark) University Hospital, Odense, said in an interview.

Moreover, Dr. Cold noted, while this study didn’t find an increased recurrence risk with MHT for women taking aromatase inhibitors, other studies have. One in particular was stopped because of harm. The reason for the difference here is likely that the previous sample was small – just 133 women.

“Our study is mainly focusing on the use of vaginal estrogen. We had so few patients using systemic menopausal hormone therapy, those data don’t mean much. ... The risk with systemic therapy has been established. The vaginal use hasn’t been thoroughly studied before,” he noted.
 

Breast cancer recurrence elevated with VET and aromatase inhibitors

The study pool was 9,710 women who underwent complete resection for estrogen-positive breast cancer and were all allocated to 5 years of adjuvant endocrine treatment or no adjuvant treatment, according to guidelines. Overall, 3,112 received no adjuvant endocrine treatment, 2,007 were treated with tamoxifen only, 403 with an aromatase inhibitor, and 2,939 with a sequence of tamoxifen and an aromatase inhibitor.

After exclusion of 1,249 who had received VET or MHT prior to breast cancer diagnosis, there were 6,391 not prescribed any estrogen hormonal treatment, 1,957 prescribed VET, and 133 prescribed MHT with or without VET.

During an estimated median 9.8 years’ follow-up, 1,333 women (16%) had a breast cancer recurrence. Of those, 111 had received VET, 16 MHT, and 1,206 neither. Compared with those receiving no hormonal treatment, the adjusted risk of recurrence was similar for the VET users (hazard ratio, 1.08; 95% confidence interval, 0.89-1.32).

However, there was an increased risk for recurrence associated with initiating VET during aromatase inhibitor treatment (HR, 1.39, 95% CI, 1.04-1.85). For women receiving MHT, the adjusted relative risk of recurrence with aromatase inhibitors wasn’t significant (HR, 1.05; 95% CI, 0.62-1.78).

Overall, compared with women who never used hormonal treatment, the absolute 10-year breast cancer recurrence risk was 19.2% for never-users of VET or MHT, 15.4% in VET users, and 17.1% in MHT users.
 

No differences found for mortality

Of the 8,461 women in the study, 40% (3,370) died during an estimated median follow-up of 15.2 years. Of those, 497 had received VET, 47 MHT, and 2,826 neither. Compared with the never-users of estrogen therapy, the adjusted HR for overall survival in VET users was 0.78 (95% CI, 0.71-0.87). The analysis stratified by adjuvant endocrine therapy didn’t show an increase in VET users by use of aromatase inhibitors (aHR, 0.94, 95% CI, 0.70-1.26). The same was found for women prescribed MHT, compared with never-users (aHR, 0.94; 95% CI, 0.70-1.26).

Never-users of VET or MHT had an absolute 10-year overall survival of 73.8% versus 79.5% and 80.5% among the women who used VET or MHT, respectively.

Asked to comment, Nanette Santoro, MD, professor and E. Stewart Taylor Chair of Obstetrics & Gynecology at the University of Colorado at Denver, Aurora, said in an interview: “It is important to look at this issue. These findings raise but don’t answer the question that vaginal estradiol may not be as safe as we hope it is for women with breast cancer using an aromatase inhibitor.”

However, she also pointed out that “the overall increase in risk is not enormous; mortality risk was not increased. Women need to consider that there may be some risk associated with this option in their decision making about taking it. Having a satisfying sex life is also important for many women! It is really compassionate use for quality of life, so there is always that unknown element of risk in the discussion. That unknown risk has to be balanced against the benefit that the estrogen provides.”

And, Dr. Santoro also noted that the use of prescription data poses limitations. “It cannot tell us what was going on in the minds of the patient and the prescriber. There may be differences in the prescriber’s impression of the patient’s risk of recurrence that influenced the decision to provide a prescription. ... Women using AIs [aromatase inhibitors] often get pretty severe vaginal dryness symptoms and may need more estrogen to be comfortable with intercourse, but we really cannot tell this from what is in this paper.”

Indeed, Dr. Cold said: “We admit it’s not a randomized study, but we’ve done what was possible to take [confounding] factors into account, including age, tumor size, nodal status, histology, and comorbidities.”

He suggested that a potential therapeutic approach to reducing the recurrence risk might be to switch VET-treated women to tamoxifen after 2-3 years of aromatase inhibitors.

This work was supported by Breast Friends, a part of the Danish Cancer Society. Dr. Cold received support from Breast Friends for the current study. Some of the other coauthors have pharmaceutical company disclosures. Dr. Santoro is a member of the scientific advisory boards for Astellas, Menogenix, Que Oncology, and Amazon Ember, and is a consultant for Ansh Labs.

Hormone therapy did not increase mortality in postmenopausal women treated for early-stage estrogen receptor–positive breast cancer, but, in longitudinal data from Denmark, there was a recurrence risk with vaginal estrogen therapy among those treated with aromatase inhibitors.

Genitourinary syndrome of menopause (GSM) – including vaginal dryness, burning, and urinary incontinence – is common in women treated for breast cancer. Adjuvant endocrine therapy, particularly aromatase inhibitors, can aggravate these symptoms. Both local and systemic estrogen therapy are recommended for alleviating GSM symptoms in healthy women, but concerns have been raised about their use in women with breast cancer. Previous studies examining this have suggested possible risks for breast cancer recurrence, but those studies have had several limitations including small samples and short follow-up, particularly for vaginal estrogen therapy.

In the new study, from a national Danish cohort of 8,461 postmenopausal women diagnosed between 1997 and 2004 and treated for early-stage invasive estrogen receptor–positive nonmetastatic breast cancer, neither systemic menopausal hormone therapy (MHT) nor local vaginal estrogen therapy (VET) were associated with an overall increased risk for either breast cancer recurrence or mortality. However, in the subset who had received an aromatase inhibitor – with or without tamoxifen – there was a statistically significant increased risk for breast cancer recurrence, but not mortality.

The results were published in the Journal of the National Cancer Institute.

“The data are reassuring for the majority of women with no adjuvant therapy or tamoxifen. But for those using adjuvant aromatase inhibitors, there might be a small risk,” study lead author Søren Cold, MD, PhD, senior oncologist in the department of oncology at Odense (Denmark) University Hospital, Odense, said in an interview.

Moreover, Dr. Cold noted, while this study didn’t find an increased recurrence risk with MHT for women taking aromatase inhibitors, other studies have. One in particular was stopped because of harm. The reason for the difference here is likely that the previous sample was small – just 133 women.

“Our study is mainly focusing on the use of vaginal estrogen. We had so few patients using systemic menopausal hormone therapy, those data don’t mean much. ... The risk with systemic therapy has been established. The vaginal use hasn’t been thoroughly studied before,” he noted.
 

Breast cancer recurrence elevated with VET and aromatase inhibitors

The study pool was 9,710 women who underwent complete resection for estrogen-positive breast cancer and were all allocated to 5 years of adjuvant endocrine treatment or no adjuvant treatment, according to guidelines. Overall, 3,112 received no adjuvant endocrine treatment, 2,007 were treated with tamoxifen only, 403 with an aromatase inhibitor, and 2,939 with a sequence of tamoxifen and an aromatase inhibitor.

After exclusion of 1,249 who had received VET or MHT prior to breast cancer diagnosis, there were 6,391 not prescribed any estrogen hormonal treatment, 1,957 prescribed VET, and 133 prescribed MHT with or without VET.

During an estimated median 9.8 years’ follow-up, 1,333 women (16%) had a breast cancer recurrence. Of those, 111 had received VET, 16 MHT, and 1,206 neither. Compared with those receiving no hormonal treatment, the adjusted risk of recurrence was similar for the VET users (hazard ratio, 1.08; 95% confidence interval, 0.89-1.32).

However, there was an increased risk for recurrence associated with initiating VET during aromatase inhibitor treatment (HR, 1.39, 95% CI, 1.04-1.85). For women receiving MHT, the adjusted relative risk of recurrence with aromatase inhibitors wasn’t significant (HR, 1.05; 95% CI, 0.62-1.78).

Overall, compared with women who never used hormonal treatment, the absolute 10-year breast cancer recurrence risk was 19.2% for never-users of VET or MHT, 15.4% in VET users, and 17.1% in MHT users.
 

No differences found for mortality

Of the 8,461 women in the study, 40% (3,370) died during an estimated median follow-up of 15.2 years. Of those, 497 had received VET, 47 MHT, and 2,826 neither. Compared with the never-users of estrogen therapy, the adjusted HR for overall survival in VET users was 0.78 (95% CI, 0.71-0.87). The analysis stratified by adjuvant endocrine therapy didn’t show an increase in VET users by use of aromatase inhibitors (aHR, 0.94, 95% CI, 0.70-1.26). The same was found for women prescribed MHT, compared with never-users (aHR, 0.94; 95% CI, 0.70-1.26).

Never-users of VET or MHT had an absolute 10-year overall survival of 73.8% versus 79.5% and 80.5% among the women who used VET or MHT, respectively.

Asked to comment, Nanette Santoro, MD, professor and E. Stewart Taylor Chair of Obstetrics & Gynecology at the University of Colorado at Denver, Aurora, said in an interview: “It is important to look at this issue. These findings raise but don’t answer the question that vaginal estradiol may not be as safe as we hope it is for women with breast cancer using an aromatase inhibitor.”

However, she also pointed out that “the overall increase in risk is not enormous; mortality risk was not increased. Women need to consider that there may be some risk associated with this option in their decision making about taking it. Having a satisfying sex life is also important for many women! It is really compassionate use for quality of life, so there is always that unknown element of risk in the discussion. That unknown risk has to be balanced against the benefit that the estrogen provides.”

And, Dr. Santoro also noted that the use of prescription data poses limitations. “It cannot tell us what was going on in the minds of the patient and the prescriber. There may be differences in the prescriber’s impression of the patient’s risk of recurrence that influenced the decision to provide a prescription. ... Women using AIs [aromatase inhibitors] often get pretty severe vaginal dryness symptoms and may need more estrogen to be comfortable with intercourse, but we really cannot tell this from what is in this paper.”

Indeed, Dr. Cold said: “We admit it’s not a randomized study, but we’ve done what was possible to take [confounding] factors into account, including age, tumor size, nodal status, histology, and comorbidities.”

He suggested that a potential therapeutic approach to reducing the recurrence risk might be to switch VET-treated women to tamoxifen after 2-3 years of aromatase inhibitors.

This work was supported by Breast Friends, a part of the Danish Cancer Society. Dr. Cold received support from Breast Friends for the current study. Some of the other coauthors have pharmaceutical company disclosures. Dr. Santoro is a member of the scientific advisory boards for Astellas, Menogenix, Que Oncology, and Amazon Ember, and is a consultant for Ansh Labs.

This year’s Menopause Update focuses on 2 menopause-related issues relevant to ObGyns and our menopausal patients:

• choosing the safest regimens, particularly with respect to risk of breast cancer, when prescribing hormone therapy (HT) to menopausal women
• reviewing the risks and benefits of premenopausal bilateral salpingo-oophorectomy and the pros and cons of replacement HT in surgically menopausal patients.

We hope that you find this updated information useful as you care for menopausal women.

Revisiting menopausal HT  and the risk of breast cancer:  What we know now

Abenhaim HA, Suissa S,  Azoulay L, et al. Menopausal hormone therapy formulation and breast cancer risk. Obstet Gynecol. 2022;139:1103-1110. doi: 10.1097/AOG.0000000000004723.

Reevaluation of the Women’s Health Initiative randomized controlled trials (WHI RCTs), long-term (median follow-up more than 20 years) cumulative  follow-up data, and results from additional studies have suggested that estrogen therapy (ET) alone in menopausal women with prior hysterectomy does not increase the risk of breast cancer. By contrast, estrogen with progestin (synthetic progestogens that include medroxyprogesterone acetate [MPA] and norethindrone acetate) slightly increases the risk of breast cancer. In the past 10 years, several publications have shed light on whether the type of progestogen affects the risk of breast cancer and can help provide evidence-based information to guide clinicians.

Breast cancer risk with combined HT and synthetic progestin

In the first part of the WHI RCT, women were randomly assigned to receive either conjugated equine estrogen (CEE) plus synthetic progestin (MPA) or a placebo. Combined estrogen-progestin therapy (EPT) was associated with a modestly elevated risk of breast cancer.¹ In the second part of the WHI trial, CEE only (estrogen alone, ET) was compared with placebo among women with prior  hysterectomy, with no effect found on breast cancer incidence.²

Most older observational studies published in 2003 to 2005 found that neither CEE nor estradiol appeared to increase the risk of breast cancer when used alone.^3-5 However, estrogen use in combination with synthetic progestins (MPA, norethindrone, levonorgestrel, and norgestrel) has been associated with an increased risk of breast cancer,^4,6 while the elevated risk of breast cancer with micronized progesterone has been less substantial.^7,8

Continue to: Newer data suggest the type of progestogen used affects risk...

In a report published in the June 2022 issue of Obstetrics and Gynecology, Abenhaim and colleagues used a nested population-based case-control study of administrative data available in the UK Clinical Practice Research Datalink and provider prescriptions to evaluate the additive effect on the risk of breast cancer of the type of progestogen (micronized progesterone or synthetic progestins) when combined with estradiol for the treatment of menopausal symptoms.⁹ A cohort of 561,379 women was included in the case-control study (10:1 ratio), 43,183 in the case group (patients diagnosed with invasive breast cancer), and 431,830 in the matched control group.

Overall, in the stratified analysis, a small but significant increase in the risk of breast cancer was found in ever users of menopausal HT (odds ratio [OR], 1.12; 95% confidence interval [CI], 1.09–1.15). Neither estradiol (OR, 1.04; 95% CI, 1.00–1.09) nor CEE (OR, 1.01; 95% CI, 0.96–1.06) was associated with an elevated risk of being diagnosed with invasive breast cancer. Of note, no elevated risk of breast cancer was associated with combination estrogen-progesterone therapy. However, the risk of breast cancer for women who had used synthetic progestins, mostly MPA, was significantly elevated (OR, 1.28; 95% CI, 1.22-1.35). Notably, this modestly elevated odds ratio with the use of estrogen-progestin HT is almost identical to that observed with CEE/ MPA in the WHI.¹ Similar findings were found in women aged 50 to 60 years.

The adjusted analyses from the large WHI RCTs provide additional support: the synthetic progestin MPA combined with CEE showed a higher risk of breast cancer than CEE alone in women with prior hysterectomy.¹⁰

In the long-term follow-up of the WHI RCTs, after a median of 20.3 years postrandomization, prior randomization to CEE alone for postmenopausal women with prior hysterectomy was associated with a significantly lowered risk of breast cancer incidence and mortality.¹¹ By contrast, prior randomization to CEE plus MPA (EPT) for women with an intact uterus was associated with a small but significantly increased incidence of breast cancer but no significant difference in breast cancer mortality.

In the French E3N EPIC population-based prospective cohort study, Fournier and colleagues^4,5 found that women who received estrogen combined with synthetic progestins (mostly MPA) had a higher risk of breast cancer, with an age-adjusted relative risk of 1.4 (95% CI, 1.2–1.7), a finding not seen in women who received estrogen combined with micronized progesterone, similar to findings by Cordina-Duverger and colleagues and Simin and colleagues.^12,13 In the E3N study, only 948 women were identified with breast cancer; 268 of these had used synthetic progestins.^4,5

Both the Abenhaim cohort⁹ and the longterm outcomes of WHI RCT trial data¹¹ found a significant contributing effect of MPA (synthetic progestin) in the risk of breast cancer. Progestogens are not thought to exert a class effect. Although it is clear that progestogens (progesterone or progestins) prevent estrogeninduced endometrial neoplasia when dosed adequately, different types of progestogens have a differential risk of breast epithelium proliferation and carcinogenic potential.¹⁴ A systematic review by Stute and colleagues found that micronized progesterone did not appear to alter mammographic breast density assessments or breast biopsy results.¹⁵

Race considerations

The study by Abenhaim and colleagues was unable to address the issues of race or ethnicity.⁹ However, in the racially diverse WHI trial of women with prior hysterectomy, estrogen-alone use significantly reduced breast cancer incidence in all participants.^10,16 Post hoc analysis of the 1,616 Black women with prior hysterectomy in the WHI RCT showed a significantly decreased breast cancer incidence with use of estrogen alone (hazard ratio [HR], 0.47; 95% CI, 0.26–0.82).¹ When race was evaluated in the long-term cumulative follow-up of the WHI trial, estrogen-alone use significantly reduced breast cancer incidence in Black women, with no adverse effect on coronary heart disease, global index, or all-cause mortality, and with fewer cases of venous thromboembolism.¹⁷ The global index findings were favorable for Black women in their 50s and those with vasomotor symptoms.

Continue to: Impact of HT in women with an elevated risk of breast cancer...

Impact of HT in women with an elevated risk of breast cancer

Abenhaim and colleagues could not evaluate the effect of HT in women with a baseline elevated risk of breast cancer.⁹ For these women, HT may be recommended after premature surgical menopause due to increased risks for coronary heart disease, osteoporosis, genitourinary syndrome of menopause, and cognitive changes when estrogen is not taken postsurgery through to at least the average age of menopause, considered age 51.^18,19

Marchetti and colleagues reviewed 3 clinical trials that assessed breast cancer events in 1,100 BRCA gene mutation carriers with intact breasts who underwent risk-reducing salpingo-oophorectomy (RRSO) who used or did not use HT.²⁰ For BRCA1 and BRCA2 mutation carriers who received HT after RRSO, no elevated risk of breast cancer risk was seen (HR, 0.98; 95% CI, 0.63–1.52). There was a nonsignificant reduction in breast cancer risk for the estrogen-alone users compared with EPT HT (OR, 0.53; 95% CI, 0.25–1.15). Thus, short-term use of HT, estrogen alone or EPT, does not appear to elevate the risk of breast cancer after RRSO in these high-risk women.

Individualizing HT  for menopausal symptoms

The data presented provide reassuring evidence that longer-term use of ET does not appear to increase breast cancer risk, regardless of the type of estrogen (CEE or estradiol).^4,5,9,11 For women with a uterus, micronized progesterone has less (if any) effect on breast cancer risk. By contrast, the use of synthetic progestins (such as MPA), when combined with estrogen, has been associated with a small but real increased breast cancer risk.

The most evident benefit of HT is in treating vasomotor symptoms and preventing bone loss for those at elevated risk in healthy women without contraindications who initiate systemic HT when younger than age 60 or within 10 years of menopause onset. Benefit and risk ratio depends on age and time from menopause onset when HT is initiated. Hormone therapy safety varies depending on type, dose, duration, route of administration, timing of initiation, and whether, and type, of progestogen is used. Transdermal estradiol, particularly when dosed at 0.05 mg or less, has been shown to have less thrombotic and stroke risk than oral estrogen.²¹

Individualizing treatment includes using the best available evidence to maximize benefits and minimize risks, with periodic reevaluation of benefits and risks of continuing or discontinuing HT or changing to lower doses. ObGyns who follow best practices in prescribing systemic HT can now help menopausal patients with bothersome symptoms take advantage of systemic HT’s benefits while providing reassurance regarding menopausal HT’s safety.¹⁸ Transdermal therapy is a safer option for women at elevated baseline risk of venous thrombosis (for example, obese women) and older patients. Likewise, given its safety with respect to risk of breast cancer, the use of micronized progesterone over synthetic progestins should be considered when prescribing EPT to women with an intact uterus.

Continue to: Benefits of avoiding BSO in women at average risk of ovarian cancer...

Benefits of avoiding BSO in women at average risk of ovarian cancer

Erickson Z, Rocca WA, Smith CY, et al. Time trends in unilateral and bilateral oophorectomy in a geographically defined American population. Obstet Gynecol. 2022;139:724-734. doi: 10.1097/ AOG.0000000000004728.

In 2005, gynecologist William Parker, MD, and colleagues used modeling methodology to assess the long-term risks and benefits of performing bilateral salpingo-oophorectomy (BSO) at the time of hysterectomy for benign disease in women at average risk for ovarian cancer.²³ They concluded that practicing ovarian conservation until age 65 increased women’s long-term survival. Among their findings were that women with BSO before age 55 had an 8.6% excess overall mortality by age 80, while those with oophorectomy before age 59 had 3.9% excess mortality. They noted a sustained, but decreasing, mortality benefit until the age of 75 and stated that at no age did their model suggest higher mortality in women who chose ovarian conservation. Parker and colleagues concluded that ovarian conservation until at least age 65 benefited long-term survival for women at average risk for ovarian cancer when undergoing hysterectomy for benign disease.²³

Certain risks decreased, others increased

A second report in 2009 by Parker and colleagues from the large prospective Nurses’ Health Study found that, while BSO at the time of hysterectomy for benign disease was associated with a decreased risk of breast and ovarian cancer, BSO was associated with an increased risk of all-cause mortality, fatal and nonfatal coronary heart disease, and lung cancer.²⁴ Similar to the findings of the 2005 report, the authors noted that in no analysis or age group was BSO associated with increased survival. They also noted that compared with those who underwent BSO before age 50 and used ET, women with no history of ET use had an approximately 2-fold elevated risk of new onset coronary heart disease (HR, 1.98; 95% CI, 1.18–3.32).²⁴

In 2007, Walter Rocca, MD, a Mayo Clinic neurologist with a particular interest in the epidemiology of dementia, and colleagues at the Mayo Clinic published results of a study that assessed a cohort of women who had undergone unilateral oophorectomy or BSO prior to the onset of menopause.²⁵ The risk of cognitive impairment or dementia was higher in these women compared with women who had intact ovaries (HR, 1.46; 95% CI, 1.13-1.90). Of note, this elevated risk was confined to those who underwent oophorectomy before 49 years of age and were not prescribed estrogen until age 50 or older.²⁵

In a subsequent publication, Rocca and colleagues pointed out that BSO prior to menopause not only is associated with higher rates of all-cause mortality and cognitive impairment but also with coronary heart disease, parkinsonism, osteoporosis, and other chronic conditions associated with aging, including metabolic, mental health, and arthritic disorders.²⁶

Oophorectomy trends tracked

Given these and other reports²⁷ that highlighted the health risks of premenopausal BSO in women at average risk for ovarian cancer, Rocca and colleagues recently assessed trends in the occurrence of unilateral oophorectomy or BSO versus ovarian conservation among all women residing in the Minnesota county (Olmsted) in which Mayo Clinic is located, and who underwent gynecologic surgery between 1950 and 2018.²⁸

The investigators limited their analysis to women who had undergone unilateral oophorectomy or BSO between ages 18 and 49 years (these women are assumed to have been premenopausal). The authors considered as indications for oophorectomy primary or metastatic ovarian cancer, risk-reducing BSO for women at elevated risk for ovarian cancer (for example, strong family history or known BRCA gene mutation), adnexal mass, endometriosis, torsion, and other benign gynecologic conditions that included pelvic pain, abscess, oophoritis, or ectopic pregnancy. When more than 1 indication for ovarian surgery was present, the authors used the most clinically important indication. Unilateral oophorectomy or BSO was considered not indicated if the surgery was performed during another primary procedure (usually hysterectomy) without indication, or if the surgeon referred to the ovarian surgery as elective.

Results. Among 5,154 women who had oophorectomies between 1950 and 2018, the proportion of these women who underwent unilateral oophorectomy and BSO was 40.6% and 59.4%, respectively.

For most years between 1950 and 1979, the incidence of unilateral oophorectomy was higher than BSO. However, from 1980 to 2004, the incidence of BSO increased more than 2-fold while the incidence of unilateral surgery declined. After 2005, however, both types of ovarian surgery declined. During the years 2005–2018, a marked decline in BSO occurred, with the reduced incidence in premenopausal BSO most notable among women undergoing hysterectomy or those without an indication for oophorectomy.

Historically, ObGyns were taught that the benefits of removing normal ovaries (to prevent ovarian cancer) in average-risk women at the time of hysterectomy outweighed the risks. We agree with the authors’ speculation that beginning with Parker’s 2005 publication,²³ ObGyns have become more conservative in performing unindicated BSO in women at average risk for ovarian cancer, now recognizing that the harms of this procedure often outweigh any benefits.²⁸

Women with BRCA1 and BRCA2 gene mutations are at elevated risk for ovarian, tubal, and breast malignancies. In this population, risk-reducing BSO dramatically lowers future risk of ovarian and tubal cancer.

Data addressing the effect of RRSO in BRCA1 and BRCA2 gene mutation carriers continue to be evaluated, with differences between the 2 mutations, but they suggest that the surgery reduces not only ovarian cancer and tubal cancer but also possibly breast cancer.²⁹

Continue to: Trends show decline in ET use in surgically menopausal women... 

Trends show decline in ET use in surgically menopausal women 

Suzuki Y, Huang Y, Melamed A, et al. Use of estrogen therapy after surgical menopause in women who are premenopausal. Obstet Gynecol. 2022;139:756-763. doi: 10.1097/AOG.0000000000004762.

In addition to highlighting the risks associated with premenopausal BSO in women at average risk for ovarian cancer, the reports referred to above also underscore that the use of replacement menopausal HT in premenopausal women who undergo BSO prevents morbidity and mortality that otherwise accompanies surgical menopause. In addition, the North American Menopause Society (NAMS) recommends replacement menopausal HT in the setting of induced early menopause when no contraindications are present.¹⁸

To assess the prevalence of HT use in surgically menopausal women, investigators at Columbia University College of Physicians and Surgeons used a national database that captures health insurance claims for some 280 million US patients, focusing on women aged 18 to 50 years who underwent BSO from 2008 to 2019.³⁰ The great majority of women in this database have private insurance. Although the authors used the term estrogen therapy in their article, this term refers to systemic estrogen alone or with progestogen, as well as vaginal ET (personal communication with Jason Wright, MD, a coauthor of the study, May 19, 2022). In this Update section, we use the term HT to include use of any systemic HT or vaginal estrogen.

Prevalence of HT use changed over time period and patient age range

Among almost 61,980 evaluable women who had undergone BSO (median age, 45 years; 75.1% with concomitant hysterectomy; median follow-up time, 27 months), with no history of gynecologic or breast cancer, HT was used within 3 years of BSO by 64.5%. The highest percentage of women in this cohort who used HT peaked in 2008 (69.5%), declining to 58.2% by 2016. The median duration of HT use was 5.3 months. The prevalence of HT use 3 years after BSO declined with age, from 79.1% in women aged 18–29 to 60.0% in women aged 45–50.³⁰

This report, published in the June 2022 issue of Obstetrics and Gynecology, makes several sobering observations: Many surgically menopausal women aged 50 years and younger are not prescribed HT, the proportion of such women receiving a prescription for HT is declining over time, and the duration of HT use following BSO is short. ●

This year’s Menopause Update focuses on 2 menopause-related issues relevant to ObGyns and our menopausal patients:

• choosing the safest regimens, particularly with respect to risk of breast cancer, when prescribing hormone therapy (HT) to menopausal women
• reviewing the risks and benefits of premenopausal bilateral salpingo-oophorectomy and the pros and cons of replacement HT in surgically menopausal patients.

We hope that you find this updated information useful as you care for menopausal women.

Revisiting menopausal HT  and the risk of breast cancer:  What we know now

Abenhaim HA, Suissa S,  Azoulay L, et al. Menopausal hormone therapy formulation and breast cancer risk. Obstet Gynecol. 2022;139:1103-1110. doi: 10.1097/AOG.0000000000004723.

Reevaluation of the Women’s Health Initiative randomized controlled trials (WHI RCTs), long-term (median follow-up more than 20 years) cumulative  follow-up data, and results from additional studies have suggested that estrogen therapy (ET) alone in menopausal women with prior hysterectomy does not increase the risk of breast cancer. By contrast, estrogen with progestin (synthetic progestogens that include medroxyprogesterone acetate [MPA] and norethindrone acetate) slightly increases the risk of breast cancer. In the past 10 years, several publications have shed light on whether the type of progestogen affects the risk of breast cancer and can help provide evidence-based information to guide clinicians.

Breast cancer risk with combined HT and synthetic progestin

In the first part of the WHI RCT, women were randomly assigned to receive either conjugated equine estrogen (CEE) plus synthetic progestin (MPA) or a placebo. Combined estrogen-progestin therapy (EPT) was associated with a modestly elevated risk of breast cancer.¹ In the second part of the WHI trial, CEE only (estrogen alone, ET) was compared with placebo among women with prior  hysterectomy, with no effect found on breast cancer incidence.²

Most older observational studies published in 2003 to 2005 found that neither CEE nor estradiol appeared to increase the risk of breast cancer when used alone.^3-5 However, estrogen use in combination with synthetic progestins (MPA, norethindrone, levonorgestrel, and norgestrel) has been associated with an increased risk of breast cancer,^4,6 while the elevated risk of breast cancer with micronized progesterone has been less substantial.^7,8

Continue to: Newer data suggest the type of progestogen used affects risk...

In a report published in the June 2022 issue of Obstetrics and Gynecology, Abenhaim and colleagues used a nested population-based case-control study of administrative data available in the UK Clinical Practice Research Datalink and provider prescriptions to evaluate the additive effect on the risk of breast cancer of the type of progestogen (micronized progesterone or synthetic progestins) when combined with estradiol for the treatment of menopausal symptoms.⁹ A cohort of 561,379 women was included in the case-control study (10:1 ratio), 43,183 in the case group (patients diagnosed with invasive breast cancer), and 431,830 in the matched control group.

Overall, in the stratified analysis, a small but significant increase in the risk of breast cancer was found in ever users of menopausal HT (odds ratio [OR], 1.12; 95% confidence interval [CI], 1.09–1.15). Neither estradiol (OR, 1.04; 95% CI, 1.00–1.09) nor CEE (OR, 1.01; 95% CI, 0.96–1.06) was associated with an elevated risk of being diagnosed with invasive breast cancer. Of note, no elevated risk of breast cancer was associated with combination estrogen-progesterone therapy. However, the risk of breast cancer for women who had used synthetic progestins, mostly MPA, was significantly elevated (OR, 1.28; 95% CI, 1.22-1.35). Notably, this modestly elevated odds ratio with the use of estrogen-progestin HT is almost identical to that observed with CEE/ MPA in the WHI.¹ Similar findings were found in women aged 50 to 60 years.

The adjusted analyses from the large WHI RCTs provide additional support: the synthetic progestin MPA combined with CEE showed a higher risk of breast cancer than CEE alone in women with prior hysterectomy.¹⁰

In the long-term follow-up of the WHI RCTs, after a median of 20.3 years postrandomization, prior randomization to CEE alone for postmenopausal women with prior hysterectomy was associated with a significantly lowered risk of breast cancer incidence and mortality.¹¹ By contrast, prior randomization to CEE plus MPA (EPT) for women with an intact uterus was associated with a small but significantly increased incidence of breast cancer but no significant difference in breast cancer mortality.

In the French E3N EPIC population-based prospective cohort study, Fournier and colleagues^4,5 found that women who received estrogen combined with synthetic progestins (mostly MPA) had a higher risk of breast cancer, with an age-adjusted relative risk of 1.4 (95% CI, 1.2–1.7), a finding not seen in women who received estrogen combined with micronized progesterone, similar to findings by Cordina-Duverger and colleagues and Simin and colleagues.^12,13 In the E3N study, only 948 women were identified with breast cancer; 268 of these had used synthetic progestins.^4,5

Both the Abenhaim cohort⁹ and the longterm outcomes of WHI RCT trial data¹¹ found a significant contributing effect of MPA (synthetic progestin) in the risk of breast cancer. Progestogens are not thought to exert a class effect. Although it is clear that progestogens (progesterone or progestins) prevent estrogeninduced endometrial neoplasia when dosed adequately, different types of progestogens have a differential risk of breast epithelium proliferation and carcinogenic potential.¹⁴ A systematic review by Stute and colleagues found that micronized progesterone did not appear to alter mammographic breast density assessments or breast biopsy results.¹⁵

Race considerations

The study by Abenhaim and colleagues was unable to address the issues of race or ethnicity.⁹ However, in the racially diverse WHI trial of women with prior hysterectomy, estrogen-alone use significantly reduced breast cancer incidence in all participants.^10,16 Post hoc analysis of the 1,616 Black women with prior hysterectomy in the WHI RCT showed a significantly decreased breast cancer incidence with use of estrogen alone (hazard ratio [HR], 0.47; 95% CI, 0.26–0.82).¹ When race was evaluated in the long-term cumulative follow-up of the WHI trial, estrogen-alone use significantly reduced breast cancer incidence in Black women, with no adverse effect on coronary heart disease, global index, or all-cause mortality, and with fewer cases of venous thromboembolism.¹⁷ The global index findings were favorable for Black women in their 50s and those with vasomotor symptoms.

Continue to: Impact of HT in women with an elevated risk of breast cancer...

Impact of HT in women with an elevated risk of breast cancer

Abenhaim and colleagues could not evaluate the effect of HT in women with a baseline elevated risk of breast cancer.⁹ For these women, HT may be recommended after premature surgical menopause due to increased risks for coronary heart disease, osteoporosis, genitourinary syndrome of menopause, and cognitive changes when estrogen is not taken postsurgery through to at least the average age of menopause, considered age 51.^18,19

Marchetti and colleagues reviewed 3 clinical trials that assessed breast cancer events in 1,100 BRCA gene mutation carriers with intact breasts who underwent risk-reducing salpingo-oophorectomy (RRSO) who used or did not use HT.²⁰ For BRCA1 and BRCA2 mutation carriers who received HT after RRSO, no elevated risk of breast cancer risk was seen (HR, 0.98; 95% CI, 0.63–1.52). There was a nonsignificant reduction in breast cancer risk for the estrogen-alone users compared with EPT HT (OR, 0.53; 95% CI, 0.25–1.15). Thus, short-term use of HT, estrogen alone or EPT, does not appear to elevate the risk of breast cancer after RRSO in these high-risk women.

Individualizing HT  for menopausal symptoms

The data presented provide reassuring evidence that longer-term use of ET does not appear to increase breast cancer risk, regardless of the type of estrogen (CEE or estradiol).^4,5,9,11 For women with a uterus, micronized progesterone has less (if any) effect on breast cancer risk. By contrast, the use of synthetic progestins (such as MPA), when combined with estrogen, has been associated with a small but real increased breast cancer risk.

The most evident benefit of HT is in treating vasomotor symptoms and preventing bone loss for those at elevated risk in healthy women without contraindications who initiate systemic HT when younger than age 60 or within 10 years of menopause onset. Benefit and risk ratio depends on age and time from menopause onset when HT is initiated. Hormone therapy safety varies depending on type, dose, duration, route of administration, timing of initiation, and whether, and type, of progestogen is used. Transdermal estradiol, particularly when dosed at 0.05 mg or less, has been shown to have less thrombotic and stroke risk than oral estrogen.²¹

Individualizing treatment includes using the best available evidence to maximize benefits and minimize risks, with periodic reevaluation of benefits and risks of continuing or discontinuing HT or changing to lower doses. ObGyns who follow best practices in prescribing systemic HT can now help menopausal patients with bothersome symptoms take advantage of systemic HT’s benefits while providing reassurance regarding menopausal HT’s safety.¹⁸ Transdermal therapy is a safer option for women at elevated baseline risk of venous thrombosis (for example, obese women) and older patients. Likewise, given its safety with respect to risk of breast cancer, the use of micronized progesterone over synthetic progestins should be considered when prescribing EPT to women with an intact uterus.

Continue to: Benefits of avoiding BSO in women at average risk of ovarian cancer...

Benefits of avoiding BSO in women at average risk of ovarian cancer

Erickson Z, Rocca WA, Smith CY, et al. Time trends in unilateral and bilateral oophorectomy in a geographically defined American population. Obstet Gynecol. 2022;139:724-734. doi: 10.1097/ AOG.0000000000004728.

In 2005, gynecologist William Parker, MD, and colleagues used modeling methodology to assess the long-term risks and benefits of performing bilateral salpingo-oophorectomy (BSO) at the time of hysterectomy for benign disease in women at average risk for ovarian cancer.²³ They concluded that practicing ovarian conservation until age 65 increased women’s long-term survival. Among their findings were that women with BSO before age 55 had an 8.6% excess overall mortality by age 80, while those with oophorectomy before age 59 had 3.9% excess mortality. They noted a sustained, but decreasing, mortality benefit until the age of 75 and stated that at no age did their model suggest higher mortality in women who chose ovarian conservation. Parker and colleagues concluded that ovarian conservation until at least age 65 benefited long-term survival for women at average risk for ovarian cancer when undergoing hysterectomy for benign disease.²³

Certain risks decreased, others increased

A second report in 2009 by Parker and colleagues from the large prospective Nurses’ Health Study found that, while BSO at the time of hysterectomy for benign disease was associated with a decreased risk of breast and ovarian cancer, BSO was associated with an increased risk of all-cause mortality, fatal and nonfatal coronary heart disease, and lung cancer.²⁴ Similar to the findings of the 2005 report, the authors noted that in no analysis or age group was BSO associated with increased survival. They also noted that compared with those who underwent BSO before age 50 and used ET, women with no history of ET use had an approximately 2-fold elevated risk of new onset coronary heart disease (HR, 1.98; 95% CI, 1.18–3.32).²⁴

In 2007, Walter Rocca, MD, a Mayo Clinic neurologist with a particular interest in the epidemiology of dementia, and colleagues at the Mayo Clinic published results of a study that assessed a cohort of women who had undergone unilateral oophorectomy or BSO prior to the onset of menopause.²⁵ The risk of cognitive impairment or dementia was higher in these women compared with women who had intact ovaries (HR, 1.46; 95% CI, 1.13-1.90). Of note, this elevated risk was confined to those who underwent oophorectomy before 49 years of age and were not prescribed estrogen until age 50 or older.²⁵

In a subsequent publication, Rocca and colleagues pointed out that BSO prior to menopause not only is associated with higher rates of all-cause mortality and cognitive impairment but also with coronary heart disease, parkinsonism, osteoporosis, and other chronic conditions associated with aging, including metabolic, mental health, and arthritic disorders.²⁶

Oophorectomy trends tracked

Given these and other reports²⁷ that highlighted the health risks of premenopausal BSO in women at average risk for ovarian cancer, Rocca and colleagues recently assessed trends in the occurrence of unilateral oophorectomy or BSO versus ovarian conservation among all women residing in the Minnesota county (Olmsted) in which Mayo Clinic is located, and who underwent gynecologic surgery between 1950 and 2018.²⁸

The investigators limited their analysis to women who had undergone unilateral oophorectomy or BSO between ages 18 and 49 years (these women are assumed to have been premenopausal). The authors considered as indications for oophorectomy primary or metastatic ovarian cancer, risk-reducing BSO for women at elevated risk for ovarian cancer (for example, strong family history or known BRCA gene mutation), adnexal mass, endometriosis, torsion, and other benign gynecologic conditions that included pelvic pain, abscess, oophoritis, or ectopic pregnancy. When more than 1 indication for ovarian surgery was present, the authors used the most clinically important indication. Unilateral oophorectomy or BSO was considered not indicated if the surgery was performed during another primary procedure (usually hysterectomy) without indication, or if the surgeon referred to the ovarian surgery as elective.

Results. Among 5,154 women who had oophorectomies between 1950 and 2018, the proportion of these women who underwent unilateral oophorectomy and BSO was 40.6% and 59.4%, respectively.

For most years between 1950 and 1979, the incidence of unilateral oophorectomy was higher than BSO. However, from 1980 to 2004, the incidence of BSO increased more than 2-fold while the incidence of unilateral surgery declined. After 2005, however, both types of ovarian surgery declined. During the years 2005–2018, a marked decline in BSO occurred, with the reduced incidence in premenopausal BSO most notable among women undergoing hysterectomy or those without an indication for oophorectomy.

Historically, ObGyns were taught that the benefits of removing normal ovaries (to prevent ovarian cancer) in average-risk women at the time of hysterectomy outweighed the risks. We agree with the authors’ speculation that beginning with Parker’s 2005 publication,²³ ObGyns have become more conservative in performing unindicated BSO in women at average risk for ovarian cancer, now recognizing that the harms of this procedure often outweigh any benefits.²⁸

Women with BRCA1 and BRCA2 gene mutations are at elevated risk for ovarian, tubal, and breast malignancies. In this population, risk-reducing BSO dramatically lowers future risk of ovarian and tubal cancer.

Data addressing the effect of RRSO in BRCA1 and BRCA2 gene mutation carriers continue to be evaluated, with differences between the 2 mutations, but they suggest that the surgery reduces not only ovarian cancer and tubal cancer but also possibly breast cancer.²⁹

Continue to: Trends show decline in ET use in surgically menopausal women... 

Trends show decline in ET use in surgically menopausal women 

Suzuki Y, Huang Y, Melamed A, et al. Use of estrogen therapy after surgical menopause in women who are premenopausal. Obstet Gynecol. 2022;139:756-763. doi: 10.1097/AOG.0000000000004762.

In addition to highlighting the risks associated with premenopausal BSO in women at average risk for ovarian cancer, the reports referred to above also underscore that the use of replacement menopausal HT in premenopausal women who undergo BSO prevents morbidity and mortality that otherwise accompanies surgical menopause. In addition, the North American Menopause Society (NAMS) recommends replacement menopausal HT in the setting of induced early menopause when no contraindications are present.¹⁸

To assess the prevalence of HT use in surgically menopausal women, investigators at Columbia University College of Physicians and Surgeons used a national database that captures health insurance claims for some 280 million US patients, focusing on women aged 18 to 50 years who underwent BSO from 2008 to 2019.³⁰ The great majority of women in this database have private insurance. Although the authors used the term estrogen therapy in their article, this term refers to systemic estrogen alone or with progestogen, as well as vaginal ET (personal communication with Jason Wright, MD, a coauthor of the study, May 19, 2022). In this Update section, we use the term HT to include use of any systemic HT or vaginal estrogen.

Prevalence of HT use changed over time period and patient age range

Among almost 61,980 evaluable women who had undergone BSO (median age, 45 years; 75.1% with concomitant hysterectomy; median follow-up time, 27 months), with no history of gynecologic or breast cancer, HT was used within 3 years of BSO by 64.5%. The highest percentage of women in this cohort who used HT peaked in 2008 (69.5%), declining to 58.2% by 2016. The median duration of HT use was 5.3 months. The prevalence of HT use 3 years after BSO declined with age, from 79.1% in women aged 18–29 to 60.0% in women aged 45–50.³⁰

This report, published in the June 2022 issue of Obstetrics and Gynecology, makes several sobering observations: Many surgically menopausal women aged 50 years and younger are not prescribed HT, the proportion of such women receiving a prescription for HT is declining over time, and the duration of HT use following BSO is short. ●

This year’s Menopause Update focuses on 2 menopause-related issues relevant to ObGyns and our menopausal patients:

• choosing the safest regimens, particularly with respect to risk of breast cancer, when prescribing hormone therapy (HT) to menopausal women
• reviewing the risks and benefits of premenopausal bilateral salpingo-oophorectomy and the pros and cons of replacement HT in surgically menopausal patients.

We hope that you find this updated information useful as you care for menopausal women.

Revisiting menopausal HT  and the risk of breast cancer:  What we know now

Abenhaim HA, Suissa S,  Azoulay L, et al. Menopausal hormone therapy formulation and breast cancer risk. Obstet Gynecol. 2022;139:1103-1110. doi: 10.1097/AOG.0000000000004723.

Reevaluation of the Women’s Health Initiative randomized controlled trials (WHI RCTs), long-term (median follow-up more than 20 years) cumulative  follow-up data, and results from additional studies have suggested that estrogen therapy (ET) alone in menopausal women with prior hysterectomy does not increase the risk of breast cancer. By contrast, estrogen with progestin (synthetic progestogens that include medroxyprogesterone acetate [MPA] and norethindrone acetate) slightly increases the risk of breast cancer. In the past 10 years, several publications have shed light on whether the type of progestogen affects the risk of breast cancer and can help provide evidence-based information to guide clinicians.

Breast cancer risk with combined HT and synthetic progestin

In the first part of the WHI RCT, women were randomly assigned to receive either conjugated equine estrogen (CEE) plus synthetic progestin (MPA) or a placebo. Combined estrogen-progestin therapy (EPT) was associated with a modestly elevated risk of breast cancer.¹ In the second part of the WHI trial, CEE only (estrogen alone, ET) was compared with placebo among women with prior  hysterectomy, with no effect found on breast cancer incidence.²

Most older observational studies published in 2003 to 2005 found that neither CEE nor estradiol appeared to increase the risk of breast cancer when used alone.^3-5 However, estrogen use in combination with synthetic progestins (MPA, norethindrone, levonorgestrel, and norgestrel) has been associated with an increased risk of breast cancer,^4,6 while the elevated risk of breast cancer with micronized progesterone has been less substantial.^7,8

Continue to: Newer data suggest the type of progestogen used affects risk...

In a report published in the June 2022 issue of Obstetrics and Gynecology, Abenhaim and colleagues used a nested population-based case-control study of administrative data available in the UK Clinical Practice Research Datalink and provider prescriptions to evaluate the additive effect on the risk of breast cancer of the type of progestogen (micronized progesterone or synthetic progestins) when combined with estradiol for the treatment of menopausal symptoms.⁹ A cohort of 561,379 women was included in the case-control study (10:1 ratio), 43,183 in the case group (patients diagnosed with invasive breast cancer), and 431,830 in the matched control group.

Overall, in the stratified analysis, a small but significant increase in the risk of breast cancer was found in ever users of menopausal HT (odds ratio [OR], 1.12; 95% confidence interval [CI], 1.09–1.15). Neither estradiol (OR, 1.04; 95% CI, 1.00–1.09) nor CEE (OR, 1.01; 95% CI, 0.96–1.06) was associated with an elevated risk of being diagnosed with invasive breast cancer. Of note, no elevated risk of breast cancer was associated with combination estrogen-progesterone therapy. However, the risk of breast cancer for women who had used synthetic progestins, mostly MPA, was significantly elevated (OR, 1.28; 95% CI, 1.22-1.35). Notably, this modestly elevated odds ratio with the use of estrogen-progestin HT is almost identical to that observed with CEE/ MPA in the WHI.¹ Similar findings were found in women aged 50 to 60 years.

The adjusted analyses from the large WHI RCTs provide additional support: the synthetic progestin MPA combined with CEE showed a higher risk of breast cancer than CEE alone in women with prior hysterectomy.¹⁰

In the long-term follow-up of the WHI RCTs, after a median of 20.3 years postrandomization, prior randomization to CEE alone for postmenopausal women with prior hysterectomy was associated with a significantly lowered risk of breast cancer incidence and mortality.¹¹ By contrast, prior randomization to CEE plus MPA (EPT) for women with an intact uterus was associated with a small but significantly increased incidence of breast cancer but no significant difference in breast cancer mortality.

In the French E3N EPIC population-based prospective cohort study, Fournier and colleagues^4,5 found that women who received estrogen combined with synthetic progestins (mostly MPA) had a higher risk of breast cancer, with an age-adjusted relative risk of 1.4 (95% CI, 1.2–1.7), a finding not seen in women who received estrogen combined with micronized progesterone, similar to findings by Cordina-Duverger and colleagues and Simin and colleagues.^12,13 In the E3N study, only 948 women were identified with breast cancer; 268 of these had used synthetic progestins.^4,5

Both the Abenhaim cohort⁹ and the longterm outcomes of WHI RCT trial data¹¹ found a significant contributing effect of MPA (synthetic progestin) in the risk of breast cancer. Progestogens are not thought to exert a class effect. Although it is clear that progestogens (progesterone or progestins) prevent estrogeninduced endometrial neoplasia when dosed adequately, different types of progestogens have a differential risk of breast epithelium proliferation and carcinogenic potential.¹⁴ A systematic review by Stute and colleagues found that micronized progesterone did not appear to alter mammographic breast density assessments or breast biopsy results.¹⁵

Race considerations

The study by Abenhaim and colleagues was unable to address the issues of race or ethnicity.⁹ However, in the racially diverse WHI trial of women with prior hysterectomy, estrogen-alone use significantly reduced breast cancer incidence in all participants.^10,16 Post hoc analysis of the 1,616 Black women with prior hysterectomy in the WHI RCT showed a significantly decreased breast cancer incidence with use of estrogen alone (hazard ratio [HR], 0.47; 95% CI, 0.26–0.82).¹ When race was evaluated in the long-term cumulative follow-up of the WHI trial, estrogen-alone use significantly reduced breast cancer incidence in Black women, with no adverse effect on coronary heart disease, global index, or all-cause mortality, and with fewer cases of venous thromboembolism.¹⁷ The global index findings were favorable for Black women in their 50s and those with vasomotor symptoms.

Continue to: Impact of HT in women with an elevated risk of breast cancer...

Impact of HT in women with an elevated risk of breast cancer

Abenhaim and colleagues could not evaluate the effect of HT in women with a baseline elevated risk of breast cancer.⁹ For these women, HT may be recommended after premature surgical menopause due to increased risks for coronary heart disease, osteoporosis, genitourinary syndrome of menopause, and cognitive changes when estrogen is not taken postsurgery through to at least the average age of menopause, considered age 51.^18,19

Marchetti and colleagues reviewed 3 clinical trials that assessed breast cancer events in 1,100 BRCA gene mutation carriers with intact breasts who underwent risk-reducing salpingo-oophorectomy (RRSO) who used or did not use HT.²⁰ For BRCA1 and BRCA2 mutation carriers who received HT after RRSO, no elevated risk of breast cancer risk was seen (HR, 0.98; 95% CI, 0.63–1.52). There was a nonsignificant reduction in breast cancer risk for the estrogen-alone users compared with EPT HT (OR, 0.53; 95% CI, 0.25–1.15). Thus, short-term use of HT, estrogen alone or EPT, does not appear to elevate the risk of breast cancer after RRSO in these high-risk women.

Individualizing HT  for menopausal symptoms

The data presented provide reassuring evidence that longer-term use of ET does not appear to increase breast cancer risk, regardless of the type of estrogen (CEE or estradiol).^4,5,9,11 For women with a uterus, micronized progesterone has less (if any) effect on breast cancer risk. By contrast, the use of synthetic progestins (such as MPA), when combined with estrogen, has been associated with a small but real increased breast cancer risk.

The most evident benefit of HT is in treating vasomotor symptoms and preventing bone loss for those at elevated risk in healthy women without contraindications who initiate systemic HT when younger than age 60 or within 10 years of menopause onset. Benefit and risk ratio depends on age and time from menopause onset when HT is initiated. Hormone therapy safety varies depending on type, dose, duration, route of administration, timing of initiation, and whether, and type, of progestogen is used. Transdermal estradiol, particularly when dosed at 0.05 mg or less, has been shown to have less thrombotic and stroke risk than oral estrogen.²¹

Individualizing treatment includes using the best available evidence to maximize benefits and minimize risks, with periodic reevaluation of benefits and risks of continuing or discontinuing HT or changing to lower doses. ObGyns who follow best practices in prescribing systemic HT can now help menopausal patients with bothersome symptoms take advantage of systemic HT’s benefits while providing reassurance regarding menopausal HT’s safety.¹⁸ Transdermal therapy is a safer option for women at elevated baseline risk of venous thrombosis (for example, obese women) and older patients. Likewise, given its safety with respect to risk of breast cancer, the use of micronized progesterone over synthetic progestins should be considered when prescribing EPT to women with an intact uterus.

Continue to: Benefits of avoiding BSO in women at average risk of ovarian cancer...

Benefits of avoiding BSO in women at average risk of ovarian cancer

Erickson Z, Rocca WA, Smith CY, et al. Time trends in unilateral and bilateral oophorectomy in a geographically defined American population. Obstet Gynecol. 2022;139:724-734. doi: 10.1097/ AOG.0000000000004728.

In 2005, gynecologist William Parker, MD, and colleagues used modeling methodology to assess the long-term risks and benefits of performing bilateral salpingo-oophorectomy (BSO) at the time of hysterectomy for benign disease in women at average risk for ovarian cancer.²³ They concluded that practicing ovarian conservation until age 65 increased women’s long-term survival. Among their findings were that women with BSO before age 55 had an 8.6% excess overall mortality by age 80, while those with oophorectomy before age 59 had 3.9% excess mortality. They noted a sustained, but decreasing, mortality benefit until the age of 75 and stated that at no age did their model suggest higher mortality in women who chose ovarian conservation. Parker and colleagues concluded that ovarian conservation until at least age 65 benefited long-term survival for women at average risk for ovarian cancer when undergoing hysterectomy for benign disease.²³

Certain risks decreased, others increased

A second report in 2009 by Parker and colleagues from the large prospective Nurses’ Health Study found that, while BSO at the time of hysterectomy for benign disease was associated with a decreased risk of breast and ovarian cancer, BSO was associated with an increased risk of all-cause mortality, fatal and nonfatal coronary heart disease, and lung cancer.²⁴ Similar to the findings of the 2005 report, the authors noted that in no analysis or age group was BSO associated with increased survival. They also noted that compared with those who underwent BSO before age 50 and used ET, women with no history of ET use had an approximately 2-fold elevated risk of new onset coronary heart disease (HR, 1.98; 95% CI, 1.18–3.32).²⁴

In 2007, Walter Rocca, MD, a Mayo Clinic neurologist with a particular interest in the epidemiology of dementia, and colleagues at the Mayo Clinic published results of a study that assessed a cohort of women who had undergone unilateral oophorectomy or BSO prior to the onset of menopause.²⁵ The risk of cognitive impairment or dementia was higher in these women compared with women who had intact ovaries (HR, 1.46; 95% CI, 1.13-1.90). Of note, this elevated risk was confined to those who underwent oophorectomy before 49 years of age and were not prescribed estrogen until age 50 or older.²⁵

In a subsequent publication, Rocca and colleagues pointed out that BSO prior to menopause not only is associated with higher rates of all-cause mortality and cognitive impairment but also with coronary heart disease, parkinsonism, osteoporosis, and other chronic conditions associated with aging, including metabolic, mental health, and arthritic disorders.²⁶

Oophorectomy trends tracked

Given these and other reports²⁷ that highlighted the health risks of premenopausal BSO in women at average risk for ovarian cancer, Rocca and colleagues recently assessed trends in the occurrence of unilateral oophorectomy or BSO versus ovarian conservation among all women residing in the Minnesota county (Olmsted) in which Mayo Clinic is located, and who underwent gynecologic surgery between 1950 and 2018.²⁸

The investigators limited their analysis to women who had undergone unilateral oophorectomy or BSO between ages 18 and 49 years (these women are assumed to have been premenopausal). The authors considered as indications for oophorectomy primary or metastatic ovarian cancer, risk-reducing BSO for women at elevated risk for ovarian cancer (for example, strong family history or known BRCA gene mutation), adnexal mass, endometriosis, torsion, and other benign gynecologic conditions that included pelvic pain, abscess, oophoritis, or ectopic pregnancy. When more than 1 indication for ovarian surgery was present, the authors used the most clinically important indication. Unilateral oophorectomy or BSO was considered not indicated if the surgery was performed during another primary procedure (usually hysterectomy) without indication, or if the surgeon referred to the ovarian surgery as elective.

Results. Among 5,154 women who had oophorectomies between 1950 and 2018, the proportion of these women who underwent unilateral oophorectomy and BSO was 40.6% and 59.4%, respectively.

For most years between 1950 and 1979, the incidence of unilateral oophorectomy was higher than BSO. However, from 1980 to 2004, the incidence of BSO increased more than 2-fold while the incidence of unilateral surgery declined. After 2005, however, both types of ovarian surgery declined. During the years 2005–2018, a marked decline in BSO occurred, with the reduced incidence in premenopausal BSO most notable among women undergoing hysterectomy or those without an indication for oophorectomy.

Historically, ObGyns were taught that the benefits of removing normal ovaries (to prevent ovarian cancer) in average-risk women at the time of hysterectomy outweighed the risks. We agree with the authors’ speculation that beginning with Parker’s 2005 publication,²³ ObGyns have become more conservative in performing unindicated BSO in women at average risk for ovarian cancer, now recognizing that the harms of this procedure often outweigh any benefits.²⁸

Women with BRCA1 and BRCA2 gene mutations are at elevated risk for ovarian, tubal, and breast malignancies. In this population, risk-reducing BSO dramatically lowers future risk of ovarian and tubal cancer.

Data addressing the effect of RRSO in BRCA1 and BRCA2 gene mutation carriers continue to be evaluated, with differences between the 2 mutations, but they suggest that the surgery reduces not only ovarian cancer and tubal cancer but also possibly breast cancer.²⁹

Continue to: Trends show decline in ET use in surgically menopausal women... 

Trends show decline in ET use in surgically menopausal women 

Suzuki Y, Huang Y, Melamed A, et al. Use of estrogen therapy after surgical menopause in women who are premenopausal. Obstet Gynecol. 2022;139:756-763. doi: 10.1097/AOG.0000000000004762.

In addition to highlighting the risks associated with premenopausal BSO in women at average risk for ovarian cancer, the reports referred to above also underscore that the use of replacement menopausal HT in premenopausal women who undergo BSO prevents morbidity and mortality that otherwise accompanies surgical menopause. In addition, the North American Menopause Society (NAMS) recommends replacement menopausal HT in the setting of induced early menopause when no contraindications are present.¹⁸

To assess the prevalence of HT use in surgically menopausal women, investigators at Columbia University College of Physicians and Surgeons used a national database that captures health insurance claims for some 280 million US patients, focusing on women aged 18 to 50 years who underwent BSO from 2008 to 2019.³⁰ The great majority of women in this database have private insurance. Although the authors used the term estrogen therapy in their article, this term refers to systemic estrogen alone or with progestogen, as well as vaginal ET (personal communication with Jason Wright, MD, a coauthor of the study, May 19, 2022). In this Update section, we use the term HT to include use of any systemic HT or vaginal estrogen.

Prevalence of HT use changed over time period and patient age range

Among almost 61,980 evaluable women who had undergone BSO (median age, 45 years; 75.1% with concomitant hysterectomy; median follow-up time, 27 months), with no history of gynecologic or breast cancer, HT was used within 3 years of BSO by 64.5%. The highest percentage of women in this cohort who used HT peaked in 2008 (69.5%), declining to 58.2% by 2016. The median duration of HT use was 5.3 months. The prevalence of HT use 3 years after BSO declined with age, from 79.1% in women aged 18–29 to 60.0% in women aged 45–50.³⁰

This report, published in the June 2022 issue of Obstetrics and Gynecology, makes several sobering observations: Many surgically menopausal women aged 50 years and younger are not prescribed HT, the proportion of such women receiving a prescription for HT is declining over time, and the duration of HT use following BSO is short. ●