Key clinical point: Gut microbiota may have a potential casual association with migraine symptoms, with evidence indicating a connection between gut microbiota and increased or decreased risk for migraine.

Major finding: A higher abundance of genus Lactobacillus (inverse variance weighted [IVW] odds ratio [OR] 1.10; P = .004) and family Prevotellaceae (IVW OR 0.89; P = .02) were causally associated with a higher and lower risk for migraine, respectively.

Study details: This study used a two-sample Mendelian randomization framework to assess the causal effects of gut microbiota on migraine risk using 2651 single nucleotide polymorphisms as instrumental variables. Large-scale genome-wide association studies consisting of 18,340 participants from 24 cohorts provided the summary-level statistics for gut microbiota.

Disclosures: This study was funded by the National Key Research and Development Program. The authors declared no conflicts of interest.

Source: Meng X et al. Exploring the role of gut microbiota in migraine risk: A two-sample Mendelian randomization study. Scand J Gastroenterol. 2023 (Dec 27). doi: 10.1080/00365521.2023.2298370

Key clinical point: Gut microbiota may have a potential casual association with migraine symptoms, with evidence indicating a connection between gut microbiota and increased or decreased risk for migraine.

Major finding: A higher abundance of genus Lactobacillus (inverse variance weighted [IVW] odds ratio [OR] 1.10; P = .004) and family Prevotellaceae (IVW OR 0.89; P = .02) were causally associated with a higher and lower risk for migraine, respectively.

Study details: This study used a two-sample Mendelian randomization framework to assess the causal effects of gut microbiota on migraine risk using 2651 single nucleotide polymorphisms as instrumental variables. Large-scale genome-wide association studies consisting of 18,340 participants from 24 cohorts provided the summary-level statistics for gut microbiota.

Disclosures: This study was funded by the National Key Research and Development Program. The authors declared no conflicts of interest.

Source: Meng X et al. Exploring the role of gut microbiota in migraine risk: A two-sample Mendelian randomization study. Scand J Gastroenterol. 2023 (Dec 27). doi: 10.1080/00365521.2023.2298370

Key clinical point: Gut microbiota may have a potential casual association with migraine symptoms, with evidence indicating a connection between gut microbiota and increased or decreased risk for migraine.

Major finding: A higher abundance of genus Lactobacillus (inverse variance weighted [IVW] odds ratio [OR] 1.10; P = .004) and family Prevotellaceae (IVW OR 0.89; P = .02) were causally associated with a higher and lower risk for migraine, respectively.

Study details: This study used a two-sample Mendelian randomization framework to assess the causal effects of gut microbiota on migraine risk using 2651 single nucleotide polymorphisms as instrumental variables. Large-scale genome-wide association studies consisting of 18,340 participants from 24 cohorts provided the summary-level statistics for gut microbiota.

Disclosures: This study was funded by the National Key Research and Development Program. The authors declared no conflicts of interest.

Source: Meng X et al. Exploring the role of gut microbiota in migraine risk: A two-sample Mendelian randomization study. Scand J Gastroenterol. 2023 (Dec 27). doi: 10.1080/00365521.2023.2298370

Key clinical point: High-dose eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) supplementation demonstrated highest efficacy and acceptability among all studied treatments, emphasizing its potential as a first-choice treatment for migraine prophylaxis.

Major finding: Among all prophylactic treatments, high-dose EPA/DHA supplementation showed the highest decrease in migraine frequency (standardized mean difference [SMD] ─1.36; 95% CI ─2.32 to ─0.39) and severity (SMD ─2.23; 95% CI ─3.17 to ─1.30) and the most favorable acceptability rate (odds ratio 1.00; 95% CI 0.06 to 17.41) compared with placebo.

Study details: The data come from a network meta-analysis of 40 randomized controlled trials that included 6616 patients with either episodic or chronic migraine.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Tseng PT et al. Efficacy of high dosage anti-inflammatory eicosapentaenoic acid/docosahexaenoic acid for migraine prophylaxis: A network meta-analysis. Adv Nutr. 2023;15(2):100163 (Dec 16). doi: 10.1016/j.advnut.2023.100163

Key clinical point: High-dose eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) supplementation demonstrated highest efficacy and acceptability among all studied treatments, emphasizing its potential as a first-choice treatment for migraine prophylaxis.

Major finding: Among all prophylactic treatments, high-dose EPA/DHA supplementation showed the highest decrease in migraine frequency (standardized mean difference [SMD] ─1.36; 95% CI ─2.32 to ─0.39) and severity (SMD ─2.23; 95% CI ─3.17 to ─1.30) and the most favorable acceptability rate (odds ratio 1.00; 95% CI 0.06 to 17.41) compared with placebo.

Study details: The data come from a network meta-analysis of 40 randomized controlled trials that included 6616 patients with either episodic or chronic migraine.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Tseng PT et al. Efficacy of high dosage anti-inflammatory eicosapentaenoic acid/docosahexaenoic acid for migraine prophylaxis: A network meta-analysis. Adv Nutr. 2023;15(2):100163 (Dec 16). doi: 10.1016/j.advnut.2023.100163

Key clinical point: High-dose eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) supplementation demonstrated highest efficacy and acceptability among all studied treatments, emphasizing its potential as a first-choice treatment for migraine prophylaxis.

Major finding: Among all prophylactic treatments, high-dose EPA/DHA supplementation showed the highest decrease in migraine frequency (standardized mean difference [SMD] ─1.36; 95% CI ─2.32 to ─0.39) and severity (SMD ─2.23; 95% CI ─3.17 to ─1.30) and the most favorable acceptability rate (odds ratio 1.00; 95% CI 0.06 to 17.41) compared with placebo.

Study details: The data come from a network meta-analysis of 40 randomized controlled trials that included 6616 patients with either episodic or chronic migraine.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Tseng PT et al. Efficacy of high dosage anti-inflammatory eicosapentaenoic acid/docosahexaenoic acid for migraine prophylaxis: A network meta-analysis. Adv Nutr. 2023;15(2):100163 (Dec 16). doi: 10.1016/j.advnut.2023.100163

Key clinical point: The likelihood of motor vehicle crashes (MVC) in the year following diagnosis is significantly higher among older drivers who have recently been diagnosed with migraine, emphasizing the necessity for driving safety interventions for these individuals.

Major finding: The risk for an MVC in the year after migraine onset was > 3 times higher among older adult drivers with new-onset migraine compared with those who never had a migraine (adjusted odds ratio [aOR] 3.27; P = .019). Prevalent migraine was not associated with MVC in the subsequent 2 years (aOR 0.97; P = .88).

Study details: Findings are from the AAA Longitudinal Research on Aging Drivers study, which included 2589 older drivers (age 65-79 years) with a valid driver’s license, of whom 12.5% and 1.3% reported prevalent and incident migraines, respectively.

Disclosures: This study was funded by the AAA Foundation for Traffic Safety and National Center for Advancing Translational Sciences. The authors declared no conflicts of interest.

Source: DiGuiseppi CG et al. Migraine headaches are associated with motor vehicle crashes and driving habits among older drivers: Prospective cohort study. J Am Geriatr Soc. 2023 (Dec 22). doi: 10.1111/jgs.18719

Key clinical point: The likelihood of motor vehicle crashes (MVC) in the year following diagnosis is significantly higher among older drivers who have recently been diagnosed with migraine, emphasizing the necessity for driving safety interventions for these individuals.

Major finding: The risk for an MVC in the year after migraine onset was > 3 times higher among older adult drivers with new-onset migraine compared with those who never had a migraine (adjusted odds ratio [aOR] 3.27; P = .019). Prevalent migraine was not associated with MVC in the subsequent 2 years (aOR 0.97; P = .88).

Study details: Findings are from the AAA Longitudinal Research on Aging Drivers study, which included 2589 older drivers (age 65-79 years) with a valid driver’s license, of whom 12.5% and 1.3% reported prevalent and incident migraines, respectively.

Disclosures: This study was funded by the AAA Foundation for Traffic Safety and National Center for Advancing Translational Sciences. The authors declared no conflicts of interest.

Source: DiGuiseppi CG et al. Migraine headaches are associated with motor vehicle crashes and driving habits among older drivers: Prospective cohort study. J Am Geriatr Soc. 2023 (Dec 22). doi: 10.1111/jgs.18719

Key clinical point: The likelihood of motor vehicle crashes (MVC) in the year following diagnosis is significantly higher among older drivers who have recently been diagnosed with migraine, emphasizing the necessity for driving safety interventions for these individuals.

Major finding: The risk for an MVC in the year after migraine onset was > 3 times higher among older adult drivers with new-onset migraine compared with those who never had a migraine (adjusted odds ratio [aOR] 3.27; P = .019). Prevalent migraine was not associated with MVC in the subsequent 2 years (aOR 0.97; P = .88).

Study details: Findings are from the AAA Longitudinal Research on Aging Drivers study, which included 2589 older drivers (age 65-79 years) with a valid driver’s license, of whom 12.5% and 1.3% reported prevalent and incident migraines, respectively.

Disclosures: This study was funded by the AAA Foundation for Traffic Safety and National Center for Advancing Translational Sciences. The authors declared no conflicts of interest.

Source: DiGuiseppi CG et al. Migraine headaches are associated with motor vehicle crashes and driving habits among older drivers: Prospective cohort study. J Am Geriatr Soc. 2023 (Dec 22). doi: 10.1111/jgs.18719

Annette Gillaspie, a nurse in a small Oregon hospital, hoped she would be back working with patients by now. She contracted COVID-19 on the job early in the pandemic and ended up with long COVID.

After recovering a bit, her fatigue and dizziness returned, and today she is still working a desk job. She has also experienced more severe menstrual periods than before she had COVID.

“Being a female with long COVID definitely does add to the roller-coaster effect of symptoms,” Ms. Gillaspie said.

Long COVID affects nearly twice as many women as men, with 6.6% of women reporting long COVID compared with 4% of men, according to a recent Census Bureau survey reported by the Centers for Disease Control and Prevention (CDC). Researchers are trying to determine why, what causes the gender disparity, and how best to treat it.

Scientists are also starting to look at the impact of long COVID on female reproductive health, including menstruation, pregnancy, and menopause.

Sex differences are common in infection-associated illnesses, said Beth Pollack, MS, a research scientist specializing in long COVID in the Massachusetts Institute of Technology’s Department of Biological Engineering, Cambridge, Massachusetts. “It informs research priorities and the lens with which we understand long COVID.”

For example, reproductive health issues for women, such as puberty, pregnancy, and menopause, can alter the course of illness in a subset of women in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and postural orthostatic tachycardia syndrome (POTS), a condition that can cause dizziness and worse.

“This suggests that sex hormones may play key roles in immune responses to infections,” Ms. Pollack said.

ME/CFS and a Possible Link to Long COVID in Women

Some of the research into long COVID is being led by teams studying infection-associated chronic illnesses like ME/CFS.

The problem: Advocates say ME/CFS has been under-researched. Poorly understood for years, the condition is one of a handful of chronic illnesses linked to infections, including Lyme disease and now long COVID. Perhaps not coincidently, they are more likely to affect women.

Many of the research findings about long COVID mirror data that emerged in past ME/CFS research, said Jaime Seltzer, the scientific director at #MEAction, Santa Monica, California, an advocacy group. One point in particular: ME/CFS strikes women about twice as much as men, according to the CDC.

Ms. Seltzer said the response to long COVID could be much further ahead if the research community acknowledged the work done over the years on ME/CFS. Many of the potential biomarkers and risk factors emerging for long COVID were also suspected in ME/CFS, but not thoroughly studied, she said.

She also said not enough work has been done to unravel the links between gender and these chronic conditions.

“We’re stuck in this Groundhog Day situation,” she said. “There isn’t any research, so we can’t say anything definitively.”

Some New Research, Some New Clues

Scientists like Ms. Pollack are slowly making inroads. She was lead author on a 2023 review investigating the impact of long COVID on female reproductive health. The paper highlights long COVID links to ME/CFS, POTS, and Ehlers-Danlos syndrome (EDS), as well as a resulting laundry list of female reproductive health issues. The hope is physicians will examine how the menstrual cycle, pregnancy, and menopause affect symptoms and illness progression of long COVID.

The Tal Research group at MIT (where Ms. Pollack works) has also added long COVID to the list of infection-associated illnesses it studies. The lab is conducting a large study looking into both Lyme disease and long COVID. The goals are to identify biomarkers that can predict who will not recover and to advance available treatments.

Another MIT program, “SEXX + Immunity” holds seminars and networking sessions for scientists looking into the role of female and male biology in immune responses to infection.

Barriers to Progress Remain

On the clinical side, female patients with long COVID also have to deal with a historical bias that still lurks in medicine when it comes to women’s health, said Alba Azola, MD, an assistant professor of physical medicine at Johns Hopkins Medicine, Baltimore, Maryland.

Dr. Azola said she has discovered clinical descriptions of ME/CFE in the literature archives that describe it as “neurasthenia” and dismiss it as psychological.

Patients say that it is still happening, and while it may not be so blunt, “you can read between the lines,” Dr. Azola said.

Dr. Azola, who has worked with long COVID patients and is now seeing people with ME/CFS, said the symptoms of infection-associated chronic illness can mimic menopause, and many of her patients received that misdiagnosis. She recommends that doctors rule out long COVID for women with multiple symptoms before attributing symptoms to menopause.

Seeing that some long COVID patients were developing ME/CFS, staff at the Bateman Horne Center in Salt Lake City, Utah, set up a program for the condition in 2021. They were already treating patients with ME/CFS and what they call “multi-symptom chronic complex diseases.”

Jennifer Bell, a certified nurse practitioner at the center, said she has not seen any patients with ovarian failure but plenty with reproductive health issues.

“There definitely is a hormonal connection, but I don’t think there’s a good understanding about what is happening,” she said.

Most of her patients are female, and the more serious patients tend to go through a worsening of their symptoms in the week prior to getting a period, she said.

One thing Ms. Bell said she’s noticed in the past year is an increase in patients with EDS, which is also more common in women.

Like long COVID, many of the conditions traditionally treated at the center have no cure. But Ms. Bell said the center has developed an expertise in treating post-exertional malaise, a common symptom of long COVID, and keeps up with the literature for treatments to try, like the combination of guanfacine and the antioxidant N-acetyl cysteine to treat brain fog, an approach developed at Yale.

“It’s a very challenging illness to treat,” Ms. Bell said.

Since the emergence of long COVID, researchers have warned that symptoms vary so much from person to person that treatment will need to be targeted.

Ms. Pollack of MIT agrees and sees a big role for personalized medicine.

We need to “identify phenotypes within and across these overlapping and co-occurring illnesses so that we can identify the right therapeutics for each person,” she said.

As for Annette Gillaspie, she still hopes her long COVID will subside so she can get out from behind the desk and return to her normal nursing duties.

“I just got to a point where I realized I’m likely never going to be able to do my job,” she said. “It was incredibly heart breaking, but it’s the reality of long COVID, and I know I’m not the only one to have to step away from a job I loved.”

A version of this article appeared on Medscape.com.

Annette Gillaspie, a nurse in a small Oregon hospital, hoped she would be back working with patients by now. She contracted COVID-19 on the job early in the pandemic and ended up with long COVID.

After recovering a bit, her fatigue and dizziness returned, and today she is still working a desk job. She has also experienced more severe menstrual periods than before she had COVID.

“Being a female with long COVID definitely does add to the roller-coaster effect of symptoms,” Ms. Gillaspie said.

Long COVID affects nearly twice as many women as men, with 6.6% of women reporting long COVID compared with 4% of men, according to a recent Census Bureau survey reported by the Centers for Disease Control and Prevention (CDC). Researchers are trying to determine why, what causes the gender disparity, and how best to treat it.

Scientists are also starting to look at the impact of long COVID on female reproductive health, including menstruation, pregnancy, and menopause.

Sex differences are common in infection-associated illnesses, said Beth Pollack, MS, a research scientist specializing in long COVID in the Massachusetts Institute of Technology’s Department of Biological Engineering, Cambridge, Massachusetts. “It informs research priorities and the lens with which we understand long COVID.”

For example, reproductive health issues for women, such as puberty, pregnancy, and menopause, can alter the course of illness in a subset of women in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and postural orthostatic tachycardia syndrome (POTS), a condition that can cause dizziness and worse.

“This suggests that sex hormones may play key roles in immune responses to infections,” Ms. Pollack said.

ME/CFS and a Possible Link to Long COVID in Women

Some of the research into long COVID is being led by teams studying infection-associated chronic illnesses like ME/CFS.

The problem: Advocates say ME/CFS has been under-researched. Poorly understood for years, the condition is one of a handful of chronic illnesses linked to infections, including Lyme disease and now long COVID. Perhaps not coincidently, they are more likely to affect women.

Many of the research findings about long COVID mirror data that emerged in past ME/CFS research, said Jaime Seltzer, the scientific director at #MEAction, Santa Monica, California, an advocacy group. One point in particular: ME/CFS strikes women about twice as much as men, according to the CDC.

Ms. Seltzer said the response to long COVID could be much further ahead if the research community acknowledged the work done over the years on ME/CFS. Many of the potential biomarkers and risk factors emerging for long COVID were also suspected in ME/CFS, but not thoroughly studied, she said.

She also said not enough work has been done to unravel the links between gender and these chronic conditions.

“We’re stuck in this Groundhog Day situation,” she said. “There isn’t any research, so we can’t say anything definitively.”

Some New Research, Some New Clues

Scientists like Ms. Pollack are slowly making inroads. She was lead author on a 2023 review investigating the impact of long COVID on female reproductive health. The paper highlights long COVID links to ME/CFS, POTS, and Ehlers-Danlos syndrome (EDS), as well as a resulting laundry list of female reproductive health issues. The hope is physicians will examine how the menstrual cycle, pregnancy, and menopause affect symptoms and illness progression of long COVID.

The Tal Research group at MIT (where Ms. Pollack works) has also added long COVID to the list of infection-associated illnesses it studies. The lab is conducting a large study looking into both Lyme disease and long COVID. The goals are to identify biomarkers that can predict who will not recover and to advance available treatments.

Another MIT program, “SEXX + Immunity” holds seminars and networking sessions for scientists looking into the role of female and male biology in immune responses to infection.

Barriers to Progress Remain

On the clinical side, female patients with long COVID also have to deal with a historical bias that still lurks in medicine when it comes to women’s health, said Alba Azola, MD, an assistant professor of physical medicine at Johns Hopkins Medicine, Baltimore, Maryland.

Dr. Azola said she has discovered clinical descriptions of ME/CFE in the literature archives that describe it as “neurasthenia” and dismiss it as psychological.

Patients say that it is still happening, and while it may not be so blunt, “you can read between the lines,” Dr. Azola said.

Dr. Azola, who has worked with long COVID patients and is now seeing people with ME/CFS, said the symptoms of infection-associated chronic illness can mimic menopause, and many of her patients received that misdiagnosis. She recommends that doctors rule out long COVID for women with multiple symptoms before attributing symptoms to menopause.

Seeing that some long COVID patients were developing ME/CFS, staff at the Bateman Horne Center in Salt Lake City, Utah, set up a program for the condition in 2021. They were already treating patients with ME/CFS and what they call “multi-symptom chronic complex diseases.”

Jennifer Bell, a certified nurse practitioner at the center, said she has not seen any patients with ovarian failure but plenty with reproductive health issues.

“There definitely is a hormonal connection, but I don’t think there’s a good understanding about what is happening,” she said.

Most of her patients are female, and the more serious patients tend to go through a worsening of their symptoms in the week prior to getting a period, she said.

One thing Ms. Bell said she’s noticed in the past year is an increase in patients with EDS, which is also more common in women.

Like long COVID, many of the conditions traditionally treated at the center have no cure. But Ms. Bell said the center has developed an expertise in treating post-exertional malaise, a common symptom of long COVID, and keeps up with the literature for treatments to try, like the combination of guanfacine and the antioxidant N-acetyl cysteine to treat brain fog, an approach developed at Yale.

“It’s a very challenging illness to treat,” Ms. Bell said.

Since the emergence of long COVID, researchers have warned that symptoms vary so much from person to person that treatment will need to be targeted.

Ms. Pollack of MIT agrees and sees a big role for personalized medicine.

We need to “identify phenotypes within and across these overlapping and co-occurring illnesses so that we can identify the right therapeutics for each person,” she said.

As for Annette Gillaspie, she still hopes her long COVID will subside so she can get out from behind the desk and return to her normal nursing duties.

“I just got to a point where I realized I’m likely never going to be able to do my job,” she said. “It was incredibly heart breaking, but it’s the reality of long COVID, and I know I’m not the only one to have to step away from a job I loved.”

A version of this article appeared on Medscape.com.

Annette Gillaspie, a nurse in a small Oregon hospital, hoped she would be back working with patients by now. She contracted COVID-19 on the job early in the pandemic and ended up with long COVID.

After recovering a bit, her fatigue and dizziness returned, and today she is still working a desk job. She has also experienced more severe menstrual periods than before she had COVID.

“Being a female with long COVID definitely does add to the roller-coaster effect of symptoms,” Ms. Gillaspie said.

Long COVID affects nearly twice as many women as men, with 6.6% of women reporting long COVID compared with 4% of men, according to a recent Census Bureau survey reported by the Centers for Disease Control and Prevention (CDC). Researchers are trying to determine why, what causes the gender disparity, and how best to treat it.

Scientists are also starting to look at the impact of long COVID on female reproductive health, including menstruation, pregnancy, and menopause.

Sex differences are common in infection-associated illnesses, said Beth Pollack, MS, a research scientist specializing in long COVID in the Massachusetts Institute of Technology’s Department of Biological Engineering, Cambridge, Massachusetts. “It informs research priorities and the lens with which we understand long COVID.”

For example, reproductive health issues for women, such as puberty, pregnancy, and menopause, can alter the course of illness in a subset of women in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and postural orthostatic tachycardia syndrome (POTS), a condition that can cause dizziness and worse.

“This suggests that sex hormones may play key roles in immune responses to infections,” Ms. Pollack said.

ME/CFS and a Possible Link to Long COVID in Women

Some of the research into long COVID is being led by teams studying infection-associated chronic illnesses like ME/CFS.

The problem: Advocates say ME/CFS has been under-researched. Poorly understood for years, the condition is one of a handful of chronic illnesses linked to infections, including Lyme disease and now long COVID. Perhaps not coincidently, they are more likely to affect women.

Many of the research findings about long COVID mirror data that emerged in past ME/CFS research, said Jaime Seltzer, the scientific director at #MEAction, Santa Monica, California, an advocacy group. One point in particular: ME/CFS strikes women about twice as much as men, according to the CDC.

Ms. Seltzer said the response to long COVID could be much further ahead if the research community acknowledged the work done over the years on ME/CFS. Many of the potential biomarkers and risk factors emerging for long COVID were also suspected in ME/CFS, but not thoroughly studied, she said.

She also said not enough work has been done to unravel the links between gender and these chronic conditions.

“We’re stuck in this Groundhog Day situation,” she said. “There isn’t any research, so we can’t say anything definitively.”

Some New Research, Some New Clues

Scientists like Ms. Pollack are slowly making inroads. She was lead author on a 2023 review investigating the impact of long COVID on female reproductive health. The paper highlights long COVID links to ME/CFS, POTS, and Ehlers-Danlos syndrome (EDS), as well as a resulting laundry list of female reproductive health issues. The hope is physicians will examine how the menstrual cycle, pregnancy, and menopause affect symptoms and illness progression of long COVID.

The Tal Research group at MIT (where Ms. Pollack works) has also added long COVID to the list of infection-associated illnesses it studies. The lab is conducting a large study looking into both Lyme disease and long COVID. The goals are to identify biomarkers that can predict who will not recover and to advance available treatments.

Another MIT program, “SEXX + Immunity” holds seminars and networking sessions for scientists looking into the role of female and male biology in immune responses to infection.

Barriers to Progress Remain

On the clinical side, female patients with long COVID also have to deal with a historical bias that still lurks in medicine when it comes to women’s health, said Alba Azola, MD, an assistant professor of physical medicine at Johns Hopkins Medicine, Baltimore, Maryland.

Dr. Azola said she has discovered clinical descriptions of ME/CFE in the literature archives that describe it as “neurasthenia” and dismiss it as psychological.

Patients say that it is still happening, and while it may not be so blunt, “you can read between the lines,” Dr. Azola said.

Dr. Azola, who has worked with long COVID patients and is now seeing people with ME/CFS, said the symptoms of infection-associated chronic illness can mimic menopause, and many of her patients received that misdiagnosis. She recommends that doctors rule out long COVID for women with multiple symptoms before attributing symptoms to menopause.

Seeing that some long COVID patients were developing ME/CFS, staff at the Bateman Horne Center in Salt Lake City, Utah, set up a program for the condition in 2021. They were already treating patients with ME/CFS and what they call “multi-symptom chronic complex diseases.”

Jennifer Bell, a certified nurse practitioner at the center, said she has not seen any patients with ovarian failure but plenty with reproductive health issues.

“There definitely is a hormonal connection, but I don’t think there’s a good understanding about what is happening,” she said.

Most of her patients are female, and the more serious patients tend to go through a worsening of their symptoms in the week prior to getting a period, she said.

One thing Ms. Bell said she’s noticed in the past year is an increase in patients with EDS, which is also more common in women.

Like long COVID, many of the conditions traditionally treated at the center have no cure. But Ms. Bell said the center has developed an expertise in treating post-exertional malaise, a common symptom of long COVID, and keeps up with the literature for treatments to try, like the combination of guanfacine and the antioxidant N-acetyl cysteine to treat brain fog, an approach developed at Yale.

“It’s a very challenging illness to treat,” Ms. Bell said.

Since the emergence of long COVID, researchers have warned that symptoms vary so much from person to person that treatment will need to be targeted.

Ms. Pollack of MIT agrees and sees a big role for personalized medicine.

We need to “identify phenotypes within and across these overlapping and co-occurring illnesses so that we can identify the right therapeutics for each person,” she said.

As for Annette Gillaspie, she still hopes her long COVID will subside so she can get out from behind the desk and return to her normal nursing duties.

“I just got to a point where I realized I’m likely never going to be able to do my job,” she said. “It was incredibly heart breaking, but it’s the reality of long COVID, and I know I’m not the only one to have to step away from a job I loved.”

A version of this article appeared on Medscape.com.

Once considered a luxury, hiring a nurse, nurse practitioner, or physician assistant is becoming a necessity in many rheumatology practices.

Seeing the wait lists pile up in her Florida practice, Stacy Yonker, MBA, chief executive officer of Sarasota Arthritis Center, knew she had to make some changes. “Everyone’s aging in the boomer generations. Particularly in Florida, we have a lot of people who retire here. In the more southern demographics, it is a very difficult challenge for practices to get new patients in,” she said.

Ms. Yonker is in the process of hiring several nurse practitioners (NPs) to assist in the clinics and infusion suites, lightening the load for the practice’s 11 rheumatologists.

Hiring an advanced practice provider (APP) to support the practice is just a first step. Getting these additional personnel up to speed means an investment in education and fostering good working relationships with NPs, PAs, and the staff’s physicians. Even more importantly, practices need to set realistic expectations on workload for these new hires.

“I tried to hire them, but I couldn’t keep them,” is a statement Christine A. Stamatos, DNP, ANP-C, hears all the time from rheumatologists. Oftentimes it’s because the practice saddles the new hire with 20 patients a day, said Dr. Stamatos, director of the Fibromyalgia Wellness Center within the division of rheumatology at Northwell Health in Huntington, New York. She is also an assistant professor at Hofstra Northwell School of Graduate Nursing and Physician Assistant Studies in Hempstead, New York.

“Twenty patients a day is too much,” Dr. Stamatos said. Overload someone, and they won’t stay. Offer them the support, mentoring, and tools they need to practice in their setting ­­— and they will.
 

Why the Profession Needs APPs

Rheumatology is a much smaller specialty than most, with only a set number of rheumatologists in the field that can provide care to patients. A growing shortage is also looming. Reports from the American College of Rheumatology have projected troubling shortfalls in rheumatologists over the next decade in all regions of the United States.

Many of them aging into retirement “poses a significant issue on being able to continue providing care for the population that experiences the rheumatic disease,” said Ms. Yonker, a director of the National Organization of Rheumatology Management (NORM), a forum that promotes education and advocacy for rheumatology practice managers. People are also living longer, which means more patients are developing arthritis and autoimmune diseases.

Julia M. Swafford, PA-C, a rheumatology physician assistant in Battle Creek, Michigan, sees many advantages of hiring NPs and PAs, and not just from a financial perspective.

Salaries for PAs and NPs aren’t as high and they’re also more accessible than a rheumatologist. “You could train an NP or PA a lot quicker during that same time frame it would take to find a new rheumatology provider,” she offered. And while they may not be as experienced as rheumatologists, “you can kind of mold me on how you like to practice, what medications you may like to use, how you like to treat your patients,” Ms. Swafford said.
 

Hiring Someone With Experience

Recruiting and retaining APPs is not without its challenges.

Finding individuals compatible with this specialty isn’t easy, noted Mark Box, MD, medical director of Carondelet Rheumatology in Kansas City, Missouri. Ideally, APPs should be inquisitive, compassionate, and ready to learn. “Rheumatology is a cognitive specialty where you have to fit many pieces together. You need an APP who wants to embrace that,” he said.

The profession isn’t that “sexy” either, noted Katie Taylor, Carondelet’s practice manager. Patients are often in head-to-toe pain, and miserable. Many have been to other specialists without answers to their questions. For these reasons, rheumatology can be a hard sell for some PAs and NPs.

Nurse practitioners aren’t always comfortable with administering things such as controlled medications, for example. “It’s a hard patient population, and it’s a specialty of exclusion. You’ve got to be really smart to understand our diseases and our processes and our drugs,” Ms. Taylor said. In other words, it’s a difficult environment for an NP to walk into if their previous experience has been limited to upper respiratory issues and urinary tract infections in the primary care setting.

When hiring an APP, rheumatologists should look for someone who demonstrates an interest in lifelong learning, because the field is changing every day. They should exhibit good scores in educational training and have experience working in an emergency department or another field that translates well into rheumatology such as critical care, immunology, hematology, and orthopedics, she said.

Carondelet Rheumatology was specifically looking for an NP with rheumatology experience to support Dr. Box’s solo practice.

He was facing enormous pressure to be in the office every single day of the week. The practice had to cancel patients for its infusion suite on a regular basis when he was out of the office, Ms. Taylor said. “We couldn’t see new patients, and he wasn’t able to touch as many patients as he wanted to. The doctor takes the oath of touching as many in your community as possible, and you’re limited when you’re a one-man show.”

The practice eventually found an NP who already knew how to do joint injections. “We started her with easier diagnoses for things like osteoporosis and gout. She had an orthopedic background, so she was familiar with some of those diseases,” she said.

Even so, she often leaves with questions every day. “It’s a commitment for her to understand and learn so much,” Ms. Taylor said.

New hires will need support from the practice to get comfortable with rheumatology, Dr. Stamatos said. Responsibility should come in gradual steps.

Instead of loading an NP with 20 patients a day, 2 or 3 patients in the first quarter, eventually graduating to 6-8 patients is a more realistic expectation, Dr. Stamatos advised.
 

Shadowing the Physician

Partnerships with physicians is a critical component to this onboarding process.

A nurse practitioner recently hired at Dr. Stamatos’ practice works alongside a physician to manage a panel of 25 patients. “We make sure she gets her training, the resources she needs. I personally meet with her to make sure her education is moving forward, connecting her with radiology, pulmonary, hematology,” and other areas of the practice relevant to her training, she added.

The NP also attends weekly grand rounds and case conferences with the fellows. This is the type of well-rounded support any APP needs, she stressed. “Without proper training, you lose people.”

At Sarasota Arthritis Center, NPs help cover the suites but also get assigned to specific physicians so that they can familiarize themselves with that physician’s panel of patients.

“When we start an APP, they shadow for about twice as long as a new physician would. Usually, they’re shadowing for about 6 weeks, just kind of learning the space. There’s a lot of nurse practitioners or PAs who may not have prior rheumatology experience, so we’re essentially training them from the ground up on rheumatology,” Ms. Yonker said.

Pairing them with one provider often directs what type of disease state they focus on, she continued. This dynamic relationship helps guide decisions on whether to include these NPs in the care of patients with more complex diseases.

At least in her practice, the NPs do not see any new patients. They are simply part of the larger care team. “That’s kind of how we present it to our patients, and it makes them feel more comfortable just because they know that they’re not necessarily being handed off to somebody — that the doctor is still overseeing their care,” Ms. Yonker said.

At the same time, the NPs know that they’re supported, that they too have access to tools and mentorship if they need it, she added.

The new NP at Carondelet Rheumatology piggybacked on the doctor’s schedule for 3 months, slowly taking on infusion patients so she could get familiar with their diseases and respective drugs. Eventually, she got her own schedule and was able to take on new patients.

It’s a team effort, Ms. Taylor noted. The NP does the preliminary workup and then the physician comes in and greets the new patient. Together, they develop a follow-up plan for the patient.
 

Education Resources for Practices

In the case of Dr. Box’s one-physician practice, he was looking for an NP who was willing to be independent and cover things in his absence. “The training has to be there to accomplish that,” said Dr. Box, who likened the training of APPs to a medical residency.

Encouraging them to ask questions, do continuing medical education online and outside reading, are important steps, he added.

In a recent editorial, rheumatologists Eli M. Miloslavsky, MD, and Bethany Marston, MD, offered some strategies for better prepping the APP workforce to meet the demands of rheumatology practices. “Consideration should be given to formal curricula or training programs to help APPs achieve both competence and confidence in treating rheumatologic conditions,” they offered, suggesting an online curriculum developed by the ACR for such a purpose. Fellowship training should also focus on working effectively with APPs, they added.

“Finally, incorporating APPs more effectively into rheumatology professional societies and supporting practices in hiring and training APPs will all be important steps in addressing the rheumatology workforce shortage,” Dr. Miloslavsky and Dr. Marston wrote.

Ms. Yonker said all her APPs take various courses that the ACR and other organizations provide for rheumatology-specific, midlevel positions. “We provide as much training as possible for them to feel comfortable in this space. They are set directly with a physician for a long time and then eventually go into their own space.”

In addition to ACR, the Rheumatology Nurses Society and the Association of Women in Rheumatology offer excellent online training resources for APPs, Ms. Yonker said. “Also, the Bone Health and Osteoporosis Foundation offers an osteoporosis fracture liaison certification which we put APPs through as well,” she added.

Rheumatology practices should also look into an important clinical training grant program from the Rheumatology Research Foundation, Dr. Stamatos advised.

To date, they have “funded almost everyone that applies,” she said. Each grantee receives $25,000 to support training and education involved in onboarding an APP to a rheumatology practice. The money covers attendance at a live rheumatology conference, online educational programs, textbooks, and any society memberships while defraying the cost of training this employee. To increase awareness of the program, the foundation has since expanded the number of available submission dates and the number of grant awardees per year. Currently, the application deadlines for the grants are December 1 and March 1.

For her own health system, Dr. Stamatos has been working on a rheumatology fellowship program for APPs. Through simulation labs, leadership exercises, and other activities, these APPs will learn how to transition from being a new provider to someone who can become part of a practice, she said.

APPs themselves can also get proactive in this learning cycle, Ms. Swafford said. In her view, both APPs and rheumatologists should be conducting didactic lectures and organizing elective rotations with medical students to get them excited about the field. This would establish a good education base that would encourage PAs and NPs to choose rheumatology.

“That’s a huge thing that’s probably missing,” Ms. Swafford said.
 

Buy-in From the Doctor

No recruitment effort is going to work if the rheumatologists in the practice aren’t committed to the model of having an APP, Ms. Yonker said. “Everybody wants to know their purpose in their company and that they’re valued and they’re needed. And so, I think a pitfall would be if your rheumatologist is not sold on the model of expanding the care team. Because this takes work on behalf of the doctor.”

Rheumatologists are very busy, so it’s a hard sell for them to take time out of their busy clinics to train somebody to do a good job taking care of their patients, Ms. Taylor agreed. “I think that we need the physicians that have had success with this and allow them to coach the physicians that are still resistant.”

In his small practice, Dr. Box has encouraged his NP to assist with practice improvements, working with the office manager. These workers are providers and need to be treated as such, he said. “They need to feel like they contribute to the practice more than just grinding through patients.”

Peer support is another successful ingredient for these workers. Ms. Taylor’s NP finds the time to commiserate with her fellow nurse practitioners — other rheumatology nurses who are also learning the ropes. Rheumatologists are smart, and they can be very intimidating, Ms. Taylor said. In their small office, the rheumatologist is her only peer.

“She likes to get out and sort of integrate with other nurse practitioners that are learning too.”
 

When APPs Make a Difference

Practices that take on APPs are reporting positive metrics — mainly, shorter wait times for patients. Ms. Yonker’s physicians have been able to add on one to two new patients a day. Wait times have since dwindled from a 5-month to a 3-month wait with the addition of the NPs. “Three months is still long, but we’re working on getting it to that ideal 6-week wait period, which we’re hoping we can accomplish. So we’re able to get more new patients in for sure,” she said.

Prior to hiring an NP, Ms. Taylor’s practice had to defer acceptances for new patients by at least a year. Now, they’re able to accept about half of all new patient referrals. With the NP on board, “We can get them in within 30 days,” she said.

Sometimes, an APP will go beyond their scope of work to make a difference and better support patients.

Patients with rheumatic and osteopathic conditions are often underdiagnosed in the primary care space. As a result, they are not treated as often as they should be. Seeing a need for specialty care, Ms. Swafford took action.

She currently runs the only bone health clinic in southwest Michigan, coordinating with rheumatologists, NPs, urgent care, hospitalists, and interventional radiologists to attend to these patients more quickly and reduce wait times for care. Specialists will flag things such as nontraumatic hip fractures and vertebral fractures and refer them to Ms. Swafford’s clinic, which is part of Bronson Rheumatology Specialists.

The clinic gets quite a few referrals, and the practice is growing. “Usually, they don’t take as long as a rheumatology referral for a workup, so we can see them a little bit quicker,” usually within 3 weeks, she added.

APPs have an opportunity to make their mark in rheumatology at a time when the profession is experiencing significant gaps in care, Ms. Swafford continued. “Unless we find a way to fill that niche, we’re going to be in a world of trouble in the next 10, 20 years.”

None of the sources reported any disclosures or conflicts of interest.

Once considered a luxury, hiring a nurse, nurse practitioner, or physician assistant is becoming a necessity in many rheumatology practices.

Seeing the wait lists pile up in her Florida practice, Stacy Yonker, MBA, chief executive officer of Sarasota Arthritis Center, knew she had to make some changes. “Everyone’s aging in the boomer generations. Particularly in Florida, we have a lot of people who retire here. In the more southern demographics, it is a very difficult challenge for practices to get new patients in,” she said.

Ms. Yonker is in the process of hiring several nurse practitioners (NPs) to assist in the clinics and infusion suites, lightening the load for the practice’s 11 rheumatologists.

Hiring an advanced practice provider (APP) to support the practice is just a first step. Getting these additional personnel up to speed means an investment in education and fostering good working relationships with NPs, PAs, and the staff’s physicians. Even more importantly, practices need to set realistic expectations on workload for these new hires.

“I tried to hire them, but I couldn’t keep them,” is a statement Christine A. Stamatos, DNP, ANP-C, hears all the time from rheumatologists. Oftentimes it’s because the practice saddles the new hire with 20 patients a day, said Dr. Stamatos, director of the Fibromyalgia Wellness Center within the division of rheumatology at Northwell Health in Huntington, New York. She is also an assistant professor at Hofstra Northwell School of Graduate Nursing and Physician Assistant Studies in Hempstead, New York.

“Twenty patients a day is too much,” Dr. Stamatos said. Overload someone, and they won’t stay. Offer them the support, mentoring, and tools they need to practice in their setting ­­— and they will.
 

Why the Profession Needs APPs

Rheumatology is a much smaller specialty than most, with only a set number of rheumatologists in the field that can provide care to patients. A growing shortage is also looming. Reports from the American College of Rheumatology have projected troubling shortfalls in rheumatologists over the next decade in all regions of the United States.

Many of them aging into retirement “poses a significant issue on being able to continue providing care for the population that experiences the rheumatic disease,” said Ms. Yonker, a director of the National Organization of Rheumatology Management (NORM), a forum that promotes education and advocacy for rheumatology practice managers. People are also living longer, which means more patients are developing arthritis and autoimmune diseases.

Julia M. Swafford, PA-C, a rheumatology physician assistant in Battle Creek, Michigan, sees many advantages of hiring NPs and PAs, and not just from a financial perspective.

Salaries for PAs and NPs aren’t as high and they’re also more accessible than a rheumatologist. “You could train an NP or PA a lot quicker during that same time frame it would take to find a new rheumatology provider,” she offered. And while they may not be as experienced as rheumatologists, “you can kind of mold me on how you like to practice, what medications you may like to use, how you like to treat your patients,” Ms. Swafford said.
 

Hiring Someone With Experience

Recruiting and retaining APPs is not without its challenges.

Finding individuals compatible with this specialty isn’t easy, noted Mark Box, MD, medical director of Carondelet Rheumatology in Kansas City, Missouri. Ideally, APPs should be inquisitive, compassionate, and ready to learn. “Rheumatology is a cognitive specialty where you have to fit many pieces together. You need an APP who wants to embrace that,” he said.

The profession isn’t that “sexy” either, noted Katie Taylor, Carondelet’s practice manager. Patients are often in head-to-toe pain, and miserable. Many have been to other specialists without answers to their questions. For these reasons, rheumatology can be a hard sell for some PAs and NPs.

Nurse practitioners aren’t always comfortable with administering things such as controlled medications, for example. “It’s a hard patient population, and it’s a specialty of exclusion. You’ve got to be really smart to understand our diseases and our processes and our drugs,” Ms. Taylor said. In other words, it’s a difficult environment for an NP to walk into if their previous experience has been limited to upper respiratory issues and urinary tract infections in the primary care setting.

When hiring an APP, rheumatologists should look for someone who demonstrates an interest in lifelong learning, because the field is changing every day. They should exhibit good scores in educational training and have experience working in an emergency department or another field that translates well into rheumatology such as critical care, immunology, hematology, and orthopedics, she said.

Carondelet Rheumatology was specifically looking for an NP with rheumatology experience to support Dr. Box’s solo practice.

He was facing enormous pressure to be in the office every single day of the week. The practice had to cancel patients for its infusion suite on a regular basis when he was out of the office, Ms. Taylor said. “We couldn’t see new patients, and he wasn’t able to touch as many patients as he wanted to. The doctor takes the oath of touching as many in your community as possible, and you’re limited when you’re a one-man show.”

The practice eventually found an NP who already knew how to do joint injections. “We started her with easier diagnoses for things like osteoporosis and gout. She had an orthopedic background, so she was familiar with some of those diseases,” she said.

Even so, she often leaves with questions every day. “It’s a commitment for her to understand and learn so much,” Ms. Taylor said.

New hires will need support from the practice to get comfortable with rheumatology, Dr. Stamatos said. Responsibility should come in gradual steps.

Instead of loading an NP with 20 patients a day, 2 or 3 patients in the first quarter, eventually graduating to 6-8 patients is a more realistic expectation, Dr. Stamatos advised.
 

Shadowing the Physician

Partnerships with physicians is a critical component to this onboarding process.

A nurse practitioner recently hired at Dr. Stamatos’ practice works alongside a physician to manage a panel of 25 patients. “We make sure she gets her training, the resources she needs. I personally meet with her to make sure her education is moving forward, connecting her with radiology, pulmonary, hematology,” and other areas of the practice relevant to her training, she added.

The NP also attends weekly grand rounds and case conferences with the fellows. This is the type of well-rounded support any APP needs, she stressed. “Without proper training, you lose people.”

At Sarasota Arthritis Center, NPs help cover the suites but also get assigned to specific physicians so that they can familiarize themselves with that physician’s panel of patients.

“When we start an APP, they shadow for about twice as long as a new physician would. Usually, they’re shadowing for about 6 weeks, just kind of learning the space. There’s a lot of nurse practitioners or PAs who may not have prior rheumatology experience, so we’re essentially training them from the ground up on rheumatology,” Ms. Yonker said.

Pairing them with one provider often directs what type of disease state they focus on, she continued. This dynamic relationship helps guide decisions on whether to include these NPs in the care of patients with more complex diseases.

At least in her practice, the NPs do not see any new patients. They are simply part of the larger care team. “That’s kind of how we present it to our patients, and it makes them feel more comfortable just because they know that they’re not necessarily being handed off to somebody — that the doctor is still overseeing their care,” Ms. Yonker said.

At the same time, the NPs know that they’re supported, that they too have access to tools and mentorship if they need it, she added.

The new NP at Carondelet Rheumatology piggybacked on the doctor’s schedule for 3 months, slowly taking on infusion patients so she could get familiar with their diseases and respective drugs. Eventually, she got her own schedule and was able to take on new patients.

It’s a team effort, Ms. Taylor noted. The NP does the preliminary workup and then the physician comes in and greets the new patient. Together, they develop a follow-up plan for the patient.
 

Education Resources for Practices

In the case of Dr. Box’s one-physician practice, he was looking for an NP who was willing to be independent and cover things in his absence. “The training has to be there to accomplish that,” said Dr. Box, who likened the training of APPs to a medical residency.

Encouraging them to ask questions, do continuing medical education online and outside reading, are important steps, he added.

In a recent editorial, rheumatologists Eli M. Miloslavsky, MD, and Bethany Marston, MD, offered some strategies for better prepping the APP workforce to meet the demands of rheumatology practices. “Consideration should be given to formal curricula or training programs to help APPs achieve both competence and confidence in treating rheumatologic conditions,” they offered, suggesting an online curriculum developed by the ACR for such a purpose. Fellowship training should also focus on working effectively with APPs, they added.

“Finally, incorporating APPs more effectively into rheumatology professional societies and supporting practices in hiring and training APPs will all be important steps in addressing the rheumatology workforce shortage,” Dr. Miloslavsky and Dr. Marston wrote.

Ms. Yonker said all her APPs take various courses that the ACR and other organizations provide for rheumatology-specific, midlevel positions. “We provide as much training as possible for them to feel comfortable in this space. They are set directly with a physician for a long time and then eventually go into their own space.”

In addition to ACR, the Rheumatology Nurses Society and the Association of Women in Rheumatology offer excellent online training resources for APPs, Ms. Yonker said. “Also, the Bone Health and Osteoporosis Foundation offers an osteoporosis fracture liaison certification which we put APPs through as well,” she added.

Rheumatology practices should also look into an important clinical training grant program from the Rheumatology Research Foundation, Dr. Stamatos advised.

To date, they have “funded almost everyone that applies,” she said. Each grantee receives $25,000 to support training and education involved in onboarding an APP to a rheumatology practice. The money covers attendance at a live rheumatology conference, online educational programs, textbooks, and any society memberships while defraying the cost of training this employee. To increase awareness of the program, the foundation has since expanded the number of available submission dates and the number of grant awardees per year. Currently, the application deadlines for the grants are December 1 and March 1.

For her own health system, Dr. Stamatos has been working on a rheumatology fellowship program for APPs. Through simulation labs, leadership exercises, and other activities, these APPs will learn how to transition from being a new provider to someone who can become part of a practice, she said.

APPs themselves can also get proactive in this learning cycle, Ms. Swafford said. In her view, both APPs and rheumatologists should be conducting didactic lectures and organizing elective rotations with medical students to get them excited about the field. This would establish a good education base that would encourage PAs and NPs to choose rheumatology.

“That’s a huge thing that’s probably missing,” Ms. Swafford said.
 

Buy-in From the Doctor

No recruitment effort is going to work if the rheumatologists in the practice aren’t committed to the model of having an APP, Ms. Yonker said. “Everybody wants to know their purpose in their company and that they’re valued and they’re needed. And so, I think a pitfall would be if your rheumatologist is not sold on the model of expanding the care team. Because this takes work on behalf of the doctor.”

Rheumatologists are very busy, so it’s a hard sell for them to take time out of their busy clinics to train somebody to do a good job taking care of their patients, Ms. Taylor agreed. “I think that we need the physicians that have had success with this and allow them to coach the physicians that are still resistant.”

In his small practice, Dr. Box has encouraged his NP to assist with practice improvements, working with the office manager. These workers are providers and need to be treated as such, he said. “They need to feel like they contribute to the practice more than just grinding through patients.”

Peer support is another successful ingredient for these workers. Ms. Taylor’s NP finds the time to commiserate with her fellow nurse practitioners — other rheumatology nurses who are also learning the ropes. Rheumatologists are smart, and they can be very intimidating, Ms. Taylor said. In their small office, the rheumatologist is her only peer.

“She likes to get out and sort of integrate with other nurse practitioners that are learning too.”
 

When APPs Make a Difference

Practices that take on APPs are reporting positive metrics — mainly, shorter wait times for patients. Ms. Yonker’s physicians have been able to add on one to two new patients a day. Wait times have since dwindled from a 5-month to a 3-month wait with the addition of the NPs. “Three months is still long, but we’re working on getting it to that ideal 6-week wait period, which we’re hoping we can accomplish. So we’re able to get more new patients in for sure,” she said.

Prior to hiring an NP, Ms. Taylor’s practice had to defer acceptances for new patients by at least a year. Now, they’re able to accept about half of all new patient referrals. With the NP on board, “We can get them in within 30 days,” she said.

Sometimes, an APP will go beyond their scope of work to make a difference and better support patients.

Patients with rheumatic and osteopathic conditions are often underdiagnosed in the primary care space. As a result, they are not treated as often as they should be. Seeing a need for specialty care, Ms. Swafford took action.

She currently runs the only bone health clinic in southwest Michigan, coordinating with rheumatologists, NPs, urgent care, hospitalists, and interventional radiologists to attend to these patients more quickly and reduce wait times for care. Specialists will flag things such as nontraumatic hip fractures and vertebral fractures and refer them to Ms. Swafford’s clinic, which is part of Bronson Rheumatology Specialists.

The clinic gets quite a few referrals, and the practice is growing. “Usually, they don’t take as long as a rheumatology referral for a workup, so we can see them a little bit quicker,” usually within 3 weeks, she added.

APPs have an opportunity to make their mark in rheumatology at a time when the profession is experiencing significant gaps in care, Ms. Swafford continued. “Unless we find a way to fill that niche, we’re going to be in a world of trouble in the next 10, 20 years.”

None of the sources reported any disclosures or conflicts of interest.

Once considered a luxury, hiring a nurse, nurse practitioner, or physician assistant is becoming a necessity in many rheumatology practices.

Seeing the wait lists pile up in her Florida practice, Stacy Yonker, MBA, chief executive officer of Sarasota Arthritis Center, knew she had to make some changes. “Everyone’s aging in the boomer generations. Particularly in Florida, we have a lot of people who retire here. In the more southern demographics, it is a very difficult challenge for practices to get new patients in,” she said.

Ms. Yonker is in the process of hiring several nurse practitioners (NPs) to assist in the clinics and infusion suites, lightening the load for the practice’s 11 rheumatologists.

Hiring an advanced practice provider (APP) to support the practice is just a first step. Getting these additional personnel up to speed means an investment in education and fostering good working relationships with NPs, PAs, and the staff’s physicians. Even more importantly, practices need to set realistic expectations on workload for these new hires.

“I tried to hire them, but I couldn’t keep them,” is a statement Christine A. Stamatos, DNP, ANP-C, hears all the time from rheumatologists. Oftentimes it’s because the practice saddles the new hire with 20 patients a day, said Dr. Stamatos, director of the Fibromyalgia Wellness Center within the division of rheumatology at Northwell Health in Huntington, New York. She is also an assistant professor at Hofstra Northwell School of Graduate Nursing and Physician Assistant Studies in Hempstead, New York.

“Twenty patients a day is too much,” Dr. Stamatos said. Overload someone, and they won’t stay. Offer them the support, mentoring, and tools they need to practice in their setting ­­— and they will.
 

Why the Profession Needs APPs

Rheumatology is a much smaller specialty than most, with only a set number of rheumatologists in the field that can provide care to patients. A growing shortage is also looming. Reports from the American College of Rheumatology have projected troubling shortfalls in rheumatologists over the next decade in all regions of the United States.

Many of them aging into retirement “poses a significant issue on being able to continue providing care for the population that experiences the rheumatic disease,” said Ms. Yonker, a director of the National Organization of Rheumatology Management (NORM), a forum that promotes education and advocacy for rheumatology practice managers. People are also living longer, which means more patients are developing arthritis and autoimmune diseases.

Julia M. Swafford, PA-C, a rheumatology physician assistant in Battle Creek, Michigan, sees many advantages of hiring NPs and PAs, and not just from a financial perspective.

Salaries for PAs and NPs aren’t as high and they’re also more accessible than a rheumatologist. “You could train an NP or PA a lot quicker during that same time frame it would take to find a new rheumatology provider,” she offered. And while they may not be as experienced as rheumatologists, “you can kind of mold me on how you like to practice, what medications you may like to use, how you like to treat your patients,” Ms. Swafford said.
 

Hiring Someone With Experience

Recruiting and retaining APPs is not without its challenges.

Finding individuals compatible with this specialty isn’t easy, noted Mark Box, MD, medical director of Carondelet Rheumatology in Kansas City, Missouri. Ideally, APPs should be inquisitive, compassionate, and ready to learn. “Rheumatology is a cognitive specialty where you have to fit many pieces together. You need an APP who wants to embrace that,” he said.

The profession isn’t that “sexy” either, noted Katie Taylor, Carondelet’s practice manager. Patients are often in head-to-toe pain, and miserable. Many have been to other specialists without answers to their questions. For these reasons, rheumatology can be a hard sell for some PAs and NPs.

Nurse practitioners aren’t always comfortable with administering things such as controlled medications, for example. “It’s a hard patient population, and it’s a specialty of exclusion. You’ve got to be really smart to understand our diseases and our processes and our drugs,” Ms. Taylor said. In other words, it’s a difficult environment for an NP to walk into if their previous experience has been limited to upper respiratory issues and urinary tract infections in the primary care setting.

When hiring an APP, rheumatologists should look for someone who demonstrates an interest in lifelong learning, because the field is changing every day. They should exhibit good scores in educational training and have experience working in an emergency department or another field that translates well into rheumatology such as critical care, immunology, hematology, and orthopedics, she said.

Carondelet Rheumatology was specifically looking for an NP with rheumatology experience to support Dr. Box’s solo practice.

He was facing enormous pressure to be in the office every single day of the week. The practice had to cancel patients for its infusion suite on a regular basis when he was out of the office, Ms. Taylor said. “We couldn’t see new patients, and he wasn’t able to touch as many patients as he wanted to. The doctor takes the oath of touching as many in your community as possible, and you’re limited when you’re a one-man show.”

The practice eventually found an NP who already knew how to do joint injections. “We started her with easier diagnoses for things like osteoporosis and gout. She had an orthopedic background, so she was familiar with some of those diseases,” she said.

Even so, she often leaves with questions every day. “It’s a commitment for her to understand and learn so much,” Ms. Taylor said.

New hires will need support from the practice to get comfortable with rheumatology, Dr. Stamatos said. Responsibility should come in gradual steps.

Instead of loading an NP with 20 patients a day, 2 or 3 patients in the first quarter, eventually graduating to 6-8 patients is a more realistic expectation, Dr. Stamatos advised.
 

Shadowing the Physician

Partnerships with physicians is a critical component to this onboarding process.

A nurse practitioner recently hired at Dr. Stamatos’ practice works alongside a physician to manage a panel of 25 patients. “We make sure she gets her training, the resources she needs. I personally meet with her to make sure her education is moving forward, connecting her with radiology, pulmonary, hematology,” and other areas of the practice relevant to her training, she added.

The NP also attends weekly grand rounds and case conferences with the fellows. This is the type of well-rounded support any APP needs, she stressed. “Without proper training, you lose people.”

At Sarasota Arthritis Center, NPs help cover the suites but also get assigned to specific physicians so that they can familiarize themselves with that physician’s panel of patients.

“When we start an APP, they shadow for about twice as long as a new physician would. Usually, they’re shadowing for about 6 weeks, just kind of learning the space. There’s a lot of nurse practitioners or PAs who may not have prior rheumatology experience, so we’re essentially training them from the ground up on rheumatology,” Ms. Yonker said.

Pairing them with one provider often directs what type of disease state they focus on, she continued. This dynamic relationship helps guide decisions on whether to include these NPs in the care of patients with more complex diseases.

At least in her practice, the NPs do not see any new patients. They are simply part of the larger care team. “That’s kind of how we present it to our patients, and it makes them feel more comfortable just because they know that they’re not necessarily being handed off to somebody — that the doctor is still overseeing their care,” Ms. Yonker said.

At the same time, the NPs know that they’re supported, that they too have access to tools and mentorship if they need it, she added.

The new NP at Carondelet Rheumatology piggybacked on the doctor’s schedule for 3 months, slowly taking on infusion patients so she could get familiar with their diseases and respective drugs. Eventually, she got her own schedule and was able to take on new patients.

It’s a team effort, Ms. Taylor noted. The NP does the preliminary workup and then the physician comes in and greets the new patient. Together, they develop a follow-up plan for the patient.
 

Education Resources for Practices

In the case of Dr. Box’s one-physician practice, he was looking for an NP who was willing to be independent and cover things in his absence. “The training has to be there to accomplish that,” said Dr. Box, who likened the training of APPs to a medical residency.

Encouraging them to ask questions, do continuing medical education online and outside reading, are important steps, he added.

In a recent editorial, rheumatologists Eli M. Miloslavsky, MD, and Bethany Marston, MD, offered some strategies for better prepping the APP workforce to meet the demands of rheumatology practices. “Consideration should be given to formal curricula or training programs to help APPs achieve both competence and confidence in treating rheumatologic conditions,” they offered, suggesting an online curriculum developed by the ACR for such a purpose. Fellowship training should also focus on working effectively with APPs, they added.

“Finally, incorporating APPs more effectively into rheumatology professional societies and supporting practices in hiring and training APPs will all be important steps in addressing the rheumatology workforce shortage,” Dr. Miloslavsky and Dr. Marston wrote.

Ms. Yonker said all her APPs take various courses that the ACR and other organizations provide for rheumatology-specific, midlevel positions. “We provide as much training as possible for them to feel comfortable in this space. They are set directly with a physician for a long time and then eventually go into their own space.”

In addition to ACR, the Rheumatology Nurses Society and the Association of Women in Rheumatology offer excellent online training resources for APPs, Ms. Yonker said. “Also, the Bone Health and Osteoporosis Foundation offers an osteoporosis fracture liaison certification which we put APPs through as well,” she added.

Rheumatology practices should also look into an important clinical training grant program from the Rheumatology Research Foundation, Dr. Stamatos advised.

To date, they have “funded almost everyone that applies,” she said. Each grantee receives $25,000 to support training and education involved in onboarding an APP to a rheumatology practice. The money covers attendance at a live rheumatology conference, online educational programs, textbooks, and any society memberships while defraying the cost of training this employee. To increase awareness of the program, the foundation has since expanded the number of available submission dates and the number of grant awardees per year. Currently, the application deadlines for the grants are December 1 and March 1.

For her own health system, Dr. Stamatos has been working on a rheumatology fellowship program for APPs. Through simulation labs, leadership exercises, and other activities, these APPs will learn how to transition from being a new provider to someone who can become part of a practice, she said.

APPs themselves can also get proactive in this learning cycle, Ms. Swafford said. In her view, both APPs and rheumatologists should be conducting didactic lectures and organizing elective rotations with medical students to get them excited about the field. This would establish a good education base that would encourage PAs and NPs to choose rheumatology.

“That’s a huge thing that’s probably missing,” Ms. Swafford said.
 

Buy-in From the Doctor

No recruitment effort is going to work if the rheumatologists in the practice aren’t committed to the model of having an APP, Ms. Yonker said. “Everybody wants to know their purpose in their company and that they’re valued and they’re needed. And so, I think a pitfall would be if your rheumatologist is not sold on the model of expanding the care team. Because this takes work on behalf of the doctor.”

Rheumatologists are very busy, so it’s a hard sell for them to take time out of their busy clinics to train somebody to do a good job taking care of their patients, Ms. Taylor agreed. “I think that we need the physicians that have had success with this and allow them to coach the physicians that are still resistant.”

In his small practice, Dr. Box has encouraged his NP to assist with practice improvements, working with the office manager. These workers are providers and need to be treated as such, he said. “They need to feel like they contribute to the practice more than just grinding through patients.”

Peer support is another successful ingredient for these workers. Ms. Taylor’s NP finds the time to commiserate with her fellow nurse practitioners — other rheumatology nurses who are also learning the ropes. Rheumatologists are smart, and they can be very intimidating, Ms. Taylor said. In their small office, the rheumatologist is her only peer.

“She likes to get out and sort of integrate with other nurse practitioners that are learning too.”
 

When APPs Make a Difference

Practices that take on APPs are reporting positive metrics — mainly, shorter wait times for patients. Ms. Yonker’s physicians have been able to add on one to two new patients a day. Wait times have since dwindled from a 5-month to a 3-month wait with the addition of the NPs. “Three months is still long, but we’re working on getting it to that ideal 6-week wait period, which we’re hoping we can accomplish. So we’re able to get more new patients in for sure,” she said.

Prior to hiring an NP, Ms. Taylor’s practice had to defer acceptances for new patients by at least a year. Now, they’re able to accept about half of all new patient referrals. With the NP on board, “We can get them in within 30 days,” she said.

Sometimes, an APP will go beyond their scope of work to make a difference and better support patients.

Patients with rheumatic and osteopathic conditions are often underdiagnosed in the primary care space. As a result, they are not treated as often as they should be. Seeing a need for specialty care, Ms. Swafford took action.

She currently runs the only bone health clinic in southwest Michigan, coordinating with rheumatologists, NPs, urgent care, hospitalists, and interventional radiologists to attend to these patients more quickly and reduce wait times for care. Specialists will flag things such as nontraumatic hip fractures and vertebral fractures and refer them to Ms. Swafford’s clinic, which is part of Bronson Rheumatology Specialists.

The clinic gets quite a few referrals, and the practice is growing. “Usually, they don’t take as long as a rheumatology referral for a workup, so we can see them a little bit quicker,” usually within 3 weeks, she added.

APPs have an opportunity to make their mark in rheumatology at a time when the profession is experiencing significant gaps in care, Ms. Swafford continued. “Unless we find a way to fill that niche, we’re going to be in a world of trouble in the next 10, 20 years.”

None of the sources reported any disclosures or conflicts of interest.

This transcript has been edited for clarity.

I am showing you a graph without any labels.

Dr. F. Perry Wilson

Dr. F. Perry Wilson

The New England Journal of Medicine

THE NEW ENGLAND JOURNAL OF MEDICINE

Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

I am showing you a graph without any labels.

Dr. F. Perry Wilson

Dr. F. Perry Wilson

The New England Journal of Medicine

THE NEW ENGLAND JOURNAL OF MEDICINE

Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

I am showing you a graph without any labels.

Dr. F. Perry Wilson

Dr. F. Perry Wilson

The New England Journal of Medicine

THE NEW ENGLAND JOURNAL OF MEDICINE

Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Conn. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Men who have smoked or currently smoke are significantly more likely to develop androgenetic alopecia (AGA) than men who have never smoked, according to a new study.

In addition, the odds of developing AGA are higher among those who smoke at least 10 cigarettes per day than among those who smoke less, the study authors found.

“Men who smoke are more likely to develop and experience progression of male pattern hair loss,” lead author Aditya Gupta, MD, PhD, professor of medicine at the University of Toronto, Toronto, and director of clinical research at Mediprobe Research Inc., London, Ontario, Canada, told this news organization.

“Our patients with male pattern baldness need to be educated about the negative effects of smoking, given that this condition can have a profound negative psychological impact on those who suffer from it,” he said.

The study was published online in the Journal of Cosmetic Dermatology.
 

Analyzing Smoking’s Effects

Smoking generally has been accepted as a risk factor for the development and progression of AGA or the most common form of hair loss. The research evidence on this association has been inconsistent, however, the authors wrote.

The investigators conducted a review and meta-analysis of eight observational studies to understand the links between smoking and AGA. Ever-smokers were defined as current and former smokers.

Overall, based on six studies, men who have ever smoked are 1.8 times more likely (P < .05) to develop AGA.

Based on two studies, men who smoke 10 or more cigarettes daily are about twice as likely (P < .05) to develop AGA than those who smoke up to 10 cigarettes per day.

Based on four studies, ever smoking is associated with 1.3 times higher odds of AGA progressing from mild (ie, Norwood-Hamilton stages I-III) to more severe (stages IV-VII) than among those who have never smoked.

Based on two studies, there’s no association between AGA progression and smoking intensity (as defined as smoking up to 20 cigarettes daily vs smoking 20 or more cigarettes per day).

“Though our pooled analysis found no significant association between smoking intensity and severity of male AGA, a positive correlation may exist and be detected through an analysis that is statistically better powered,” said Dr. Gupta.

The investigators noted the limitations of their analysis, such as its reliance on observational studies and its lack of data about nicotine levels, smoking intensity, and smoking cessation among study participants.

Additional studies are needed to better understand the links between smoking and hair loss, said Dr. Gupta, as well as the effects of smoking cessation.

Improving Practice and Research

Commenting on the findings for this news organization, Arash Babadjouni, MD, a dermatologist at Midwestern University, Glendale, Arizona, said, “Smoking is not only a preventable cause of significant systemic disease but also affects the follicular growth cycle and fiber pigmentation. The prevalence of hair loss and premature hair graying is higher in smokers than nonsmokers.”

Dr. Babadjouni, who wasn’t involved with this study, has researched the associations between smoking and hair loss and premature hair graying.

“Evidence of this association can be used to clinically promote smoking cessation and emphasize the consequences of smoking on hair,” he said. “Smoking status should be assessed in patients who are presenting to their dermatologist and physicians alike for evaluation of alopecia and premature hair graying.”

The study was conducted without outside funding, and the authors declared no conflicts of interest. Dr. Babadjouni reported no relevant disclosures.

A version of this article appeared on Medscape.com.

Men who have smoked or currently smoke are significantly more likely to develop androgenetic alopecia (AGA) than men who have never smoked, according to a new study.

In addition, the odds of developing AGA are higher among those who smoke at least 10 cigarettes per day than among those who smoke less, the study authors found.

“Men who smoke are more likely to develop and experience progression of male pattern hair loss,” lead author Aditya Gupta, MD, PhD, professor of medicine at the University of Toronto, Toronto, and director of clinical research at Mediprobe Research Inc., London, Ontario, Canada, told this news organization.

“Our patients with male pattern baldness need to be educated about the negative effects of smoking, given that this condition can have a profound negative psychological impact on those who suffer from it,” he said.

The study was published online in the Journal of Cosmetic Dermatology.
 

Analyzing Smoking’s Effects

Smoking generally has been accepted as a risk factor for the development and progression of AGA or the most common form of hair loss. The research evidence on this association has been inconsistent, however, the authors wrote.

The investigators conducted a review and meta-analysis of eight observational studies to understand the links between smoking and AGA. Ever-smokers were defined as current and former smokers.

Overall, based on six studies, men who have ever smoked are 1.8 times more likely (P < .05) to develop AGA.

Based on two studies, men who smoke 10 or more cigarettes daily are about twice as likely (P < .05) to develop AGA than those who smoke up to 10 cigarettes per day.

Based on four studies, ever smoking is associated with 1.3 times higher odds of AGA progressing from mild (ie, Norwood-Hamilton stages I-III) to more severe (stages IV-VII) than among those who have never smoked.

Based on two studies, there’s no association between AGA progression and smoking intensity (as defined as smoking up to 20 cigarettes daily vs smoking 20 or more cigarettes per day).

“Though our pooled analysis found no significant association between smoking intensity and severity of male AGA, a positive correlation may exist and be detected through an analysis that is statistically better powered,” said Dr. Gupta.

The investigators noted the limitations of their analysis, such as its reliance on observational studies and its lack of data about nicotine levels, smoking intensity, and smoking cessation among study participants.

Additional studies are needed to better understand the links between smoking and hair loss, said Dr. Gupta, as well as the effects of smoking cessation.

Improving Practice and Research

Commenting on the findings for this news organization, Arash Babadjouni, MD, a dermatologist at Midwestern University, Glendale, Arizona, said, “Smoking is not only a preventable cause of significant systemic disease but also affects the follicular growth cycle and fiber pigmentation. The prevalence of hair loss and premature hair graying is higher in smokers than nonsmokers.”

Dr. Babadjouni, who wasn’t involved with this study, has researched the associations between smoking and hair loss and premature hair graying.

“Evidence of this association can be used to clinically promote smoking cessation and emphasize the consequences of smoking on hair,” he said. “Smoking status should be assessed in patients who are presenting to their dermatologist and physicians alike for evaluation of alopecia and premature hair graying.”

The study was conducted without outside funding, and the authors declared no conflicts of interest. Dr. Babadjouni reported no relevant disclosures.

A version of this article appeared on Medscape.com.

Men who have smoked or currently smoke are significantly more likely to develop androgenetic alopecia (AGA) than men who have never smoked, according to a new study.

In addition, the odds of developing AGA are higher among those who smoke at least 10 cigarettes per day than among those who smoke less, the study authors found.

“Men who smoke are more likely to develop and experience progression of male pattern hair loss,” lead author Aditya Gupta, MD, PhD, professor of medicine at the University of Toronto, Toronto, and director of clinical research at Mediprobe Research Inc., London, Ontario, Canada, told this news organization.

“Our patients with male pattern baldness need to be educated about the negative effects of smoking, given that this condition can have a profound negative psychological impact on those who suffer from it,” he said.

The study was published online in the Journal of Cosmetic Dermatology.
 

Analyzing Smoking’s Effects

Smoking generally has been accepted as a risk factor for the development and progression of AGA or the most common form of hair loss. The research evidence on this association has been inconsistent, however, the authors wrote.

The investigators conducted a review and meta-analysis of eight observational studies to understand the links between smoking and AGA. Ever-smokers were defined as current and former smokers.

Overall, based on six studies, men who have ever smoked are 1.8 times more likely (P < .05) to develop AGA.

Based on two studies, men who smoke 10 or more cigarettes daily are about twice as likely (P < .05) to develop AGA than those who smoke up to 10 cigarettes per day.

Based on four studies, ever smoking is associated with 1.3 times higher odds of AGA progressing from mild (ie, Norwood-Hamilton stages I-III) to more severe (stages IV-VII) than among those who have never smoked.

Based on two studies, there’s no association between AGA progression and smoking intensity (as defined as smoking up to 20 cigarettes daily vs smoking 20 or more cigarettes per day).

“Though our pooled analysis found no significant association between smoking intensity and severity of male AGA, a positive correlation may exist and be detected through an analysis that is statistically better powered,” said Dr. Gupta.

The investigators noted the limitations of their analysis, such as its reliance on observational studies and its lack of data about nicotine levels, smoking intensity, and smoking cessation among study participants.

Additional studies are needed to better understand the links between smoking and hair loss, said Dr. Gupta, as well as the effects of smoking cessation.

Improving Practice and Research

Commenting on the findings for this news organization, Arash Babadjouni, MD, a dermatologist at Midwestern University, Glendale, Arizona, said, “Smoking is not only a preventable cause of significant systemic disease but also affects the follicular growth cycle and fiber pigmentation. The prevalence of hair loss and premature hair graying is higher in smokers than nonsmokers.”

Dr. Babadjouni, who wasn’t involved with this study, has researched the associations between smoking and hair loss and premature hair graying.

“Evidence of this association can be used to clinically promote smoking cessation and emphasize the consequences of smoking on hair,” he said. “Smoking status should be assessed in patients who are presenting to their dermatologist and physicians alike for evaluation of alopecia and premature hair graying.”

The study was conducted without outside funding, and the authors declared no conflicts of interest. Dr. Babadjouni reported no relevant disclosures.

A version of this article appeared on Medscape.com.

The report from the 2023 annual conference of French Urology Association (AFU), which was dedicated to male fertility, focused heavily on the diagnosis and treatment of varicocele, the most common reversible cause of infertility in men. Long a controversial subject, it has now been determined that treating this condition improves sperm analysis results, spontaneous fertility, and outcomes from medically assisted reproduction techniques. The AFU’s conference was a chance to present an overall snapshot of the issue.

Between 1973 and 2018, male sperm concentration dropped by 51.6% around the world, whereas total sperm counts dropped by 62.3%, according to Charlotte Methorst, MD, urological surgeon in Saint Cloud, France, president of the French Language Andrology Society, and coordinator of the AFU 2023 Report on Male Fertility. What’s more, sperm plasma concentrations are going down year-on-year at a rate twice as fast since before 2000 compared with the post-1972 period (from 1.16% to 2.64%).
 

Declining Fertility

Nowadays, around 15% of couples experience infertility (60,000 new cases/year in France). About 20% of these are strictly attributed to male infertility and 40% are mixed, implying a male factor. Consequently, Dr. Methorst explained that “we must routinely assess male fertility within the context of a medically assisted reproduction (MAR) pathway, without limiting testing to semen analysis. Varicocele, one of the causes of infertility that men should be screened for and defined as an abnormal and/or tortuous enlargement of the pampiniform plexus veins, is present in 15%-20% of the overall male population, 35% of men with primary infertility, and more than 70% of those experiencing secondary infertility.”

In infertile men, varicocele is mostly unilateral, occurring on the left side (85%-90% of cases). A link has been established between varicocele and insufficiency at the saphenofemoral junction, as well as venous insufficiency of the lower limbs (odds ratio, 2.34; P < .0001), suggesting a predisposition towards a vascular network favoring the presence of varicoceles.
 

Varicocele Underdiagnosed

Analysis of a large multicenter database recently suggested the underdiagnosis of varicocele in men being assessed for infertility. Diagnosis is primarily based on physical examination, with physicians finding a soft, serpiginous swelling in the upper and posterior part of the affected side of the scrotum. Testicular Doppler ultrasonography provides confirmation of a varicocele, taking into account aspects such as size and reflux duration during the Valsalva maneuver. Generally, this is enough to make a differential diagnosis, but MRI may be considered, especially in cases where a millimeter-sized nodule is also found.
 

Reversal Improves Fertility

A Cochrane meta-analysis, despite containing significant bias, raised doubts about the efficacy of varicocele treatment. Nevertheless, over the past 10 years, a randomized trial and several meta-analyses have put an end to the controversy, confirming that treatment for varicocele significantly improves natural pregnancy rates.

Microscopic subinguinal varicocelectomy is the gold-standard option for cases of clinical varicocele and for those in which sperm analysis findings are abnormal. This approach is associated with superior efficacy outcomes, such as improvement in sperm analysis results and pregnancy rates while leading to lower rates of recurrence (< 4%) and a favorable outcome in terms of complications. It should be noted that treating subclinical varicocele is not recommended.

Specifically, microscopic subinguinal varicocelectomy improves live birth and pregnancy rates, both naturally and via in vitro fertilization. What’s more, it has a positive impact on sperm count, total and progressive motility, morphology, and DNA fragmentation levels. Overall, this surgery changes the MAR approach used in around one in two cases. The grade and unilateral or bilateral nature of varicocele are important predictive factors of improvement in sperm analysis findings and pregnancy rates associated with this interventional procedure. Treating clinical varicocele (grades 1-3) leads to improved sperm analysis results, observed in 60%-70% of cases. According to a meta-analysis, the mean increase is said to be a concentration of 12 million spermatozoids per milliliter, as well as a mean improvement of 11% in sperm motility.

Notably, embolization can be considered as an alternative to surgery. This minimally invasive X-ray-guided procedure performed by an interventional radiologist attempts to block the dilated testicular vein.

Guidelines for clinical practice in treating varicocele were recently published by the AFU’s Andrology committee.

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

The report from the 2023 annual conference of French Urology Association (AFU), which was dedicated to male fertility, focused heavily on the diagnosis and treatment of varicocele, the most common reversible cause of infertility in men. Long a controversial subject, it has now been determined that treating this condition improves sperm analysis results, spontaneous fertility, and outcomes from medically assisted reproduction techniques. The AFU’s conference was a chance to present an overall snapshot of the issue.

Between 1973 and 2018, male sperm concentration dropped by 51.6% around the world, whereas total sperm counts dropped by 62.3%, according to Charlotte Methorst, MD, urological surgeon in Saint Cloud, France, president of the French Language Andrology Society, and coordinator of the AFU 2023 Report on Male Fertility. What’s more, sperm plasma concentrations are going down year-on-year at a rate twice as fast since before 2000 compared with the post-1972 period (from 1.16% to 2.64%).
 

Declining Fertility

Nowadays, around 15% of couples experience infertility (60,000 new cases/year in France). About 20% of these are strictly attributed to male infertility and 40% are mixed, implying a male factor. Consequently, Dr. Methorst explained that “we must routinely assess male fertility within the context of a medically assisted reproduction (MAR) pathway, without limiting testing to semen analysis. Varicocele, one of the causes of infertility that men should be screened for and defined as an abnormal and/or tortuous enlargement of the pampiniform plexus veins, is present in 15%-20% of the overall male population, 35% of men with primary infertility, and more than 70% of those experiencing secondary infertility.”

In infertile men, varicocele is mostly unilateral, occurring on the left side (85%-90% of cases). A link has been established between varicocele and insufficiency at the saphenofemoral junction, as well as venous insufficiency of the lower limbs (odds ratio, 2.34; P < .0001), suggesting a predisposition towards a vascular network favoring the presence of varicoceles.
 

Varicocele Underdiagnosed

Analysis of a large multicenter database recently suggested the underdiagnosis of varicocele in men being assessed for infertility. Diagnosis is primarily based on physical examination, with physicians finding a soft, serpiginous swelling in the upper and posterior part of the affected side of the scrotum. Testicular Doppler ultrasonography provides confirmation of a varicocele, taking into account aspects such as size and reflux duration during the Valsalva maneuver. Generally, this is enough to make a differential diagnosis, but MRI may be considered, especially in cases where a millimeter-sized nodule is also found.
 

Reversal Improves Fertility

A Cochrane meta-analysis, despite containing significant bias, raised doubts about the efficacy of varicocele treatment. Nevertheless, over the past 10 years, a randomized trial and several meta-analyses have put an end to the controversy, confirming that treatment for varicocele significantly improves natural pregnancy rates.

Microscopic subinguinal varicocelectomy is the gold-standard option for cases of clinical varicocele and for those in which sperm analysis findings are abnormal. This approach is associated with superior efficacy outcomes, such as improvement in sperm analysis results and pregnancy rates while leading to lower rates of recurrence (< 4%) and a favorable outcome in terms of complications. It should be noted that treating subclinical varicocele is not recommended.

Specifically, microscopic subinguinal varicocelectomy improves live birth and pregnancy rates, both naturally and via in vitro fertilization. What’s more, it has a positive impact on sperm count, total and progressive motility, morphology, and DNA fragmentation levels. Overall, this surgery changes the MAR approach used in around one in two cases. The grade and unilateral or bilateral nature of varicocele are important predictive factors of improvement in sperm analysis findings and pregnancy rates associated with this interventional procedure. Treating clinical varicocele (grades 1-3) leads to improved sperm analysis results, observed in 60%-70% of cases. According to a meta-analysis, the mean increase is said to be a concentration of 12 million spermatozoids per milliliter, as well as a mean improvement of 11% in sperm motility.

Notably, embolization can be considered as an alternative to surgery. This minimally invasive X-ray-guided procedure performed by an interventional radiologist attempts to block the dilated testicular vein.

Guidelines for clinical practice in treating varicocele were recently published by the AFU’s Andrology committee.

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

The report from the 2023 annual conference of French Urology Association (AFU), which was dedicated to male fertility, focused heavily on the diagnosis and treatment of varicocele, the most common reversible cause of infertility in men. Long a controversial subject, it has now been determined that treating this condition improves sperm analysis results, spontaneous fertility, and outcomes from medically assisted reproduction techniques. The AFU’s conference was a chance to present an overall snapshot of the issue.

Between 1973 and 2018, male sperm concentration dropped by 51.6% around the world, whereas total sperm counts dropped by 62.3%, according to Charlotte Methorst, MD, urological surgeon in Saint Cloud, France, president of the French Language Andrology Society, and coordinator of the AFU 2023 Report on Male Fertility. What’s more, sperm plasma concentrations are going down year-on-year at a rate twice as fast since before 2000 compared with the post-1972 period (from 1.16% to 2.64%).
 

Declining Fertility

Nowadays, around 15% of couples experience infertility (60,000 new cases/year in France). About 20% of these are strictly attributed to male infertility and 40% are mixed, implying a male factor. Consequently, Dr. Methorst explained that “we must routinely assess male fertility within the context of a medically assisted reproduction (MAR) pathway, without limiting testing to semen analysis. Varicocele, one of the causes of infertility that men should be screened for and defined as an abnormal and/or tortuous enlargement of the pampiniform plexus veins, is present in 15%-20% of the overall male population, 35% of men with primary infertility, and more than 70% of those experiencing secondary infertility.”

In infertile men, varicocele is mostly unilateral, occurring on the left side (85%-90% of cases). A link has been established between varicocele and insufficiency at the saphenofemoral junction, as well as venous insufficiency of the lower limbs (odds ratio, 2.34; P < .0001), suggesting a predisposition towards a vascular network favoring the presence of varicoceles.
 

Varicocele Underdiagnosed

Analysis of a large multicenter database recently suggested the underdiagnosis of varicocele in men being assessed for infertility. Diagnosis is primarily based on physical examination, with physicians finding a soft, serpiginous swelling in the upper and posterior part of the affected side of the scrotum. Testicular Doppler ultrasonography provides confirmation of a varicocele, taking into account aspects such as size and reflux duration during the Valsalva maneuver. Generally, this is enough to make a differential diagnosis, but MRI may be considered, especially in cases where a millimeter-sized nodule is also found.
 

Reversal Improves Fertility

A Cochrane meta-analysis, despite containing significant bias, raised doubts about the efficacy of varicocele treatment. Nevertheless, over the past 10 years, a randomized trial and several meta-analyses have put an end to the controversy, confirming that treatment for varicocele significantly improves natural pregnancy rates.

Microscopic subinguinal varicocelectomy is the gold-standard option for cases of clinical varicocele and for those in which sperm analysis findings are abnormal. This approach is associated with superior efficacy outcomes, such as improvement in sperm analysis results and pregnancy rates while leading to lower rates of recurrence (< 4%) and a favorable outcome in terms of complications. It should be noted that treating subclinical varicocele is not recommended.

Specifically, microscopic subinguinal varicocelectomy improves live birth and pregnancy rates, both naturally and via in vitro fertilization. What’s more, it has a positive impact on sperm count, total and progressive motility, morphology, and DNA fragmentation levels. Overall, this surgery changes the MAR approach used in around one in two cases. The grade and unilateral or bilateral nature of varicocele are important predictive factors of improvement in sperm analysis findings and pregnancy rates associated with this interventional procedure. Treating clinical varicocele (grades 1-3) leads to improved sperm analysis results, observed in 60%-70% of cases. According to a meta-analysis, the mean increase is said to be a concentration of 12 million spermatozoids per milliliter, as well as a mean improvement of 11% in sperm motility.

Notably, embolization can be considered as an alternative to surgery. This minimally invasive X-ray-guided procedure performed by an interventional radiologist attempts to block the dilated testicular vein.

Guidelines for clinical practice in treating varicocele were recently published by the AFU’s Andrology committee.

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

The long-term impact of traumatic brain injury (TBI) on neurologic and psychiatric function is well-established, but a growing body of research is pointing to unexpected medical sequalae, including cardiovascular disease (CVD).

A recent review looked at the investigation to date into this surprising connection, not only summarizing study findings but also suggesting potential mechanisms that might account for the association.

“This work offers further evidence that individuals with TBI are at an elevated risk of unfavorable cardiovascular outcomes for an extended period following the initial incident; consequently, they should undergo regular monitoring,” senior author Ross Zafonte, DO, president of Spaulding Rehabilitation Network, Boston, and lead author Saef Izzy, MD, MBChB, a neurologist at the Stroke and Cerebrovascular Center of Brigham and Women’s Hospital, Boston, Massachusetts, told this news organization.

“This holds significant importance for healthcare practitioners, as there exist several strategies to mitigate cardiovascular disease risk — including weight management, adopting a healthy diet, engaging in regular physical activity, and quitting smoking,” they stated.

Leslie Croll, MD, American Heart Association volunteer and assistant professor of clinical neurology at the Temple University Lewis Katz School of Medicine, Philadelphia, Pennsylvania, told this news organization that it’s “extremely important to learn more about the interplay between TBI, neurologic disease, psychiatric complications, and the cardiovascular system.”

Hopefully, she added, “future research will help us understand what kind of cardiovascular disease monitoring and prevention measures stand to give TBI patients the most benefit.”
 

Chronic Condition

TBI is “a major cause of long-term disability and premature death,” and is “highly prevalent among contact sports players, military personnel (eg, due to injuries sustained during conflict), and the general population (eg, due to falls and road traffic incidents),” the authors wrote.

Most studies pertaining to TBI have “primarily focused on establishing connections between single TBI, repetitive TBI, and their acute and chronic neurological and psychiatric consequences, such as Parkinson’s disease, Alzheimer’s disease, and chronic traumatic encephalopathy (CTE),” Drs. Zafonte and Izzy noted. By contrast, there has been a “notable lack of research attention given to non-neurological conditions associated with TBI.”

They pointed out that recent insights into TBI — particularly the acknowledgment of TBI as an “emerging chronic condition rather than merely an acute aftermath of brain injury” — have come to light through epidemiologic and pathologic investigations involving military veterans, professional American-style football players, and the civilian population. “This recognition opens up an opportunity to broaden our perspective and delve into the medical aspects of health that may be influenced by TBI.”

To broaden the investigation, the researchers reviewed literature published between January 1, 2001, and June 18, 2023. Of 26,335 articles, they narrowed their review down to 15 studies that investigated CVD, CVD risk factors, and cerebrovascular disease in the chronic phase of TBI, including community, military, or sport-related brain trauma, regardless of the timing of disease occurrence with respect to brain injury via TBI or repetitive head impact.
 

New Cardiovascular Risk

Studies that used national or local registries tended to be retrospective and predominantly conducted in people with preexisting cardiovascular conditions. In these studies, TBI was found to be an independent risk factor for myocardial dysfunction. However, although these studies do provide evidence of elevated cardiovascular risk subsequent to a single TBI, including individuals with preexisting medical comorbidities “makes it difficult to determine the timing of incident cardiovascular disease and cardiovascular risk factors subsequent to brain injury,” they wrote.

However, some studies showed that even individuals with TBI but without preexisting myocardial dysfunction at baseline had a significantly higher risk for CVD than those without a history of TBI.

In fact, several studies included populations without preexisting medical and cardiovascular comorbidities to “better refine the order and timing of CVD and other risk factors in individuals with TBI.”

For example, one study of concussion survivors without preexisting diagnoses showed that cardiovascular, endocrinological, and neuropsychiatric comorbidities occurred at a “significantly higher incidence within 5 years after concussive TBI compared with healthy individuals who were matched in terms of age, race, and sex and didn’t have a TBI exposure.” Other studies yielded similar findings.

Because cardiovascular risk factors and events become more common with age, it’s important to account for age in evaluating the effects of TBI. Although many studies of TBI and subsequent CVD didn’t stratify individuals by age, one 10-year study of people without any known cardiovascular or neuropsychiatric conditions who sustained TBI found that people as young as 18-40 years were more likely to develop hypertension, hyperlipidemia, obesity, and diabetes within 3-5 years following brain injury than matched individuals in the control group.

“Individuals who have encountered TBI, surprisingly even those who are young and in good health with no prior comorbid conditions, face an increased risk of adverse cardiovascular outcomes for an extended duration after the initial event,” Drs. Zafonte and Izzy summarized. “Therefore, it’s imperative that they receive regular and long-term screenings for CVD and associated risk factors.”
 

Bidirectional Relationship

Brain injury has been associated with acute cardiovascular dysfunction, including autonomic heart-brain axis dysregulation, imbalances between the sympathetic and parasympathetic nervous systems, and excessive catecholamine release, the authors noted.

Drs. Zafonte and Izzy suggested several plausible links between TBI and cardiovascular dysfunction, noting that they are “likely multifaceted, potentially encompassing risk factors that span the pre-injury, injury, and post-injury phases of the condition.”

TBI may induce alterations in neurobiological processes, which have been reported to be associated with an increased risk for CVD (eg, chronic dysfunction of the autonomic system, systemic inflammation, and modifications in the brain-gut connection).

Patients with TBI might develop additional risk factors following the injury, including conditions like posttraumatic stress disorder, depression, and other psychiatric illnesses, which are “known to augment the risk of CVD.”

TBI can lead to subsequent behavioral and lifestyle changes that place patients at an elevated risk for both cardiovascular and cognitive dysfunction when compared to the general population of TBI survivors.

There may be additional as yet undefined risks.

They believe there’s a bidirectional relationship between TBI and CVD. “On one hand, TBI has been associated with an elevated risk of CVD,” they said. “Conversely, cardiovascular risk factors such as diabetes, hypertension, hyperlipidemia, and sleep disturbances that have been demonstrated to negatively influence cognitive function and heighten the risk of dementia. Consequently, this interplay can further compound the long-term consequences of the injury.”

Their work aims to try and disentangle this “complex series of relationships.”

They recommend screening to identify diseases in their earliest and “most manageable phases” because TBI has been “unveiled as an underappreciated risk factor for CVD within contact sports, military, and community setting.”

An effective screening program “should rely on quantifiable and dependable biomarkers such as blood pressure, BMI, waist circumference, blood lipid levels, and glucose. Additionally, it should take into account other factors like smoking habits, physical activity, and dietary choices,” they recommended.
 

Heart-Brain Connection

Dr. Croll noted that TBI is “associated with many poorly understood physiologic changes and complications, so it’s exciting to see research aimed at clarifying this chronic disease process.”

In recent years, “we have seen a greater appreciation and understanding of the heart-brain connection,” she said. “Moving forward, more research, including TBI research, will target that connection.”

She added that there are probably “multiple mechanisms” at play underlying the connection between TBI and CVD.

Most importantly, “we are increasingly learning that TBI is not only a discrete event that requires immediate treatment but also a chronic disease process,” and when we “think about the substantial long-term morbidity associated with TBI, we should keep increased risk for CVD on top of mind,” said Dr. Croll.

The review received no funding. Izzy reported receiving grants from the US National Institutes of Health (NIH) and 2023 Stepping Strong Innovator Award. Dr. Zafonte reported receiving grants from the NIH and royalties from Springer and Demos publishing for serving as a coeditor of Brain Injury Medicine. Dr. Zafonte has also served as an adviser to Myomo, Oncare.ai, Nanodiagnostics, and Kisbee. He reported evaluating patients in the Massachusetts General Hospital Brain and Body–TRUST Program, which is funded by the NFL Players Association. The other authors’ disclosures are listed on the original paper. Dr. Croll declared no relevant financial relationships.

A version of this article appeared on Medscape.com.

The long-term impact of traumatic brain injury (TBI) on neurologic and psychiatric function is well-established, but a growing body of research is pointing to unexpected medical sequalae, including cardiovascular disease (CVD).

A recent review looked at the investigation to date into this surprising connection, not only summarizing study findings but also suggesting potential mechanisms that might account for the association.

“This work offers further evidence that individuals with TBI are at an elevated risk of unfavorable cardiovascular outcomes for an extended period following the initial incident; consequently, they should undergo regular monitoring,” senior author Ross Zafonte, DO, president of Spaulding Rehabilitation Network, Boston, and lead author Saef Izzy, MD, MBChB, a neurologist at the Stroke and Cerebrovascular Center of Brigham and Women’s Hospital, Boston, Massachusetts, told this news organization.

“This holds significant importance for healthcare practitioners, as there exist several strategies to mitigate cardiovascular disease risk — including weight management, adopting a healthy diet, engaging in regular physical activity, and quitting smoking,” they stated.

Leslie Croll, MD, American Heart Association volunteer and assistant professor of clinical neurology at the Temple University Lewis Katz School of Medicine, Philadelphia, Pennsylvania, told this news organization that it’s “extremely important to learn more about the interplay between TBI, neurologic disease, psychiatric complications, and the cardiovascular system.”

Hopefully, she added, “future research will help us understand what kind of cardiovascular disease monitoring and prevention measures stand to give TBI patients the most benefit.”
 

Chronic Condition

TBI is “a major cause of long-term disability and premature death,” and is “highly prevalent among contact sports players, military personnel (eg, due to injuries sustained during conflict), and the general population (eg, due to falls and road traffic incidents),” the authors wrote.

Most studies pertaining to TBI have “primarily focused on establishing connections between single TBI, repetitive TBI, and their acute and chronic neurological and psychiatric consequences, such as Parkinson’s disease, Alzheimer’s disease, and chronic traumatic encephalopathy (CTE),” Drs. Zafonte and Izzy noted. By contrast, there has been a “notable lack of research attention given to non-neurological conditions associated with TBI.”

They pointed out that recent insights into TBI — particularly the acknowledgment of TBI as an “emerging chronic condition rather than merely an acute aftermath of brain injury” — have come to light through epidemiologic and pathologic investigations involving military veterans, professional American-style football players, and the civilian population. “This recognition opens up an opportunity to broaden our perspective and delve into the medical aspects of health that may be influenced by TBI.”

To broaden the investigation, the researchers reviewed literature published between January 1, 2001, and June 18, 2023. Of 26,335 articles, they narrowed their review down to 15 studies that investigated CVD, CVD risk factors, and cerebrovascular disease in the chronic phase of TBI, including community, military, or sport-related brain trauma, regardless of the timing of disease occurrence with respect to brain injury via TBI or repetitive head impact.
 

New Cardiovascular Risk

Studies that used national or local registries tended to be retrospective and predominantly conducted in people with preexisting cardiovascular conditions. In these studies, TBI was found to be an independent risk factor for myocardial dysfunction. However, although these studies do provide evidence of elevated cardiovascular risk subsequent to a single TBI, including individuals with preexisting medical comorbidities “makes it difficult to determine the timing of incident cardiovascular disease and cardiovascular risk factors subsequent to brain injury,” they wrote.

However, some studies showed that even individuals with TBI but without preexisting myocardial dysfunction at baseline had a significantly higher risk for CVD than those without a history of TBI.

In fact, several studies included populations without preexisting medical and cardiovascular comorbidities to “better refine the order and timing of CVD and other risk factors in individuals with TBI.”

For example, one study of concussion survivors without preexisting diagnoses showed that cardiovascular, endocrinological, and neuropsychiatric comorbidities occurred at a “significantly higher incidence within 5 years after concussive TBI compared with healthy individuals who were matched in terms of age, race, and sex and didn’t have a TBI exposure.” Other studies yielded similar findings.

Because cardiovascular risk factors and events become more common with age, it’s important to account for age in evaluating the effects of TBI. Although many studies of TBI and subsequent CVD didn’t stratify individuals by age, one 10-year study of people without any known cardiovascular or neuropsychiatric conditions who sustained TBI found that people as young as 18-40 years were more likely to develop hypertension, hyperlipidemia, obesity, and diabetes within 3-5 years following brain injury than matched individuals in the control group.

“Individuals who have encountered TBI, surprisingly even those who are young and in good health with no prior comorbid conditions, face an increased risk of adverse cardiovascular outcomes for an extended duration after the initial event,” Drs. Zafonte and Izzy summarized. “Therefore, it’s imperative that they receive regular and long-term screenings for CVD and associated risk factors.”
 

Bidirectional Relationship

Brain injury has been associated with acute cardiovascular dysfunction, including autonomic heart-brain axis dysregulation, imbalances between the sympathetic and parasympathetic nervous systems, and excessive catecholamine release, the authors noted.

Drs. Zafonte and Izzy suggested several plausible links between TBI and cardiovascular dysfunction, noting that they are “likely multifaceted, potentially encompassing risk factors that span the pre-injury, injury, and post-injury phases of the condition.”

TBI may induce alterations in neurobiological processes, which have been reported to be associated with an increased risk for CVD (eg, chronic dysfunction of the autonomic system, systemic inflammation, and modifications in the brain-gut connection).

Patients with TBI might develop additional risk factors following the injury, including conditions like posttraumatic stress disorder, depression, and other psychiatric illnesses, which are “known to augment the risk of CVD.”

TBI can lead to subsequent behavioral and lifestyle changes that place patients at an elevated risk for both cardiovascular and cognitive dysfunction when compared to the general population of TBI survivors.

There may be additional as yet undefined risks.

They believe there’s a bidirectional relationship between TBI and CVD. “On one hand, TBI has been associated with an elevated risk of CVD,” they said. “Conversely, cardiovascular risk factors such as diabetes, hypertension, hyperlipidemia, and sleep disturbances that have been demonstrated to negatively influence cognitive function and heighten the risk of dementia. Consequently, this interplay can further compound the long-term consequences of the injury.”

Their work aims to try and disentangle this “complex series of relationships.”

They recommend screening to identify diseases in their earliest and “most manageable phases” because TBI has been “unveiled as an underappreciated risk factor for CVD within contact sports, military, and community setting.”

An effective screening program “should rely on quantifiable and dependable biomarkers such as blood pressure, BMI, waist circumference, blood lipid levels, and glucose. Additionally, it should take into account other factors like smoking habits, physical activity, and dietary choices,” they recommended.
 

Heart-Brain Connection

Dr. Croll noted that TBI is “associated with many poorly understood physiologic changes and complications, so it’s exciting to see research aimed at clarifying this chronic disease process.”

In recent years, “we have seen a greater appreciation and understanding of the heart-brain connection,” she said. “Moving forward, more research, including TBI research, will target that connection.”

She added that there are probably “multiple mechanisms” at play underlying the connection between TBI and CVD.

Most importantly, “we are increasingly learning that TBI is not only a discrete event that requires immediate treatment but also a chronic disease process,” and when we “think about the substantial long-term morbidity associated with TBI, we should keep increased risk for CVD on top of mind,” said Dr. Croll.

The review received no funding. Izzy reported receiving grants from the US National Institutes of Health (NIH) and 2023 Stepping Strong Innovator Award. Dr. Zafonte reported receiving grants from the NIH and royalties from Springer and Demos publishing for serving as a coeditor of Brain Injury Medicine. Dr. Zafonte has also served as an adviser to Myomo, Oncare.ai, Nanodiagnostics, and Kisbee. He reported evaluating patients in the Massachusetts General Hospital Brain and Body–TRUST Program, which is funded by the NFL Players Association. The other authors’ disclosures are listed on the original paper. Dr. Croll declared no relevant financial relationships.

A version of this article appeared on Medscape.com.

The long-term impact of traumatic brain injury (TBI) on neurologic and psychiatric function is well-established, but a growing body of research is pointing to unexpected medical sequalae, including cardiovascular disease (CVD).

A recent review looked at the investigation to date into this surprising connection, not only summarizing study findings but also suggesting potential mechanisms that might account for the association.

“This work offers further evidence that individuals with TBI are at an elevated risk of unfavorable cardiovascular outcomes for an extended period following the initial incident; consequently, they should undergo regular monitoring,” senior author Ross Zafonte, DO, president of Spaulding Rehabilitation Network, Boston, and lead author Saef Izzy, MD, MBChB, a neurologist at the Stroke and Cerebrovascular Center of Brigham and Women’s Hospital, Boston, Massachusetts, told this news organization.

“This holds significant importance for healthcare practitioners, as there exist several strategies to mitigate cardiovascular disease risk — including weight management, adopting a healthy diet, engaging in regular physical activity, and quitting smoking,” they stated.

Leslie Croll, MD, American Heart Association volunteer and assistant professor of clinical neurology at the Temple University Lewis Katz School of Medicine, Philadelphia, Pennsylvania, told this news organization that it’s “extremely important to learn more about the interplay between TBI, neurologic disease, psychiatric complications, and the cardiovascular system.”

Hopefully, she added, “future research will help us understand what kind of cardiovascular disease monitoring and prevention measures stand to give TBI patients the most benefit.”
 

Chronic Condition

TBI is “a major cause of long-term disability and premature death,” and is “highly prevalent among contact sports players, military personnel (eg, due to injuries sustained during conflict), and the general population (eg, due to falls and road traffic incidents),” the authors wrote.

Most studies pertaining to TBI have “primarily focused on establishing connections between single TBI, repetitive TBI, and their acute and chronic neurological and psychiatric consequences, such as Parkinson’s disease, Alzheimer’s disease, and chronic traumatic encephalopathy (CTE),” Drs. Zafonte and Izzy noted. By contrast, there has been a “notable lack of research attention given to non-neurological conditions associated with TBI.”

They pointed out that recent insights into TBI — particularly the acknowledgment of TBI as an “emerging chronic condition rather than merely an acute aftermath of brain injury” — have come to light through epidemiologic and pathologic investigations involving military veterans, professional American-style football players, and the civilian population. “This recognition opens up an opportunity to broaden our perspective and delve into the medical aspects of health that may be influenced by TBI.”

To broaden the investigation, the researchers reviewed literature published between January 1, 2001, and June 18, 2023. Of 26,335 articles, they narrowed their review down to 15 studies that investigated CVD, CVD risk factors, and cerebrovascular disease in the chronic phase of TBI, including community, military, or sport-related brain trauma, regardless of the timing of disease occurrence with respect to brain injury via TBI or repetitive head impact.
 

New Cardiovascular Risk

Studies that used national or local registries tended to be retrospective and predominantly conducted in people with preexisting cardiovascular conditions. In these studies, TBI was found to be an independent risk factor for myocardial dysfunction. However, although these studies do provide evidence of elevated cardiovascular risk subsequent to a single TBI, including individuals with preexisting medical comorbidities “makes it difficult to determine the timing of incident cardiovascular disease and cardiovascular risk factors subsequent to brain injury,” they wrote.

However, some studies showed that even individuals with TBI but without preexisting myocardial dysfunction at baseline had a significantly higher risk for CVD than those without a history of TBI.

In fact, several studies included populations without preexisting medical and cardiovascular comorbidities to “better refine the order and timing of CVD and other risk factors in individuals with TBI.”

For example, one study of concussion survivors without preexisting diagnoses showed that cardiovascular, endocrinological, and neuropsychiatric comorbidities occurred at a “significantly higher incidence within 5 years after concussive TBI compared with healthy individuals who were matched in terms of age, race, and sex and didn’t have a TBI exposure.” Other studies yielded similar findings.

Because cardiovascular risk factors and events become more common with age, it’s important to account for age in evaluating the effects of TBI. Although many studies of TBI and subsequent CVD didn’t stratify individuals by age, one 10-year study of people without any known cardiovascular or neuropsychiatric conditions who sustained TBI found that people as young as 18-40 years were more likely to develop hypertension, hyperlipidemia, obesity, and diabetes within 3-5 years following brain injury than matched individuals in the control group.

“Individuals who have encountered TBI, surprisingly even those who are young and in good health with no prior comorbid conditions, face an increased risk of adverse cardiovascular outcomes for an extended duration after the initial event,” Drs. Zafonte and Izzy summarized. “Therefore, it’s imperative that they receive regular and long-term screenings for CVD and associated risk factors.”
 

Bidirectional Relationship

Brain injury has been associated with acute cardiovascular dysfunction, including autonomic heart-brain axis dysregulation, imbalances between the sympathetic and parasympathetic nervous systems, and excessive catecholamine release, the authors noted.

Drs. Zafonte and Izzy suggested several plausible links between TBI and cardiovascular dysfunction, noting that they are “likely multifaceted, potentially encompassing risk factors that span the pre-injury, injury, and post-injury phases of the condition.”

TBI may induce alterations in neurobiological processes, which have been reported to be associated with an increased risk for CVD (eg, chronic dysfunction of the autonomic system, systemic inflammation, and modifications in the brain-gut connection).

Patients with TBI might develop additional risk factors following the injury, including conditions like posttraumatic stress disorder, depression, and other psychiatric illnesses, which are “known to augment the risk of CVD.”

TBI can lead to subsequent behavioral and lifestyle changes that place patients at an elevated risk for both cardiovascular and cognitive dysfunction when compared to the general population of TBI survivors.

There may be additional as yet undefined risks.

They believe there’s a bidirectional relationship between TBI and CVD. “On one hand, TBI has been associated with an elevated risk of CVD,” they said. “Conversely, cardiovascular risk factors such as diabetes, hypertension, hyperlipidemia, and sleep disturbances that have been demonstrated to negatively influence cognitive function and heighten the risk of dementia. Consequently, this interplay can further compound the long-term consequences of the injury.”

Their work aims to try and disentangle this “complex series of relationships.”

They recommend screening to identify diseases in their earliest and “most manageable phases” because TBI has been “unveiled as an underappreciated risk factor for CVD within contact sports, military, and community setting.”

An effective screening program “should rely on quantifiable and dependable biomarkers such as blood pressure, BMI, waist circumference, blood lipid levels, and glucose. Additionally, it should take into account other factors like smoking habits, physical activity, and dietary choices,” they recommended.
 

Heart-Brain Connection

Dr. Croll noted that TBI is “associated with many poorly understood physiologic changes and complications, so it’s exciting to see research aimed at clarifying this chronic disease process.”

In recent years, “we have seen a greater appreciation and understanding of the heart-brain connection,” she said. “Moving forward, more research, including TBI research, will target that connection.”

She added that there are probably “multiple mechanisms” at play underlying the connection between TBI and CVD.

Most importantly, “we are increasingly learning that TBI is not only a discrete event that requires immediate treatment but also a chronic disease process,” and when we “think about the substantial long-term morbidity associated with TBI, we should keep increased risk for CVD on top of mind,” said Dr. Croll.

The review received no funding. Izzy reported receiving grants from the US National Institutes of Health (NIH) and 2023 Stepping Strong Innovator Award. Dr. Zafonte reported receiving grants from the NIH and royalties from Springer and Demos publishing for serving as a coeditor of Brain Injury Medicine. Dr. Zafonte has also served as an adviser to Myomo, Oncare.ai, Nanodiagnostics, and Kisbee. He reported evaluating patients in the Massachusetts General Hospital Brain and Body–TRUST Program, which is funded by the NFL Players Association. The other authors’ disclosures are listed on the original paper. Dr. Croll declared no relevant financial relationships.

A version of this article appeared on Medscape.com.

Underdiagnosis, reluctant doctors, patient preconceptions: Treating low testosterone levels is a tricky business in France despite the proven benefits of replacement therapy. About 20% of patients with symptomatic low testosterone levels are treated for the deficiency, said Eric Huygue, MD, PhD, urologic surgeon at Toulouse University Hospital in France, at the 117th annual conference of the French Urology Association (AFU).

“Treatment for low testosterone is effective and risk-free. It improves a patient’s quality of life and general health,” particularly affecting fatigue, mood, and libido, said Dr. Huygue, who was involved in drawing up the first French recommendations on treating low testosterone in 2021.

“We must keep up communication efforts to make patients and doctors aware” of the benefits of supplementation, he said.
 

Testosterone Levels

Testosterone deficiency mostly affects men older than 40 years. A drop in androgen levels, which varies by individual, can lead to sexual problems (such as erectile dysfunction and low libido), physical symptoms (fatigue, hot flashes, loss of muscle mass, and osteoporosis), and mental disorders (anxiety, irritability, and depression).

There are an estimated 340,000 men with symptomatic testosterone deficiency in France. Just 70,000 of these are receiving replacement therapy (see box), which accounts for only 20% of those affected. For Dr. Huygue, this low treatment rate is due to underdiagnosis, as well as reluctance on the part of doctors and patients.

Although routine screening of low testosterone in the general population is not recommended, some individuals are particularly at risk, noted the urologist.

This is especially true for patients with metabolic disorders associated with insulin resistance (such as obesity and type 2 diabetes), cardiovascular diseases (hypertension, heart failure, and atrial fibrillation), or other chronic conditions (chronic obstructive pulmonary disease, cancer, and depression). Some medications (corticosteroids, antipsychotics, chemotherapy drugs, and antiretroviral therapies) can also lead to low testosterone.

Per the French recommendations for managing low testosterone, diagnosis must be based on free or bioavailable testosterone and not total testosterone levels, which can give a skewed result. Levels must be tested twice, 1 month apart, in the morning and while fasting. The reference range is determined by taking the lower threshold level of young men as measured in the laboratory.

Threshold Values

The current practice of using the reference range associated with the patient’s age group undoubtedly contributes to the underdiagnosis of low testosterone, said Dr. Huygue. According to a survey of AFU members in 2021, the year in which the recommendations were published, 77% of urologists interviewed reported referring to reference ranges for patients of the same age.

In their defense, “this method has long been in use, but it has eventually become apparent that symptomatic patients with an undiagnosed deficiency could be in the reference patients’ group,” Dr. Huygue explained.

Once a deficiency has been diagnosed, doctors may be reluctant to prescribe replacement therapy due to the perceived risk of developing prostate cancer. Several international studies have shown that “the risk of prostate cancer is the single biggest reason for doctors refusing to prescribe testosterone,” said Dr. Huygue.

Despite this reluctance, numerous studies have clearly shown that there is no link between a high testosterone level and the risk of developing prostate cancer. It even seems that a low testosterone level might expose a person to an increased risk for an aggressive form of cancer.

“This is a time of many surprising discoveries concerning the link between the prostate and testosterone, which go against what we have thought up to now. It has been observed that men with low testosterone develop more serious types of cancer,” said Dr. Huygue at a previous meeting of the AFU, during which he announced the publication of the French recommendations.
 

Prostate Cancer Recurrence

Urologists are also wary of testosterone supplementation in patients with a previous history of prostate cancer. According to the AFU’s survey, 40% of urologists questioned think that testosterone is contraindicated in this population. One in two urologists prescribe testosterone after radical prostatectomy for low or intermediate risk and most commonly after 3 years of undetectable prostate-specific antigen (PSA) levels.

Nevertheless, “several retrospective studies show the safety of testosterone replacement therapy in men who have undergone radical prostatectomy or radiotherapy or who are under active monitoring,” said Dr. Huygue. Testosterone “does not appear to increase the risk of relapse” after treatment of prostate cancer.

Dr. Huygue invited prescribing physicians to refer to the French recommendations, which specify that 1 year of undetectable PSA after prostatectomy is sufficient before prescribing replacement therapy. “This is clearly indicated in the recommendations for patients with a previous history of prostate cancer.”

Neither prostate cancer nor benign prostatic hyperplasia is a contraindication. According to the recommendations, the only contraindications to testosterone prescription are the following:

• Hematocrit > 54%
• Current breast or prostate cancer
• Cardiovascular event less than 3-6 months prior
• Trying to conceive

Cardiovascular Benefits

Another more commonly used argument by general practitioners and endocrinologists to justify their reluctance to prescribe testosterone is the risk to cardiovascular health. In early 2010, a series of American studies alerted clinicians to this risk when taking testosterone. Since then, other studies have had reassuring findings.

In response to the alert issued by the United States, the European Medicines Agency specified that “the data are not sufficient for a warning,” before the American Heart Association colleagues concluded that testosterone should only be avoided in the first 6 months following a severe cardiovascular event.

Conversely, in 2021, the European Society of Cardiology put forward the benefits of testosterone in an article in favor of replacement therapy to prevent cardiovascular risk. In particular, the hormone is thought to have a beneficial effect on arterial stiffness, the appearance of calcified plaques, and coronary artery dilatation.

The final hurdle to overcome before a testosterone prescription is filled relates to patients themselves, who often regard such treatment unfavorably. Many wrongly believe that androgens are hormones that “increase the risk of cancer, make you aggressive, cause weight gain, lead to hair loss, and cause body hair growth,” said Dr. Huygue.

Finally, breaks in the supply chain for Androtardyl, the only injectable form available for reimbursement by French social security schemes, were reported in the country in 2023, said Dr. Huygue. This situation only complicates further the prescription and use of testosterone replacement therapy.
 

Which Supplement?

Testosterone replacement therapies are available on the market in the following formulations:

Via transcutaneous administration: Testosterone-based gels, not covered by the French social security system (Androgel and Fortigel), to be applied daily. Users must be careful to avoid any potential transfer of the product to women or children in case of contact with the site after application.

Via an injection: Androtardyl (testosterone enanthate), covered by French social security, to be administered intramuscularly once a month. Nebido (testosterone undecanoate), not covered by French social security, with a more beneficial bioavailability profile, to be administered once every 3 months.

Pantestone (testosterone undecanoate), administered orally, is not marketed since 2021. It had the major disadvantage of requiring a high-fat diet to ensure optimal absorption.

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

Underdiagnosis, reluctant doctors, patient preconceptions: Treating low testosterone levels is a tricky business in France despite the proven benefits of replacement therapy. About 20% of patients with symptomatic low testosterone levels are treated for the deficiency, said Eric Huygue, MD, PhD, urologic surgeon at Toulouse University Hospital in France, at the 117th annual conference of the French Urology Association (AFU).

“Treatment for low testosterone is effective and risk-free. It improves a patient’s quality of life and general health,” particularly affecting fatigue, mood, and libido, said Dr. Huygue, who was involved in drawing up the first French recommendations on treating low testosterone in 2021.

“We must keep up communication efforts to make patients and doctors aware” of the benefits of supplementation, he said.
 

Testosterone Levels

Testosterone deficiency mostly affects men older than 40 years. A drop in androgen levels, which varies by individual, can lead to sexual problems (such as erectile dysfunction and low libido), physical symptoms (fatigue, hot flashes, loss of muscle mass, and osteoporosis), and mental disorders (anxiety, irritability, and depression).

There are an estimated 340,000 men with symptomatic testosterone deficiency in France. Just 70,000 of these are receiving replacement therapy (see box), which accounts for only 20% of those affected. For Dr. Huygue, this low treatment rate is due to underdiagnosis, as well as reluctance on the part of doctors and patients.

Although routine screening of low testosterone in the general population is not recommended, some individuals are particularly at risk, noted the urologist.

This is especially true for patients with metabolic disorders associated with insulin resistance (such as obesity and type 2 diabetes), cardiovascular diseases (hypertension, heart failure, and atrial fibrillation), or other chronic conditions (chronic obstructive pulmonary disease, cancer, and depression). Some medications (corticosteroids, antipsychotics, chemotherapy drugs, and antiretroviral therapies) can also lead to low testosterone.

Per the French recommendations for managing low testosterone, diagnosis must be based on free or bioavailable testosterone and not total testosterone levels, which can give a skewed result. Levels must be tested twice, 1 month apart, in the morning and while fasting. The reference range is determined by taking the lower threshold level of young men as measured in the laboratory.

Threshold Values

The current practice of using the reference range associated with the patient’s age group undoubtedly contributes to the underdiagnosis of low testosterone, said Dr. Huygue. According to a survey of AFU members in 2021, the year in which the recommendations were published, 77% of urologists interviewed reported referring to reference ranges for patients of the same age.

In their defense, “this method has long been in use, but it has eventually become apparent that symptomatic patients with an undiagnosed deficiency could be in the reference patients’ group,” Dr. Huygue explained.

Once a deficiency has been diagnosed, doctors may be reluctant to prescribe replacement therapy due to the perceived risk of developing prostate cancer. Several international studies have shown that “the risk of prostate cancer is the single biggest reason for doctors refusing to prescribe testosterone,” said Dr. Huygue.

Despite this reluctance, numerous studies have clearly shown that there is no link between a high testosterone level and the risk of developing prostate cancer. It even seems that a low testosterone level might expose a person to an increased risk for an aggressive form of cancer.

“This is a time of many surprising discoveries concerning the link between the prostate and testosterone, which go against what we have thought up to now. It has been observed that men with low testosterone develop more serious types of cancer,” said Dr. Huygue at a previous meeting of the AFU, during which he announced the publication of the French recommendations.
 

Prostate Cancer Recurrence

Urologists are also wary of testosterone supplementation in patients with a previous history of prostate cancer. According to the AFU’s survey, 40% of urologists questioned think that testosterone is contraindicated in this population. One in two urologists prescribe testosterone after radical prostatectomy for low or intermediate risk and most commonly after 3 years of undetectable prostate-specific antigen (PSA) levels.

Nevertheless, “several retrospective studies show the safety of testosterone replacement therapy in men who have undergone radical prostatectomy or radiotherapy or who are under active monitoring,” said Dr. Huygue. Testosterone “does not appear to increase the risk of relapse” after treatment of prostate cancer.

Dr. Huygue invited prescribing physicians to refer to the French recommendations, which specify that 1 year of undetectable PSA after prostatectomy is sufficient before prescribing replacement therapy. “This is clearly indicated in the recommendations for patients with a previous history of prostate cancer.”

Neither prostate cancer nor benign prostatic hyperplasia is a contraindication. According to the recommendations, the only contraindications to testosterone prescription are the following:

• Hematocrit > 54%
• Current breast or prostate cancer
• Cardiovascular event less than 3-6 months prior
• Trying to conceive

Cardiovascular Benefits

Another more commonly used argument by general practitioners and endocrinologists to justify their reluctance to prescribe testosterone is the risk to cardiovascular health. In early 2010, a series of American studies alerted clinicians to this risk when taking testosterone. Since then, other studies have had reassuring findings.

In response to the alert issued by the United States, the European Medicines Agency specified that “the data are not sufficient for a warning,” before the American Heart Association colleagues concluded that testosterone should only be avoided in the first 6 months following a severe cardiovascular event.

Conversely, in 2021, the European Society of Cardiology put forward the benefits of testosterone in an article in favor of replacement therapy to prevent cardiovascular risk. In particular, the hormone is thought to have a beneficial effect on arterial stiffness, the appearance of calcified plaques, and coronary artery dilatation.

The final hurdle to overcome before a testosterone prescription is filled relates to patients themselves, who often regard such treatment unfavorably. Many wrongly believe that androgens are hormones that “increase the risk of cancer, make you aggressive, cause weight gain, lead to hair loss, and cause body hair growth,” said Dr. Huygue.

Finally, breaks in the supply chain for Androtardyl, the only injectable form available for reimbursement by French social security schemes, were reported in the country in 2023, said Dr. Huygue. This situation only complicates further the prescription and use of testosterone replacement therapy.
 

Which Supplement?

Testosterone replacement therapies are available on the market in the following formulations:

Via transcutaneous administration: Testosterone-based gels, not covered by the French social security system (Androgel and Fortigel), to be applied daily. Users must be careful to avoid any potential transfer of the product to women or children in case of contact with the site after application.

Via an injection: Androtardyl (testosterone enanthate), covered by French social security, to be administered intramuscularly once a month. Nebido (testosterone undecanoate), not covered by French social security, with a more beneficial bioavailability profile, to be administered once every 3 months.

Pantestone (testosterone undecanoate), administered orally, is not marketed since 2021. It had the major disadvantage of requiring a high-fat diet to ensure optimal absorption.

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

Underdiagnosis, reluctant doctors, patient preconceptions: Treating low testosterone levels is a tricky business in France despite the proven benefits of replacement therapy. About 20% of patients with symptomatic low testosterone levels are treated for the deficiency, said Eric Huygue, MD, PhD, urologic surgeon at Toulouse University Hospital in France, at the 117th annual conference of the French Urology Association (AFU).

“Treatment for low testosterone is effective and risk-free. It improves a patient’s quality of life and general health,” particularly affecting fatigue, mood, and libido, said Dr. Huygue, who was involved in drawing up the first French recommendations on treating low testosterone in 2021.

“We must keep up communication efforts to make patients and doctors aware” of the benefits of supplementation, he said.
 

Testosterone Levels

Testosterone deficiency mostly affects men older than 40 years. A drop in androgen levels, which varies by individual, can lead to sexual problems (such as erectile dysfunction and low libido), physical symptoms (fatigue, hot flashes, loss of muscle mass, and osteoporosis), and mental disorders (anxiety, irritability, and depression).

There are an estimated 340,000 men with symptomatic testosterone deficiency in France. Just 70,000 of these are receiving replacement therapy (see box), which accounts for only 20% of those affected. For Dr. Huygue, this low treatment rate is due to underdiagnosis, as well as reluctance on the part of doctors and patients.

Although routine screening of low testosterone in the general population is not recommended, some individuals are particularly at risk, noted the urologist.

This is especially true for patients with metabolic disorders associated with insulin resistance (such as obesity and type 2 diabetes), cardiovascular diseases (hypertension, heart failure, and atrial fibrillation), or other chronic conditions (chronic obstructive pulmonary disease, cancer, and depression). Some medications (corticosteroids, antipsychotics, chemotherapy drugs, and antiretroviral therapies) can also lead to low testosterone.

Per the French recommendations for managing low testosterone, diagnosis must be based on free or bioavailable testosterone and not total testosterone levels, which can give a skewed result. Levels must be tested twice, 1 month apart, in the morning and while fasting. The reference range is determined by taking the lower threshold level of young men as measured in the laboratory.

Threshold Values

The current practice of using the reference range associated with the patient’s age group undoubtedly contributes to the underdiagnosis of low testosterone, said Dr. Huygue. According to a survey of AFU members in 2021, the year in which the recommendations were published, 77% of urologists interviewed reported referring to reference ranges for patients of the same age.

In their defense, “this method has long been in use, but it has eventually become apparent that symptomatic patients with an undiagnosed deficiency could be in the reference patients’ group,” Dr. Huygue explained.

Once a deficiency has been diagnosed, doctors may be reluctant to prescribe replacement therapy due to the perceived risk of developing prostate cancer. Several international studies have shown that “the risk of prostate cancer is the single biggest reason for doctors refusing to prescribe testosterone,” said Dr. Huygue.

Despite this reluctance, numerous studies have clearly shown that there is no link between a high testosterone level and the risk of developing prostate cancer. It even seems that a low testosterone level might expose a person to an increased risk for an aggressive form of cancer.

“This is a time of many surprising discoveries concerning the link between the prostate and testosterone, which go against what we have thought up to now. It has been observed that men with low testosterone develop more serious types of cancer,” said Dr. Huygue at a previous meeting of the AFU, during which he announced the publication of the French recommendations.
 

Prostate Cancer Recurrence

Urologists are also wary of testosterone supplementation in patients with a previous history of prostate cancer. According to the AFU’s survey, 40% of urologists questioned think that testosterone is contraindicated in this population. One in two urologists prescribe testosterone after radical prostatectomy for low or intermediate risk and most commonly after 3 years of undetectable prostate-specific antigen (PSA) levels.

Nevertheless, “several retrospective studies show the safety of testosterone replacement therapy in men who have undergone radical prostatectomy or radiotherapy or who are under active monitoring,” said Dr. Huygue. Testosterone “does not appear to increase the risk of relapse” after treatment of prostate cancer.

Dr. Huygue invited prescribing physicians to refer to the French recommendations, which specify that 1 year of undetectable PSA after prostatectomy is sufficient before prescribing replacement therapy. “This is clearly indicated in the recommendations for patients with a previous history of prostate cancer.”

Neither prostate cancer nor benign prostatic hyperplasia is a contraindication. According to the recommendations, the only contraindications to testosterone prescription are the following:

• Hematocrit > 54%
• Current breast or prostate cancer
• Cardiovascular event less than 3-6 months prior
• Trying to conceive

Cardiovascular Benefits

Another more commonly used argument by general practitioners and endocrinologists to justify their reluctance to prescribe testosterone is the risk to cardiovascular health. In early 2010, a series of American studies alerted clinicians to this risk when taking testosterone. Since then, other studies have had reassuring findings.

In response to the alert issued by the United States, the European Medicines Agency specified that “the data are not sufficient for a warning,” before the American Heart Association colleagues concluded that testosterone should only be avoided in the first 6 months following a severe cardiovascular event.

Conversely, in 2021, the European Society of Cardiology put forward the benefits of testosterone in an article in favor of replacement therapy to prevent cardiovascular risk. In particular, the hormone is thought to have a beneficial effect on arterial stiffness, the appearance of calcified plaques, and coronary artery dilatation.

The final hurdle to overcome before a testosterone prescription is filled relates to patients themselves, who often regard such treatment unfavorably. Many wrongly believe that androgens are hormones that “increase the risk of cancer, make you aggressive, cause weight gain, lead to hair loss, and cause body hair growth,” said Dr. Huygue.

Finally, breaks in the supply chain for Androtardyl, the only injectable form available for reimbursement by French social security schemes, were reported in the country in 2023, said Dr. Huygue. This situation only complicates further the prescription and use of testosterone replacement therapy.
 

Which Supplement?

Testosterone replacement therapies are available on the market in the following formulations:

Via transcutaneous administration: Testosterone-based gels, not covered by the French social security system (Androgel and Fortigel), to be applied daily. Users must be careful to avoid any potential transfer of the product to women or children in case of contact with the site after application.

Via an injection: Androtardyl (testosterone enanthate), covered by French social security, to be administered intramuscularly once a month. Nebido (testosterone undecanoate), not covered by French social security, with a more beneficial bioavailability profile, to be administered once every 3 months.

Pantestone (testosterone undecanoate), administered orally, is not marketed since 2021. It had the major disadvantage of requiring a high-fat diet to ensure optimal absorption.

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