Kathy Blackwell is not going to allow a couple of aching joints stop her from living her best life.
 

The 73-year-old resident of Simi Valley, Calif., a bedroom community about 30 miles northwest of downtown Los Angeles, organizes regular activities for her group of seniors. The 20- to 30-member-strong band of seasoned citizens, mostly women, keep active. Over the coming weeks, they plan to catch the Beach Boys at the historic Hollywood Bowl and take a cruise to Alaska. 

The busy schedule is why Ms. Blackwell intends to delay her second hip replacement surgery, opting instead for a cortisone shot in hopes of easing the pain enough to enjoy the upcoming excursions.

Not that she is shy about joint replacement. If her orthopedic surgeon offered a frequent customer punch card like the ones you get at the local coffee shop, hers would be nearly full. Ms. Blackwell’s knees and a hip have been replaced, and her other hip will be, too, once her calendar clears up.

“If you go on enough with chronic pain where there’s no relief, you get cranky,” Ms. Blackwell said.
 

More than 1 million new knees, hips

Joint replacements are getting more common, with about 790,000 total knee replacements and more than 450,000 hip replacements performed annually in the United States, according to the American College of Rheumatology.

Experts agree age is not a factor when considering candidates for joint replacement. Rafael Sierra, MD, of the Mayo Clinic, Rochester, Minn., said he’s done hip replacements on patients as young as 12 and as old as 102. Orthopedic surgeon John Wang, MD, of the Hospital for Special Surgery, New York, has performed a total knee arthroscopy on a patient in their mid-90s. At 73, Ms. Blackwell is on the older side of the average age of 66 for a hip replacement.

“A lot of research and studies have shown that no matter what the age ranges, people end up doing great,” Dr. Wang said.

More importantly than age, older patients should be prepared for postsurgery therapy and treatment. For younger patients, the biggest drawback is outliving the estimated 25-year life span of a joint replacement. Complications are rare and occur in about 2% of procedures. These include infection, dislocation of the joint, and blood clots; other health issues you also have are not a factor.

Considering Ms. Blackwell’s hard time with her first knee replacement, it’s no small wonder that she ever set foot in a surgeon’s office again.

After putting it off for 7 years, Ms. Blackwell finally agreed to her doctor’s advice to replace her left knee in 2017 to relieve what she described as a “grinding,” chronic, bone-on-bone pain.

“It got to the point where there were no alternatives,” she said.

But her first orthopedic surgeon did a “lousy job,” leaving her with a gaping, festering wound that resulted in sepsis and required wound vacuum therapy to close the lesion. She eventually found another surgeon who removed and cleaned up her artificial knee before replacing the prosthesis. Luckily, the sepsis didn’t spread, and eight surgeries later, she was in the clear.

Ms. Blackwell’s second knee replacement in 2018 was a textbook surgery, as was a hip replacement in late 2019 .

“Your whole attitude changes,” she said.
 

What generalists should know

Orthopedic surgeons recommend that primary care doctors ask two things when weighing joint replacements: Have they exhausted nonsurgical treatments, and is the pain intolerable? They also advise avoiding narcotics to treat the symptoms.

The top issue to consider for a primary care doctor when weighing whether their patient may be a candidate for joint replacement is if the pain and the imaging are bad enough to warrant surgery.

“You don’t want to do it too soon,” Dr. Sierra said.

Dr. Sierra likes to tell the story of the golfer whose knee stiffens after playing 18 holes. To those patients, he recommends dialing back the activity; in this case, using a cart or playing only nine holes.

Dr. Wang agrees, asking if the pain is “lifestyle altering” and if the patient was unresponsive to nonsurgical treatments such as over-the-counter medications, anti-inflammatory medication and shots, home exercises or physical therapy, wearing a brace or sleeve, or simply changing their activity.

And no addictive pain pills to treat arthritis that can lead to other serious issues.

“This is not going to heal itself,” Dr. Wang said. “It’s not going to improve on its own. So, we don’t want to throw narcotics at it just to cover it up.”

Karen Smith, MD, has been a family doctor in rural North Carolina for more than 30 years. When she sees patients complaining about their joints, she first looks at function and pain. From there, she explores why they’re having discomfort. For example, is the problem an ergonomic issue at work or the result of carrying a lot of body weight?

“We look at those areas to determine what can be modified,” she said. “All of that’s done even before we get to having the orthopedic involvement.”

Dr. Smith said she also considers things beyond basic medicine: What is the patient’s mental status and tolerance for pain? Do they have a support system at home for post-operative care? And can they afford to miss work?

“We look at all of those factors together because that is going to determine the outcome that we’re hoping to achieve,” Dr. Smith said.
 

Great expectations

A recent study shows that older patients respond better to knee replacements than younger patients, particularly with pain relief and quality of life. The reason for this is believed to boil down to expectations. Whereas a younger person may want to return to the racquetball court and perform like they used to, older patients may just wish to walk down the hall without discomfort.

“It’s possible that these under 55-age-old patients may just take a little longer to heal to be satisfied,” Dr. Wang said. “We really can’t speak to why this is happening, but it’s possible that the younger patients are more active, and they expect more out of their knee.”

Jeevan Sall, MD, is a primary care sports medicine doctor with Providence Mission Heritage Medical Group in Laguna Niguel, Calif. He first discusses conservative management for patients struggling with arthritis in their joints. These measures include rehabilitation exercises, braces, shoe inserts, medication, and weight loss efforts. If these steps don’t improve a patient’s pain or lifestyle, surgery is on the table. Managing expectations is a significant factor.

“Is the patient mentally ready for surgery?” Dr. Sall said. “This includes what they hope to achieve with surgery as well as the risk and benefits of the procedure.”

Ms. Blackwell’s hip and knee pain came simply from a life well lived, with no marathon running or life-changing accident to speak of. She worked as a housewife raising her two children and owned an elevator company with her late husband, Robert Blackwell.

Yes, the elevator construction business has jokes.

“We have our ups and downs,” Ms. Blackwell said.

And with her new joints, so does she.

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

Kathy Blackwell is not going to allow a couple of aching joints stop her from living her best life.
 

The 73-year-old resident of Simi Valley, Calif., a bedroom community about 30 miles northwest of downtown Los Angeles, organizes regular activities for her group of seniors. The 20- to 30-member-strong band of seasoned citizens, mostly women, keep active. Over the coming weeks, they plan to catch the Beach Boys at the historic Hollywood Bowl and take a cruise to Alaska. 

The busy schedule is why Ms. Blackwell intends to delay her second hip replacement surgery, opting instead for a cortisone shot in hopes of easing the pain enough to enjoy the upcoming excursions.

Not that she is shy about joint replacement. If her orthopedic surgeon offered a frequent customer punch card like the ones you get at the local coffee shop, hers would be nearly full. Ms. Blackwell’s knees and a hip have been replaced, and her other hip will be, too, once her calendar clears up.

“If you go on enough with chronic pain where there’s no relief, you get cranky,” Ms. Blackwell said.
 

More than 1 million new knees, hips

Joint replacements are getting more common, with about 790,000 total knee replacements and more than 450,000 hip replacements performed annually in the United States, according to the American College of Rheumatology.

Experts agree age is not a factor when considering candidates for joint replacement. Rafael Sierra, MD, of the Mayo Clinic, Rochester, Minn., said he’s done hip replacements on patients as young as 12 and as old as 102. Orthopedic surgeon John Wang, MD, of the Hospital for Special Surgery, New York, has performed a total knee arthroscopy on a patient in their mid-90s. At 73, Ms. Blackwell is on the older side of the average age of 66 for a hip replacement.

“A lot of research and studies have shown that no matter what the age ranges, people end up doing great,” Dr. Wang said.

More importantly than age, older patients should be prepared for postsurgery therapy and treatment. For younger patients, the biggest drawback is outliving the estimated 25-year life span of a joint replacement. Complications are rare and occur in about 2% of procedures. These include infection, dislocation of the joint, and blood clots; other health issues you also have are not a factor.

Considering Ms. Blackwell’s hard time with her first knee replacement, it’s no small wonder that she ever set foot in a surgeon’s office again.

After putting it off for 7 years, Ms. Blackwell finally agreed to her doctor’s advice to replace her left knee in 2017 to relieve what she described as a “grinding,” chronic, bone-on-bone pain.

“It got to the point where there were no alternatives,” she said.

But her first orthopedic surgeon did a “lousy job,” leaving her with a gaping, festering wound that resulted in sepsis and required wound vacuum therapy to close the lesion. She eventually found another surgeon who removed and cleaned up her artificial knee before replacing the prosthesis. Luckily, the sepsis didn’t spread, and eight surgeries later, she was in the clear.

Ms. Blackwell’s second knee replacement in 2018 was a textbook surgery, as was a hip replacement in late 2019 .

“Your whole attitude changes,” she said.
 

What generalists should know

Orthopedic surgeons recommend that primary care doctors ask two things when weighing joint replacements: Have they exhausted nonsurgical treatments, and is the pain intolerable? They also advise avoiding narcotics to treat the symptoms.

The top issue to consider for a primary care doctor when weighing whether their patient may be a candidate for joint replacement is if the pain and the imaging are bad enough to warrant surgery.

“You don’t want to do it too soon,” Dr. Sierra said.

Dr. Sierra likes to tell the story of the golfer whose knee stiffens after playing 18 holes. To those patients, he recommends dialing back the activity; in this case, using a cart or playing only nine holes.

Dr. Wang agrees, asking if the pain is “lifestyle altering” and if the patient was unresponsive to nonsurgical treatments such as over-the-counter medications, anti-inflammatory medication and shots, home exercises or physical therapy, wearing a brace or sleeve, or simply changing their activity.

And no addictive pain pills to treat arthritis that can lead to other serious issues.

“This is not going to heal itself,” Dr. Wang said. “It’s not going to improve on its own. So, we don’t want to throw narcotics at it just to cover it up.”

Karen Smith, MD, has been a family doctor in rural North Carolina for more than 30 years. When she sees patients complaining about their joints, she first looks at function and pain. From there, she explores why they’re having discomfort. For example, is the problem an ergonomic issue at work or the result of carrying a lot of body weight?

“We look at those areas to determine what can be modified,” she said. “All of that’s done even before we get to having the orthopedic involvement.”

Dr. Smith said she also considers things beyond basic medicine: What is the patient’s mental status and tolerance for pain? Do they have a support system at home for post-operative care? And can they afford to miss work?

“We look at all of those factors together because that is going to determine the outcome that we’re hoping to achieve,” Dr. Smith said.
 

Great expectations

A recent study shows that older patients respond better to knee replacements than younger patients, particularly with pain relief and quality of life. The reason for this is believed to boil down to expectations. Whereas a younger person may want to return to the racquetball court and perform like they used to, older patients may just wish to walk down the hall without discomfort.

“It’s possible that these under 55-age-old patients may just take a little longer to heal to be satisfied,” Dr. Wang said. “We really can’t speak to why this is happening, but it’s possible that the younger patients are more active, and they expect more out of their knee.”

Jeevan Sall, MD, is a primary care sports medicine doctor with Providence Mission Heritage Medical Group in Laguna Niguel, Calif. He first discusses conservative management for patients struggling with arthritis in their joints. These measures include rehabilitation exercises, braces, shoe inserts, medication, and weight loss efforts. If these steps don’t improve a patient’s pain or lifestyle, surgery is on the table. Managing expectations is a significant factor.

“Is the patient mentally ready for surgery?” Dr. Sall said. “This includes what they hope to achieve with surgery as well as the risk and benefits of the procedure.”

Ms. Blackwell’s hip and knee pain came simply from a life well lived, with no marathon running or life-changing accident to speak of. She worked as a housewife raising her two children and owned an elevator company with her late husband, Robert Blackwell.

Yes, the elevator construction business has jokes.

“We have our ups and downs,” Ms. Blackwell said.

And with her new joints, so does she.

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

Kathy Blackwell is not going to allow a couple of aching joints stop her from living her best life.
 

The 73-year-old resident of Simi Valley, Calif., a bedroom community about 30 miles northwest of downtown Los Angeles, organizes regular activities for her group of seniors. The 20- to 30-member-strong band of seasoned citizens, mostly women, keep active. Over the coming weeks, they plan to catch the Beach Boys at the historic Hollywood Bowl and take a cruise to Alaska. 

The busy schedule is why Ms. Blackwell intends to delay her second hip replacement surgery, opting instead for a cortisone shot in hopes of easing the pain enough to enjoy the upcoming excursions.

Not that she is shy about joint replacement. If her orthopedic surgeon offered a frequent customer punch card like the ones you get at the local coffee shop, hers would be nearly full. Ms. Blackwell’s knees and a hip have been replaced, and her other hip will be, too, once her calendar clears up.

“If you go on enough with chronic pain where there’s no relief, you get cranky,” Ms. Blackwell said.
 

More than 1 million new knees, hips

Joint replacements are getting more common, with about 790,000 total knee replacements and more than 450,000 hip replacements performed annually in the United States, according to the American College of Rheumatology.

Experts agree age is not a factor when considering candidates for joint replacement. Rafael Sierra, MD, of the Mayo Clinic, Rochester, Minn., said he’s done hip replacements on patients as young as 12 and as old as 102. Orthopedic surgeon John Wang, MD, of the Hospital for Special Surgery, New York, has performed a total knee arthroscopy on a patient in their mid-90s. At 73, Ms. Blackwell is on the older side of the average age of 66 for a hip replacement.

“A lot of research and studies have shown that no matter what the age ranges, people end up doing great,” Dr. Wang said.

More importantly than age, older patients should be prepared for postsurgery therapy and treatment. For younger patients, the biggest drawback is outliving the estimated 25-year life span of a joint replacement. Complications are rare and occur in about 2% of procedures. These include infection, dislocation of the joint, and blood clots; other health issues you also have are not a factor.

Considering Ms. Blackwell’s hard time with her first knee replacement, it’s no small wonder that she ever set foot in a surgeon’s office again.

After putting it off for 7 years, Ms. Blackwell finally agreed to her doctor’s advice to replace her left knee in 2017 to relieve what she described as a “grinding,” chronic, bone-on-bone pain.

“It got to the point where there were no alternatives,” she said.

But her first orthopedic surgeon did a “lousy job,” leaving her with a gaping, festering wound that resulted in sepsis and required wound vacuum therapy to close the lesion. She eventually found another surgeon who removed and cleaned up her artificial knee before replacing the prosthesis. Luckily, the sepsis didn’t spread, and eight surgeries later, she was in the clear.

Ms. Blackwell’s second knee replacement in 2018 was a textbook surgery, as was a hip replacement in late 2019 .

“Your whole attitude changes,” she said.
 

What generalists should know

Orthopedic surgeons recommend that primary care doctors ask two things when weighing joint replacements: Have they exhausted nonsurgical treatments, and is the pain intolerable? They also advise avoiding narcotics to treat the symptoms.

The top issue to consider for a primary care doctor when weighing whether their patient may be a candidate for joint replacement is if the pain and the imaging are bad enough to warrant surgery.

“You don’t want to do it too soon,” Dr. Sierra said.

Dr. Sierra likes to tell the story of the golfer whose knee stiffens after playing 18 holes. To those patients, he recommends dialing back the activity; in this case, using a cart or playing only nine holes.

Dr. Wang agrees, asking if the pain is “lifestyle altering” and if the patient was unresponsive to nonsurgical treatments such as over-the-counter medications, anti-inflammatory medication and shots, home exercises or physical therapy, wearing a brace or sleeve, or simply changing their activity.

And no addictive pain pills to treat arthritis that can lead to other serious issues.

“This is not going to heal itself,” Dr. Wang said. “It’s not going to improve on its own. So, we don’t want to throw narcotics at it just to cover it up.”

Karen Smith, MD, has been a family doctor in rural North Carolina for more than 30 years. When she sees patients complaining about their joints, she first looks at function and pain. From there, she explores why they’re having discomfort. For example, is the problem an ergonomic issue at work or the result of carrying a lot of body weight?

“We look at those areas to determine what can be modified,” she said. “All of that’s done even before we get to having the orthopedic involvement.”

Dr. Smith said she also considers things beyond basic medicine: What is the patient’s mental status and tolerance for pain? Do they have a support system at home for post-operative care? And can they afford to miss work?

“We look at all of those factors together because that is going to determine the outcome that we’re hoping to achieve,” Dr. Smith said.
 

Great expectations

A recent study shows that older patients respond better to knee replacements than younger patients, particularly with pain relief and quality of life. The reason for this is believed to boil down to expectations. Whereas a younger person may want to return to the racquetball court and perform like they used to, older patients may just wish to walk down the hall without discomfort.

“It’s possible that these under 55-age-old patients may just take a little longer to heal to be satisfied,” Dr. Wang said. “We really can’t speak to why this is happening, but it’s possible that the younger patients are more active, and they expect more out of their knee.”

Jeevan Sall, MD, is a primary care sports medicine doctor with Providence Mission Heritage Medical Group in Laguna Niguel, Calif. He first discusses conservative management for patients struggling with arthritis in their joints. These measures include rehabilitation exercises, braces, shoe inserts, medication, and weight loss efforts. If these steps don’t improve a patient’s pain or lifestyle, surgery is on the table. Managing expectations is a significant factor.

“Is the patient mentally ready for surgery?” Dr. Sall said. “This includes what they hope to achieve with surgery as well as the risk and benefits of the procedure.”

Ms. Blackwell’s hip and knee pain came simply from a life well lived, with no marathon running or life-changing accident to speak of. She worked as a housewife raising her two children and owned an elevator company with her late husband, Robert Blackwell.

Yes, the elevator construction business has jokes.

“We have our ups and downs,” Ms. Blackwell said.

And with her new joints, so does she.

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

Micronized oral progesterone might decrease night sweats and improve sleep in perimenopausal women, according to new research.

In a randomized, placebo-controlled trial of about 180 women with vasomotor symptoms (VMS), women who received progesterone perceived a significantly greater decrease in night sweats (P = .023) and improved sleep quality (P = .005), compared with controls. VMS score did not differ significantly by treatment group, however.

“Women who have menstruated within the last year, who are waking twice or more times a week with night sweats and bothered by sleep disturbances would benefit from taking oral micronized progesterone 300 mg at bedtime,” principal investigator Jerilynn C. Prior, MD, professor of endocrinology at the University of British Columbia in Vancouver, British Columbia, Canada, said in an interview.

The study was published online in Scientific Reports.
 

A neglected group?

The best management for symptoms in perimenopause is an often-neglected topic of research, said Dr. Prior. Yet perimenopause is often associated with significant symptoms for women, including heavy menstrual bleeding, sore breasts, mood swings, night sweats, and insomnia – all when many women are at the peak of their careers.

Dr. Prior herself had a difficult perimenopause. “I began having cyclic night sweats, clustered around flow, when I was still having regular menstrual cycles, plus breast tenderness and sleep problems,” she said. “I knew from my research and my own experience that my estrogen levels were very high. Higher estrogen levels are not suppressible by exogenous estrogen, so it made no sense to me to ask my family doctor for a prescription for estrogen – or hormone replacement therapy, as it was then called. However, medroxyprogesterone acetate had been reported to be effective for menopausal hot flushes. I tried it, and it helped my night sweats and hot flushes but not my sleep. When oral micronized progesterone became available, I switched to that.”

In the current study, which was performed at the UBC Centre for Menstrual Cycle and Ovulation Research, the investigators studied 189 community-dwelling women from across Canada who were aged 35-58 years, had menstruated in the past year, and were bothered by daytime flushes or night sweats at least twice per week.

Participants were randomly assigned to receive either 300 mg of oral micronized progesterone or placebo at bedtime for 3 months. They recorded VMS number and intensity while awake and asleep each day. Some women participated remotely by web conference, telephone, or email. The experimental medicine was delivered to these participants by courier. The primary outcome was VMS score during the 3rd month.

Most (87%) participants were White, and about 57% had a college degree. The population’s average body mass index was 26.7, and 66.7% of participants were in late perimenopause.

The mean baseline VMS score among the women was 12.2. The average frequency of VMS per 24-hour day was 4.9. Average VMS intensity was 2.3 on a scale of 0-4. VMS scores decreased over time in both treatment groups.

At month 3, the VMS score was 5.5 in the progesterone group and 7.1 in the placebo group. The difference between groups was not statistically significant.

Compared with controls, however, women in the progesterone group perceived a significantly greater decrease in night sweats and improved sleep quality. Progesterone also was associated with significantly decreased perception of physical and emotional interference with their daily activities, compared with placebo (P = .017). Moreover, progesterone did not increase depression.

There were no serious adverse events.

“I hope that when women who look young and are still menstruating in their late 30s to early 50s go to the doctor and ask for help with night sweats and sleep problems, they will be told about this trial and offered progesterone therapy. I also hope they won’t be told, ‘You are too young,’ or ‘You are not in menopause,’ with the inference that the issue is all in their minds,” said Dr. Prior.
 

Useful dosing information

Mitchell S. Kramer, MD, chair of obstetrics and gynecology at Huntington (N.Y.) Hospital Northwell Health, said in a comment that “progesterone has been used for quite a while. I’ve been treating menopausal and perimenopausal hormonal disturbances and VMS for many years, and progesterone has been a real staple of treatment for these symptoms, especially in perimenopausal patients who are not good candidates for estrogen or who won’t accept treatment with estrogen. It’s actually nice to see a study that addresses this issue in a randomized controlled fashion and that confirms the efficacy of progesterone.”

The most helpful aspect of the study is the dosing information, Dr. Kramer added. “They recommend a 300-mg dose of oral micronized progesterone, which is much higher than I normally use. I may start to prescribe the higher dose and perhaps get a better or more complete response. There were no adverse events reported in this study, so the higher dose was enlightening to me,” he said.

Perimenopause is a time that is challenging to manage, said Michelle Jacobson, MD, of the department of obstetrics and gynecology at the University of Toronto, and obstetrician-gynecologist at Women’s College and Mount Sinai Hospitals in Toronto.

“There are so many nuances to the management. Women are suffering oftentimes from classic menopausal symptoms. There are fluctuating levels of estrogen, sometimes high. Sometimes there are complications of bleeding. There is the potential need for contraception because they are still menstruating,” she said in an interview.

“It’s important to specifically study this group of women with their own unique needs. Dr. Prior is a longtime proponent of using progesterone therapy, and kudos to her for doing this study in perimenopausal women, which is a group that is probably underrepresented in the menopause management literature,” she said.

Dr. Prior and Dr. Kramer reported no relevant financial relationships. Dr. Jacobson reported financial relationships with Astellas, AbbVie, Bayer, BioSyent, Duchesnay, Eisai, Lupin, Organon, Pfizer, and Searchlight.

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

Micronized oral progesterone might decrease night sweats and improve sleep in perimenopausal women, according to new research.

In a randomized, placebo-controlled trial of about 180 women with vasomotor symptoms (VMS), women who received progesterone perceived a significantly greater decrease in night sweats (P = .023) and improved sleep quality (P = .005), compared with controls. VMS score did not differ significantly by treatment group, however.

“Women who have menstruated within the last year, who are waking twice or more times a week with night sweats and bothered by sleep disturbances would benefit from taking oral micronized progesterone 300 mg at bedtime,” principal investigator Jerilynn C. Prior, MD, professor of endocrinology at the University of British Columbia in Vancouver, British Columbia, Canada, said in an interview.

The study was published online in Scientific Reports.
 

A neglected group?

The best management for symptoms in perimenopause is an often-neglected topic of research, said Dr. Prior. Yet perimenopause is often associated with significant symptoms for women, including heavy menstrual bleeding, sore breasts, mood swings, night sweats, and insomnia – all when many women are at the peak of their careers.

Dr. Prior herself had a difficult perimenopause. “I began having cyclic night sweats, clustered around flow, when I was still having regular menstrual cycles, plus breast tenderness and sleep problems,” she said. “I knew from my research and my own experience that my estrogen levels were very high. Higher estrogen levels are not suppressible by exogenous estrogen, so it made no sense to me to ask my family doctor for a prescription for estrogen – or hormone replacement therapy, as it was then called. However, medroxyprogesterone acetate had been reported to be effective for menopausal hot flushes. I tried it, and it helped my night sweats and hot flushes but not my sleep. When oral micronized progesterone became available, I switched to that.”

In the current study, which was performed at the UBC Centre for Menstrual Cycle and Ovulation Research, the investigators studied 189 community-dwelling women from across Canada who were aged 35-58 years, had menstruated in the past year, and were bothered by daytime flushes or night sweats at least twice per week.

Participants were randomly assigned to receive either 300 mg of oral micronized progesterone or placebo at bedtime for 3 months. They recorded VMS number and intensity while awake and asleep each day. Some women participated remotely by web conference, telephone, or email. The experimental medicine was delivered to these participants by courier. The primary outcome was VMS score during the 3rd month.

Most (87%) participants were White, and about 57% had a college degree. The population’s average body mass index was 26.7, and 66.7% of participants were in late perimenopause.

The mean baseline VMS score among the women was 12.2. The average frequency of VMS per 24-hour day was 4.9. Average VMS intensity was 2.3 on a scale of 0-4. VMS scores decreased over time in both treatment groups.

At month 3, the VMS score was 5.5 in the progesterone group and 7.1 in the placebo group. The difference between groups was not statistically significant.

Compared with controls, however, women in the progesterone group perceived a significantly greater decrease in night sweats and improved sleep quality. Progesterone also was associated with significantly decreased perception of physical and emotional interference with their daily activities, compared with placebo (P = .017). Moreover, progesterone did not increase depression.

There were no serious adverse events.

“I hope that when women who look young and are still menstruating in their late 30s to early 50s go to the doctor and ask for help with night sweats and sleep problems, they will be told about this trial and offered progesterone therapy. I also hope they won’t be told, ‘You are too young,’ or ‘You are not in menopause,’ with the inference that the issue is all in their minds,” said Dr. Prior.
 

Useful dosing information

Mitchell S. Kramer, MD, chair of obstetrics and gynecology at Huntington (N.Y.) Hospital Northwell Health, said in a comment that “progesterone has been used for quite a while. I’ve been treating menopausal and perimenopausal hormonal disturbances and VMS for many years, and progesterone has been a real staple of treatment for these symptoms, especially in perimenopausal patients who are not good candidates for estrogen or who won’t accept treatment with estrogen. It’s actually nice to see a study that addresses this issue in a randomized controlled fashion and that confirms the efficacy of progesterone.”

The most helpful aspect of the study is the dosing information, Dr. Kramer added. “They recommend a 300-mg dose of oral micronized progesterone, which is much higher than I normally use. I may start to prescribe the higher dose and perhaps get a better or more complete response. There were no adverse events reported in this study, so the higher dose was enlightening to me,” he said.

Perimenopause is a time that is challenging to manage, said Michelle Jacobson, MD, of the department of obstetrics and gynecology at the University of Toronto, and obstetrician-gynecologist at Women’s College and Mount Sinai Hospitals in Toronto.

“There are so many nuances to the management. Women are suffering oftentimes from classic menopausal symptoms. There are fluctuating levels of estrogen, sometimes high. Sometimes there are complications of bleeding. There is the potential need for contraception because they are still menstruating,” she said in an interview.

“It’s important to specifically study this group of women with their own unique needs. Dr. Prior is a longtime proponent of using progesterone therapy, and kudos to her for doing this study in perimenopausal women, which is a group that is probably underrepresented in the menopause management literature,” she said.

Dr. Prior and Dr. Kramer reported no relevant financial relationships. Dr. Jacobson reported financial relationships with Astellas, AbbVie, Bayer, BioSyent, Duchesnay, Eisai, Lupin, Organon, Pfizer, and Searchlight.

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

Micronized oral progesterone might decrease night sweats and improve sleep in perimenopausal women, according to new research.

In a randomized, placebo-controlled trial of about 180 women with vasomotor symptoms (VMS), women who received progesterone perceived a significantly greater decrease in night sweats (P = .023) and improved sleep quality (P = .005), compared with controls. VMS score did not differ significantly by treatment group, however.

“Women who have menstruated within the last year, who are waking twice or more times a week with night sweats and bothered by sleep disturbances would benefit from taking oral micronized progesterone 300 mg at bedtime,” principal investigator Jerilynn C. Prior, MD, professor of endocrinology at the University of British Columbia in Vancouver, British Columbia, Canada, said in an interview.

The study was published online in Scientific Reports.
 

A neglected group?

The best management for symptoms in perimenopause is an often-neglected topic of research, said Dr. Prior. Yet perimenopause is often associated with significant symptoms for women, including heavy menstrual bleeding, sore breasts, mood swings, night sweats, and insomnia – all when many women are at the peak of their careers.

Dr. Prior herself had a difficult perimenopause. “I began having cyclic night sweats, clustered around flow, when I was still having regular menstrual cycles, plus breast tenderness and sleep problems,” she said. “I knew from my research and my own experience that my estrogen levels were very high. Higher estrogen levels are not suppressible by exogenous estrogen, so it made no sense to me to ask my family doctor for a prescription for estrogen – or hormone replacement therapy, as it was then called. However, medroxyprogesterone acetate had been reported to be effective for menopausal hot flushes. I tried it, and it helped my night sweats and hot flushes but not my sleep. When oral micronized progesterone became available, I switched to that.”

In the current study, which was performed at the UBC Centre for Menstrual Cycle and Ovulation Research, the investigators studied 189 community-dwelling women from across Canada who were aged 35-58 years, had menstruated in the past year, and were bothered by daytime flushes or night sweats at least twice per week.

Participants were randomly assigned to receive either 300 mg of oral micronized progesterone or placebo at bedtime for 3 months. They recorded VMS number and intensity while awake and asleep each day. Some women participated remotely by web conference, telephone, or email. The experimental medicine was delivered to these participants by courier. The primary outcome was VMS score during the 3rd month.

Most (87%) participants were White, and about 57% had a college degree. The population’s average body mass index was 26.7, and 66.7% of participants were in late perimenopause.

The mean baseline VMS score among the women was 12.2. The average frequency of VMS per 24-hour day was 4.9. Average VMS intensity was 2.3 on a scale of 0-4. VMS scores decreased over time in both treatment groups.

At month 3, the VMS score was 5.5 in the progesterone group and 7.1 in the placebo group. The difference between groups was not statistically significant.

Compared with controls, however, women in the progesterone group perceived a significantly greater decrease in night sweats and improved sleep quality. Progesterone also was associated with significantly decreased perception of physical and emotional interference with their daily activities, compared with placebo (P = .017). Moreover, progesterone did not increase depression.

There were no serious adverse events.

“I hope that when women who look young and are still menstruating in their late 30s to early 50s go to the doctor and ask for help with night sweats and sleep problems, they will be told about this trial and offered progesterone therapy. I also hope they won’t be told, ‘You are too young,’ or ‘You are not in menopause,’ with the inference that the issue is all in their minds,” said Dr. Prior.
 

Useful dosing information

Mitchell S. Kramer, MD, chair of obstetrics and gynecology at Huntington (N.Y.) Hospital Northwell Health, said in a comment that “progesterone has been used for quite a while. I’ve been treating menopausal and perimenopausal hormonal disturbances and VMS for many years, and progesterone has been a real staple of treatment for these symptoms, especially in perimenopausal patients who are not good candidates for estrogen or who won’t accept treatment with estrogen. It’s actually nice to see a study that addresses this issue in a randomized controlled fashion and that confirms the efficacy of progesterone.”

The most helpful aspect of the study is the dosing information, Dr. Kramer added. “They recommend a 300-mg dose of oral micronized progesterone, which is much higher than I normally use. I may start to prescribe the higher dose and perhaps get a better or more complete response. There were no adverse events reported in this study, so the higher dose was enlightening to me,” he said.

Perimenopause is a time that is challenging to manage, said Michelle Jacobson, MD, of the department of obstetrics and gynecology at the University of Toronto, and obstetrician-gynecologist at Women’s College and Mount Sinai Hospitals in Toronto.

“There are so many nuances to the management. Women are suffering oftentimes from classic menopausal symptoms. There are fluctuating levels of estrogen, sometimes high. Sometimes there are complications of bleeding. There is the potential need for contraception because they are still menstruating,” she said in an interview.

“It’s important to specifically study this group of women with their own unique needs. Dr. Prior is a longtime proponent of using progesterone therapy, and kudos to her for doing this study in perimenopausal women, which is a group that is probably underrepresented in the menopause management literature,” she said.

Dr. Prior and Dr. Kramer reported no relevant financial relationships. Dr. Jacobson reported financial relationships with Astellas, AbbVie, Bayer, BioSyent, Duchesnay, Eisai, Lupin, Organon, Pfizer, and Searchlight.

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

The history and findings in this case are suggestive of late-onset familial AD (onset after age 65 years).

AD is a common neurodegenerative disease associated with progressive impairment of behavioral and cognitive functions, including memory, comprehension, language, attention, reasoning, and judgment. In 2020, 5.8 million Americans were living with AD. By 2050, this number is projected to increase to 13.9 million people, or almost 3.3% of the US population. Globally, 152 million people are projected to have AD and other dementias by 2050. The worldwide increase in incidence and prevalence of AD is at least partially explained by an aging population and increased life expectancy. 

The cause of AD remains unclear, but there is substantial evidence that AD is a highly heritable disorder. Familial AD is characterized by having more than one member in more than one generation with AD. The autosomal-dominant form of AD is linked to mutations in three genes: AAP on chromosome 21, PSEN1 on chromosome 14, and PSEN2 on chromosome 1. APP mutations may cause increased generation and aggregation of beta-amyloid peptide, whereas PSEN1 and PSEN2 mutations result in aggregation of beta-amyloid by interfering with the processing of gamma-secretase.

APOE is another genetic marker that increases the risk for AD. Isoform e4 of the APOE gene (located on chromosome 19) has been associated with more sporadic and familial forms of AD that present after age 65 years. Approximately 50% of individuals carrying one APOEe4 develop AD, and 90% of individuals who have two alleles develop AD. Variants in the gene for the sortilin receptor, SORT1, have also been found in familial and sporadic forms of AD.

The cognitive and behavioral impairment associated with AD significantly affects a patient's social and occupational functioning. Insidiously progressive memory loss is a characteristic symptoms seen in patients presenting with AD. As the disease advances over the course of several years, other areas of cognition are impaired. Patients may develop language disorders (eg, anomic aphasia or anomia) and impairment in visuospatial skills and executive functions. A slow progression of behavioral changes may also occur in individuals with AD.

Clinical criteria for the diagnosis of AD (eg, insidious onset of cognitive impairment, clear history of worsening symptoms) have been developed and are often used to diagnose patients. In addition, biomarker evidence may help to increase the diagnostic certainty. Several cerebrospinal fluid and blood biomarkers have shown excellent diagnostic ability by identifying tau pathology and cerebral amyloid-beta for AD.

Neuroimaging is becoming increasingly important for identifying the underlying causes of cognitive impairment. Currently, MRI is considered the preferred neuroimaging modality for AD because it allows for accurate measurement of the three-dimensional volume of brain structures, particularly the size of the hippocampus and related regions. CT can be used when MRI is not available or is contraindicated, such as in a patient with a pacemaker. PET is another noninvasive method for depicting tau pathology deposition and distribution in patients with cognitive impairment. In 2020, US Food and Drug Administration approved the first tau PET tracer, ¹⁸F-flortaucipir, which marked a significant achievement to improve AD diagnosis. 

At present, the only therapies available for AD are symptomatic therapies. Cholinesterase inhibitors and a partial N-methyl-D-aspartate antagonist are the standard medical treatments for AD. Antiamyloid therapies are also available for patients with mild cognitive impairment or mild dementia. These include aducanumab, a first-in-class amyloid-beta–directed antibody that was approved in 2021, and lecanemab, another amyloid-beta–directed antibody that was approved in 2023. Both aducanumab and lecanemab are recommended for the treatment of patients with mild cognitive impairment or mild dementia stage of disease, the population in which the safety and efficacy of these newer agents were demonstrated in clinical trials. 

Secondary symptoms of AD, such as depression, agitation, aggression, hallucinations, delusions, and/or sleep disorders, can be treated with psychotropic agents. Behavioral interventions including patient-centered approaches and caregiver training can also be helpful for managing the cognitive and behavioral manifestations of AD, often in combination with pharmacologic interventions (eg, anxiolytics for anxiety and agitation, neuroleptics for delusions or hallucinations, and antidepressants or mood stabilizers for mood disorders). Regular physical activity and exercise may also play a role in delaying AD progression and possibly conferring a protective effect on brain health. 

Jasvinder Chawla, MD, Professor of Neurology, Loyola University Medical Center, Maywood; Director, Clinical Neurophysiology Lab, Department of Neurology, Hines VA Hospital, Hines, IL.

Jasvinder Chawla, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
 

The history and findings in this case are suggestive of late-onset familial AD (onset after age 65 years).

AD is a common neurodegenerative disease associated with progressive impairment of behavioral and cognitive functions, including memory, comprehension, language, attention, reasoning, and judgment. In 2020, 5.8 million Americans were living with AD. By 2050, this number is projected to increase to 13.9 million people, or almost 3.3% of the US population. Globally, 152 million people are projected to have AD and other dementias by 2050. The worldwide increase in incidence and prevalence of AD is at least partially explained by an aging population and increased life expectancy. 

The cause of AD remains unclear, but there is substantial evidence that AD is a highly heritable disorder. Familial AD is characterized by having more than one member in more than one generation with AD. The autosomal-dominant form of AD is linked to mutations in three genes: AAP on chromosome 21, PSEN1 on chromosome 14, and PSEN2 on chromosome 1. APP mutations may cause increased generation and aggregation of beta-amyloid peptide, whereas PSEN1 and PSEN2 mutations result in aggregation of beta-amyloid by interfering with the processing of gamma-secretase.

APOE is another genetic marker that increases the risk for AD. Isoform e4 of the APOE gene (located on chromosome 19) has been associated with more sporadic and familial forms of AD that present after age 65 years. Approximately 50% of individuals carrying one APOEe4 develop AD, and 90% of individuals who have two alleles develop AD. Variants in the gene for the sortilin receptor, SORT1, have also been found in familial and sporadic forms of AD.

The cognitive and behavioral impairment associated with AD significantly affects a patient's social and occupational functioning. Insidiously progressive memory loss is a characteristic symptoms seen in patients presenting with AD. As the disease advances over the course of several years, other areas of cognition are impaired. Patients may develop language disorders (eg, anomic aphasia or anomia) and impairment in visuospatial skills and executive functions. A slow progression of behavioral changes may also occur in individuals with AD.

Clinical criteria for the diagnosis of AD (eg, insidious onset of cognitive impairment, clear history of worsening symptoms) have been developed and are often used to diagnose patients. In addition, biomarker evidence may help to increase the diagnostic certainty. Several cerebrospinal fluid and blood biomarkers have shown excellent diagnostic ability by identifying tau pathology and cerebral amyloid-beta for AD.

Neuroimaging is becoming increasingly important for identifying the underlying causes of cognitive impairment. Currently, MRI is considered the preferred neuroimaging modality for AD because it allows for accurate measurement of the three-dimensional volume of brain structures, particularly the size of the hippocampus and related regions. CT can be used when MRI is not available or is contraindicated, such as in a patient with a pacemaker. PET is another noninvasive method for depicting tau pathology deposition and distribution in patients with cognitive impairment. In 2020, US Food and Drug Administration approved the first tau PET tracer, ¹⁸F-flortaucipir, which marked a significant achievement to improve AD diagnosis. 

At present, the only therapies available for AD are symptomatic therapies. Cholinesterase inhibitors and a partial N-methyl-D-aspartate antagonist are the standard medical treatments for AD. Antiamyloid therapies are also available for patients with mild cognitive impairment or mild dementia. These include aducanumab, a first-in-class amyloid-beta–directed antibody that was approved in 2021, and lecanemab, another amyloid-beta–directed antibody that was approved in 2023. Both aducanumab and lecanemab are recommended for the treatment of patients with mild cognitive impairment or mild dementia stage of disease, the population in which the safety and efficacy of these newer agents were demonstrated in clinical trials. 

Secondary symptoms of AD, such as depression, agitation, aggression, hallucinations, delusions, and/or sleep disorders, can be treated with psychotropic agents. Behavioral interventions including patient-centered approaches and caregiver training can also be helpful for managing the cognitive and behavioral manifestations of AD, often in combination with pharmacologic interventions (eg, anxiolytics for anxiety and agitation, neuroleptics for delusions or hallucinations, and antidepressants or mood stabilizers for mood disorders). Regular physical activity and exercise may also play a role in delaying AD progression and possibly conferring a protective effect on brain health. 

Jasvinder Chawla, MD, Professor of Neurology, Loyola University Medical Center, Maywood; Director, Clinical Neurophysiology Lab, Department of Neurology, Hines VA Hospital, Hines, IL.

Jasvinder Chawla, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
 

The history and findings in this case are suggestive of late-onset familial AD (onset after age 65 years).

AD is a common neurodegenerative disease associated with progressive impairment of behavioral and cognitive functions, including memory, comprehension, language, attention, reasoning, and judgment. In 2020, 5.8 million Americans were living with AD. By 2050, this number is projected to increase to 13.9 million people, or almost 3.3% of the US population. Globally, 152 million people are projected to have AD and other dementias by 2050. The worldwide increase in incidence and prevalence of AD is at least partially explained by an aging population and increased life expectancy. 

The cause of AD remains unclear, but there is substantial evidence that AD is a highly heritable disorder. Familial AD is characterized by having more than one member in more than one generation with AD. The autosomal-dominant form of AD is linked to mutations in three genes: AAP on chromosome 21, PSEN1 on chromosome 14, and PSEN2 on chromosome 1. APP mutations may cause increased generation and aggregation of beta-amyloid peptide, whereas PSEN1 and PSEN2 mutations result in aggregation of beta-amyloid by interfering with the processing of gamma-secretase.

APOE is another genetic marker that increases the risk for AD. Isoform e4 of the APOE gene (located on chromosome 19) has been associated with more sporadic and familial forms of AD that present after age 65 years. Approximately 50% of individuals carrying one APOEe4 develop AD, and 90% of individuals who have two alleles develop AD. Variants in the gene for the sortilin receptor, SORT1, have also been found in familial and sporadic forms of AD.

The cognitive and behavioral impairment associated with AD significantly affects a patient's social and occupational functioning. Insidiously progressive memory loss is a characteristic symptoms seen in patients presenting with AD. As the disease advances over the course of several years, other areas of cognition are impaired. Patients may develop language disorders (eg, anomic aphasia or anomia) and impairment in visuospatial skills and executive functions. A slow progression of behavioral changes may also occur in individuals with AD.

Clinical criteria for the diagnosis of AD (eg, insidious onset of cognitive impairment, clear history of worsening symptoms) have been developed and are often used to diagnose patients. In addition, biomarker evidence may help to increase the diagnostic certainty. Several cerebrospinal fluid and blood biomarkers have shown excellent diagnostic ability by identifying tau pathology and cerebral amyloid-beta for AD.

Neuroimaging is becoming increasingly important for identifying the underlying causes of cognitive impairment. Currently, MRI is considered the preferred neuroimaging modality for AD because it allows for accurate measurement of the three-dimensional volume of brain structures, particularly the size of the hippocampus and related regions. CT can be used when MRI is not available or is contraindicated, such as in a patient with a pacemaker. PET is another noninvasive method for depicting tau pathology deposition and distribution in patients with cognitive impairment. In 2020, US Food and Drug Administration approved the first tau PET tracer, ¹⁸F-flortaucipir, which marked a significant achievement to improve AD diagnosis. 

At present, the only therapies available for AD are symptomatic therapies. Cholinesterase inhibitors and a partial N-methyl-D-aspartate antagonist are the standard medical treatments for AD. Antiamyloid therapies are also available for patients with mild cognitive impairment or mild dementia. These include aducanumab, a first-in-class amyloid-beta–directed antibody that was approved in 2021, and lecanemab, another amyloid-beta–directed antibody that was approved in 2023. Both aducanumab and lecanemab are recommended for the treatment of patients with mild cognitive impairment or mild dementia stage of disease, the population in which the safety and efficacy of these newer agents were demonstrated in clinical trials. 

Secondary symptoms of AD, such as depression, agitation, aggression, hallucinations, delusions, and/or sleep disorders, can be treated with psychotropic agents. Behavioral interventions including patient-centered approaches and caregiver training can also be helpful for managing the cognitive and behavioral manifestations of AD, often in combination with pharmacologic interventions (eg, anxiolytics for anxiety and agitation, neuroleptics for delusions or hallucinations, and antidepressants or mood stabilizers for mood disorders). Regular physical activity and exercise may also play a role in delaying AD progression and possibly conferring a protective effect on brain health. 

Jasvinder Chawla, MD, Professor of Neurology, Loyola University Medical Center, Maywood; Director, Clinical Neurophysiology Lab, Department of Neurology, Hines VA Hospital, Hines, IL.

Jasvinder Chawla, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
 

The COVID-19 vaccines have been a game changer for millions of people worldwide in preventing death or disability from the virus. Research suggests that they offer significant protection against long COVID.

Studies have consistently found that these vaccines prevent the new onset of long COVID as well as flare-ups for people who already have the condition.

False and unfounded claims made by some antivaccine groups that the vaccines themselves may cause long COVID persist and serve as barriers to vaccination.

To help separate the facts from falsehoods, here’s a checklist for doctors on what scientific studies have determined about vaccination and long COVID.
 

What the research shows

Doctors who work in long COVID clinics have for years suspected that vaccination may help protect against the development of long COVID, noted Lawrence Purpura, MD, MPH, an infectious disease specialist at New York–Presbyterian/Columbia University Irving Medical Center, who treats patients with long COVID in his clinic.

Over the past year, several large, well-conducted studies have borne out that theory, including the following studies:

• In the RECOVER study, published in May in the journal Nature Communications, researchers examined the electronic health records of more than 5 million people who had been diagnosed with COVID and found that vaccination reduced the risk that they would develop long COVID. Although the researchers didn’t compare the effects of having boosters to being fully vaccinated without them, experts have suggested that having a full round of recommended shots may offer the most protection. “My thoughts are that more shots are better, and other work has shown compelling evidence that the protective effect of vaccination on COVID-19 wanes over time,” said study coauthor Daniel Brannock, MS, a research scientist at RTI International in Research Triangle Park, N.C. “It stands to reason that the same is true for long COVID.”
• A review published in February in BMJ Medicine concluded that 10 studies showed a significant reduction in the incidence of long COVID among vaccinated patients. Even one dose of a vaccine was protective.
• A meta-analysis of six studies published last December in Antimicrobial Stewardship and Healthcare Epidemiology found that one or more doses of a COVID-19 vaccine were 29% effective in preventing symptoms of long COVID.
• In a June meta-analysis published in JAMA Internal Medicine, researchers analyzed more than 40 studies that included 860,000 patients and found that two doses of a COVID-19 vaccine reduced the risk of long COVID by almost half.

The message? COVID vaccination is very effective in reducing the risk of long COVID.

“It’s important to emphasize that many of the risk factors [for long COVID] cannot be changed, or at least cannot be changed easily, but vaccination is a decision that can be taken by everyone,” said Vassilios Vassiliou, MBBS, PhD, clinical professor of cardiac medicine at Norwich Medical School in England, who coauthored the article in JAMA Internal Medicine.
 

Why vaccines may be protective

The COVID-19 vaccines work well to prevent serious illness from the virus, noted Aaron Friedberg, MD, clinical coleader of the Post COVID Recovery Program at the Ohio State University Wexner Medical Center. That may be a clue to why the vaccines help prevent long COVID symptoms.

“When you get COVID and you’ve been vaccinated, the virus may still attach in your nose and respiratory tract, but it’s less likely to spread throughout your body,” he explained. “It’s like a forest fire – if the ground is wet or it starts to rain, it’s less likely to create a great blaze. As a result, your body is less likely to experience inflammation and damage that makes it more likely that you’ll develop long COVID.”

Dr. Friedberg stressed that even for patients who have had COVID, it’s important to get vaccinated – a message he consistently delivers to his own patients.

“There is some protection that comes from having COVID before, but for some people, that’s not enough,” he said. “It’s true that after infection, your body creates antibodies that help protect you against the virus. But I explain to patients that these may be like old Velcro: They barely grab on enough to stay on for the moment, but they don’t last long term. You’re much more likely to get a reliable immune response from the vaccine.”

In addition, a second or third bout of COVID could be the one that gives patients long COVID, Dr. Friedberg adds.

“I have a number of patients in my clinic who were fine after their first bout of COVID but experienced debilitating long COVID symptoms after they developed COVID again,” he said. “Why leave it to chance?”
 

Vaccines and ‘long vax’

The COVID vaccines are considered very safe but have been linked to very rare side effects, such as blood clots and heart inflammation. There have also been anecdotal reports of symptoms that resemble long COVID – a syndrome that has come to be known as “long Vax” – an extremely rare condition that may or may not be tied to vaccination.

“I have seen people in my clinic who developed symptoms suggestive of long COVID that linger for months – brain fog, fatigue, heart palpitations – soon after they got the COVID-19 vaccine,” said Dr. Purpura. But no published studies have suggested a link, he cautions.

A study called LISTEN is being organized at Yale in an effort to better understand postvaccine adverse events and a potential link to long COVID.
 

Talking to patients

Discussions of vaccination with patients, including those with COVID or long COVID, are often fraught and challenging, said Dr. Purpura.

“There’s a lot of fear that they will have a worsening of their symptoms,” he explained. The conversation he has with his patients mirrors the conversation all physicians should have with their patients about COVID-19 vaccination, even if they don’t have long COVID. He stresses the importance of highlighting the following components:

• Show compassion and empathy. “A lot of people have strongly held opinions – it’s worth it to try to find out why they feel the way that they do,” said Dr. Friedberg.
• Walk them through side effects. “Many people are afraid of the side effects of the vaccine, especially if they already have long COVID,” explained Dr. Purpura. Such patients can be asked how they felt after their last vaccination, such a shingles or flu shot. Then explain that the COVID-19 vaccine is not much different and that they may experience temporary side effects such as fatigue, headache, or a mild fever for 24-48 hours.
• Explain the benefits. Eighty-five percent of people say their health care provider is a trusted source of information on COVID-19 vaccines, according to the Kaiser Family Foundation. That trust is conducive to talks about the vaccine’s benefits, including its ability to protect against long COVID.

Other ways to reduce risk of long COVID

Vaccines can lower the chances of a patient’s developing long COVID. So can the antiviral medication nirmatrelvir (Paxlovid). A March 2023 study published in JAMA Internal Medicine included more than 280,000 people with COVID. The researchers found that vaccination reduced the risk for developing the condition by about 25%.

“I mention that study to all of my long COVID patients who become reinfected with the virus,” said Dr. Purpura. “It not only appears protective against long COVID, but since it lowers levels of virus circulating in their body, it seems to help prevent a flare-up of symptoms.”

Another treatment that may help is the diabetes drug metformin, he added.

A June 2023 study published in The Lancet Infectious Diseases found that when metformin was given within 3 days of symptom onset, the incidence of long COVID was reduced by about 41%.

“We’re still trying to wrap our brains around this one, but the thought is it may help to lower inflammation, which plays a role in long COVID,” Dr. Purpura explained. More studies need to be conducted, though, before recommending its use.

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

The COVID-19 vaccines have been a game changer for millions of people worldwide in preventing death or disability from the virus. Research suggests that they offer significant protection against long COVID.

Studies have consistently found that these vaccines prevent the new onset of long COVID as well as flare-ups for people who already have the condition.

False and unfounded claims made by some antivaccine groups that the vaccines themselves may cause long COVID persist and serve as barriers to vaccination.

To help separate the facts from falsehoods, here’s a checklist for doctors on what scientific studies have determined about vaccination and long COVID.
 

What the research shows

Doctors who work in long COVID clinics have for years suspected that vaccination may help protect against the development of long COVID, noted Lawrence Purpura, MD, MPH, an infectious disease specialist at New York–Presbyterian/Columbia University Irving Medical Center, who treats patients with long COVID in his clinic.

Over the past year, several large, well-conducted studies have borne out that theory, including the following studies:

• In the RECOVER study, published in May in the journal Nature Communications, researchers examined the electronic health records of more than 5 million people who had been diagnosed with COVID and found that vaccination reduced the risk that they would develop long COVID. Although the researchers didn’t compare the effects of having boosters to being fully vaccinated without them, experts have suggested that having a full round of recommended shots may offer the most protection. “My thoughts are that more shots are better, and other work has shown compelling evidence that the protective effect of vaccination on COVID-19 wanes over time,” said study coauthor Daniel Brannock, MS, a research scientist at RTI International in Research Triangle Park, N.C. “It stands to reason that the same is true for long COVID.”
• A review published in February in BMJ Medicine concluded that 10 studies showed a significant reduction in the incidence of long COVID among vaccinated patients. Even one dose of a vaccine was protective.
• A meta-analysis of six studies published last December in Antimicrobial Stewardship and Healthcare Epidemiology found that one or more doses of a COVID-19 vaccine were 29% effective in preventing symptoms of long COVID.
• In a June meta-analysis published in JAMA Internal Medicine, researchers analyzed more than 40 studies that included 860,000 patients and found that two doses of a COVID-19 vaccine reduced the risk of long COVID by almost half.

The message? COVID vaccination is very effective in reducing the risk of long COVID.

“It’s important to emphasize that many of the risk factors [for long COVID] cannot be changed, or at least cannot be changed easily, but vaccination is a decision that can be taken by everyone,” said Vassilios Vassiliou, MBBS, PhD, clinical professor of cardiac medicine at Norwich Medical School in England, who coauthored the article in JAMA Internal Medicine.
 

Why vaccines may be protective

The COVID-19 vaccines work well to prevent serious illness from the virus, noted Aaron Friedberg, MD, clinical coleader of the Post COVID Recovery Program at the Ohio State University Wexner Medical Center. That may be a clue to why the vaccines help prevent long COVID symptoms.

“When you get COVID and you’ve been vaccinated, the virus may still attach in your nose and respiratory tract, but it’s less likely to spread throughout your body,” he explained. “It’s like a forest fire – if the ground is wet or it starts to rain, it’s less likely to create a great blaze. As a result, your body is less likely to experience inflammation and damage that makes it more likely that you’ll develop long COVID.”

Dr. Friedberg stressed that even for patients who have had COVID, it’s important to get vaccinated – a message he consistently delivers to his own patients.

“There is some protection that comes from having COVID before, but for some people, that’s not enough,” he said. “It’s true that after infection, your body creates antibodies that help protect you against the virus. But I explain to patients that these may be like old Velcro: They barely grab on enough to stay on for the moment, but they don’t last long term. You’re much more likely to get a reliable immune response from the vaccine.”

In addition, a second or third bout of COVID could be the one that gives patients long COVID, Dr. Friedberg adds.

“I have a number of patients in my clinic who were fine after their first bout of COVID but experienced debilitating long COVID symptoms after they developed COVID again,” he said. “Why leave it to chance?”
 

Vaccines and ‘long vax’

The COVID vaccines are considered very safe but have been linked to very rare side effects, such as blood clots and heart inflammation. There have also been anecdotal reports of symptoms that resemble long COVID – a syndrome that has come to be known as “long Vax” – an extremely rare condition that may or may not be tied to vaccination.

“I have seen people in my clinic who developed symptoms suggestive of long COVID that linger for months – brain fog, fatigue, heart palpitations – soon after they got the COVID-19 vaccine,” said Dr. Purpura. But no published studies have suggested a link, he cautions.

A study called LISTEN is being organized at Yale in an effort to better understand postvaccine adverse events and a potential link to long COVID.
 

Talking to patients

Discussions of vaccination with patients, including those with COVID or long COVID, are often fraught and challenging, said Dr. Purpura.

“There’s a lot of fear that they will have a worsening of their symptoms,” he explained. The conversation he has with his patients mirrors the conversation all physicians should have with their patients about COVID-19 vaccination, even if they don’t have long COVID. He stresses the importance of highlighting the following components:

• Show compassion and empathy. “A lot of people have strongly held opinions – it’s worth it to try to find out why they feel the way that they do,” said Dr. Friedberg.
• Walk them through side effects. “Many people are afraid of the side effects of the vaccine, especially if they already have long COVID,” explained Dr. Purpura. Such patients can be asked how they felt after their last vaccination, such a shingles or flu shot. Then explain that the COVID-19 vaccine is not much different and that they may experience temporary side effects such as fatigue, headache, or a mild fever for 24-48 hours.
• Explain the benefits. Eighty-five percent of people say their health care provider is a trusted source of information on COVID-19 vaccines, according to the Kaiser Family Foundation. That trust is conducive to talks about the vaccine’s benefits, including its ability to protect against long COVID.

Other ways to reduce risk of long COVID

Vaccines can lower the chances of a patient’s developing long COVID. So can the antiviral medication nirmatrelvir (Paxlovid). A March 2023 study published in JAMA Internal Medicine included more than 280,000 people with COVID. The researchers found that vaccination reduced the risk for developing the condition by about 25%.

“I mention that study to all of my long COVID patients who become reinfected with the virus,” said Dr. Purpura. “It not only appears protective against long COVID, but since it lowers levels of virus circulating in their body, it seems to help prevent a flare-up of symptoms.”

Another treatment that may help is the diabetes drug metformin, he added.

A June 2023 study published in The Lancet Infectious Diseases found that when metformin was given within 3 days of symptom onset, the incidence of long COVID was reduced by about 41%.

“We’re still trying to wrap our brains around this one, but the thought is it may help to lower inflammation, which plays a role in long COVID,” Dr. Purpura explained. More studies need to be conducted, though, before recommending its use.

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

The COVID-19 vaccines have been a game changer for millions of people worldwide in preventing death or disability from the virus. Research suggests that they offer significant protection against long COVID.

Studies have consistently found that these vaccines prevent the new onset of long COVID as well as flare-ups for people who already have the condition.

False and unfounded claims made by some antivaccine groups that the vaccines themselves may cause long COVID persist and serve as barriers to vaccination.

To help separate the facts from falsehoods, here’s a checklist for doctors on what scientific studies have determined about vaccination and long COVID.
 

What the research shows

Doctors who work in long COVID clinics have for years suspected that vaccination may help protect against the development of long COVID, noted Lawrence Purpura, MD, MPH, an infectious disease specialist at New York–Presbyterian/Columbia University Irving Medical Center, who treats patients with long COVID in his clinic.

Over the past year, several large, well-conducted studies have borne out that theory, including the following studies:

• In the RECOVER study, published in May in the journal Nature Communications, researchers examined the electronic health records of more than 5 million people who had been diagnosed with COVID and found that vaccination reduced the risk that they would develop long COVID. Although the researchers didn’t compare the effects of having boosters to being fully vaccinated without them, experts have suggested that having a full round of recommended shots may offer the most protection. “My thoughts are that more shots are better, and other work has shown compelling evidence that the protective effect of vaccination on COVID-19 wanes over time,” said study coauthor Daniel Brannock, MS, a research scientist at RTI International in Research Triangle Park, N.C. “It stands to reason that the same is true for long COVID.”
• A review published in February in BMJ Medicine concluded that 10 studies showed a significant reduction in the incidence of long COVID among vaccinated patients. Even one dose of a vaccine was protective.
• A meta-analysis of six studies published last December in Antimicrobial Stewardship and Healthcare Epidemiology found that one or more doses of a COVID-19 vaccine were 29% effective in preventing symptoms of long COVID.
• In a June meta-analysis published in JAMA Internal Medicine, researchers analyzed more than 40 studies that included 860,000 patients and found that two doses of a COVID-19 vaccine reduced the risk of long COVID by almost half.

The message? COVID vaccination is very effective in reducing the risk of long COVID.

“It’s important to emphasize that many of the risk factors [for long COVID] cannot be changed, or at least cannot be changed easily, but vaccination is a decision that can be taken by everyone,” said Vassilios Vassiliou, MBBS, PhD, clinical professor of cardiac medicine at Norwich Medical School in England, who coauthored the article in JAMA Internal Medicine.
 

Why vaccines may be protective

The COVID-19 vaccines work well to prevent serious illness from the virus, noted Aaron Friedberg, MD, clinical coleader of the Post COVID Recovery Program at the Ohio State University Wexner Medical Center. That may be a clue to why the vaccines help prevent long COVID symptoms.

“When you get COVID and you’ve been vaccinated, the virus may still attach in your nose and respiratory tract, but it’s less likely to spread throughout your body,” he explained. “It’s like a forest fire – if the ground is wet or it starts to rain, it’s less likely to create a great blaze. As a result, your body is less likely to experience inflammation and damage that makes it more likely that you’ll develop long COVID.”

Dr. Friedberg stressed that even for patients who have had COVID, it’s important to get vaccinated – a message he consistently delivers to his own patients.

“There is some protection that comes from having COVID before, but for some people, that’s not enough,” he said. “It’s true that after infection, your body creates antibodies that help protect you against the virus. But I explain to patients that these may be like old Velcro: They barely grab on enough to stay on for the moment, but they don’t last long term. You’re much more likely to get a reliable immune response from the vaccine.”

In addition, a second or third bout of COVID could be the one that gives patients long COVID, Dr. Friedberg adds.

“I have a number of patients in my clinic who were fine after their first bout of COVID but experienced debilitating long COVID symptoms after they developed COVID again,” he said. “Why leave it to chance?”
 

Vaccines and ‘long vax’

The COVID vaccines are considered very safe but have been linked to very rare side effects, such as blood clots and heart inflammation. There have also been anecdotal reports of symptoms that resemble long COVID – a syndrome that has come to be known as “long Vax” – an extremely rare condition that may or may not be tied to vaccination.

“I have seen people in my clinic who developed symptoms suggestive of long COVID that linger for months – brain fog, fatigue, heart palpitations – soon after they got the COVID-19 vaccine,” said Dr. Purpura. But no published studies have suggested a link, he cautions.

A study called LISTEN is being organized at Yale in an effort to better understand postvaccine adverse events and a potential link to long COVID.
 

Talking to patients

Discussions of vaccination with patients, including those with COVID or long COVID, are often fraught and challenging, said Dr. Purpura.

“There’s a lot of fear that they will have a worsening of their symptoms,” he explained. The conversation he has with his patients mirrors the conversation all physicians should have with their patients about COVID-19 vaccination, even if they don’t have long COVID. He stresses the importance of highlighting the following components:

• Show compassion and empathy. “A lot of people have strongly held opinions – it’s worth it to try to find out why they feel the way that they do,” said Dr. Friedberg.
• Walk them through side effects. “Many people are afraid of the side effects of the vaccine, especially if they already have long COVID,” explained Dr. Purpura. Such patients can be asked how they felt after their last vaccination, such a shingles or flu shot. Then explain that the COVID-19 vaccine is not much different and that they may experience temporary side effects such as fatigue, headache, or a mild fever for 24-48 hours.
• Explain the benefits. Eighty-five percent of people say their health care provider is a trusted source of information on COVID-19 vaccines, according to the Kaiser Family Foundation. That trust is conducive to talks about the vaccine’s benefits, including its ability to protect against long COVID.

Other ways to reduce risk of long COVID

Vaccines can lower the chances of a patient’s developing long COVID. So can the antiviral medication nirmatrelvir (Paxlovid). A March 2023 study published in JAMA Internal Medicine included more than 280,000 people with COVID. The researchers found that vaccination reduced the risk for developing the condition by about 25%.

“I mention that study to all of my long COVID patients who become reinfected with the virus,” said Dr. Purpura. “It not only appears protective against long COVID, but since it lowers levels of virus circulating in their body, it seems to help prevent a flare-up of symptoms.”

Another treatment that may help is the diabetes drug metformin, he added.

A June 2023 study published in The Lancet Infectious Diseases found that when metformin was given within 3 days of symptom onset, the incidence of long COVID was reduced by about 41%.

“We’re still trying to wrap our brains around this one, but the thought is it may help to lower inflammation, which plays a role in long COVID,” Dr. Purpura explained. More studies need to be conducted, though, before recommending its use.

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

TOPLINE:

Adults who take part in group-based, teacher-led mindfulness-based programs (MBPs) have reduced psychological distress.

METHODOLOGY:

Evidence suggests the effect of MBPs, which combine elements of meditation, body awareness, and modern psychology, vary as a function of individual, participant-level differences.

After a literature search, researchers selected 13 trials of in-person, teacher-led group-based MBPs that had a passive control group such as no intervention, a waitlist, or treatment-as-usual, in a total of 2,371 community adults (median age, 34 years; 71% female) who reported psychological distress levels.

Researchers conducted a systematic review and individual-participant data (IPD) meta-analysis, which allowed them to explore how intervention effects vary as a function of individual differences.

The primary outcome was self-reported psychological distress, which includes anxiety and depression, measured between 1 and 6 months after program completion using psychometrically valid questionnaires.
 

TAKEAWAY:

The trials were conducted across eight countries, had a cohort size ranging from 44 to 670 participants, and represented diverse populations including university students, law enforcement officers, and health care professionals.

Compared with passive control groups, MBPs reduced distress (standardized mean difference, –0.32; 95% CI, –0.41 to –0.24; P < .001; 95% prediction interval, –0.41 to –0.24), with no evidence of statistical heterogeneity.

Results were similar for psychological distress measured less than a month after completing the program and beyond 6 months.

There was no clear indication that baseline distress, gender, age, education level, or dispositional mindfulness (a construct reflecting an individual’s focus and quality of attention) modified the effect of MBPs on the primary outcome.
 

IN PRACTICE:

The results “encourage implementation of teacher-led MBPs for adults in nonclinical settings,” said the authors, noting that while it was difficult to ascertain clinical significance of the results because different instruments were combined, the effect size was within the range of being minimally important.

SOURCE:

The study was conducted by Julieta Galante, PhD, department of psychiatry, University of Cambridge (England), and colleagues. It was published online July 10 in Nature Mental Health.

LIMITATIONS:

The findings are limited to voluntary MBPs and don’t extend to self-guided MBPs such as those delivered through smartphone applications. Individuals with less than 12 years of education, men, and those over age 70 years were underrepresented in the dataset. The analysis was unable to consider certain effect modifiers such as participant expectations and beliefs, and personality and cognitive factors. There is risk of bias regarding the lack of blinding and self-reported outcomes, and psychological distress is an inherently subjective outcome.

DISCLOSURES:

The study received funding from the National Institute for Health Research. Dr. Galante has no relevant conflicts of interest.

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

TOPLINE:

Adults who take part in group-based, teacher-led mindfulness-based programs (MBPs) have reduced psychological distress.

METHODOLOGY:

Evidence suggests the effect of MBPs, which combine elements of meditation, body awareness, and modern psychology, vary as a function of individual, participant-level differences.

After a literature search, researchers selected 13 trials of in-person, teacher-led group-based MBPs that had a passive control group such as no intervention, a waitlist, or treatment-as-usual, in a total of 2,371 community adults (median age, 34 years; 71% female) who reported psychological distress levels.

Researchers conducted a systematic review and individual-participant data (IPD) meta-analysis, which allowed them to explore how intervention effects vary as a function of individual differences.

The primary outcome was self-reported psychological distress, which includes anxiety and depression, measured between 1 and 6 months after program completion using psychometrically valid questionnaires.
 

TAKEAWAY:

The trials were conducted across eight countries, had a cohort size ranging from 44 to 670 participants, and represented diverse populations including university students, law enforcement officers, and health care professionals.

Compared with passive control groups, MBPs reduced distress (standardized mean difference, –0.32; 95% CI, –0.41 to –0.24; P < .001; 95% prediction interval, –0.41 to –0.24), with no evidence of statistical heterogeneity.

Results were similar for psychological distress measured less than a month after completing the program and beyond 6 months.

There was no clear indication that baseline distress, gender, age, education level, or dispositional mindfulness (a construct reflecting an individual’s focus and quality of attention) modified the effect of MBPs on the primary outcome.
 

IN PRACTICE:

The results “encourage implementation of teacher-led MBPs for adults in nonclinical settings,” said the authors, noting that while it was difficult to ascertain clinical significance of the results because different instruments were combined, the effect size was within the range of being minimally important.

SOURCE:

The study was conducted by Julieta Galante, PhD, department of psychiatry, University of Cambridge (England), and colleagues. It was published online July 10 in Nature Mental Health.

LIMITATIONS:

The findings are limited to voluntary MBPs and don’t extend to self-guided MBPs such as those delivered through smartphone applications. Individuals with less than 12 years of education, men, and those over age 70 years were underrepresented in the dataset. The analysis was unable to consider certain effect modifiers such as participant expectations and beliefs, and personality and cognitive factors. There is risk of bias regarding the lack of blinding and self-reported outcomes, and psychological distress is an inherently subjective outcome.

DISCLOSURES:

The study received funding from the National Institute for Health Research. Dr. Galante has no relevant conflicts of interest.

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

TOPLINE:

Adults who take part in group-based, teacher-led mindfulness-based programs (MBPs) have reduced psychological distress.

METHODOLOGY:

Evidence suggests the effect of MBPs, which combine elements of meditation, body awareness, and modern psychology, vary as a function of individual, participant-level differences.

After a literature search, researchers selected 13 trials of in-person, teacher-led group-based MBPs that had a passive control group such as no intervention, a waitlist, or treatment-as-usual, in a total of 2,371 community adults (median age, 34 years; 71% female) who reported psychological distress levels.

Researchers conducted a systematic review and individual-participant data (IPD) meta-analysis, which allowed them to explore how intervention effects vary as a function of individual differences.

The primary outcome was self-reported psychological distress, which includes anxiety and depression, measured between 1 and 6 months after program completion using psychometrically valid questionnaires.
 

TAKEAWAY:

The trials were conducted across eight countries, had a cohort size ranging from 44 to 670 participants, and represented diverse populations including university students, law enforcement officers, and health care professionals.

Compared with passive control groups, MBPs reduced distress (standardized mean difference, –0.32; 95% CI, –0.41 to –0.24; P < .001; 95% prediction interval, –0.41 to –0.24), with no evidence of statistical heterogeneity.

Results were similar for psychological distress measured less than a month after completing the program and beyond 6 months.

There was no clear indication that baseline distress, gender, age, education level, or dispositional mindfulness (a construct reflecting an individual’s focus and quality of attention) modified the effect of MBPs on the primary outcome.
 

IN PRACTICE:

The results “encourage implementation of teacher-led MBPs for adults in nonclinical settings,” said the authors, noting that while it was difficult to ascertain clinical significance of the results because different instruments were combined, the effect size was within the range of being minimally important.

SOURCE:

The study was conducted by Julieta Galante, PhD, department of psychiatry, University of Cambridge (England), and colleagues. It was published online July 10 in Nature Mental Health.

LIMITATIONS:

The findings are limited to voluntary MBPs and don’t extend to self-guided MBPs such as those delivered through smartphone applications. Individuals with less than 12 years of education, men, and those over age 70 years were underrepresented in the dataset. The analysis was unable to consider certain effect modifiers such as participant expectations and beliefs, and personality and cognitive factors. There is risk of bias regarding the lack of blinding and self-reported outcomes, and psychological distress is an inherently subjective outcome.

DISCLOSURES:

The study received funding from the National Institute for Health Research. Dr. Galante has no relevant conflicts of interest.

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

We are all searching for happiness. But how do we achieve it? What are its greatest determinants?

The Harvard Study of Adult Development may be the most comprehensive study ever conducted, as it followed its participants for their entire adult lives. The study was started in Boston in 1938 and has already covered three generations: grandparents, parents, and children, who are now considered “baby boomers.” It analyzed more than 2,000 people throughout 85 years of longitudinal study.

In January, Robert J. Waldinger, MD, the current director of this incredible study, published the book The Good Life: Lessons From the World’s Longest Scientific Study of Happiness, coauthored with the study’s associate director, Marc Schulz, PhD.

By following this large population for more than 8 decades, the study uncovered the factors most correlated with well-being and happiness. Here, I have summarized some of the authors’ main concepts.
 

Most important factors

The study’s happiest participants had two major factors in common throughout its 85 years: Taking care of their health and building loving relationships with others.

It seems obvious that being in good health is essential to live well. However, to some surprise, researchers determined that good relationships were the most significant predictor of health and happiness during aging. Other authors have confirmed this finding, and research has sought to analyze the physiological mechanisms associated with this benefit.
 

Professional success insufficient

Professional success on its own does not guarantee happiness, even though it may be gratifying. The study revealed that those who were happiest were not isolated. In fact, the happiest people valued and fostered relationships. Levels of education and cultural awareness, which tend to be higher among those with higher salaries, were also important factors for adopting healthy habits (promoted more often as of the 1960s) and for better access to health care.

Social skills

Loneliness is increasingly common and creates challenges when dealing with stressful situations. It is essential to have someone with whom we can vent. Therefore, Dr. Waldinger recommends assessing how to foster, strengthen, and broaden relationships. He calls this maintaining social connections and, just as with physical fitness, it also requires constant practice. Friendships and relationships need regular commitment to keep them from fizzling out. A simple telephone call can help. Participating in activities that bring joy and encourage camaraderie, such as sports, hobbies, and volunteer work, may broaden the relationship network.

Happiness not constant

Social media almost always shows the positive side of people’s lives and suggests that everyone lives worry-free. However, the truth is that no one’s life is free of difficulties and challenges. Social skills contribute to resilience.

It is never too late for a turnaround and for people to change their lives through new relationships and experiences. Those who think they know everything about life are very mistaken. The study showed that good things happened to those who had given up on changing their situation, and good news appeared when they least expected it.

This study highlights the importance of having social skills and always cultivating our relationships to help us become healthier, overcome challenging moments, and achieve the happiness that we all desire.

We finally have robust evidence-based data to use when speaking on happiness.

Dr. Wajngarten is professor of cardiology, University of São Paulo, Brazil. He has disclosed no relevant financial relationships.

This article was translated from the Medscape Portuguese Edition. A version of this article appeared on Medscape.com.

We are all searching for happiness. But how do we achieve it? What are its greatest determinants?

The Harvard Study of Adult Development may be the most comprehensive study ever conducted, as it followed its participants for their entire adult lives. The study was started in Boston in 1938 and has already covered three generations: grandparents, parents, and children, who are now considered “baby boomers.” It analyzed more than 2,000 people throughout 85 years of longitudinal study.

In January, Robert J. Waldinger, MD, the current director of this incredible study, published the book The Good Life: Lessons From the World’s Longest Scientific Study of Happiness, coauthored with the study’s associate director, Marc Schulz, PhD.

By following this large population for more than 8 decades, the study uncovered the factors most correlated with well-being and happiness. Here, I have summarized some of the authors’ main concepts.
 

Most important factors

The study’s happiest participants had two major factors in common throughout its 85 years: Taking care of their health and building loving relationships with others.

It seems obvious that being in good health is essential to live well. However, to some surprise, researchers determined that good relationships were the most significant predictor of health and happiness during aging. Other authors have confirmed this finding, and research has sought to analyze the physiological mechanisms associated with this benefit.
 

Professional success insufficient

Professional success on its own does not guarantee happiness, even though it may be gratifying. The study revealed that those who were happiest were not isolated. In fact, the happiest people valued and fostered relationships. Levels of education and cultural awareness, which tend to be higher among those with higher salaries, were also important factors for adopting healthy habits (promoted more often as of the 1960s) and for better access to health care.

Social skills

Loneliness is increasingly common and creates challenges when dealing with stressful situations. It is essential to have someone with whom we can vent. Therefore, Dr. Waldinger recommends assessing how to foster, strengthen, and broaden relationships. He calls this maintaining social connections and, just as with physical fitness, it also requires constant practice. Friendships and relationships need regular commitment to keep them from fizzling out. A simple telephone call can help. Participating in activities that bring joy and encourage camaraderie, such as sports, hobbies, and volunteer work, may broaden the relationship network.

Happiness not constant

Social media almost always shows the positive side of people’s lives and suggests that everyone lives worry-free. However, the truth is that no one’s life is free of difficulties and challenges. Social skills contribute to resilience.

It is never too late for a turnaround and for people to change their lives through new relationships and experiences. Those who think they know everything about life are very mistaken. The study showed that good things happened to those who had given up on changing their situation, and good news appeared when they least expected it.

This study highlights the importance of having social skills and always cultivating our relationships to help us become healthier, overcome challenging moments, and achieve the happiness that we all desire.

We finally have robust evidence-based data to use when speaking on happiness.

Dr. Wajngarten is professor of cardiology, University of São Paulo, Brazil. He has disclosed no relevant financial relationships.

This article was translated from the Medscape Portuguese Edition. A version of this article appeared on Medscape.com.

We are all searching for happiness. But how do we achieve it? What are its greatest determinants?

The Harvard Study of Adult Development may be the most comprehensive study ever conducted, as it followed its participants for their entire adult lives. The study was started in Boston in 1938 and has already covered three generations: grandparents, parents, and children, who are now considered “baby boomers.” It analyzed more than 2,000 people throughout 85 years of longitudinal study.

In January, Robert J. Waldinger, MD, the current director of this incredible study, published the book The Good Life: Lessons From the World’s Longest Scientific Study of Happiness, coauthored with the study’s associate director, Marc Schulz, PhD.

By following this large population for more than 8 decades, the study uncovered the factors most correlated with well-being and happiness. Here, I have summarized some of the authors’ main concepts.
 

Most important factors

The study’s happiest participants had two major factors in common throughout its 85 years: Taking care of their health and building loving relationships with others.

It seems obvious that being in good health is essential to live well. However, to some surprise, researchers determined that good relationships were the most significant predictor of health and happiness during aging. Other authors have confirmed this finding, and research has sought to analyze the physiological mechanisms associated with this benefit.
 

Professional success insufficient

Professional success on its own does not guarantee happiness, even though it may be gratifying. The study revealed that those who were happiest were not isolated. In fact, the happiest people valued and fostered relationships. Levels of education and cultural awareness, which tend to be higher among those with higher salaries, were also important factors for adopting healthy habits (promoted more often as of the 1960s) and for better access to health care.

Social skills

Loneliness is increasingly common and creates challenges when dealing with stressful situations. It is essential to have someone with whom we can vent. Therefore, Dr. Waldinger recommends assessing how to foster, strengthen, and broaden relationships. He calls this maintaining social connections and, just as with physical fitness, it also requires constant practice. Friendships and relationships need regular commitment to keep them from fizzling out. A simple telephone call can help. Participating in activities that bring joy and encourage camaraderie, such as sports, hobbies, and volunteer work, may broaden the relationship network.

Happiness not constant

Social media almost always shows the positive side of people’s lives and suggests that everyone lives worry-free. However, the truth is that no one’s life is free of difficulties and challenges. Social skills contribute to resilience.

It is never too late for a turnaround and for people to change their lives through new relationships and experiences. Those who think they know everything about life are very mistaken. The study showed that good things happened to those who had given up on changing their situation, and good news appeared when they least expected it.

This study highlights the importance of having social skills and always cultivating our relationships to help us become healthier, overcome challenging moments, and achieve the happiness that we all desire.

We finally have robust evidence-based data to use when speaking on happiness.

Dr. Wajngarten is professor of cardiology, University of São Paulo, Brazil. He has disclosed no relevant financial relationships.

This article was translated from the Medscape Portuguese Edition. A version of this article appeared on Medscape.com.

The antiplatelet of choice for long-term, secondary prevention for patients with established coronary artery disease (CAD) may well be a P2Y12 inhibitor such as clopidogrel or ticagrelor rather than aspirin, suggests a patient-level meta-analysis of seven randomized trials.

The more than 24,000 patients in the meta-analysis, called PANTHER, had documented stable CAD, prior myocardial infarction (MI), or recent or remote surgical or percutaneous coronary revascularization.

About half of patients in each antiplatelet monotherapy trial received clopidogrel or ticagrelor, and the other half received aspirin. Follow-ups ranged from 6 months to 3 years.

Those taking a P2Y12 inhibitor showed a 12% reduction in risk (P = .012) for the primary efficacy outcome, a composite of cardiovascular (CV) death, MI, and stroke, over a median of about 1.35 years. The difference was driven primarily by a 23% reduction in risk for MI (P < .001); mortality seemed unaffected by antiplatelet treatment assignment.

Although the P2Y12 inhibitor and aspirin groups were similar with respect to risk of major bleeding, the P2Y12 inhibitor group showed significant reductions in risk for gastrointestinal (GI) bleeding, definite stent thrombosis, and hemorrhagic stroke; rates of hemorrhagic stroke were well under 1% in both groups.

The treatment effects were consistent across patient subgroups, including whether the aspirin comparison was with clopidogrel or ticagrelor.

“Taken together, our data challenge the central role of aspirin in secondary prevention and support a paradigm shift toward P2Y12 inhibitor monotherapy as long-term antiplatelet strategy in the sizable population of patients with coronary atherosclerosis,” Felice Gragnano, MD, PhD, said in an interview. “Given [their] superior efficacy and similar overall safety, P2Y12 inhibitors may be preferred [over] aspirin for the prevention of cardiovascular events in patients with CAD.”

Dr. Gragnano, of the University of Campania Luigi Vanvitelli, Caserta, Italy, who called PANTHER “the largest and most comprehensive synthesis of individual patient data from randomized trials comparing P2Y12 inhibitor monotherapy with aspirin monotherapy,” is lead author of the study, which was published online in the Journal of the American College of Cardiology.

Current guidelines recommend aspirin for antiplatelet monotherapy for patients with established CAD, Dr. Gragnano said, but “the primacy of aspirin in secondary prevention is based on historical trials conducted in the 1970s and 1980s and may not apply to contemporary practice.”

Moreover, later trials that compared P2Y12 inhibitors with aspirin for secondary prevention produced “inconsistent results,” possibly owing to their heterogeneous populations of patients with coronary, cerebrovascular, or peripheral vascular disease, he said. Study-level meta-analyses in this area “provide inconclusive evidence” because they haven’t evaluated treatment effects exclusively in patients with established CAD.

Most of the seven trials’ 24,325 participants had a history of MI, and some had peripheral artery disease (PAD); the rates were 56.2% and 9.1%, respectively. Coronary revascularization, either percutaneous or surgical, had been performed for about 70%. Most (61%) had presented with acute coronary syndromes, and the remainder had presented with chronic CAD.

About 76% of the combined cohorts were from Europe or North America; the rest were from Asia. The mean age of the patients was 64 years, and about 22% were women.

In all, 12,175 had been assigned to P2Y12 inhibitor monotherapy (62% received clopidogrel and 38% received ticagrelor); 12,147 received aspirin at dosages ranging from 75 mg to 325 mg daily.

The hazard ratio (HR) for the primary efficacy outcome, P2Y12 inhibitors vs. aspirin, was significantly reduced, at 0.88 (95% confidence interval [CI], 0.79-0.97; P = .012); the number needed to treat (NNT) to prevent one primary event over 2 years was 121, the report states.

The corresponding HR for MI was 0.77 (95% CI, 0.66-0.90; P < .001), for an NNT benefit of 136. For net adverse clinical events, the HR was 0.89 (95% CI, 0.81-0.98; P = .020), for an NNT benefit of 121.

Risk for major bleeding was not significantly different (HR, 0.87; 95% CI, 0.70-1.09; P = .23), nor were risks for stroke (HR, 0.84; 95% CI, 0.70-1.02; P = .076) or cardiovascular death (HR, 1.02; 95% CI, 0.86-1.20; P = .82).

Still, the P2Y12 inhibitor group showed significant risk reductions for the following:

• GI bleeding: HR, 0.75 (95% CI, 0.57-0.97; P = .027)
• Definite stent thrombosis: HR, 0.42 (95% CI, 0.19-0.97; P = .028)
• Hemorrhagic stroke: HR, 0.43 (95% CI, 0.23-0.83; P = .012)

The current findings are “hypothesis-generating but not definitive,” Dharam Kumbhani, MD, University of Texas Southwestern, Dallas, said in an interview.

It remains unclear “whether aspirin or P2Y12 inhibitor monotherapy is better for long-term maintenance use among patients with established CAD. Aspirin has historically been the agent of choice for this indication,” said Dr. Kumbhani, who with James A. de Lemos, MD, of the same institution, wrote an editorial accompanying the PANTHER report.

“It certainly would be appropriate to consider P2Y12 monotherapy preferentially for patients with prior or currently at high risk for GI or intracranial bleeding, for instance,” Dr. Kumbhani said. For the remainder, aspirin and P2Y12 inhibitors are both “reasonable alternatives.”

In their editorial, Dr. Kumbhani and Dr. de Lemos call the PANTHER meta-analysis “a well-done study with potentially important clinical implications.” The findings “make biological sense: P2Y12 inhibitors are more potent antiplatelet agents than aspirin and have less effect on gastrointestinal mucosal integrity.”

But for now, they wrote, “both aspirin and P2Y12 inhibitors remain viable alternatives for prevention of atherothrombotic events among patients with established CAD.”

Dr. Gragnano had no disclosures; potential conflicts for the other authors are in the report. Dr. Kumbhani reports no relevant relationships; Dr. de Lemos has received honoraria for participation in data safety monitoring boards from Eli Lilly, Novo Nordisk, AstraZeneca, and Janssen.

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

The antiplatelet of choice for long-term, secondary prevention for patients with established coronary artery disease (CAD) may well be a P2Y12 inhibitor such as clopidogrel or ticagrelor rather than aspirin, suggests a patient-level meta-analysis of seven randomized trials.

The more than 24,000 patients in the meta-analysis, called PANTHER, had documented stable CAD, prior myocardial infarction (MI), or recent or remote surgical or percutaneous coronary revascularization.

About half of patients in each antiplatelet monotherapy trial received clopidogrel or ticagrelor, and the other half received aspirin. Follow-ups ranged from 6 months to 3 years.

Those taking a P2Y12 inhibitor showed a 12% reduction in risk (P = .012) for the primary efficacy outcome, a composite of cardiovascular (CV) death, MI, and stroke, over a median of about 1.35 years. The difference was driven primarily by a 23% reduction in risk for MI (P < .001); mortality seemed unaffected by antiplatelet treatment assignment.

Although the P2Y12 inhibitor and aspirin groups were similar with respect to risk of major bleeding, the P2Y12 inhibitor group showed significant reductions in risk for gastrointestinal (GI) bleeding, definite stent thrombosis, and hemorrhagic stroke; rates of hemorrhagic stroke were well under 1% in both groups.

The treatment effects were consistent across patient subgroups, including whether the aspirin comparison was with clopidogrel or ticagrelor.

“Taken together, our data challenge the central role of aspirin in secondary prevention and support a paradigm shift toward P2Y12 inhibitor monotherapy as long-term antiplatelet strategy in the sizable population of patients with coronary atherosclerosis,” Felice Gragnano, MD, PhD, said in an interview. “Given [their] superior efficacy and similar overall safety, P2Y12 inhibitors may be preferred [over] aspirin for the prevention of cardiovascular events in patients with CAD.”

Dr. Gragnano, of the University of Campania Luigi Vanvitelli, Caserta, Italy, who called PANTHER “the largest and most comprehensive synthesis of individual patient data from randomized trials comparing P2Y12 inhibitor monotherapy with aspirin monotherapy,” is lead author of the study, which was published online in the Journal of the American College of Cardiology.

Current guidelines recommend aspirin for antiplatelet monotherapy for patients with established CAD, Dr. Gragnano said, but “the primacy of aspirin in secondary prevention is based on historical trials conducted in the 1970s and 1980s and may not apply to contemporary practice.”

Moreover, later trials that compared P2Y12 inhibitors with aspirin for secondary prevention produced “inconsistent results,” possibly owing to their heterogeneous populations of patients with coronary, cerebrovascular, or peripheral vascular disease, he said. Study-level meta-analyses in this area “provide inconclusive evidence” because they haven’t evaluated treatment effects exclusively in patients with established CAD.

Most of the seven trials’ 24,325 participants had a history of MI, and some had peripheral artery disease (PAD); the rates were 56.2% and 9.1%, respectively. Coronary revascularization, either percutaneous or surgical, had been performed for about 70%. Most (61%) had presented with acute coronary syndromes, and the remainder had presented with chronic CAD.

About 76% of the combined cohorts were from Europe or North America; the rest were from Asia. The mean age of the patients was 64 years, and about 22% were women.

In all, 12,175 had been assigned to P2Y12 inhibitor monotherapy (62% received clopidogrel and 38% received ticagrelor); 12,147 received aspirin at dosages ranging from 75 mg to 325 mg daily.

The hazard ratio (HR) for the primary efficacy outcome, P2Y12 inhibitors vs. aspirin, was significantly reduced, at 0.88 (95% confidence interval [CI], 0.79-0.97; P = .012); the number needed to treat (NNT) to prevent one primary event over 2 years was 121, the report states.

The corresponding HR for MI was 0.77 (95% CI, 0.66-0.90; P < .001), for an NNT benefit of 136. For net adverse clinical events, the HR was 0.89 (95% CI, 0.81-0.98; P = .020), for an NNT benefit of 121.

Risk for major bleeding was not significantly different (HR, 0.87; 95% CI, 0.70-1.09; P = .23), nor were risks for stroke (HR, 0.84; 95% CI, 0.70-1.02; P = .076) or cardiovascular death (HR, 1.02; 95% CI, 0.86-1.20; P = .82).

Still, the P2Y12 inhibitor group showed significant risk reductions for the following:

• GI bleeding: HR, 0.75 (95% CI, 0.57-0.97; P = .027)
• Definite stent thrombosis: HR, 0.42 (95% CI, 0.19-0.97; P = .028)
• Hemorrhagic stroke: HR, 0.43 (95% CI, 0.23-0.83; P = .012)

The current findings are “hypothesis-generating but not definitive,” Dharam Kumbhani, MD, University of Texas Southwestern, Dallas, said in an interview.

It remains unclear “whether aspirin or P2Y12 inhibitor monotherapy is better for long-term maintenance use among patients with established CAD. Aspirin has historically been the agent of choice for this indication,” said Dr. Kumbhani, who with James A. de Lemos, MD, of the same institution, wrote an editorial accompanying the PANTHER report.

“It certainly would be appropriate to consider P2Y12 monotherapy preferentially for patients with prior or currently at high risk for GI or intracranial bleeding, for instance,” Dr. Kumbhani said. For the remainder, aspirin and P2Y12 inhibitors are both “reasonable alternatives.”

In their editorial, Dr. Kumbhani and Dr. de Lemos call the PANTHER meta-analysis “a well-done study with potentially important clinical implications.” The findings “make biological sense: P2Y12 inhibitors are more potent antiplatelet agents than aspirin and have less effect on gastrointestinal mucosal integrity.”

But for now, they wrote, “both aspirin and P2Y12 inhibitors remain viable alternatives for prevention of atherothrombotic events among patients with established CAD.”

Dr. Gragnano had no disclosures; potential conflicts for the other authors are in the report. Dr. Kumbhani reports no relevant relationships; Dr. de Lemos has received honoraria for participation in data safety monitoring boards from Eli Lilly, Novo Nordisk, AstraZeneca, and Janssen.

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

The antiplatelet of choice for long-term, secondary prevention for patients with established coronary artery disease (CAD) may well be a P2Y12 inhibitor such as clopidogrel or ticagrelor rather than aspirin, suggests a patient-level meta-analysis of seven randomized trials.

The more than 24,000 patients in the meta-analysis, called PANTHER, had documented stable CAD, prior myocardial infarction (MI), or recent or remote surgical or percutaneous coronary revascularization.

About half of patients in each antiplatelet monotherapy trial received clopidogrel or ticagrelor, and the other half received aspirin. Follow-ups ranged from 6 months to 3 years.

Those taking a P2Y12 inhibitor showed a 12% reduction in risk (P = .012) for the primary efficacy outcome, a composite of cardiovascular (CV) death, MI, and stroke, over a median of about 1.35 years. The difference was driven primarily by a 23% reduction in risk for MI (P < .001); mortality seemed unaffected by antiplatelet treatment assignment.

Although the P2Y12 inhibitor and aspirin groups were similar with respect to risk of major bleeding, the P2Y12 inhibitor group showed significant reductions in risk for gastrointestinal (GI) bleeding, definite stent thrombosis, and hemorrhagic stroke; rates of hemorrhagic stroke were well under 1% in both groups.

The treatment effects were consistent across patient subgroups, including whether the aspirin comparison was with clopidogrel or ticagrelor.

“Taken together, our data challenge the central role of aspirin in secondary prevention and support a paradigm shift toward P2Y12 inhibitor monotherapy as long-term antiplatelet strategy in the sizable population of patients with coronary atherosclerosis,” Felice Gragnano, MD, PhD, said in an interview. “Given [their] superior efficacy and similar overall safety, P2Y12 inhibitors may be preferred [over] aspirin for the prevention of cardiovascular events in patients with CAD.”

Dr. Gragnano, of the University of Campania Luigi Vanvitelli, Caserta, Italy, who called PANTHER “the largest and most comprehensive synthesis of individual patient data from randomized trials comparing P2Y12 inhibitor monotherapy with aspirin monotherapy,” is lead author of the study, which was published online in the Journal of the American College of Cardiology.

Current guidelines recommend aspirin for antiplatelet monotherapy for patients with established CAD, Dr. Gragnano said, but “the primacy of aspirin in secondary prevention is based on historical trials conducted in the 1970s and 1980s and may not apply to contemporary practice.”

Moreover, later trials that compared P2Y12 inhibitors with aspirin for secondary prevention produced “inconsistent results,” possibly owing to their heterogeneous populations of patients with coronary, cerebrovascular, or peripheral vascular disease, he said. Study-level meta-analyses in this area “provide inconclusive evidence” because they haven’t evaluated treatment effects exclusively in patients with established CAD.

Most of the seven trials’ 24,325 participants had a history of MI, and some had peripheral artery disease (PAD); the rates were 56.2% and 9.1%, respectively. Coronary revascularization, either percutaneous or surgical, had been performed for about 70%. Most (61%) had presented with acute coronary syndromes, and the remainder had presented with chronic CAD.

About 76% of the combined cohorts were from Europe or North America; the rest were from Asia. The mean age of the patients was 64 years, and about 22% were women.

In all, 12,175 had been assigned to P2Y12 inhibitor monotherapy (62% received clopidogrel and 38% received ticagrelor); 12,147 received aspirin at dosages ranging from 75 mg to 325 mg daily.

The hazard ratio (HR) for the primary efficacy outcome, P2Y12 inhibitors vs. aspirin, was significantly reduced, at 0.88 (95% confidence interval [CI], 0.79-0.97; P = .012); the number needed to treat (NNT) to prevent one primary event over 2 years was 121, the report states.

The corresponding HR for MI was 0.77 (95% CI, 0.66-0.90; P < .001), for an NNT benefit of 136. For net adverse clinical events, the HR was 0.89 (95% CI, 0.81-0.98; P = .020), for an NNT benefit of 121.

Risk for major bleeding was not significantly different (HR, 0.87; 95% CI, 0.70-1.09; P = .23), nor were risks for stroke (HR, 0.84; 95% CI, 0.70-1.02; P = .076) or cardiovascular death (HR, 1.02; 95% CI, 0.86-1.20; P = .82).

Still, the P2Y12 inhibitor group showed significant risk reductions for the following:

• GI bleeding: HR, 0.75 (95% CI, 0.57-0.97; P = .027)
• Definite stent thrombosis: HR, 0.42 (95% CI, 0.19-0.97; P = .028)
• Hemorrhagic stroke: HR, 0.43 (95% CI, 0.23-0.83; P = .012)

The current findings are “hypothesis-generating but not definitive,” Dharam Kumbhani, MD, University of Texas Southwestern, Dallas, said in an interview.

It remains unclear “whether aspirin or P2Y12 inhibitor monotherapy is better for long-term maintenance use among patients with established CAD. Aspirin has historically been the agent of choice for this indication,” said Dr. Kumbhani, who with James A. de Lemos, MD, of the same institution, wrote an editorial accompanying the PANTHER report.

“It certainly would be appropriate to consider P2Y12 monotherapy preferentially for patients with prior or currently at high risk for GI or intracranial bleeding, for instance,” Dr. Kumbhani said. For the remainder, aspirin and P2Y12 inhibitors are both “reasonable alternatives.”

In their editorial, Dr. Kumbhani and Dr. de Lemos call the PANTHER meta-analysis “a well-done study with potentially important clinical implications.” The findings “make biological sense: P2Y12 inhibitors are more potent antiplatelet agents than aspirin and have less effect on gastrointestinal mucosal integrity.”

But for now, they wrote, “both aspirin and P2Y12 inhibitors remain viable alternatives for prevention of atherothrombotic events among patients with established CAD.”

Dr. Gragnano had no disclosures; potential conflicts for the other authors are in the report. Dr. Kumbhani reports no relevant relationships; Dr. de Lemos has received honoraria for participation in data safety monitoring boards from Eli Lilly, Novo Nordisk, AstraZeneca, and Janssen.

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

Although multiple international medical societies over recent years have recommended lowering the threshold for bariatric surgery to a body mass index (BMI) of 30-35 (class 1 obesity) in certain patients, very few patients in this weight category have had such surgery, according to a new study.

On the basis of data from a large U.S. national registry, during 2015 through 2021, just 3.5% of metabolic and bariatric surgeries were performed in patients with class 1 obesity each year.

Most surgeries (96.5%) were in patients with a BMI greater than 35. This reflects advice from a 1991 consensus statement by the National Institutes of Health stating that bariatric surgery can be offered to patients with BMI greater than or equal to 40, or greater than or equal to 35 with comorbidities.

However, medical societies have recommended lower cutoffs in position statements in 2016, 2018, and 2022.

Paul Wisniowski, MD, a surgical resident at Keck School of Medicine of University of Southern California, Los Angeles, presented the study findings in an e-poster at the annual meeting of the American Society for Metabolic & Bariatric Surgery.

“Professional guidelines and increasing data support bariatric surgery for patients beginning at BMI 30, which is a tipping point for disease progression. Now it needs to happen in the real world,” outgoing ASMBS president Teresa LaMasters, MD, who was not involved with this research, said in an ASMBS press release.

‘Not unexpected,’ ‘need to expand eligibility’

“We expected that there had been little widespread adoption of the new BMI criteria/cutoffs,” senior study author Matthew J. Martin, MD, said in an interview.

“We know that bariatric surgery is already underutilized, as only about 1%-2% of eligible patients who would benefit end up getting surgery,” added Dr. Martin, Chief, Emergency General Surgery, and Director, Acute Care Surgery Research, USC Medical Center and Keck School of Medicine.

He suggests that the main reason that more patients with lower BMIs are not being offered surgery is related to insurance coverage and reimbursement.

“Even though the professional society guidelines have changed, based on the scientific evidence, most insurers are still using the very outdated (1990s) NIH consensus criteria of BMI greater than 35 with comorbidities, or BMI greater than 40.”

Another potential reason is “the lack of awareness of the changing guidelines and recommendation among primary care physicians who refer patients for a bariatric surgery evaluation.”

“I think it is too early in the experience with the new, more effective antiobesity medications to say which group will benefit the most or will prefer them over surgery,” he said.

“There is still only a small minority of patients who end up getting the [newer antiobesity] medications or surgery.”

“The takeaway,” Dr. Martin summarized, “is that bariatric surgery remains the only intervention with a high success rate for patients with class 1 or higher obesity in terms of weight loss, comorbidity improvement or resolution, and sustained health benefits.”

“We need to expand the availability of bariatric surgery for all eligible patients, particularly the class 1 obesity population who are currently the most underserved,” he said.

“This will take continued lobbying and working with the insurance companies to update their guidelines/criteria, education of patients, and education of primary care physicians so that patients can be appropriately referred for a surgical evaluation.”
 

Surgery vs. pharmacotherapy

Invited to comment on this study, Neil Skolnik, MD, who was not involved with this research, noted that data from patients with a lower BMI “has continued to accumulate, showing much greater safety than earlier studies and giving further support of efficacy.”

However, “[new] recommendations take time to take hold,” noted Dr. Skolnik, a family physician and professor in the department of family medicine, Thomas Jefferson University, Philadelphia.

“And from March of 2020 through 2021, surgery referrals were likely influenced by the COVID pandemic,” he added in an email.

Dr. Skolnik authored a commentary sharing his reservations about ASMBS recommendations issued in 2022 for lower BMI thresholds for this surgery.

“Medications are a safe, effective option for patients with a BMI from 30 to 35,” he said, “and [they] achieve approximately a 15%-20% average weight loss, which is enough to markedly improved both metabolic parameters and biomechanical issues such as knee pain, hip pain, and back pain.”

However, “bariatric surgery remains an excellent option for patients who do not respond sufficiently to pharmacotherapy,” he acknowledged.
 

National registry study, 2015-2021

Dr. Wisniowski and colleagues analyzed data from around 900 U.S. centers that are currently part of the Metabolic Bariatric Surgery Accreditation Quality Improvement Program.

They found that from 2015 to 2021, 38,669 patients (3.5%) with type 1 obesity and 1,1067,094 patients (96.5%) with a higher BMI had metabolic and bariatric surgery.

Compared with patients with BMI greater than 35, those with class 1 obesity had shorter operating times and hospital stays, but they lost less weight on short-term evaluation, after multivariable adjustment.

There were no significant differences between the two patient groups in rates of postoperative complications (< 5%) or mortality (< 0.1%).

Sleeve gastrectomy was the most common procedure and increased from 70% to 76% of all procedures during the study period.
 

Single-center study

In a second e-poster presented at the meeting, Tina T. Thomas, MD, New Jersey Bariatric Center, analyzed data from 23 patients with BMI less than 35 or less than 30 with comorbidities who had sleeve gastrectomy or Roux-en-Y gastric bypass at their center during 2017 to 2021 and who had 6 months of follow-up data.

At study entry, the patients had a mean BMI of 33.5. At 6 months after the surgery, they had a mean BMI of 25.6, and on average, they had lost 55% of their excess weight.

Nearly 60% of the patients had lost at least 50% of their excess weight, and 9 of 16 patients (56%) with comorbidities had improved or resolved comorbidities. None of the patients died or had surgery-related complications.

“Our study shows significant weight loss and health benefits, as well as the safety and efficacy of the gastric bypass and gastric sleeve procedures, for this patient population,” Ajay Goyal, MD, senior author, and bariatric surgeon at New Jersey Bariatric Center, said in an ASMBS press release.

“Often by the time a patient qualifies for bariatric surgery, their weight-related medical conditions such as [type 2] diabetes and hypertension are severe. By expanding access to bariatric surgery to patients with a lower BMI with obesity-related illnesses, patients can halt the progression, and in some cases resolve, significant and uncontrolled weight-related chronic diseases through weight loss.”
 

Societies call for lower BMI thresholds

Providers, hospitals, and insurers currently use BMI thresholds greater than or equal to 40, or greater than or equal to 35 with an obesity-related comorbidity, to define patients eligible for metabolic and bariatric surgery, based on criteria established in a 1991 consensus statement by NIH.

As more data accumulated, in 2016, a position statement from 45 societies recommended that bariatric surgery should be “considered for patients with [type 2 diabetes] and BMI 30.0-34.9 kg/m² if hyperglycemia is inadequately controlled” despite optimal medical treatment.

Similarly, in 2018, the ASMBS issued a position statement saying that “for patients with BMI 30-35 kg/m² and obesity-related comorbidities who do not achieve substantial, durable weight loss and comorbidity improvement with reasonable nonsurgical methods, bariatric surgery should be offered” to suitable individuals.

Then in October 2022, the ASMBS and International Federation for the Surgery of Obesity and Metabolic Disorders issued a joint statement that recommended lowering the thresholds for bariatric surgery to a BMI greater than or equal to 35 or greater than or equal to 30 with weight-related comorbidities.

A version of this article appeared on Medscape.com.

Although multiple international medical societies over recent years have recommended lowering the threshold for bariatric surgery to a body mass index (BMI) of 30-35 (class 1 obesity) in certain patients, very few patients in this weight category have had such surgery, according to a new study.

On the basis of data from a large U.S. national registry, during 2015 through 2021, just 3.5% of metabolic and bariatric surgeries were performed in patients with class 1 obesity each year.

Most surgeries (96.5%) were in patients with a BMI greater than 35. This reflects advice from a 1991 consensus statement by the National Institutes of Health stating that bariatric surgery can be offered to patients with BMI greater than or equal to 40, or greater than or equal to 35 with comorbidities.

However, medical societies have recommended lower cutoffs in position statements in 2016, 2018, and 2022.

Paul Wisniowski, MD, a surgical resident at Keck School of Medicine of University of Southern California, Los Angeles, presented the study findings in an e-poster at the annual meeting of the American Society for Metabolic & Bariatric Surgery.

“Professional guidelines and increasing data support bariatric surgery for patients beginning at BMI 30, which is a tipping point for disease progression. Now it needs to happen in the real world,” outgoing ASMBS president Teresa LaMasters, MD, who was not involved with this research, said in an ASMBS press release.

‘Not unexpected,’ ‘need to expand eligibility’

“We expected that there had been little widespread adoption of the new BMI criteria/cutoffs,” senior study author Matthew J. Martin, MD, said in an interview.

“We know that bariatric surgery is already underutilized, as only about 1%-2% of eligible patients who would benefit end up getting surgery,” added Dr. Martin, Chief, Emergency General Surgery, and Director, Acute Care Surgery Research, USC Medical Center and Keck School of Medicine.

He suggests that the main reason that more patients with lower BMIs are not being offered surgery is related to insurance coverage and reimbursement.

“Even though the professional society guidelines have changed, based on the scientific evidence, most insurers are still using the very outdated (1990s) NIH consensus criteria of BMI greater than 35 with comorbidities, or BMI greater than 40.”

Another potential reason is “the lack of awareness of the changing guidelines and recommendation among primary care physicians who refer patients for a bariatric surgery evaluation.”

“I think it is too early in the experience with the new, more effective antiobesity medications to say which group will benefit the most or will prefer them over surgery,” he said.

“There is still only a small minority of patients who end up getting the [newer antiobesity] medications or surgery.”

“The takeaway,” Dr. Martin summarized, “is that bariatric surgery remains the only intervention with a high success rate for patients with class 1 or higher obesity in terms of weight loss, comorbidity improvement or resolution, and sustained health benefits.”

“We need to expand the availability of bariatric surgery for all eligible patients, particularly the class 1 obesity population who are currently the most underserved,” he said.

“This will take continued lobbying and working with the insurance companies to update their guidelines/criteria, education of patients, and education of primary care physicians so that patients can be appropriately referred for a surgical evaluation.”
 

Surgery vs. pharmacotherapy

Invited to comment on this study, Neil Skolnik, MD, who was not involved with this research, noted that data from patients with a lower BMI “has continued to accumulate, showing much greater safety than earlier studies and giving further support of efficacy.”

However, “[new] recommendations take time to take hold,” noted Dr. Skolnik, a family physician and professor in the department of family medicine, Thomas Jefferson University, Philadelphia.

“And from March of 2020 through 2021, surgery referrals were likely influenced by the COVID pandemic,” he added in an email.

Dr. Skolnik authored a commentary sharing his reservations about ASMBS recommendations issued in 2022 for lower BMI thresholds for this surgery.

“Medications are a safe, effective option for patients with a BMI from 30 to 35,” he said, “and [they] achieve approximately a 15%-20% average weight loss, which is enough to markedly improved both metabolic parameters and biomechanical issues such as knee pain, hip pain, and back pain.”

However, “bariatric surgery remains an excellent option for patients who do not respond sufficiently to pharmacotherapy,” he acknowledged.
 

National registry study, 2015-2021

Dr. Wisniowski and colleagues analyzed data from around 900 U.S. centers that are currently part of the Metabolic Bariatric Surgery Accreditation Quality Improvement Program.

They found that from 2015 to 2021, 38,669 patients (3.5%) with type 1 obesity and 1,1067,094 patients (96.5%) with a higher BMI had metabolic and bariatric surgery.

Compared with patients with BMI greater than 35, those with class 1 obesity had shorter operating times and hospital stays, but they lost less weight on short-term evaluation, after multivariable adjustment.

There were no significant differences between the two patient groups in rates of postoperative complications (< 5%) or mortality (< 0.1%).

Sleeve gastrectomy was the most common procedure and increased from 70% to 76% of all procedures during the study period.
 

Single-center study

In a second e-poster presented at the meeting, Tina T. Thomas, MD, New Jersey Bariatric Center, analyzed data from 23 patients with BMI less than 35 or less than 30 with comorbidities who had sleeve gastrectomy or Roux-en-Y gastric bypass at their center during 2017 to 2021 and who had 6 months of follow-up data.

At study entry, the patients had a mean BMI of 33.5. At 6 months after the surgery, they had a mean BMI of 25.6, and on average, they had lost 55% of their excess weight.

Nearly 60% of the patients had lost at least 50% of their excess weight, and 9 of 16 patients (56%) with comorbidities had improved or resolved comorbidities. None of the patients died or had surgery-related complications.

“Our study shows significant weight loss and health benefits, as well as the safety and efficacy of the gastric bypass and gastric sleeve procedures, for this patient population,” Ajay Goyal, MD, senior author, and bariatric surgeon at New Jersey Bariatric Center, said in an ASMBS press release.

“Often by the time a patient qualifies for bariatric surgery, their weight-related medical conditions such as [type 2] diabetes and hypertension are severe. By expanding access to bariatric surgery to patients with a lower BMI with obesity-related illnesses, patients can halt the progression, and in some cases resolve, significant and uncontrolled weight-related chronic diseases through weight loss.”
 

Societies call for lower BMI thresholds

Providers, hospitals, and insurers currently use BMI thresholds greater than or equal to 40, or greater than or equal to 35 with an obesity-related comorbidity, to define patients eligible for metabolic and bariatric surgery, based on criteria established in a 1991 consensus statement by NIH.

As more data accumulated, in 2016, a position statement from 45 societies recommended that bariatric surgery should be “considered for patients with [type 2 diabetes] and BMI 30.0-34.9 kg/m² if hyperglycemia is inadequately controlled” despite optimal medical treatment.

Similarly, in 2018, the ASMBS issued a position statement saying that “for patients with BMI 30-35 kg/m² and obesity-related comorbidities who do not achieve substantial, durable weight loss and comorbidity improvement with reasonable nonsurgical methods, bariatric surgery should be offered” to suitable individuals.

Then in October 2022, the ASMBS and International Federation for the Surgery of Obesity and Metabolic Disorders issued a joint statement that recommended lowering the thresholds for bariatric surgery to a BMI greater than or equal to 35 or greater than or equal to 30 with weight-related comorbidities.

A version of this article appeared on Medscape.com.

Although multiple international medical societies over recent years have recommended lowering the threshold for bariatric surgery to a body mass index (BMI) of 30-35 (class 1 obesity) in certain patients, very few patients in this weight category have had such surgery, according to a new study.

On the basis of data from a large U.S. national registry, during 2015 through 2021, just 3.5% of metabolic and bariatric surgeries were performed in patients with class 1 obesity each year.

Most surgeries (96.5%) were in patients with a BMI greater than 35. This reflects advice from a 1991 consensus statement by the National Institutes of Health stating that bariatric surgery can be offered to patients with BMI greater than or equal to 40, or greater than or equal to 35 with comorbidities.

However, medical societies have recommended lower cutoffs in position statements in 2016, 2018, and 2022.

Paul Wisniowski, MD, a surgical resident at Keck School of Medicine of University of Southern California, Los Angeles, presented the study findings in an e-poster at the annual meeting of the American Society for Metabolic & Bariatric Surgery.

“Professional guidelines and increasing data support bariatric surgery for patients beginning at BMI 30, which is a tipping point for disease progression. Now it needs to happen in the real world,” outgoing ASMBS president Teresa LaMasters, MD, who was not involved with this research, said in an ASMBS press release.

‘Not unexpected,’ ‘need to expand eligibility’

“We expected that there had been little widespread adoption of the new BMI criteria/cutoffs,” senior study author Matthew J. Martin, MD, said in an interview.

“We know that bariatric surgery is already underutilized, as only about 1%-2% of eligible patients who would benefit end up getting surgery,” added Dr. Martin, Chief, Emergency General Surgery, and Director, Acute Care Surgery Research, USC Medical Center and Keck School of Medicine.

He suggests that the main reason that more patients with lower BMIs are not being offered surgery is related to insurance coverage and reimbursement.

“Even though the professional society guidelines have changed, based on the scientific evidence, most insurers are still using the very outdated (1990s) NIH consensus criteria of BMI greater than 35 with comorbidities, or BMI greater than 40.”

Another potential reason is “the lack of awareness of the changing guidelines and recommendation among primary care physicians who refer patients for a bariatric surgery evaluation.”

“I think it is too early in the experience with the new, more effective antiobesity medications to say which group will benefit the most or will prefer them over surgery,” he said.

“There is still only a small minority of patients who end up getting the [newer antiobesity] medications or surgery.”

“The takeaway,” Dr. Martin summarized, “is that bariatric surgery remains the only intervention with a high success rate for patients with class 1 or higher obesity in terms of weight loss, comorbidity improvement or resolution, and sustained health benefits.”

“We need to expand the availability of bariatric surgery for all eligible patients, particularly the class 1 obesity population who are currently the most underserved,” he said.

“This will take continued lobbying and working with the insurance companies to update their guidelines/criteria, education of patients, and education of primary care physicians so that patients can be appropriately referred for a surgical evaluation.”
 

Surgery vs. pharmacotherapy

Invited to comment on this study, Neil Skolnik, MD, who was not involved with this research, noted that data from patients with a lower BMI “has continued to accumulate, showing much greater safety than earlier studies and giving further support of efficacy.”

However, “[new] recommendations take time to take hold,” noted Dr. Skolnik, a family physician and professor in the department of family medicine, Thomas Jefferson University, Philadelphia.

“And from March of 2020 through 2021, surgery referrals were likely influenced by the COVID pandemic,” he added in an email.

Dr. Skolnik authored a commentary sharing his reservations about ASMBS recommendations issued in 2022 for lower BMI thresholds for this surgery.

“Medications are a safe, effective option for patients with a BMI from 30 to 35,” he said, “and [they] achieve approximately a 15%-20% average weight loss, which is enough to markedly improved both metabolic parameters and biomechanical issues such as knee pain, hip pain, and back pain.”

However, “bariatric surgery remains an excellent option for patients who do not respond sufficiently to pharmacotherapy,” he acknowledged.
 

National registry study, 2015-2021

Dr. Wisniowski and colleagues analyzed data from around 900 U.S. centers that are currently part of the Metabolic Bariatric Surgery Accreditation Quality Improvement Program.

They found that from 2015 to 2021, 38,669 patients (3.5%) with type 1 obesity and 1,1067,094 patients (96.5%) with a higher BMI had metabolic and bariatric surgery.

Compared with patients with BMI greater than 35, those with class 1 obesity had shorter operating times and hospital stays, but they lost less weight on short-term evaluation, after multivariable adjustment.

There were no significant differences between the two patient groups in rates of postoperative complications (< 5%) or mortality (< 0.1%).

Sleeve gastrectomy was the most common procedure and increased from 70% to 76% of all procedures during the study period.
 

Single-center study

In a second e-poster presented at the meeting, Tina T. Thomas, MD, New Jersey Bariatric Center, analyzed data from 23 patients with BMI less than 35 or less than 30 with comorbidities who had sleeve gastrectomy or Roux-en-Y gastric bypass at their center during 2017 to 2021 and who had 6 months of follow-up data.

At study entry, the patients had a mean BMI of 33.5. At 6 months after the surgery, they had a mean BMI of 25.6, and on average, they had lost 55% of their excess weight.

Nearly 60% of the patients had lost at least 50% of their excess weight, and 9 of 16 patients (56%) with comorbidities had improved or resolved comorbidities. None of the patients died or had surgery-related complications.

“Our study shows significant weight loss and health benefits, as well as the safety and efficacy of the gastric bypass and gastric sleeve procedures, for this patient population,” Ajay Goyal, MD, senior author, and bariatric surgeon at New Jersey Bariatric Center, said in an ASMBS press release.

“Often by the time a patient qualifies for bariatric surgery, their weight-related medical conditions such as [type 2] diabetes and hypertension are severe. By expanding access to bariatric surgery to patients with a lower BMI with obesity-related illnesses, patients can halt the progression, and in some cases resolve, significant and uncontrolled weight-related chronic diseases through weight loss.”
 

Societies call for lower BMI thresholds

Providers, hospitals, and insurers currently use BMI thresholds greater than or equal to 40, or greater than or equal to 35 with an obesity-related comorbidity, to define patients eligible for metabolic and bariatric surgery, based on criteria established in a 1991 consensus statement by NIH.

As more data accumulated, in 2016, a position statement from 45 societies recommended that bariatric surgery should be “considered for patients with [type 2 diabetes] and BMI 30.0-34.9 kg/m² if hyperglycemia is inadequately controlled” despite optimal medical treatment.

Similarly, in 2018, the ASMBS issued a position statement saying that “for patients with BMI 30-35 kg/m² and obesity-related comorbidities who do not achieve substantial, durable weight loss and comorbidity improvement with reasonable nonsurgical methods, bariatric surgery should be offered” to suitable individuals.

Then in October 2022, the ASMBS and International Federation for the Surgery of Obesity and Metabolic Disorders issued a joint statement that recommended lowering the thresholds for bariatric surgery to a BMI greater than or equal to 35 or greater than or equal to 30 with weight-related comorbidities.

A version of this article appeared on Medscape.com.

ILLUSTRATION © IRYNA INSHYNA/SHUTTERSTOCK

Patient satisfaction questionnaires were developed in the 1980s as part of the movement to better understand the patient’s experience and their perspective of the quality of care. In 1985, the Press Ganey survey—now the most widely used method to assess patient satisfaction—was developed by 2 professors in anthropology and sociology-statistics at Notre Dame. Initially intended for inpatient admissions, the survey was validated based on a few thousand survey results.¹ Given the strong interest in improving patient satisfaction at the time, it became widely adopted and quickly expanded into outpatient encounters and ambulatory surgery settings.

Although other surveys have been developed,² the Press Ganey survey is the most commonly used assessment tool for patient satisfaction metrics in the United States, with approximately 50% of all hospitals and more than 41,000 health care organizations using its services.^3,4 The survey consists of 6 domains related to satisfaction with:

1. the care provider

2. the nurse or assistant

3. personal issues

4. overall assessment

5. access

6. moving through the visit. 

Survey items are scored using a 5-point Likert scale, with scores ranging from “very poor” (a score of 1) to “very good” (a score of 5). According to the company, because this format is balanced and parallel (unlike a “poor” to “excellent” format), responses can be quantified and used statistically without violating methodologic assumptions. Also, variability in patients’ responses with this format allows for the identification of opportunities to improve, unlike “yes/no” response formats.¹ There are limitations to this design, however, which can impact data quality,⁵ as we will see.

While the distribution process varies by institution, there is an algorithm laid out by Press Ganey for administering surveys to patients in their preferred language after outpatient visits. Based on recent research into Press Ganey response rates, the typical response rate is estimated to be 16% to 19%.⁶ Although this low response rate is typical of survey data, it inherently introduces the risk of responder bias—meaning results may be skewed by patients who represent the extremes of satisfaction or dissatisfaction.

Adoption of the survey as we move toward value-based care

More recently, patients’ satisfaction with their health care has received increased attention as we move to a patient-centered care model and as health care reimbursement models shift toward value-based care. Current trends in health care policy statements include the importance of raising the standard of care and shifting from a “fee-for-service” to a “pay-for-performance” reimbursement model.^7,8 As a result, hospitals are establishing systems to measure “performance” that are not nationally standardized or extensively studied with objective measures. The changing standard of health care expectations in the United States is a topic of much public debate.⁹ And as expectations and new standards are defined, the impact of implementing novel measures of performance should be evaluated prior to widespread adoption and utilization.

Patient satisfaction also has been identified as a driver for hospital finances through loyalty, described as the “likelihood to return to that system for future medical services.”^10,11 This measure has contributed to policy changes that reinforce prioritization of patient satisfaction. For example, the Affordable Care Act tied Medicare reimbursement and patient satisfaction together in the Hospital Value-Based Purchasing Program. This program uses measures of clinical processes, efficiency, outcomes, and patient experiences to calculate a total score that results in hospital reimbursement and incentives,¹² which creates a direct pathway from patient experience to reimbursement—underscoring hospitals’ desire for ongoing assessment of patient satisfaction.

Continue to: Gender, race, and age bias...

Gender, race, and age bias

Although the rationale behind gathering patient input is important, recent data suggest that patient satisfaction surveys are subject to inherent biases.^6,13,14 These biases tend to negatively impact women and non-White physicians, adding to the systemic discrimination against women and physicians of color that already exists in health care.

In a single-site retrospective study performed in 2018 by Rogo-Gupta et al, female gynecologists were found to be 47% less likely to receive top patient satisfaction scores than their male counterparts owing to their gender alone, suggesting that gender bias may impact the results of patient satisfaction questionnaires.¹³ The authors encouraged that the results of patient satisfaction surveys be interpreted with great caution until the impact on female physicians is better understood.

A multi-center study by the same group (Rogo-Gupta et al) assessed the same construct across 5 different geographically diverse institutions.¹⁵ This study confirmed that female gynecologists were less likely to receive a top satisfaction score from their patients (19% lower odds when compared with male gynecologists). They also studied the effects of other patient demographics, including age, race/ethnicity, and race concordance. Older patients (aged ≥63 years) had an over-3-fold increase in odds of providing a top satisfaction score than younger patients. Additionally, Asian physicians had significantly lower odds of receiving a top satisfaction score when compared with White physicians, while Asian patients had significantly lower odds of providing a top satisfaction score when compared with White patients. Lastly, in most cases, when underrepresented-in-medicine patients saw an underrepresented-in-medicine physician (race concordance), there was a significant increase in odds of receiving a top satisfaction score. Asian race concordance, however, actually resulted in a lower likelihood of receiving a top satisfaction score.¹⁵

Literature from other specialties supports these findings. These results are consistent with emerging data from other medical specialties that also suggest that Press Ganey survey data are subject to inherent biases. For example, data from emergency medicine literature have shown discrepancies between patient satisfaction for providers at tertiary inner-city institutions versus those in affluent suburban populations,¹⁶ and that worse mortality is actually correlated with better patient satisfaction scores, and vice versa.¹⁷

Another study by Sotto-Santiago in 2019 assessed patient satisfaction scores in multiple specialties at a single institution where quality-related financial incentives were offered based on this metric. They found a significant difference in patient satisfaction scores between underrepresented and White physicians, which suggests a potential bias among patients and institutional practices—ultimately leading to pay inequities through differences in financial incentives.¹⁸

Percentile differences reveal small gaps in satisfaction ratings

When examining the difference between raw Press Ganey patient satisfaction data and the percentiles associated with these scores, an interesting finding arises. Looking at the 2023 multicenter study by Rogo-Gupta et al, the difference in the top raw scores between male and female gynecologists appears to be small (3.3%).¹⁵ However, in 2020, the difference in top scores separating the top (75th) and bottom (25th) percentile quartiles of physicians was also small, at only 6.9%.

Considering the percentiles, if a provider who scores in the 25th percentile is compared with a colleague who scores in the 75th percentile, they may think the reported satisfaction score differences were quite large. This may potentially invoke feelings of decreased self-worth, negatively impact their professional identity or overall well-being, and they may seek (or be told to seek) improvement opportunities. Now imagine the provider in question realizes the difference between the 25th percentile and 75th percentile is actually only 6.9%. This information may completely change how the results are interpreted and acted upon by administrators. This is further changed with the understanding that 3.3% of the difference may be due to gender alone, narrowing the gap even further. Providers would become understandably frustrated if measures of success such as reimbursement, financial bonus or incentives, promotion, or advancement are linked to these results. It violates the value of fairness and does not offer an equitable starting point.

Evolution of the data distribution. Another consideration, as noted by Robert C. Lloyd, PhD, one of the statisticians who helped develop the percentile statistical analysis mapping in 1985, is that it was based on a classic bell-shaped distribution of patient satisfaction survey scores.¹⁹ Because hospitals, medical groups, and physicians have been working these past 20 years to achieve higher Press Ganey scores, the data no longer have a bell-shaped distribution. Rather, there are significant clusters of raw scores at the high end with a very narrow response range. When these data are mapped to the percentile spectrum, they are highly inaccurate.¹⁹

Impact of sample size. According to Press Ganey, a minimum of 30 survey responses collected over the designated time period is necessary to draw meaningful conclusions of the data for a specific individual, program, or hospital. Despite this requirement to achieve statistical significance, Sullivan and DeLucia found that the firm often provides comparative data about hospital departments and individual physicians based on a smaller sample size that may create an unacceptably large margin of error.²⁰ Sullivan, for example, said his department may only have 8 to 10 Press Ganey survey responses per month and yet still receives monthly reports from the company analyzing the data. Because of the small sample size, 1 month his department ranked in the 1st percentile and 2 months later it ranked in the 99th percentile.²⁰

The effect of a high ceiling rate. A psychometrics report for the Press Ganey survey is available from the vendor that provides vague assessments of reliability and validity based on 2,762 surveys from 12 practices across 10 states. This report describes a 12-question version of the survey with “no problems encountered” with missingness and response variability. The report further states that the Press Ganey survey demonstrates construct, convergent, divergent, and predictive validities, and high reliability; however, these data are not made available.¹

In response to this report, Presson et al analyzed more than 34,000 surveys from one institution to evaluate the reliability and validity of the Press Ganey survey.21 Overall, the survey demonstrated suitable psychometric properties for most metrics. However, Presson et al noted a significantly high ceiling rate of 29.3% for the total score, which ranged from 55.4% to 84.1% across items.²¹ (Ceiling rates are considered substantial if they occur more than 20% of the time.) Ultimately, a high ceiling rate reduces the power to discriminate between patients who have high satisfaction (everyone is “happy”) with those who are just slightly less than happy, but not dissatisfied. This data quality metric can impact the reliability and validity of a survey—and substantial ceiling rates can notably impact percentile rankings of scores within an institution, offering a possible explanation for the small percentage change between the top and bottom percentiles.

Continue to: Other issues with surveys...

Other issues with surveys

In addition to the limitations associated with percentile groupings, survey data are always subject to nonresponse bias, and small sample size can lead to nonsignificant results. Skewed responses also can make it difficult to identify true outlying providers who may need remediation or may be offering a superior patient experience. Satisfaction surveys also lack an assessment of objective data and instead assess how patients perceive and feel, which introduces subjectivity to the results.

Additionally, focusing on improving patient experience ratings can incentivize unnecessary or inappropriate care (ie, overprescribing of narcotics, prescribing antibiotics when not indicated, or ordering testing that may not change management). Some physicians even state that they are not getting the type of feedback that they are asking for and that the survey is not asking the right questions to elicit patient input that is meaningful to their practice. Lastly, the incorporation of trainees and advanced practice providers in the patient care experience leads to the assessment of an alternative provider being included in the ultimate score and may not be representative of that physician.

Patients’ perception and survey results. In some circumstances, the patient’s understanding of their medical situation may affect their responses. Some may argue that patients may mistake a physician’s confidence for competence, when in reality these two entities are mutually exclusive. In a randomized controlled trial, researchers from Mount Sinai School of Medicine and Columbia University Medical Center surveyed inner-city women with newly diagnosed and surgically treated early-stage breast cancer for their perceived quality of care and the process of getting care, including referrals, test results, and treatments. They compared the responses with patient records to determine the actual quality of care. Of the 374 women who received treatment for early-stage breast cancer, 55% said they received “excellent care,” but most—88%—actually got care that was in line with the best current treatment guidelines. Interestingly, the study found African American women were less likely to report excellent care than White or Hispanic women, less likely to trust their doctor, and more likely to say they experienced bias during the process. However, there was no difference in actual quality of care received in any group.²²

You can’t improve what you can’t control. Ultimately, while many providers think patient satisfaction survey results may help inform some aspects of their practice, they cannot improve what they cannot control. For example, the multicenter study by Rogo-Gupta et al found that older patients (≥63 years) have more than a 3-fold increase in odds of giving a top satisfaction score than younger patients (≤33 years), independent of other aspects of the care experience.15 Additionally, they found that older physicians (≥56 years) had a significant increase in odds of receiving a top satisfaction score when compared with physicians who were younger than 55 years old.¹⁵ Given that physicians clearly cannot control their own age or the age of their patients, the negative impacts of these biases need to be addressed and remedied at a systems level.

Why might these biases exist?

While we cannot completely understand all of the possible explanations for these biases, it is important to emphasize the long-standing prejudice and discrimination against women and people of color in our society and how this has impacted our behavior. While strides have been made, there clearly still seems to be a difference between what we say and how our biases impact our behavior. Women are still tougher on women in professional evaluations in other fields as well²³; it is not unique to medicine. While workplace improvements are slowly changing, women still face inequities. The more research we publish to describe it, the more we hope the conversation continues, allowing us to reduce the impact of bias on our sense of self-worth and identity related to our careers, narrow the pay gap, and see women advance at the same rate as male counterparts. Considerable transformation is crucial to prevent further workforce attrition.

With regard to the lower scores provided by Asian patients, studies suggest that cultural response bias, rather than true differences in quality of care, may account for these discrepancies. Previous literature has found that Asian patients are more likely to select midpoints, rather than extremes, when completing Likert-type studies²⁴ and are not more likely to change medical providers than other race/ethnicities, indicating that lower ratings may not necessarily imply greater dissatisfaction with care.²⁵

Far-reaching effects on finances, income, well-being, job satisfaction, etc.

Depending on how the results are distributed and used, the effects of patient satisfaction surveys can extend well beyond the original intentions. At some institutions, income for physicians is directly tied to their Press Ganey satisfaction scores, which could have profound implications for female and Asian physicians,^13,15 who would be paid less—resulting in a wider pay gap than already exists.¹⁸

When negative and not constructive, patient evaluations can contribute to physician burnout and a loss of productive members of the workforce.²⁶ This is especially important in obstetrics and gynecology, where physicians are most likely to experience burnout due to multiple factors such as high-risk medical conditions, pressures of the electronic medical record (EMR), the medicolegal environment, and difficulty balancing patient expectations for autonomy with professional judgement.²⁷ Burnout also disproportionately affects women and younger physicians, which is especially concerning given that, in 2017, approximately one-third of practicing obstetrician/gynecologists were women, while that same year more than 80% of trainees matching into the field were women.²⁸ In one survey sent to members of a prominent medical society, 20% of the medical professionals who responded said they have had their employment threatened by low patient satisfaction scores, 78% reported that patient satisfaction surveys moderately or severely affected their job satisfaction, and 28% stated they had considered quitting their job or leaving the medical profession.²⁹Another related effect is the association between malpractice proceedings and a lack of satisfaction with perceived quality of physician-patient communication.³⁰ This may be an important determinant of malpractice lawsuits, and ensuring high patient satisfaction may be a form of defensive medicine.

Continue to: Controlling the narrative for the future: Proposed strategies...

Controlling the narrative for the future: Proposed strategies

The rapid, widespread adoption of the Press Ganey survey across specialties, clinical care settings, and geographic areas may have been largely due to the ease and operational benefits for hospitals rather than after rigorous study and validation. For example, repeated use of a specific measurement tool may facilitate comparison across areas within a hospital but also across institutions, which can help assess performance at a national level. Hospitals also may have a financial incentive to work with a single third-party or vendor instead of using multiple options across multiple vendors. However, the impact of adoption of novel measures of performance should be evaluated prior to widespread adoption and utilization.

A similar example of an emergence of a technological advancement that has changed the field of medicine and how we provide care is the EMR. Epic is now the most commonly used medical record system and holds the market share of the industry, covering 78% of patients in the United States.³¹ While there are certainly many potential benefits of a common EMR, such as ease of information sharing and standardization of formatting, opportunities are identified in real time and require product adjustment. For example, modifications have been made to accurately represent gender outside of the previously used dichotomous options. Diagnoses such as cervical cancer screening can now be used even if the patient gender is listed as male.

Similarly, the Press Ganey and other patient satisfaction questionnaires should be evaluated and modified to address existing societal biases. The World Health Organization estimates that it will take 300 years to fix gender inequality,³² but we have an opportunity now to control the narrative and improve patient feedback.

Future research avenues

Ultimately, there is a need to further explore currently available methods of evaluating clinical encounters to better understand the inherent biases and limitations. We hope this review will encourage other physicians to examine their specialties and hospitals and require similar analyses from vendors of such satisfaction rating products prior to using them. At the very least, health systems should be willing to partner with vendors and physicians on an ongoing basis to better understand the biases involved in these survey results and make modifications as needed. Patients also obtain information from and contribute to self-reported, publicly available websites; therefore, additional exploration into a nationalized standard for assessing patient satisfaction also may serve as an opportunity to standardize the information patients evaluate.³³ Further assessment of the potential financial and emotional impact of using the currently available patient-reported surveys on female physicians, Asian physicians, young physicians, and physicians who see young patients is needed. It is time to put pressure on a broken patient satisfaction system and improve on a national level to avoid undue negative consequences on our physicians. Use of patient satisfaction survey data should be limited until we all understand and account for the biases that are evident. ●

ILLUSTRATION © IRYNA INSHYNA/SHUTTERSTOCK

Patient satisfaction questionnaires were developed in the 1980s as part of the movement to better understand the patient’s experience and their perspective of the quality of care. In 1985, the Press Ganey survey—now the most widely used method to assess patient satisfaction—was developed by 2 professors in anthropology and sociology-statistics at Notre Dame. Initially intended for inpatient admissions, the survey was validated based on a few thousand survey results.¹ Given the strong interest in improving patient satisfaction at the time, it became widely adopted and quickly expanded into outpatient encounters and ambulatory surgery settings.

Although other surveys have been developed,² the Press Ganey survey is the most commonly used assessment tool for patient satisfaction metrics in the United States, with approximately 50% of all hospitals and more than 41,000 health care organizations using its services.^3,4 The survey consists of 6 domains related to satisfaction with:

1. the care provider

2. the nurse or assistant

3. personal issues

4. overall assessment

5. access

6. moving through the visit. 

Survey items are scored using a 5-point Likert scale, with scores ranging from “very poor” (a score of 1) to “very good” (a score of 5). According to the company, because this format is balanced and parallel (unlike a “poor” to “excellent” format), responses can be quantified and used statistically without violating methodologic assumptions. Also, variability in patients’ responses with this format allows for the identification of opportunities to improve, unlike “yes/no” response formats.¹ There are limitations to this design, however, which can impact data quality,⁵ as we will see.

While the distribution process varies by institution, there is an algorithm laid out by Press Ganey for administering surveys to patients in their preferred language after outpatient visits. Based on recent research into Press Ganey response rates, the typical response rate is estimated to be 16% to 19%.⁶ Although this low response rate is typical of survey data, it inherently introduces the risk of responder bias—meaning results may be skewed by patients who represent the extremes of satisfaction or dissatisfaction.

Adoption of the survey as we move toward value-based care

More recently, patients’ satisfaction with their health care has received increased attention as we move to a patient-centered care model and as health care reimbursement models shift toward value-based care. Current trends in health care policy statements include the importance of raising the standard of care and shifting from a “fee-for-service” to a “pay-for-performance” reimbursement model.^7,8 As a result, hospitals are establishing systems to measure “performance” that are not nationally standardized or extensively studied with objective measures. The changing standard of health care expectations in the United States is a topic of much public debate.⁹ And as expectations and new standards are defined, the impact of implementing novel measures of performance should be evaluated prior to widespread adoption and utilization.

Patient satisfaction also has been identified as a driver for hospital finances through loyalty, described as the “likelihood to return to that system for future medical services.”^10,11 This measure has contributed to policy changes that reinforce prioritization of patient satisfaction. For example, the Affordable Care Act tied Medicare reimbursement and patient satisfaction together in the Hospital Value-Based Purchasing Program. This program uses measures of clinical processes, efficiency, outcomes, and patient experiences to calculate a total score that results in hospital reimbursement and incentives,¹² which creates a direct pathway from patient experience to reimbursement—underscoring hospitals’ desire for ongoing assessment of patient satisfaction.

Continue to: Gender, race, and age bias...

Gender, race, and age bias

Although the rationale behind gathering patient input is important, recent data suggest that patient satisfaction surveys are subject to inherent biases.^6,13,14 These biases tend to negatively impact women and non-White physicians, adding to the systemic discrimination against women and physicians of color that already exists in health care.

In a single-site retrospective study performed in 2018 by Rogo-Gupta et al, female gynecologists were found to be 47% less likely to receive top patient satisfaction scores than their male counterparts owing to their gender alone, suggesting that gender bias may impact the results of patient satisfaction questionnaires.¹³ The authors encouraged that the results of patient satisfaction surveys be interpreted with great caution until the impact on female physicians is better understood.

A multi-center study by the same group (Rogo-Gupta et al) assessed the same construct across 5 different geographically diverse institutions.¹⁵ This study confirmed that female gynecologists were less likely to receive a top satisfaction score from their patients (19% lower odds when compared with male gynecologists). They also studied the effects of other patient demographics, including age, race/ethnicity, and race concordance. Older patients (aged ≥63 years) had an over-3-fold increase in odds of providing a top satisfaction score than younger patients. Additionally, Asian physicians had significantly lower odds of receiving a top satisfaction score when compared with White physicians, while Asian patients had significantly lower odds of providing a top satisfaction score when compared with White patients. Lastly, in most cases, when underrepresented-in-medicine patients saw an underrepresented-in-medicine physician (race concordance), there was a significant increase in odds of receiving a top satisfaction score. Asian race concordance, however, actually resulted in a lower likelihood of receiving a top satisfaction score.¹⁵

Literature from other specialties supports these findings. These results are consistent with emerging data from other medical specialties that also suggest that Press Ganey survey data are subject to inherent biases. For example, data from emergency medicine literature have shown discrepancies between patient satisfaction for providers at tertiary inner-city institutions versus those in affluent suburban populations,¹⁶ and that worse mortality is actually correlated with better patient satisfaction scores, and vice versa.¹⁷

Another study by Sotto-Santiago in 2019 assessed patient satisfaction scores in multiple specialties at a single institution where quality-related financial incentives were offered based on this metric. They found a significant difference in patient satisfaction scores between underrepresented and White physicians, which suggests a potential bias among patients and institutional practices—ultimately leading to pay inequities through differences in financial incentives.¹⁸

Percentile differences reveal small gaps in satisfaction ratings

When examining the difference between raw Press Ganey patient satisfaction data and the percentiles associated with these scores, an interesting finding arises. Looking at the 2023 multicenter study by Rogo-Gupta et al, the difference in the top raw scores between male and female gynecologists appears to be small (3.3%).¹⁵ However, in 2020, the difference in top scores separating the top (75th) and bottom (25th) percentile quartiles of physicians was also small, at only 6.9%.

Considering the percentiles, if a provider who scores in the 25th percentile is compared with a colleague who scores in the 75th percentile, they may think the reported satisfaction score differences were quite large. This may potentially invoke feelings of decreased self-worth, negatively impact their professional identity or overall well-being, and they may seek (or be told to seek) improvement opportunities. Now imagine the provider in question realizes the difference between the 25th percentile and 75th percentile is actually only 6.9%. This information may completely change how the results are interpreted and acted upon by administrators. This is further changed with the understanding that 3.3% of the difference may be due to gender alone, narrowing the gap even further. Providers would become understandably frustrated if measures of success such as reimbursement, financial bonus or incentives, promotion, or advancement are linked to these results. It violates the value of fairness and does not offer an equitable starting point.

Evolution of the data distribution. Another consideration, as noted by Robert C. Lloyd, PhD, one of the statisticians who helped develop the percentile statistical analysis mapping in 1985, is that it was based on a classic bell-shaped distribution of patient satisfaction survey scores.¹⁹ Because hospitals, medical groups, and physicians have been working these past 20 years to achieve higher Press Ganey scores, the data no longer have a bell-shaped distribution. Rather, there are significant clusters of raw scores at the high end with a very narrow response range. When these data are mapped to the percentile spectrum, they are highly inaccurate.¹⁹

Impact of sample size. According to Press Ganey, a minimum of 30 survey responses collected over the designated time period is necessary to draw meaningful conclusions of the data for a specific individual, program, or hospital. Despite this requirement to achieve statistical significance, Sullivan and DeLucia found that the firm often provides comparative data about hospital departments and individual physicians based on a smaller sample size that may create an unacceptably large margin of error.²⁰ Sullivan, for example, said his department may only have 8 to 10 Press Ganey survey responses per month and yet still receives monthly reports from the company analyzing the data. Because of the small sample size, 1 month his department ranked in the 1st percentile and 2 months later it ranked in the 99th percentile.²⁰

The effect of a high ceiling rate. A psychometrics report for the Press Ganey survey is available from the vendor that provides vague assessments of reliability and validity based on 2,762 surveys from 12 practices across 10 states. This report describes a 12-question version of the survey with “no problems encountered” with missingness and response variability. The report further states that the Press Ganey survey demonstrates construct, convergent, divergent, and predictive validities, and high reliability; however, these data are not made available.¹

In response to this report, Presson et al analyzed more than 34,000 surveys from one institution to evaluate the reliability and validity of the Press Ganey survey.21 Overall, the survey demonstrated suitable psychometric properties for most metrics. However, Presson et al noted a significantly high ceiling rate of 29.3% for the total score, which ranged from 55.4% to 84.1% across items.²¹ (Ceiling rates are considered substantial if they occur more than 20% of the time.) Ultimately, a high ceiling rate reduces the power to discriminate between patients who have high satisfaction (everyone is “happy”) with those who are just slightly less than happy, but not dissatisfied. This data quality metric can impact the reliability and validity of a survey—and substantial ceiling rates can notably impact percentile rankings of scores within an institution, offering a possible explanation for the small percentage change between the top and bottom percentiles.

Continue to: Other issues with surveys...

Other issues with surveys

In addition to the limitations associated with percentile groupings, survey data are always subject to nonresponse bias, and small sample size can lead to nonsignificant results. Skewed responses also can make it difficult to identify true outlying providers who may need remediation or may be offering a superior patient experience. Satisfaction surveys also lack an assessment of objective data and instead assess how patients perceive and feel, which introduces subjectivity to the results.

Additionally, focusing on improving patient experience ratings can incentivize unnecessary or inappropriate care (ie, overprescribing of narcotics, prescribing antibiotics when not indicated, or ordering testing that may not change management). Some physicians even state that they are not getting the type of feedback that they are asking for and that the survey is not asking the right questions to elicit patient input that is meaningful to their practice. Lastly, the incorporation of trainees and advanced practice providers in the patient care experience leads to the assessment of an alternative provider being included in the ultimate score and may not be representative of that physician.

Patients’ perception and survey results. In some circumstances, the patient’s understanding of their medical situation may affect their responses. Some may argue that patients may mistake a physician’s confidence for competence, when in reality these two entities are mutually exclusive. In a randomized controlled trial, researchers from Mount Sinai School of Medicine and Columbia University Medical Center surveyed inner-city women with newly diagnosed and surgically treated early-stage breast cancer for their perceived quality of care and the process of getting care, including referrals, test results, and treatments. They compared the responses with patient records to determine the actual quality of care. Of the 374 women who received treatment for early-stage breast cancer, 55% said they received “excellent care,” but most—88%—actually got care that was in line with the best current treatment guidelines. Interestingly, the study found African American women were less likely to report excellent care than White or Hispanic women, less likely to trust their doctor, and more likely to say they experienced bias during the process. However, there was no difference in actual quality of care received in any group.²²

You can’t improve what you can’t control. Ultimately, while many providers think patient satisfaction survey results may help inform some aspects of their practice, they cannot improve what they cannot control. For example, the multicenter study by Rogo-Gupta et al found that older patients (≥63 years) have more than a 3-fold increase in odds of giving a top satisfaction score than younger patients (≤33 years), independent of other aspects of the care experience.15 Additionally, they found that older physicians (≥56 years) had a significant increase in odds of receiving a top satisfaction score when compared with physicians who were younger than 55 years old.¹⁵ Given that physicians clearly cannot control their own age or the age of their patients, the negative impacts of these biases need to be addressed and remedied at a systems level.

Why might these biases exist?

While we cannot completely understand all of the possible explanations for these biases, it is important to emphasize the long-standing prejudice and discrimination against women and people of color in our society and how this has impacted our behavior. While strides have been made, there clearly still seems to be a difference between what we say and how our biases impact our behavior. Women are still tougher on women in professional evaluations in other fields as well²³; it is not unique to medicine. While workplace improvements are slowly changing, women still face inequities. The more research we publish to describe it, the more we hope the conversation continues, allowing us to reduce the impact of bias on our sense of self-worth and identity related to our careers, narrow the pay gap, and see women advance at the same rate as male counterparts. Considerable transformation is crucial to prevent further workforce attrition.

With regard to the lower scores provided by Asian patients, studies suggest that cultural response bias, rather than true differences in quality of care, may account for these discrepancies. Previous literature has found that Asian patients are more likely to select midpoints, rather than extremes, when completing Likert-type studies²⁴ and are not more likely to change medical providers than other race/ethnicities, indicating that lower ratings may not necessarily imply greater dissatisfaction with care.²⁵

Far-reaching effects on finances, income, well-being, job satisfaction, etc.

Depending on how the results are distributed and used, the effects of patient satisfaction surveys can extend well beyond the original intentions. At some institutions, income for physicians is directly tied to their Press Ganey satisfaction scores, which could have profound implications for female and Asian physicians,^13,15 who would be paid less—resulting in a wider pay gap than already exists.¹⁸

When negative and not constructive, patient evaluations can contribute to physician burnout and a loss of productive members of the workforce.²⁶ This is especially important in obstetrics and gynecology, where physicians are most likely to experience burnout due to multiple factors such as high-risk medical conditions, pressures of the electronic medical record (EMR), the medicolegal environment, and difficulty balancing patient expectations for autonomy with professional judgement.²⁷ Burnout also disproportionately affects women and younger physicians, which is especially concerning given that, in 2017, approximately one-third of practicing obstetrician/gynecologists were women, while that same year more than 80% of trainees matching into the field were women.²⁸ In one survey sent to members of a prominent medical society, 20% of the medical professionals who responded said they have had their employment threatened by low patient satisfaction scores, 78% reported that patient satisfaction surveys moderately or severely affected their job satisfaction, and 28% stated they had considered quitting their job or leaving the medical profession.²⁹Another related effect is the association between malpractice proceedings and a lack of satisfaction with perceived quality of physician-patient communication.³⁰ This may be an important determinant of malpractice lawsuits, and ensuring high patient satisfaction may be a form of defensive medicine.

Continue to: Controlling the narrative for the future: Proposed strategies...

Controlling the narrative for the future: Proposed strategies

The rapid, widespread adoption of the Press Ganey survey across specialties, clinical care settings, and geographic areas may have been largely due to the ease and operational benefits for hospitals rather than after rigorous study and validation. For example, repeated use of a specific measurement tool may facilitate comparison across areas within a hospital but also across institutions, which can help assess performance at a national level. Hospitals also may have a financial incentive to work with a single third-party or vendor instead of using multiple options across multiple vendors. However, the impact of adoption of novel measures of performance should be evaluated prior to widespread adoption and utilization.

A similar example of an emergence of a technological advancement that has changed the field of medicine and how we provide care is the EMR. Epic is now the most commonly used medical record system and holds the market share of the industry, covering 78% of patients in the United States.³¹ While there are certainly many potential benefits of a common EMR, such as ease of information sharing and standardization of formatting, opportunities are identified in real time and require product adjustment. For example, modifications have been made to accurately represent gender outside of the previously used dichotomous options. Diagnoses such as cervical cancer screening can now be used even if the patient gender is listed as male.

Similarly, the Press Ganey and other patient satisfaction questionnaires should be evaluated and modified to address existing societal biases. The World Health Organization estimates that it will take 300 years to fix gender inequality,³² but we have an opportunity now to control the narrative and improve patient feedback.

Future research avenues

Ultimately, there is a need to further explore currently available methods of evaluating clinical encounters to better understand the inherent biases and limitations. We hope this review will encourage other physicians to examine their specialties and hospitals and require similar analyses from vendors of such satisfaction rating products prior to using them. At the very least, health systems should be willing to partner with vendors and physicians on an ongoing basis to better understand the biases involved in these survey results and make modifications as needed. Patients also obtain information from and contribute to self-reported, publicly available websites; therefore, additional exploration into a nationalized standard for assessing patient satisfaction also may serve as an opportunity to standardize the information patients evaluate.³³ Further assessment of the potential financial and emotional impact of using the currently available patient-reported surveys on female physicians, Asian physicians, young physicians, and physicians who see young patients is needed. It is time to put pressure on a broken patient satisfaction system and improve on a national level to avoid undue negative consequences on our physicians. Use of patient satisfaction survey data should be limited until we all understand and account for the biases that are evident. ●

ILLUSTRATION © IRYNA INSHYNA/SHUTTERSTOCK

Patient satisfaction questionnaires were developed in the 1980s as part of the movement to better understand the patient’s experience and their perspective of the quality of care. In 1985, the Press Ganey survey—now the most widely used method to assess patient satisfaction—was developed by 2 professors in anthropology and sociology-statistics at Notre Dame. Initially intended for inpatient admissions, the survey was validated based on a few thousand survey results.¹ Given the strong interest in improving patient satisfaction at the time, it became widely adopted and quickly expanded into outpatient encounters and ambulatory surgery settings.

Although other surveys have been developed,² the Press Ganey survey is the most commonly used assessment tool for patient satisfaction metrics in the United States, with approximately 50% of all hospitals and more than 41,000 health care organizations using its services.^3,4 The survey consists of 6 domains related to satisfaction with:

1. the care provider

2. the nurse or assistant

3. personal issues

4. overall assessment

5. access

6. moving through the visit. 

Survey items are scored using a 5-point Likert scale, with scores ranging from “very poor” (a score of 1) to “very good” (a score of 5). According to the company, because this format is balanced and parallel (unlike a “poor” to “excellent” format), responses can be quantified and used statistically without violating methodologic assumptions. Also, variability in patients’ responses with this format allows for the identification of opportunities to improve, unlike “yes/no” response formats.¹ There are limitations to this design, however, which can impact data quality,⁵ as we will see.

While the distribution process varies by institution, there is an algorithm laid out by Press Ganey for administering surveys to patients in their preferred language after outpatient visits. Based on recent research into Press Ganey response rates, the typical response rate is estimated to be 16% to 19%.⁶ Although this low response rate is typical of survey data, it inherently introduces the risk of responder bias—meaning results may be skewed by patients who represent the extremes of satisfaction or dissatisfaction.

Adoption of the survey as we move toward value-based care

More recently, patients’ satisfaction with their health care has received increased attention as we move to a patient-centered care model and as health care reimbursement models shift toward value-based care. Current trends in health care policy statements include the importance of raising the standard of care and shifting from a “fee-for-service” to a “pay-for-performance” reimbursement model.^7,8 As a result, hospitals are establishing systems to measure “performance” that are not nationally standardized or extensively studied with objective measures. The changing standard of health care expectations in the United States is a topic of much public debate.⁹ And as expectations and new standards are defined, the impact of implementing novel measures of performance should be evaluated prior to widespread adoption and utilization.

Patient satisfaction also has been identified as a driver for hospital finances through loyalty, described as the “likelihood to return to that system for future medical services.”^10,11 This measure has contributed to policy changes that reinforce prioritization of patient satisfaction. For example, the Affordable Care Act tied Medicare reimbursement and patient satisfaction together in the Hospital Value-Based Purchasing Program. This program uses measures of clinical processes, efficiency, outcomes, and patient experiences to calculate a total score that results in hospital reimbursement and incentives,¹² which creates a direct pathway from patient experience to reimbursement—underscoring hospitals’ desire for ongoing assessment of patient satisfaction.

Continue to: Gender, race, and age bias...

Gender, race, and age bias

Although the rationale behind gathering patient input is important, recent data suggest that patient satisfaction surveys are subject to inherent biases.^6,13,14 These biases tend to negatively impact women and non-White physicians, adding to the systemic discrimination against women and physicians of color that already exists in health care.

In a single-site retrospective study performed in 2018 by Rogo-Gupta et al, female gynecologists were found to be 47% less likely to receive top patient satisfaction scores than their male counterparts owing to their gender alone, suggesting that gender bias may impact the results of patient satisfaction questionnaires.¹³ The authors encouraged that the results of patient satisfaction surveys be interpreted with great caution until the impact on female physicians is better understood.

A multi-center study by the same group (Rogo-Gupta et al) assessed the same construct across 5 different geographically diverse institutions.¹⁵ This study confirmed that female gynecologists were less likely to receive a top satisfaction score from their patients (19% lower odds when compared with male gynecologists). They also studied the effects of other patient demographics, including age, race/ethnicity, and race concordance. Older patients (aged ≥63 years) had an over-3-fold increase in odds of providing a top satisfaction score than younger patients. Additionally, Asian physicians had significantly lower odds of receiving a top satisfaction score when compared with White physicians, while Asian patients had significantly lower odds of providing a top satisfaction score when compared with White patients. Lastly, in most cases, when underrepresented-in-medicine patients saw an underrepresented-in-medicine physician (race concordance), there was a significant increase in odds of receiving a top satisfaction score. Asian race concordance, however, actually resulted in a lower likelihood of receiving a top satisfaction score.¹⁵

Literature from other specialties supports these findings. These results are consistent with emerging data from other medical specialties that also suggest that Press Ganey survey data are subject to inherent biases. For example, data from emergency medicine literature have shown discrepancies between patient satisfaction for providers at tertiary inner-city institutions versus those in affluent suburban populations,¹⁶ and that worse mortality is actually correlated with better patient satisfaction scores, and vice versa.¹⁷

Another study by Sotto-Santiago in 2019 assessed patient satisfaction scores in multiple specialties at a single institution where quality-related financial incentives were offered based on this metric. They found a significant difference in patient satisfaction scores between underrepresented and White physicians, which suggests a potential bias among patients and institutional practices—ultimately leading to pay inequities through differences in financial incentives.¹⁸

Percentile differences reveal small gaps in satisfaction ratings

When examining the difference between raw Press Ganey patient satisfaction data and the percentiles associated with these scores, an interesting finding arises. Looking at the 2023 multicenter study by Rogo-Gupta et al, the difference in the top raw scores between male and female gynecologists appears to be small (3.3%).¹⁵ However, in 2020, the difference in top scores separating the top (75th) and bottom (25th) percentile quartiles of physicians was also small, at only 6.9%.

Considering the percentiles, if a provider who scores in the 25th percentile is compared with a colleague who scores in the 75th percentile, they may think the reported satisfaction score differences were quite large. This may potentially invoke feelings of decreased self-worth, negatively impact their professional identity or overall well-being, and they may seek (or be told to seek) improvement opportunities. Now imagine the provider in question realizes the difference between the 25th percentile and 75th percentile is actually only 6.9%. This information may completely change how the results are interpreted and acted upon by administrators. This is further changed with the understanding that 3.3% of the difference may be due to gender alone, narrowing the gap even further. Providers would become understandably frustrated if measures of success such as reimbursement, financial bonus or incentives, promotion, or advancement are linked to these results. It violates the value of fairness and does not offer an equitable starting point.

Evolution of the data distribution. Another consideration, as noted by Robert C. Lloyd, PhD, one of the statisticians who helped develop the percentile statistical analysis mapping in 1985, is that it was based on a classic bell-shaped distribution of patient satisfaction survey scores.¹⁹ Because hospitals, medical groups, and physicians have been working these past 20 years to achieve higher Press Ganey scores, the data no longer have a bell-shaped distribution. Rather, there are significant clusters of raw scores at the high end with a very narrow response range. When these data are mapped to the percentile spectrum, they are highly inaccurate.¹⁹

Impact of sample size. According to Press Ganey, a minimum of 30 survey responses collected over the designated time period is necessary to draw meaningful conclusions of the data for a specific individual, program, or hospital. Despite this requirement to achieve statistical significance, Sullivan and DeLucia found that the firm often provides comparative data about hospital departments and individual physicians based on a smaller sample size that may create an unacceptably large margin of error.²⁰ Sullivan, for example, said his department may only have 8 to 10 Press Ganey survey responses per month and yet still receives monthly reports from the company analyzing the data. Because of the small sample size, 1 month his department ranked in the 1st percentile and 2 months later it ranked in the 99th percentile.²⁰

The effect of a high ceiling rate. A psychometrics report for the Press Ganey survey is available from the vendor that provides vague assessments of reliability and validity based on 2,762 surveys from 12 practices across 10 states. This report describes a 12-question version of the survey with “no problems encountered” with missingness and response variability. The report further states that the Press Ganey survey demonstrates construct, convergent, divergent, and predictive validities, and high reliability; however, these data are not made available.¹

In response to this report, Presson et al analyzed more than 34,000 surveys from one institution to evaluate the reliability and validity of the Press Ganey survey.21 Overall, the survey demonstrated suitable psychometric properties for most metrics. However, Presson et al noted a significantly high ceiling rate of 29.3% for the total score, which ranged from 55.4% to 84.1% across items.²¹ (Ceiling rates are considered substantial if they occur more than 20% of the time.) Ultimately, a high ceiling rate reduces the power to discriminate between patients who have high satisfaction (everyone is “happy”) with those who are just slightly less than happy, but not dissatisfied. This data quality metric can impact the reliability and validity of a survey—and substantial ceiling rates can notably impact percentile rankings of scores within an institution, offering a possible explanation for the small percentage change between the top and bottom percentiles.

Continue to: Other issues with surveys...

Other issues with surveys

In addition to the limitations associated with percentile groupings, survey data are always subject to nonresponse bias, and small sample size can lead to nonsignificant results. Skewed responses also can make it difficult to identify true outlying providers who may need remediation or may be offering a superior patient experience. Satisfaction surveys also lack an assessment of objective data and instead assess how patients perceive and feel, which introduces subjectivity to the results.

Additionally, focusing on improving patient experience ratings can incentivize unnecessary or inappropriate care (ie, overprescribing of narcotics, prescribing antibiotics when not indicated, or ordering testing that may not change management). Some physicians even state that they are not getting the type of feedback that they are asking for and that the survey is not asking the right questions to elicit patient input that is meaningful to their practice. Lastly, the incorporation of trainees and advanced practice providers in the patient care experience leads to the assessment of an alternative provider being included in the ultimate score and may not be representative of that physician.

Patients’ perception and survey results. In some circumstances, the patient’s understanding of their medical situation may affect their responses. Some may argue that patients may mistake a physician’s confidence for competence, when in reality these two entities are mutually exclusive. In a randomized controlled trial, researchers from Mount Sinai School of Medicine and Columbia University Medical Center surveyed inner-city women with newly diagnosed and surgically treated early-stage breast cancer for their perceived quality of care and the process of getting care, including referrals, test results, and treatments. They compared the responses with patient records to determine the actual quality of care. Of the 374 women who received treatment for early-stage breast cancer, 55% said they received “excellent care,” but most—88%—actually got care that was in line with the best current treatment guidelines. Interestingly, the study found African American women were less likely to report excellent care than White or Hispanic women, less likely to trust their doctor, and more likely to say they experienced bias during the process. However, there was no difference in actual quality of care received in any group.²²

You can’t improve what you can’t control. Ultimately, while many providers think patient satisfaction survey results may help inform some aspects of their practice, they cannot improve what they cannot control. For example, the multicenter study by Rogo-Gupta et al found that older patients (≥63 years) have more than a 3-fold increase in odds of giving a top satisfaction score than younger patients (≤33 years), independent of other aspects of the care experience.15 Additionally, they found that older physicians (≥56 years) had a significant increase in odds of receiving a top satisfaction score when compared with physicians who were younger than 55 years old.¹⁵ Given that physicians clearly cannot control their own age or the age of their patients, the negative impacts of these biases need to be addressed and remedied at a systems level.

Why might these biases exist?

While we cannot completely understand all of the possible explanations for these biases, it is important to emphasize the long-standing prejudice and discrimination against women and people of color in our society and how this has impacted our behavior. While strides have been made, there clearly still seems to be a difference between what we say and how our biases impact our behavior. Women are still tougher on women in professional evaluations in other fields as well²³; it is not unique to medicine. While workplace improvements are slowly changing, women still face inequities. The more research we publish to describe it, the more we hope the conversation continues, allowing us to reduce the impact of bias on our sense of self-worth and identity related to our careers, narrow the pay gap, and see women advance at the same rate as male counterparts. Considerable transformation is crucial to prevent further workforce attrition.

With regard to the lower scores provided by Asian patients, studies suggest that cultural response bias, rather than true differences in quality of care, may account for these discrepancies. Previous literature has found that Asian patients are more likely to select midpoints, rather than extremes, when completing Likert-type studies²⁴ and are not more likely to change medical providers than other race/ethnicities, indicating that lower ratings may not necessarily imply greater dissatisfaction with care.²⁵

Far-reaching effects on finances, income, well-being, job satisfaction, etc.

Depending on how the results are distributed and used, the effects of patient satisfaction surveys can extend well beyond the original intentions. At some institutions, income for physicians is directly tied to their Press Ganey satisfaction scores, which could have profound implications for female and Asian physicians,^13,15 who would be paid less—resulting in a wider pay gap than already exists.¹⁸

When negative and not constructive, patient evaluations can contribute to physician burnout and a loss of productive members of the workforce.²⁶ This is especially important in obstetrics and gynecology, where physicians are most likely to experience burnout due to multiple factors such as high-risk medical conditions, pressures of the electronic medical record (EMR), the medicolegal environment, and difficulty balancing patient expectations for autonomy with professional judgement.²⁷ Burnout also disproportionately affects women and younger physicians, which is especially concerning given that, in 2017, approximately one-third of practicing obstetrician/gynecologists were women, while that same year more than 80% of trainees matching into the field were women.²⁸ In one survey sent to members of a prominent medical society, 20% of the medical professionals who responded said they have had their employment threatened by low patient satisfaction scores, 78% reported that patient satisfaction surveys moderately or severely affected their job satisfaction, and 28% stated they had considered quitting their job or leaving the medical profession.²⁹Another related effect is the association between malpractice proceedings and a lack of satisfaction with perceived quality of physician-patient communication.³⁰ This may be an important determinant of malpractice lawsuits, and ensuring high patient satisfaction may be a form of defensive medicine.

Continue to: Controlling the narrative for the future: Proposed strategies...

Controlling the narrative for the future: Proposed strategies

The rapid, widespread adoption of the Press Ganey survey across specialties, clinical care settings, and geographic areas may have been largely due to the ease and operational benefits for hospitals rather than after rigorous study and validation. For example, repeated use of a specific measurement tool may facilitate comparison across areas within a hospital but also across institutions, which can help assess performance at a national level. Hospitals also may have a financial incentive to work with a single third-party or vendor instead of using multiple options across multiple vendors. However, the impact of adoption of novel measures of performance should be evaluated prior to widespread adoption and utilization.

A similar example of an emergence of a technological advancement that has changed the field of medicine and how we provide care is the EMR. Epic is now the most commonly used medical record system and holds the market share of the industry, covering 78% of patients in the United States.³¹ While there are certainly many potential benefits of a common EMR, such as ease of information sharing and standardization of formatting, opportunities are identified in real time and require product adjustment. For example, modifications have been made to accurately represent gender outside of the previously used dichotomous options. Diagnoses such as cervical cancer screening can now be used even if the patient gender is listed as male.

Similarly, the Press Ganey and other patient satisfaction questionnaires should be evaluated and modified to address existing societal biases. The World Health Organization estimates that it will take 300 years to fix gender inequality,³² but we have an opportunity now to control the narrative and improve patient feedback.

Future research avenues

Ultimately, there is a need to further explore currently available methods of evaluating clinical encounters to better understand the inherent biases and limitations. We hope this review will encourage other physicians to examine their specialties and hospitals and require similar analyses from vendors of such satisfaction rating products prior to using them. At the very least, health systems should be willing to partner with vendors and physicians on an ongoing basis to better understand the biases involved in these survey results and make modifications as needed. Patients also obtain information from and contribute to self-reported, publicly available websites; therefore, additional exploration into a nationalized standard for assessing patient satisfaction also may serve as an opportunity to standardize the information patients evaluate.³³ Further assessment of the potential financial and emotional impact of using the currently available patient-reported surveys on female physicians, Asian physicians, young physicians, and physicians who see young patients is needed. It is time to put pressure on a broken patient satisfaction system and improve on a national level to avoid undue negative consequences on our physicians. Use of patient satisfaction survey data should be limited until we all understand and account for the biases that are evident. ●

This year’s menopause Update highlights a highly effective nonhormonal medication that recently received approval by the US Food and Drug Administration (FDA) for the treatment of bothersome menopausal vasomotor symptoms. In addition, the Update provides guidance regarding how ObGyns should respond when an endometrial biopsy for postmenopausal bleeding reveals proliferative changes.

Breakthrough in women’s health: A new nonhormone therapy for vasomotor symptoms

Johnson KA, Martin N, Nappi RE, et al. Efficacy and safety of fezolinetant in moderate-to-severe vasomotor symptoms associated with menopause: a phase 3 RCT. J Clin Endocrinol Metab. 2023;dgad058. doi:10.1210/clinem/dgad058.
 

Lederman S, Ottery FD, Cano A, et al. Fezolinetant for treatment of moderate-to-severe vasomotor symptoms associated with menopause (SKYLIGHT 1): a phase 3 randomised controlled study. Lancet. 2023;401:1091-1102. doi:10.1016/S0140-6736(23)00085-5.

A new oral nonestrogen-containing medication for relief of moderate to severe hot flashes, fezolinetant (Veozah) 45 mg daily, has been approved by the FDA and was expected to be available by the end of May 2023. Fezolinetant is a selective neurokinin 3 (NK3) receptor antagonistthat offers a targeted nonhormonal approach to menopausal vasomotor symptoms (VMS), and it is the first in its class to make it to market.

The decline in estrogen at menopause appears to result in increased signaling at kisspeptin/neurokinin B/dynorphin (KNDy) neurons in the thermoregulatory center within the hypothalamus with resultant increases in hot flashes.^1,2 Fezolinetant works by binding to and blocking the activities of the NK3 receptor.^3-5

Key study findings

Selective NK3 receptor antagonists, including fezolinetant, effectively reduce the frequency and severity of VMS comparable to that of hormone therapy (HT). Two phase 3 clinical trials, Skylight 1 and 2, confirmed the efficacy and safety of fezolinetant 45 mg in treating VMS,^6,7 and an additional 52-week placebo-controlled study, Skylight 4, confirmed long-term safety.⁸ Onset of action occurs within a week. Reported adverse events occurred in 1% to 2% of healthy menopausal women participating in clinical trials; these included headaches, abdominal pain, diarrhea, insomnia, back pain, hot flushes, and reversible elevated hepatic transaminase levels.^6-9

The published phase 2 trials⁹ and the international randomized controlled trial (RCT) 12-week studies, Skylight 1 and 2,^6,7 found that once-daily 30-mg and 45-mg doses of fezolinetant significantly reduced VMS frequency and severity at 12 weeks among women aged 40 to 60 years who reported an average of 7 moderate to severe VMS/day; the reduction in reported VMS was sustained at 40 weeks. Phase 3 data from Skylight 1 and 2 demonstrated fezolinetant’s efficacy in reducing the frequency and severity of VMS and provided information on the safety profile of fezolinetant compared with placebo over 12 weeks and a noncontrolled extension for an additional 40 weeks.^6,7

Oral fezolinetant was associated with improved quality of life, including reduced VMS-related interference with daily life.¹⁰ Johnson and colleagues, reporting for Skylight 2, found VMS frequency and severity improvement by week 1, which achieved statistical significance at weeks 4 and 12, with this improvement maintained through week 52.⁶ A 64.3% reduction in mean daily VMS from baseline was seen at 12 weeks for fezolinetant 45 mg compared with a 45.4% reduction for placebo. VMS severity significantly decreased compared with placebo at 4 and 12 weeks.⁶

Serious treatment-emergent adverse events were infrequent, reported by 2%, 1%, and 0% of those receiving fezolinetant 30 mg, fezolinetant 45 mg, and placebo.⁶ Increases in levels of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) were noted and were described as asymptomatic, isolated, intermittent, or transient, and these levels returned to baseline during treatment or after discontinuation.⁶

Of the 5 participants taking fezolinetant in Skyline 1 with ALT or AST levels greater than 3 times the upper limit of normal in the 12-week randomized trial, levels returned to normal range while continuing treatment in 2 participants, with treatment interruption in 2, and with discontinuation in 1. No new safety signals were seen in the 40-week extension trial.⁶

Continue to: Endometrial and bone safety...

Endometrial and bone safety

Results from Skylight 4, a phase 3, randomized, double-blind, 52-week safety study, provided additional evidence that confirmed the longer-term safety of fezolinetant over a 52-week treatment period.⁸

Endometrial safety was assessed in postmenopausal women with normal baseline endometrium (n = 599).⁸ For fezolinetant 45 mg, 1 of 203 participants had endometrial hyperplasia (EH) (0.5%; upper limit of one-sided 95% confidence interval [CI], 2.3%); no cases of EH were noted in the placebo (0 of 186) or fezolinetant 30-mg (0 of 210) groups. The incidence of EH or malignancy in fezolinetant-treated participants was within prespecified limits, as assessed by blinded, centrally read endometrial biopsies. Endometrial malignancy occurred in 1 of 210 in the fezolinetant 30-mg group (0.5%; 95% CI, 2.2%) with no cases in the other groups, thus meeting FDA requirements for endometrial safety.⁸

In addition, no significant differences were noted in change from baseline endometrial thickness on transvaginal ultrasonography between fezolinetant-treated and placebo groups. Likewise, no loss of bone density was found on dual-energy x-ray absorptiometry (DEXA) scans or trabecular bone scores.⁸

Liver safety

Although no cases of severe liver injury were noted, elevations in serum transaminase concentrations greater than 3 times the upper limit of normal were observed in the clinical trials. In Skylight 4, liver enzyme elevations more than 3 times the upper limit of normal occurred in 6 of 583 participants taking placebo, 8 of 590 taking fezolinetant 30 mg, and 12 of 589 taking fezolinetant 45 mg.⁸

The prescribing information for fezolinetant includes a warning for elevated hepatic transaminases: Fezolinetant should not be started if baseline serum transaminase concentration is equal to or exceeds 2 times the upper limit of normal. Liver tests should be obtained at baseline and repeated every 3 months for the first 9 months and then if symptoms suggest liver injury.^11,12

Unmet need for nonhormone treatment of VMS

Vasomotor symptoms affect up to 80% of women, with approximately 25% bothersome enough to warrant treatment. Vasomotor symptoms persist for a median of 7 years, with duration and severity differing by race and ethnicity. Black, Hispanic, and possibly Native American women experience the highest burden of VMS.² Although VMS, including hot flashes, night sweats, and mood and sleep disturbances, often are considered an annoyance to those with mild symptoms, moderate to severe VMS impact women’s lives, including functioning at home or work, affecting relationships, and decreasing perceived quality of life, and they have been associated with workplace absenteeism and increased health care costs, both direct from medical care and testing and indirect costs from lost work.^13-15

Women with 7 or more daily moderate to severe VMS (defined as with sweating or affecting function) reported interference with sleep (94%), concentration (84%), mood (85%), energy (77%), and sexual activity (61%).¹⁶ Moderately to severely bothersome VMS have been associated with impaired psychological and general well-being, affecting work performance.¹⁷ Based on a Mayo Clinic workplace survey, Faubion and colleagues estimated an annual loss of $1.8 billion in the United States for menopause-related missed work and a $28 billion loss when medical expenses were added.¹⁵

Menopausal HT has been the primary treatment for VMS and has been shown to reduce the frequency and severity of hot flashes, with additional benefits on sleep, mood, fatigue, bone loss and reduction of fracture, and genitourinary syndrome of menopause (GSM), and with potential improvement in cardiovascular health with decreased type 2 diabetes.^18,19 For healthy women with early menopause and no contraindications, HT has been recommended until at least the age of natural menopause, as observational data suggest that HT prevents osteoporosis, cardiovascular disease, neurodegenerative changes, and sexual dysfunction for these women.^19,20 Similarly, for healthy women younger than age 60 or within 10 years of menopause, initiating HT has been shown to be safe and effective in treating bothersome VMS and preventing osteoporotic fractures and genitourinary changes.^19,21

Most systemic HT formulations are inexpensive (for example, available as generics), with multiple dosing and formulations available for use alone or combined as oral, transdermal, or vaginal therapies. Despite the fear that arose for clinicians and women from the initial 2002 findings of the Women’s Health Initiative regarding increased risk of breast cancer, stroke, venous thrombosis, cardiovascular disease, and dementia, major medical societies agree that when initiated at or soon after menopause, HT is a safe and effective therapy to relieve VMS, protect against bone loss, and treat genitourinary changes.^19,21

Many women, however, cannot take HT, including those with estrogen-sensitive cancers, such as breast or uterine cancers; prior cardiovascular disease, stroke, or venous thrombotic events; severe endometriosis; or migraine headaches with visual auras.² In addition, many symptomatic menopausal women without health contraindications choose not to take HT.² Until now, the only FDA-approved VMS nonhormone therapy has been a low-dose 7.5-mg paroxetine salt. Unfortunately, this formulation, along with the off-label use of other antidepressants (selective serotonin reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors), gabapentinoids, oxybutynin, and clonidine, are substantially less effective than HT in treating moderate to severe VMS.

Bottom line

A substantial unmet need remains for effective therapy for moderate to severe VMS for women who cannot or choose not to take menopausal HT to relieve VMS.^2,16 Effective, safe nonhormone treatment options such as the new NK3 receptor antagonist fezolinetant will address this clinically important need.

One concern is that the cost of developing and bringing to market the first of a new type of medication will be passed on to consumers, which may put it out of the price range for the many women who need it. However, the development and FDA approval of fezolinetant as the first NK3 receptor antagonist to treat menopausal VMS is potentially a practice changer. It provides a novel, effective, and safe FDA-approved nonhormonal treatment for menopausal women with moderate to severe VMS, particularly for women who cannot or will not take hormone therapy.

Continue to: When endometrial biopsy for postmenopausal bleeding reveals proliferative changes, how should we respond?...

Abraham C. Proliferative endometrium in menopause: to treat or not to treat? Obstet Gynecol. 2023;141:265-267. doi:10.1097/AOG.0000000000005054.

The following case represents a common scenario for ObGyns.

CASE Patient with proliferative endometrial changes

A menopausal patient with a body mass index (BMI) > 30 kg/m² presents with uterine bleeding. She does not use systemic menopausal hormone therapy. Endometrial biopsy indicates proliferative changes.

When endometrial biopsy performed for bleeding reveals proliferative changes in menopausal women, we traditionally have responded by reassuring the patient that the findings are benign and advising that she should let us know if future spotting or bleeding occurs.

However, a recent review by Abraham published in Obstetrics and Gynecology details the implications of proliferative endometrial changes in menopausal patients, advising that treatment, as well as monitoring, may be appropriate.²²

Endometrial changes and what they suggest

In premenopausal women, proliferative endometrial changes are physiologic and result from ovarian estrogen production early in each cycle, during what is called the proliferative (referring to the endometrium) or follicular (referring to the dominant follicle that synthesizes estrogen) phase. In menopausal women who are not using HT, however, proliferative endometrial changes, with orderly uniform glands seen on histologic evaluation, reflect aromatization of androgens by adipose and other tissues into estrogen.

The next step on the continuum to hyperplasia (benign or atypical) after proliferative endometrium is disordered proliferative endometrium. At this stage, histologic evaluation reveals scattered cystic and dilated glands that have a normal gland-to-stroma ratio with a low gland density overall and without any atypia. Randomly distributed glands may have tubal metaplasia or fibrin thrombi associated with microinfarcts, often presenting with irregular bleeding. This is a noncancerous change that occurs with excess estrogen (endogenous or exogenous).²³

Progestins reverse endometrial hyperplasia by activating progesterone receptors, which leads to stromal decidualization with thinning of the endometrium. They have a pronounced effect on the histologic appearance of the endometrium. By contrast, endometrial intraepithelial neoplasia (EIN, previously known as endometrial hyperplasiawith atypia) shows underlying molecular mutations and histologic alterations and represents a sharp transition to true neoplasia, which greatly increases the risk of endometrioid endometrial adenocarcinoma.²⁴

For decades, we have been aware that if women diagnosed with endometrial hyperplasia are not treated with progestational therapy, their future risk of endometrial cancer is elevated. More recently, we also recognize that menopausal women found to have proliferative endometrial changes, if not treated, have an increased risk of endometrial cancer.

In a retrospective cohort study of almost 300 menopausal women who were not treated after endometrial biopsy revealed proliferative changes, investigators followed participants for an average of 11 years.²⁵ These women had a mean BMI of 34 kg/m². During follow-up, almost 12% of these women were diagnosed with endometrial hyperplasia or cancer. This incidence of endometrial neoplasia was some 4 times higher than for women initially found to have atrophic endometrial changes.²⁵

Progestin treatment

Oral progestin therapy with follow-up endometrial biopsy constitutes traditional management for endometrial hyperplasia. Such therapy minimizes the likelihood that hyperplasia will progress to endometrial cancer.

We now recognize that the convenience, as well as the high endometrial progestin levels achieved, with levonorgestrel-releasing intrauterine devices (LNG-IUDs) have advantages over oral progestin therapy in treating endometrial hyperplasia. Indeed, a recent US report found that among women with EIN managed medically, use of progestin-releasing IUDs has grown from 7.7% in 2008 to 35.6% in 2020.²⁶

Although both oral and intrauterine progestin are highly effective in treating simple hyperplasia, progestin IUDs are substantially more effective than oral progestins in treating EIN.²⁷ Progestin concentrations in the endometrium have been shown to be 100-fold higher after LNG-IUD placement compared with oral progestin use.²² In addition, adverse effects, including bloating, unpleasant mood changes, and increased appetite, are more common with oral than intrauterine progestin therapy.²⁸

Unfortunately, data from randomized trials addressing progestational treatment of proliferative endometrium in menopausal women are not available to support the treatment of proliferative endometrium with either oral progestins or the LNG-IUD.²²

Role of ultrasonography

Another concern is relying on a finding of thin endometrial thickness on vaginal ultrasonography. In a simulated retrospective cohort study, use of transvaginal ultrasonography to determine the appropriateness of a biopsy was found not to be sufficiently accurate or racially equitable with regard to Black women.²⁹ In simulated data, transvaginal ultrasonography missed almost 5 times more cases of endometrial cancer among Black women compared with White women due to higher fibroid prevalence and nonendometrioid histologic type malignancies in Black women.²⁹

Assessing risk

If proliferative endometrium is found, Abraham suggests assessing risk using²²:

• age
• comorbidities (including obesity)
• endometrial echo thickness on vaginal ultrasonography.

Consider the patient’s risk and tolerance of recurrent bleeding as well as her tolerance for progestational adverse effects if medical therapy is chosen. Discussion about next steps should include reviewing the histologic findings with the patient and discussing the difference in risk of progression to endometrial cancer of a finding of proliferative endometrium compared with a histologic finding of endometrial hyperplasia.

Using this patient-centered approach, observation over time with follow-up endometrial biopsies remains a management option. Although some women may tolerate micronized progesterone over synthetic progestins, there is concern that it may be less effective in suppressing the endometrium than synthetic progestins.³⁰ Accordingly, synthetic progestins represent first-line options in this setting^.

In her review, Abraham suggests that when endometrial biopsy reveals proliferative changes in a menopausal woman, we should initiate progestin treatment and perform surveillance endometrial sampling every 3 to 6 months. If such sampling reveals benign but not proliferative endometrium, progestin therapy can be stopped and endometrial biopsy repeated if bleeding recurs.²² ●

This year’s menopause Update highlights a highly effective nonhormonal medication that recently received approval by the US Food and Drug Administration (FDA) for the treatment of bothersome menopausal vasomotor symptoms. In addition, the Update provides guidance regarding how ObGyns should respond when an endometrial biopsy for postmenopausal bleeding reveals proliferative changes.

Breakthrough in women’s health: A new nonhormone therapy for vasomotor symptoms

Johnson KA, Martin N, Nappi RE, et al. Efficacy and safety of fezolinetant in moderate-to-severe vasomotor symptoms associated with menopause: a phase 3 RCT. J Clin Endocrinol Metab. 2023;dgad058. doi:10.1210/clinem/dgad058.
 

Lederman S, Ottery FD, Cano A, et al. Fezolinetant for treatment of moderate-to-severe vasomotor symptoms associated with menopause (SKYLIGHT 1): a phase 3 randomised controlled study. Lancet. 2023;401:1091-1102. doi:10.1016/S0140-6736(23)00085-5.

A new oral nonestrogen-containing medication for relief of moderate to severe hot flashes, fezolinetant (Veozah) 45 mg daily, has been approved by the FDA and was expected to be available by the end of May 2023. Fezolinetant is a selective neurokinin 3 (NK3) receptor antagonistthat offers a targeted nonhormonal approach to menopausal vasomotor symptoms (VMS), and it is the first in its class to make it to market.

The decline in estrogen at menopause appears to result in increased signaling at kisspeptin/neurokinin B/dynorphin (KNDy) neurons in the thermoregulatory center within the hypothalamus with resultant increases in hot flashes.^1,2 Fezolinetant works by binding to and blocking the activities of the NK3 receptor.^3-5

Key study findings

Selective NK3 receptor antagonists, including fezolinetant, effectively reduce the frequency and severity of VMS comparable to that of hormone therapy (HT). Two phase 3 clinical trials, Skylight 1 and 2, confirmed the efficacy and safety of fezolinetant 45 mg in treating VMS,^6,7 and an additional 52-week placebo-controlled study, Skylight 4, confirmed long-term safety.⁸ Onset of action occurs within a week. Reported adverse events occurred in 1% to 2% of healthy menopausal women participating in clinical trials; these included headaches, abdominal pain, diarrhea, insomnia, back pain, hot flushes, and reversible elevated hepatic transaminase levels.^6-9

The published phase 2 trials⁹ and the international randomized controlled trial (RCT) 12-week studies, Skylight 1 and 2,^6,7 found that once-daily 30-mg and 45-mg doses of fezolinetant significantly reduced VMS frequency and severity at 12 weeks among women aged 40 to 60 years who reported an average of 7 moderate to severe VMS/day; the reduction in reported VMS was sustained at 40 weeks. Phase 3 data from Skylight 1 and 2 demonstrated fezolinetant’s efficacy in reducing the frequency and severity of VMS and provided information on the safety profile of fezolinetant compared with placebo over 12 weeks and a noncontrolled extension for an additional 40 weeks.^6,7

Oral fezolinetant was associated with improved quality of life, including reduced VMS-related interference with daily life.¹⁰ Johnson and colleagues, reporting for Skylight 2, found VMS frequency and severity improvement by week 1, which achieved statistical significance at weeks 4 and 12, with this improvement maintained through week 52.⁶ A 64.3% reduction in mean daily VMS from baseline was seen at 12 weeks for fezolinetant 45 mg compared with a 45.4% reduction for placebo. VMS severity significantly decreased compared with placebo at 4 and 12 weeks.⁶

Serious treatment-emergent adverse events were infrequent, reported by 2%, 1%, and 0% of those receiving fezolinetant 30 mg, fezolinetant 45 mg, and placebo.⁶ Increases in levels of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) were noted and were described as asymptomatic, isolated, intermittent, or transient, and these levels returned to baseline during treatment or after discontinuation.⁶

Of the 5 participants taking fezolinetant in Skyline 1 with ALT or AST levels greater than 3 times the upper limit of normal in the 12-week randomized trial, levels returned to normal range while continuing treatment in 2 participants, with treatment interruption in 2, and with discontinuation in 1. No new safety signals were seen in the 40-week extension trial.⁶

Continue to: Endometrial and bone safety...

Endometrial and bone safety

Results from Skylight 4, a phase 3, randomized, double-blind, 52-week safety study, provided additional evidence that confirmed the longer-term safety of fezolinetant over a 52-week treatment period.⁸

Endometrial safety was assessed in postmenopausal women with normal baseline endometrium (n = 599).⁸ For fezolinetant 45 mg, 1 of 203 participants had endometrial hyperplasia (EH) (0.5%; upper limit of one-sided 95% confidence interval [CI], 2.3%); no cases of EH were noted in the placebo (0 of 186) or fezolinetant 30-mg (0 of 210) groups. The incidence of EH or malignancy in fezolinetant-treated participants was within prespecified limits, as assessed by blinded, centrally read endometrial biopsies. Endometrial malignancy occurred in 1 of 210 in the fezolinetant 30-mg group (0.5%; 95% CI, 2.2%) with no cases in the other groups, thus meeting FDA requirements for endometrial safety.⁸

In addition, no significant differences were noted in change from baseline endometrial thickness on transvaginal ultrasonography between fezolinetant-treated and placebo groups. Likewise, no loss of bone density was found on dual-energy x-ray absorptiometry (DEXA) scans or trabecular bone scores.⁸

Liver safety

Although no cases of severe liver injury were noted, elevations in serum transaminase concentrations greater than 3 times the upper limit of normal were observed in the clinical trials. In Skylight 4, liver enzyme elevations more than 3 times the upper limit of normal occurred in 6 of 583 participants taking placebo, 8 of 590 taking fezolinetant 30 mg, and 12 of 589 taking fezolinetant 45 mg.⁸

The prescribing information for fezolinetant includes a warning for elevated hepatic transaminases: Fezolinetant should not be started if baseline serum transaminase concentration is equal to or exceeds 2 times the upper limit of normal. Liver tests should be obtained at baseline and repeated every 3 months for the first 9 months and then if symptoms suggest liver injury.^11,12

Unmet need for nonhormone treatment of VMS

Vasomotor symptoms affect up to 80% of women, with approximately 25% bothersome enough to warrant treatment. Vasomotor symptoms persist for a median of 7 years, with duration and severity differing by race and ethnicity. Black, Hispanic, and possibly Native American women experience the highest burden of VMS.² Although VMS, including hot flashes, night sweats, and mood and sleep disturbances, often are considered an annoyance to those with mild symptoms, moderate to severe VMS impact women’s lives, including functioning at home or work, affecting relationships, and decreasing perceived quality of life, and they have been associated with workplace absenteeism and increased health care costs, both direct from medical care and testing and indirect costs from lost work.^13-15

Women with 7 or more daily moderate to severe VMS (defined as with sweating or affecting function) reported interference with sleep (94%), concentration (84%), mood (85%), energy (77%), and sexual activity (61%).¹⁶ Moderately to severely bothersome VMS have been associated with impaired psychological and general well-being, affecting work performance.¹⁷ Based on a Mayo Clinic workplace survey, Faubion and colleagues estimated an annual loss of $1.8 billion in the United States for menopause-related missed work and a $28 billion loss when medical expenses were added.¹⁵

Menopausal HT has been the primary treatment for VMS and has been shown to reduce the frequency and severity of hot flashes, with additional benefits on sleep, mood, fatigue, bone loss and reduction of fracture, and genitourinary syndrome of menopause (GSM), and with potential improvement in cardiovascular health with decreased type 2 diabetes.^18,19 For healthy women with early menopause and no contraindications, HT has been recommended until at least the age of natural menopause, as observational data suggest that HT prevents osteoporosis, cardiovascular disease, neurodegenerative changes, and sexual dysfunction for these women.^19,20 Similarly, for healthy women younger than age 60 or within 10 years of menopause, initiating HT has been shown to be safe and effective in treating bothersome VMS and preventing osteoporotic fractures and genitourinary changes.^19,21

Most systemic HT formulations are inexpensive (for example, available as generics), with multiple dosing and formulations available for use alone or combined as oral, transdermal, or vaginal therapies. Despite the fear that arose for clinicians and women from the initial 2002 findings of the Women’s Health Initiative regarding increased risk of breast cancer, stroke, venous thrombosis, cardiovascular disease, and dementia, major medical societies agree that when initiated at or soon after menopause, HT is a safe and effective therapy to relieve VMS, protect against bone loss, and treat genitourinary changes.^19,21

Many women, however, cannot take HT, including those with estrogen-sensitive cancers, such as breast or uterine cancers; prior cardiovascular disease, stroke, or venous thrombotic events; severe endometriosis; or migraine headaches with visual auras.² In addition, many symptomatic menopausal women without health contraindications choose not to take HT.² Until now, the only FDA-approved VMS nonhormone therapy has been a low-dose 7.5-mg paroxetine salt. Unfortunately, this formulation, along with the off-label use of other antidepressants (selective serotonin reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors), gabapentinoids, oxybutynin, and clonidine, are substantially less effective than HT in treating moderate to severe VMS.

Bottom line

A substantial unmet need remains for effective therapy for moderate to severe VMS for women who cannot or choose not to take menopausal HT to relieve VMS.^2,16 Effective, safe nonhormone treatment options such as the new NK3 receptor antagonist fezolinetant will address this clinically important need.

One concern is that the cost of developing and bringing to market the first of a new type of medication will be passed on to consumers, which may put it out of the price range for the many women who need it. However, the development and FDA approval of fezolinetant as the first NK3 receptor antagonist to treat menopausal VMS is potentially a practice changer. It provides a novel, effective, and safe FDA-approved nonhormonal treatment for menopausal women with moderate to severe VMS, particularly for women who cannot or will not take hormone therapy.

Continue to: When endometrial biopsy for postmenopausal bleeding reveals proliferative changes, how should we respond?...

Abraham C. Proliferative endometrium in menopause: to treat or not to treat? Obstet Gynecol. 2023;141:265-267. doi:10.1097/AOG.0000000000005054.

The following case represents a common scenario for ObGyns.

CASE Patient with proliferative endometrial changes

A menopausal patient with a body mass index (BMI) > 30 kg/m² presents with uterine bleeding. She does not use systemic menopausal hormone therapy. Endometrial biopsy indicates proliferative changes.

When endometrial biopsy performed for bleeding reveals proliferative changes in menopausal women, we traditionally have responded by reassuring the patient that the findings are benign and advising that she should let us know if future spotting or bleeding occurs.

However, a recent review by Abraham published in Obstetrics and Gynecology details the implications of proliferative endometrial changes in menopausal patients, advising that treatment, as well as monitoring, may be appropriate.²²

Endometrial changes and what they suggest

In premenopausal women, proliferative endometrial changes are physiologic and result from ovarian estrogen production early in each cycle, during what is called the proliferative (referring to the endometrium) or follicular (referring to the dominant follicle that synthesizes estrogen) phase. In menopausal women who are not using HT, however, proliferative endometrial changes, with orderly uniform glands seen on histologic evaluation, reflect aromatization of androgens by adipose and other tissues into estrogen.

The next step on the continuum to hyperplasia (benign or atypical) after proliferative endometrium is disordered proliferative endometrium. At this stage, histologic evaluation reveals scattered cystic and dilated glands that have a normal gland-to-stroma ratio with a low gland density overall and without any atypia. Randomly distributed glands may have tubal metaplasia or fibrin thrombi associated with microinfarcts, often presenting with irregular bleeding. This is a noncancerous change that occurs with excess estrogen (endogenous or exogenous).²³

Progestins reverse endometrial hyperplasia by activating progesterone receptors, which leads to stromal decidualization with thinning of the endometrium. They have a pronounced effect on the histologic appearance of the endometrium. By contrast, endometrial intraepithelial neoplasia (EIN, previously known as endometrial hyperplasiawith atypia) shows underlying molecular mutations and histologic alterations and represents a sharp transition to true neoplasia, which greatly increases the risk of endometrioid endometrial adenocarcinoma.²⁴

For decades, we have been aware that if women diagnosed with endometrial hyperplasia are not treated with progestational therapy, their future risk of endometrial cancer is elevated. More recently, we also recognize that menopausal women found to have proliferative endometrial changes, if not treated, have an increased risk of endometrial cancer.

In a retrospective cohort study of almost 300 menopausal women who were not treated after endometrial biopsy revealed proliferative changes, investigators followed participants for an average of 11 years.²⁵ These women had a mean BMI of 34 kg/m². During follow-up, almost 12% of these women were diagnosed with endometrial hyperplasia or cancer. This incidence of endometrial neoplasia was some 4 times higher than for women initially found to have atrophic endometrial changes.²⁵

Progestin treatment

Oral progestin therapy with follow-up endometrial biopsy constitutes traditional management for endometrial hyperplasia. Such therapy minimizes the likelihood that hyperplasia will progress to endometrial cancer.

We now recognize that the convenience, as well as the high endometrial progestin levels achieved, with levonorgestrel-releasing intrauterine devices (LNG-IUDs) have advantages over oral progestin therapy in treating endometrial hyperplasia. Indeed, a recent US report found that among women with EIN managed medically, use of progestin-releasing IUDs has grown from 7.7% in 2008 to 35.6% in 2020.²⁶

Although both oral and intrauterine progestin are highly effective in treating simple hyperplasia, progestin IUDs are substantially more effective than oral progestins in treating EIN.²⁷ Progestin concentrations in the endometrium have been shown to be 100-fold higher after LNG-IUD placement compared with oral progestin use.²² In addition, adverse effects, including bloating, unpleasant mood changes, and increased appetite, are more common with oral than intrauterine progestin therapy.²⁸

Unfortunately, data from randomized trials addressing progestational treatment of proliferative endometrium in menopausal women are not available to support the treatment of proliferative endometrium with either oral progestins or the LNG-IUD.²²

Role of ultrasonography

Another concern is relying on a finding of thin endometrial thickness on vaginal ultrasonography. In a simulated retrospective cohort study, use of transvaginal ultrasonography to determine the appropriateness of a biopsy was found not to be sufficiently accurate or racially equitable with regard to Black women.²⁹ In simulated data, transvaginal ultrasonography missed almost 5 times more cases of endometrial cancer among Black women compared with White women due to higher fibroid prevalence and nonendometrioid histologic type malignancies in Black women.²⁹

Assessing risk

If proliferative endometrium is found, Abraham suggests assessing risk using²²:

• age
• comorbidities (including obesity)
• endometrial echo thickness on vaginal ultrasonography.

Consider the patient’s risk and tolerance of recurrent bleeding as well as her tolerance for progestational adverse effects if medical therapy is chosen. Discussion about next steps should include reviewing the histologic findings with the patient and discussing the difference in risk of progression to endometrial cancer of a finding of proliferative endometrium compared with a histologic finding of endometrial hyperplasia.

Using this patient-centered approach, observation over time with follow-up endometrial biopsies remains a management option. Although some women may tolerate micronized progesterone over synthetic progestins, there is concern that it may be less effective in suppressing the endometrium than synthetic progestins.³⁰ Accordingly, synthetic progestins represent first-line options in this setting^.

In her review, Abraham suggests that when endometrial biopsy reveals proliferative changes in a menopausal woman, we should initiate progestin treatment and perform surveillance endometrial sampling every 3 to 6 months. If such sampling reveals benign but not proliferative endometrium, progestin therapy can be stopped and endometrial biopsy repeated if bleeding recurs.²² ●

This year’s menopause Update highlights a highly effective nonhormonal medication that recently received approval by the US Food and Drug Administration (FDA) for the treatment of bothersome menopausal vasomotor symptoms. In addition, the Update provides guidance regarding how ObGyns should respond when an endometrial biopsy for postmenopausal bleeding reveals proliferative changes.

Breakthrough in women’s health: A new nonhormone therapy for vasomotor symptoms

Johnson KA, Martin N, Nappi RE, et al. Efficacy and safety of fezolinetant in moderate-to-severe vasomotor symptoms associated with menopause: a phase 3 RCT. J Clin Endocrinol Metab. 2023;dgad058. doi:10.1210/clinem/dgad058.
 

Lederman S, Ottery FD, Cano A, et al. Fezolinetant for treatment of moderate-to-severe vasomotor symptoms associated with menopause (SKYLIGHT 1): a phase 3 randomised controlled study. Lancet. 2023;401:1091-1102. doi:10.1016/S0140-6736(23)00085-5.

A new oral nonestrogen-containing medication for relief of moderate to severe hot flashes, fezolinetant (Veozah) 45 mg daily, has been approved by the FDA and was expected to be available by the end of May 2023. Fezolinetant is a selective neurokinin 3 (NK3) receptor antagonistthat offers a targeted nonhormonal approach to menopausal vasomotor symptoms (VMS), and it is the first in its class to make it to market.

The decline in estrogen at menopause appears to result in increased signaling at kisspeptin/neurokinin B/dynorphin (KNDy) neurons in the thermoregulatory center within the hypothalamus with resultant increases in hot flashes.^1,2 Fezolinetant works by binding to and blocking the activities of the NK3 receptor.^3-5

Key study findings

Selective NK3 receptor antagonists, including fezolinetant, effectively reduce the frequency and severity of VMS comparable to that of hormone therapy (HT). Two phase 3 clinical trials, Skylight 1 and 2, confirmed the efficacy and safety of fezolinetant 45 mg in treating VMS,^6,7 and an additional 52-week placebo-controlled study, Skylight 4, confirmed long-term safety.⁸ Onset of action occurs within a week. Reported adverse events occurred in 1% to 2% of healthy menopausal women participating in clinical trials; these included headaches, abdominal pain, diarrhea, insomnia, back pain, hot flushes, and reversible elevated hepatic transaminase levels.^6-9

The published phase 2 trials⁹ and the international randomized controlled trial (RCT) 12-week studies, Skylight 1 and 2,^6,7 found that once-daily 30-mg and 45-mg doses of fezolinetant significantly reduced VMS frequency and severity at 12 weeks among women aged 40 to 60 years who reported an average of 7 moderate to severe VMS/day; the reduction in reported VMS was sustained at 40 weeks. Phase 3 data from Skylight 1 and 2 demonstrated fezolinetant’s efficacy in reducing the frequency and severity of VMS and provided information on the safety profile of fezolinetant compared with placebo over 12 weeks and a noncontrolled extension for an additional 40 weeks.^6,7

Oral fezolinetant was associated with improved quality of life, including reduced VMS-related interference with daily life.¹⁰ Johnson and colleagues, reporting for Skylight 2, found VMS frequency and severity improvement by week 1, which achieved statistical significance at weeks 4 and 12, with this improvement maintained through week 52.⁶ A 64.3% reduction in mean daily VMS from baseline was seen at 12 weeks for fezolinetant 45 mg compared with a 45.4% reduction for placebo. VMS severity significantly decreased compared with placebo at 4 and 12 weeks.⁶

Serious treatment-emergent adverse events were infrequent, reported by 2%, 1%, and 0% of those receiving fezolinetant 30 mg, fezolinetant 45 mg, and placebo.⁶ Increases in levels of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) were noted and were described as asymptomatic, isolated, intermittent, or transient, and these levels returned to baseline during treatment or after discontinuation.⁶

Of the 5 participants taking fezolinetant in Skyline 1 with ALT or AST levels greater than 3 times the upper limit of normal in the 12-week randomized trial, levels returned to normal range while continuing treatment in 2 participants, with treatment interruption in 2, and with discontinuation in 1. No new safety signals were seen in the 40-week extension trial.⁶

Continue to: Endometrial and bone safety...

Endometrial and bone safety

Results from Skylight 4, a phase 3, randomized, double-blind, 52-week safety study, provided additional evidence that confirmed the longer-term safety of fezolinetant over a 52-week treatment period.⁸

Endometrial safety was assessed in postmenopausal women with normal baseline endometrium (n = 599).⁸ For fezolinetant 45 mg, 1 of 203 participants had endometrial hyperplasia (EH) (0.5%; upper limit of one-sided 95% confidence interval [CI], 2.3%); no cases of EH were noted in the placebo (0 of 186) or fezolinetant 30-mg (0 of 210) groups. The incidence of EH or malignancy in fezolinetant-treated participants was within prespecified limits, as assessed by blinded, centrally read endometrial biopsies. Endometrial malignancy occurred in 1 of 210 in the fezolinetant 30-mg group (0.5%; 95% CI, 2.2%) with no cases in the other groups, thus meeting FDA requirements for endometrial safety.⁸

In addition, no significant differences were noted in change from baseline endometrial thickness on transvaginal ultrasonography between fezolinetant-treated and placebo groups. Likewise, no loss of bone density was found on dual-energy x-ray absorptiometry (DEXA) scans or trabecular bone scores.⁸

Liver safety

Although no cases of severe liver injury were noted, elevations in serum transaminase concentrations greater than 3 times the upper limit of normal were observed in the clinical trials. In Skylight 4, liver enzyme elevations more than 3 times the upper limit of normal occurred in 6 of 583 participants taking placebo, 8 of 590 taking fezolinetant 30 mg, and 12 of 589 taking fezolinetant 45 mg.⁸

The prescribing information for fezolinetant includes a warning for elevated hepatic transaminases: Fezolinetant should not be started if baseline serum transaminase concentration is equal to or exceeds 2 times the upper limit of normal. Liver tests should be obtained at baseline and repeated every 3 months for the first 9 months and then if symptoms suggest liver injury.^11,12

Unmet need for nonhormone treatment of VMS

Vasomotor symptoms affect up to 80% of women, with approximately 25% bothersome enough to warrant treatment. Vasomotor symptoms persist for a median of 7 years, with duration and severity differing by race and ethnicity. Black, Hispanic, and possibly Native American women experience the highest burden of VMS.² Although VMS, including hot flashes, night sweats, and mood and sleep disturbances, often are considered an annoyance to those with mild symptoms, moderate to severe VMS impact women’s lives, including functioning at home or work, affecting relationships, and decreasing perceived quality of life, and they have been associated with workplace absenteeism and increased health care costs, both direct from medical care and testing and indirect costs from lost work.^13-15

Women with 7 or more daily moderate to severe VMS (defined as with sweating or affecting function) reported interference with sleep (94%), concentration (84%), mood (85%), energy (77%), and sexual activity (61%).¹⁶ Moderately to severely bothersome VMS have been associated with impaired psychological and general well-being, affecting work performance.¹⁷ Based on a Mayo Clinic workplace survey, Faubion and colleagues estimated an annual loss of $1.8 billion in the United States for menopause-related missed work and a $28 billion loss when medical expenses were added.¹⁵

Menopausal HT has been the primary treatment for VMS and has been shown to reduce the frequency and severity of hot flashes, with additional benefits on sleep, mood, fatigue, bone loss and reduction of fracture, and genitourinary syndrome of menopause (GSM), and with potential improvement in cardiovascular health with decreased type 2 diabetes.^18,19 For healthy women with early menopause and no contraindications, HT has been recommended until at least the age of natural menopause, as observational data suggest that HT prevents osteoporosis, cardiovascular disease, neurodegenerative changes, and sexual dysfunction for these women.^19,20 Similarly, for healthy women younger than age 60 or within 10 years of menopause, initiating HT has been shown to be safe and effective in treating bothersome VMS and preventing osteoporotic fractures and genitourinary changes.^19,21

Most systemic HT formulations are inexpensive (for example, available as generics), with multiple dosing and formulations available for use alone or combined as oral, transdermal, or vaginal therapies. Despite the fear that arose for clinicians and women from the initial 2002 findings of the Women’s Health Initiative regarding increased risk of breast cancer, stroke, venous thrombosis, cardiovascular disease, and dementia, major medical societies agree that when initiated at or soon after menopause, HT is a safe and effective therapy to relieve VMS, protect against bone loss, and treat genitourinary changes.^19,21

Many women, however, cannot take HT, including those with estrogen-sensitive cancers, such as breast or uterine cancers; prior cardiovascular disease, stroke, or venous thrombotic events; severe endometriosis; or migraine headaches with visual auras.² In addition, many symptomatic menopausal women without health contraindications choose not to take HT.² Until now, the only FDA-approved VMS nonhormone therapy has been a low-dose 7.5-mg paroxetine salt. Unfortunately, this formulation, along with the off-label use of other antidepressants (selective serotonin reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors), gabapentinoids, oxybutynin, and clonidine, are substantially less effective than HT in treating moderate to severe VMS.

Bottom line

A substantial unmet need remains for effective therapy for moderate to severe VMS for women who cannot or choose not to take menopausal HT to relieve VMS.^2,16 Effective, safe nonhormone treatment options such as the new NK3 receptor antagonist fezolinetant will address this clinically important need.

One concern is that the cost of developing and bringing to market the first of a new type of medication will be passed on to consumers, which may put it out of the price range for the many women who need it. However, the development and FDA approval of fezolinetant as the first NK3 receptor antagonist to treat menopausal VMS is potentially a practice changer. It provides a novel, effective, and safe FDA-approved nonhormonal treatment for menopausal women with moderate to severe VMS, particularly for women who cannot or will not take hormone therapy.

Continue to: When endometrial biopsy for postmenopausal bleeding reveals proliferative changes, how should we respond?...

Abraham C. Proliferative endometrium in menopause: to treat or not to treat? Obstet Gynecol. 2023;141:265-267. doi:10.1097/AOG.0000000000005054.

The following case represents a common scenario for ObGyns.

CASE Patient with proliferative endometrial changes

A menopausal patient with a body mass index (BMI) > 30 kg/m² presents with uterine bleeding. She does not use systemic menopausal hormone therapy. Endometrial biopsy indicates proliferative changes.

When endometrial biopsy performed for bleeding reveals proliferative changes in menopausal women, we traditionally have responded by reassuring the patient that the findings are benign and advising that she should let us know if future spotting or bleeding occurs.

However, a recent review by Abraham published in Obstetrics and Gynecology details the implications of proliferative endometrial changes in menopausal patients, advising that treatment, as well as monitoring, may be appropriate.²²

Endometrial changes and what they suggest

In premenopausal women, proliferative endometrial changes are physiologic and result from ovarian estrogen production early in each cycle, during what is called the proliferative (referring to the endometrium) or follicular (referring to the dominant follicle that synthesizes estrogen) phase. In menopausal women who are not using HT, however, proliferative endometrial changes, with orderly uniform glands seen on histologic evaluation, reflect aromatization of androgens by adipose and other tissues into estrogen.

The next step on the continuum to hyperplasia (benign or atypical) after proliferative endometrium is disordered proliferative endometrium. At this stage, histologic evaluation reveals scattered cystic and dilated glands that have a normal gland-to-stroma ratio with a low gland density overall and without any atypia. Randomly distributed glands may have tubal metaplasia or fibrin thrombi associated with microinfarcts, often presenting with irregular bleeding. This is a noncancerous change that occurs with excess estrogen (endogenous or exogenous).²³

Progestins reverse endometrial hyperplasia by activating progesterone receptors, which leads to stromal decidualization with thinning of the endometrium. They have a pronounced effect on the histologic appearance of the endometrium. By contrast, endometrial intraepithelial neoplasia (EIN, previously known as endometrial hyperplasiawith atypia) shows underlying molecular mutations and histologic alterations and represents a sharp transition to true neoplasia, which greatly increases the risk of endometrioid endometrial adenocarcinoma.²⁴

For decades, we have been aware that if women diagnosed with endometrial hyperplasia are not treated with progestational therapy, their future risk of endometrial cancer is elevated. More recently, we also recognize that menopausal women found to have proliferative endometrial changes, if not treated, have an increased risk of endometrial cancer.

In a retrospective cohort study of almost 300 menopausal women who were not treated after endometrial biopsy revealed proliferative changes, investigators followed participants for an average of 11 years.²⁵ These women had a mean BMI of 34 kg/m². During follow-up, almost 12% of these women were diagnosed with endometrial hyperplasia or cancer. This incidence of endometrial neoplasia was some 4 times higher than for women initially found to have atrophic endometrial changes.²⁵

Progestin treatment

Oral progestin therapy with follow-up endometrial biopsy constitutes traditional management for endometrial hyperplasia. Such therapy minimizes the likelihood that hyperplasia will progress to endometrial cancer.

We now recognize that the convenience, as well as the high endometrial progestin levels achieved, with levonorgestrel-releasing intrauterine devices (LNG-IUDs) have advantages over oral progestin therapy in treating endometrial hyperplasia. Indeed, a recent US report found that among women with EIN managed medically, use of progestin-releasing IUDs has grown from 7.7% in 2008 to 35.6% in 2020.²⁶

Although both oral and intrauterine progestin are highly effective in treating simple hyperplasia, progestin IUDs are substantially more effective than oral progestins in treating EIN.²⁷ Progestin concentrations in the endometrium have been shown to be 100-fold higher after LNG-IUD placement compared with oral progestin use.²² In addition, adverse effects, including bloating, unpleasant mood changes, and increased appetite, are more common with oral than intrauterine progestin therapy.²⁸

Unfortunately, data from randomized trials addressing progestational treatment of proliferative endometrium in menopausal women are not available to support the treatment of proliferative endometrium with either oral progestins or the LNG-IUD.²²

Role of ultrasonography

Another concern is relying on a finding of thin endometrial thickness on vaginal ultrasonography. In a simulated retrospective cohort study, use of transvaginal ultrasonography to determine the appropriateness of a biopsy was found not to be sufficiently accurate or racially equitable with regard to Black women.²⁹ In simulated data, transvaginal ultrasonography missed almost 5 times more cases of endometrial cancer among Black women compared with White women due to higher fibroid prevalence and nonendometrioid histologic type malignancies in Black women.²⁹

Assessing risk

If proliferative endometrium is found, Abraham suggests assessing risk using²²:

• age
• comorbidities (including obesity)
• endometrial echo thickness on vaginal ultrasonography.

Consider the patient’s risk and tolerance of recurrent bleeding as well as her tolerance for progestational adverse effects if medical therapy is chosen. Discussion about next steps should include reviewing the histologic findings with the patient and discussing the difference in risk of progression to endometrial cancer of a finding of proliferative endometrium compared with a histologic finding of endometrial hyperplasia.

Using this patient-centered approach, observation over time with follow-up endometrial biopsies remains a management option. Although some women may tolerate micronized progesterone over synthetic progestins, there is concern that it may be less effective in suppressing the endometrium than synthetic progestins.³⁰ Accordingly, synthetic progestins represent first-line options in this setting^.

In her review, Abraham suggests that when endometrial biopsy reveals proliferative changes in a menopausal woman, we should initiate progestin treatment and perform surveillance endometrial sampling every 3 to 6 months. If such sampling reveals benign but not proliferative endometrium, progestin therapy can be stopped and endometrial biopsy repeated if bleeding recurs.²² ●