Endocrinology

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.

TOPLINE:

In middle-aged and older men with hypogonadism, excluding those at high prostate cancer risk, testosterone replacement therapy (TRT) showed low rates of adverse prostate events, including cancer.

METHODOLOGY:

• Uncertainty and concern exist about a link between prostate cancer risk and testosterone levels. Most professional society guidelines recommend against TRT in men with a history of or an increased risk for prostate cancer.
• The Testosterone Replacement Therapy for Assessment of Long-Term Vascular Events and Efficacy Response in Hypogonadal Men  included 5204 men (ages 45-80, 17% Black, 80% White), randomly assigned to receive testosterone gel or placebo.
• Men with a history of cardiovascular disease or increased cardiovascular risk were evaluated to exclude those at increased prostate cancer risk (fasting testosterone < 300 ng/dL, ≥ 1 hypogonadal symptoms).
• The primary prostate safety endpoint was high-grade prostate cancer incidence (Gleason score, ≥ 4 + 3).
• Secondary endpoints were incidences of any prostate cancer, acute urinary retention, invasive procedure for benign prostatic hyperplasia, prostate biopsy, and new pharmacologic treatment for lower urinary tract symptoms.

TAKEAWAY:

• During 14,304 person-years of follow-up, high-grade prostate cancer incidence did not differ significantly between the TRT and placebo (0.19% vs 0.12%; P = .51) groups.
• The incidences of prostate cancer, acute urinary retention, invasive procedures for benign prostatic hyperplasia, prostate biopsy, and new pharmacologic treatment for lower urinary tract symptoms were also similar between the groups.
• TRT did not lead to an increase in lower urinary tract symptoms.
• The increase in prostate-specific antigen (PSA) levels was higher in the TRT group than in the placebo group (P < .001). However, the between-group difference did not widen after 12 months.

IN PRACTICE:

For “clinicians and patients who are considering testosterone replacement therapy for hypogonadism,” wrote the authors, “the study’s findings will facilitate a more informed appraisal of the potential prostate risks of testosterone replacement therapy.”

SOURCE:

Shalender Bhasin, MB, BS, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, led the study. It was published online in JAMA Network Open.

LIMITATIONS:

• The study findings do not apply to men with known prostate cancer or higher PSA values or those without confirmed hypogonadism.
• Although the TRAVERSE study was longer than many contemporary trials, carcinogens may require many years to induce malignant neoplasms.
• The trial’s structured evaluation of men after PSA testing did not include prostate imaging or other biomarker tests, which could affect the decision to perform a biopsy.

DISCLOSURES:

This study was funded by a consortium of testosterone manufacturers led by AbbVie Inc with additional financial support from Endo Pharmaceuticals, Acerus Pharmaceuticals Corp, and Upsher-Smith Laboratories. Mr. Bhasin and two coauthors declared receiving grants, consulting and personal fees, and other ties with pharmaceutical and device companies and other sources.

A version of this article appeared on Medscape.com.

TOPLINE:

In middle-aged and older men with hypogonadism, excluding those at high prostate cancer risk, testosterone replacement therapy (TRT) showed low rates of adverse prostate events, including cancer.

METHODOLOGY:

• Uncertainty and concern exist about a link between prostate cancer risk and testosterone levels. Most professional society guidelines recommend against TRT in men with a history of or an increased risk for prostate cancer.
• The Testosterone Replacement Therapy for Assessment of Long-Term Vascular Events and Efficacy Response in Hypogonadal Men  included 5204 men (ages 45-80, 17% Black, 80% White), randomly assigned to receive testosterone gel or placebo.
• Men with a history of cardiovascular disease or increased cardiovascular risk were evaluated to exclude those at increased prostate cancer risk (fasting testosterone < 300 ng/dL, ≥ 1 hypogonadal symptoms).
• The primary prostate safety endpoint was high-grade prostate cancer incidence (Gleason score, ≥ 4 + 3).
• Secondary endpoints were incidences of any prostate cancer, acute urinary retention, invasive procedure for benign prostatic hyperplasia, prostate biopsy, and new pharmacologic treatment for lower urinary tract symptoms.

TAKEAWAY:

• During 14,304 person-years of follow-up, high-grade prostate cancer incidence did not differ significantly between the TRT and placebo (0.19% vs 0.12%; P = .51) groups.
• The incidences of prostate cancer, acute urinary retention, invasive procedures for benign prostatic hyperplasia, prostate biopsy, and new pharmacologic treatment for lower urinary tract symptoms were also similar between the groups.
• TRT did not lead to an increase in lower urinary tract symptoms.
• The increase in prostate-specific antigen (PSA) levels was higher in the TRT group than in the placebo group (P < .001). However, the between-group difference did not widen after 12 months.

IN PRACTICE:

For “clinicians and patients who are considering testosterone replacement therapy for hypogonadism,” wrote the authors, “the study’s findings will facilitate a more informed appraisal of the potential prostate risks of testosterone replacement therapy.”

SOURCE:

Shalender Bhasin, MB, BS, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, led the study. It was published online in JAMA Network Open.

LIMITATIONS:

• The study findings do not apply to men with known prostate cancer or higher PSA values or those without confirmed hypogonadism.
• Although the TRAVERSE study was longer than many contemporary trials, carcinogens may require many years to induce malignant neoplasms.
• The trial’s structured evaluation of men after PSA testing did not include prostate imaging or other biomarker tests, which could affect the decision to perform a biopsy.

DISCLOSURES:

This study was funded by a consortium of testosterone manufacturers led by AbbVie Inc with additional financial support from Endo Pharmaceuticals, Acerus Pharmaceuticals Corp, and Upsher-Smith Laboratories. Mr. Bhasin and two coauthors declared receiving grants, consulting and personal fees, and other ties with pharmaceutical and device companies and other sources.

A version of this article appeared on Medscape.com.

TOPLINE:

In middle-aged and older men with hypogonadism, excluding those at high prostate cancer risk, testosterone replacement therapy (TRT) showed low rates of adverse prostate events, including cancer.

METHODOLOGY:

• Uncertainty and concern exist about a link between prostate cancer risk and testosterone levels. Most professional society guidelines recommend against TRT in men with a history of or an increased risk for prostate cancer.
• The Testosterone Replacement Therapy for Assessment of Long-Term Vascular Events and Efficacy Response in Hypogonadal Men  included 5204 men (ages 45-80, 17% Black, 80% White), randomly assigned to receive testosterone gel or placebo.
• Men with a history of cardiovascular disease or increased cardiovascular risk were evaluated to exclude those at increased prostate cancer risk (fasting testosterone < 300 ng/dL, ≥ 1 hypogonadal symptoms).
• The primary prostate safety endpoint was high-grade prostate cancer incidence (Gleason score, ≥ 4 + 3).
• Secondary endpoints were incidences of any prostate cancer, acute urinary retention, invasive procedure for benign prostatic hyperplasia, prostate biopsy, and new pharmacologic treatment for lower urinary tract symptoms.

TAKEAWAY:

• During 14,304 person-years of follow-up, high-grade prostate cancer incidence did not differ significantly between the TRT and placebo (0.19% vs 0.12%; P = .51) groups.
• The incidences of prostate cancer, acute urinary retention, invasive procedures for benign prostatic hyperplasia, prostate biopsy, and new pharmacologic treatment for lower urinary tract symptoms were also similar between the groups.
• TRT did not lead to an increase in lower urinary tract symptoms.
• The increase in prostate-specific antigen (PSA) levels was higher in the TRT group than in the placebo group (P < .001). However, the between-group difference did not widen after 12 months.

IN PRACTICE:

For “clinicians and patients who are considering testosterone replacement therapy for hypogonadism,” wrote the authors, “the study’s findings will facilitate a more informed appraisal of the potential prostate risks of testosterone replacement therapy.”

SOURCE:

Shalender Bhasin, MB, BS, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, led the study. It was published online in JAMA Network Open.

LIMITATIONS:

• The study findings do not apply to men with known prostate cancer or higher PSA values or those without confirmed hypogonadism.
• Although the TRAVERSE study was longer than many contemporary trials, carcinogens may require many years to induce malignant neoplasms.
• The trial’s structured evaluation of men after PSA testing did not include prostate imaging or other biomarker tests, which could affect the decision to perform a biopsy.

DISCLOSURES:

This study was funded by a consortium of testosterone manufacturers led by AbbVie Inc with additional financial support from Endo Pharmaceuticals, Acerus Pharmaceuticals Corp, and Upsher-Smith Laboratories. Mr. Bhasin and two coauthors declared receiving grants, consulting and personal fees, and other ties with pharmaceutical and device companies and other sources.

A version of this article appeared on Medscape.com.

Primary aldosteronism (PA) is a frequently overlooked yet common cause of secondary hypertension, presenting significant risk for cardiovascular morbidity and mortality.

But fewer than 4% of at-risk patients receive the recommended screening for PA, leaving a substantial gap in early detection and management, according to Adina F. Turcu, MD, MS, associate professor in endocrinology and internal medicine at University of Michigan Health in Ann Arbor. 

In response to this clinical challenge, Dr. Turcu and her colleagues developed a best-practice advisory (BPA) to identify patients who were at risk for PA and embedded it into electronic health record at University of Michigan ambulatory clinics. Her team found that use of the tool led to increased rates of screening for PA, particularly among primary care physicians.

Over a 15-month period, Dr. Turcu and her colleagues tested the BPA through a quality improvement study, identifying 14,603 unique candidates for PA screening, with a mean age of 65.5 years and a diverse representation of ethnic backgrounds. 

Notably, 48.1% of these candidates had treatment-resistant hypertension, 43.5% exhibited hypokalemia, 10.5% were younger than 35 years, and 3.1% had adrenal nodules. Of these candidates, 14.0% received orders for PA screening, with 70.5% completing the recommended screening within the system, and 17.4% receiving positive screening results. 

The study, conducted over 6 months in 2023, targeted adults with hypertension and at least one of the following: Those who took four or more antihypertensive medications, exhibited hypokalemia, were younger than age 35 years, or had adrenal nodules. Patients previously tested for PA were excluded from the analysis. 

The noninterruptive BPA was triggered during outpatient visits with clinicians who specialized in hypertension. The advisory would then offer an order set for PA screening and provide a link to interpretation guidance for results. Clinicians had the option to use, ignore, or decline the BPA.

“Although we were hoping for broader uptake of this EHR-embedded BPA, we were delighted to see an increase in PA screening rates to 14% of identified candidates as compared to an average of less than 3% in retrospective studies of similar populations, including in our own institution prior to implementing this BPA,” Dr. Turcu told this news organization.

Physician specialty played a crucial role in the utilization of the BPA. Internists and family medicine physicians accounted for the majority of screening orders, placing 40.0% and 28.1% of these, respectively. Family practitioners and internists predominantly used the embedded order set (80.3% and 68.9%, respectively).

“Hypertension often gets treated rather than screening for [causes of] secondary hypertension prior to treatment,” said Kaniksha Desai, MD, clinical associate professor and endocrinology quality director at Stanford University School of Medicine, Stanford, California, who was not involved in the research. But “primary hyperaldosteronism is a condition that can be treated surgically and has increased long term cardiovascular consequences if not identified. While guidelines recommend screening at-risk patients, this often can get lost in translation in clinical practice due to many factors, including time constraints and volume of patients.” 

Patients who did vs did not undergo screening were more likely to be women, Black, and younger than age 35 years. Additionally, the likelihood of screening was higher among patients with obesity and dyslipidemia, whereas it was lower in those with chronic kidney disease and established cardiovascular complications.

According to Dr. Turcu, the findings from this study suggest that noninterruptive BPAs, especially when integrated into primary care workflows, hold promise as effective tools for PA screening.

When coupled with artificial intelligence to optimize detection yield, these refined BPAs could significantly contribute to personalized care for hypertension, the investigators said. 

“Considering that in the United States almost one in two adults has hypertension, such automatized tools become instrumental to busy clinicians, particularly those in primary care,” Dr. Turcu said. “Our results indicate a promising opportunity to meaningfully improve PA awareness and enhance its diagnosis.” 

Dr. Turcu reported receiving grants from the National Heart, Lung, and Blood Institute and Doris Duke Foundation, served as an investigator in a CinCor Pharma clinical trial, and received financial support to her institution during the conduct of the study. Dr. Desai reported no relevant financial disclosures. 
 

A version of this article appeared on Medscape.com.

Primary aldosteronism (PA) is a frequently overlooked yet common cause of secondary hypertension, presenting significant risk for cardiovascular morbidity and mortality.

But fewer than 4% of at-risk patients receive the recommended screening for PA, leaving a substantial gap in early detection and management, according to Adina F. Turcu, MD, MS, associate professor in endocrinology and internal medicine at University of Michigan Health in Ann Arbor. 

In response to this clinical challenge, Dr. Turcu and her colleagues developed a best-practice advisory (BPA) to identify patients who were at risk for PA and embedded it into electronic health record at University of Michigan ambulatory clinics. Her team found that use of the tool led to increased rates of screening for PA, particularly among primary care physicians.

Over a 15-month period, Dr. Turcu and her colleagues tested the BPA through a quality improvement study, identifying 14,603 unique candidates for PA screening, with a mean age of 65.5 years and a diverse representation of ethnic backgrounds. 

Notably, 48.1% of these candidates had treatment-resistant hypertension, 43.5% exhibited hypokalemia, 10.5% were younger than 35 years, and 3.1% had adrenal nodules. Of these candidates, 14.0% received orders for PA screening, with 70.5% completing the recommended screening within the system, and 17.4% receiving positive screening results. 

The study, conducted over 6 months in 2023, targeted adults with hypertension and at least one of the following: Those who took four or more antihypertensive medications, exhibited hypokalemia, were younger than age 35 years, or had adrenal nodules. Patients previously tested for PA were excluded from the analysis. 

The noninterruptive BPA was triggered during outpatient visits with clinicians who specialized in hypertension. The advisory would then offer an order set for PA screening and provide a link to interpretation guidance for results. Clinicians had the option to use, ignore, or decline the BPA.

“Although we were hoping for broader uptake of this EHR-embedded BPA, we were delighted to see an increase in PA screening rates to 14% of identified candidates as compared to an average of less than 3% in retrospective studies of similar populations, including in our own institution prior to implementing this BPA,” Dr. Turcu told this news organization.

Physician specialty played a crucial role in the utilization of the BPA. Internists and family medicine physicians accounted for the majority of screening orders, placing 40.0% and 28.1% of these, respectively. Family practitioners and internists predominantly used the embedded order set (80.3% and 68.9%, respectively).

“Hypertension often gets treated rather than screening for [causes of] secondary hypertension prior to treatment,” said Kaniksha Desai, MD, clinical associate professor and endocrinology quality director at Stanford University School of Medicine, Stanford, California, who was not involved in the research. But “primary hyperaldosteronism is a condition that can be treated surgically and has increased long term cardiovascular consequences if not identified. While guidelines recommend screening at-risk patients, this often can get lost in translation in clinical practice due to many factors, including time constraints and volume of patients.” 

Patients who did vs did not undergo screening were more likely to be women, Black, and younger than age 35 years. Additionally, the likelihood of screening was higher among patients with obesity and dyslipidemia, whereas it was lower in those with chronic kidney disease and established cardiovascular complications.

According to Dr. Turcu, the findings from this study suggest that noninterruptive BPAs, especially when integrated into primary care workflows, hold promise as effective tools for PA screening.

When coupled with artificial intelligence to optimize detection yield, these refined BPAs could significantly contribute to personalized care for hypertension, the investigators said. 

“Considering that in the United States almost one in two adults has hypertension, such automatized tools become instrumental to busy clinicians, particularly those in primary care,” Dr. Turcu said. “Our results indicate a promising opportunity to meaningfully improve PA awareness and enhance its diagnosis.” 

Dr. Turcu reported receiving grants from the National Heart, Lung, and Blood Institute and Doris Duke Foundation, served as an investigator in a CinCor Pharma clinical trial, and received financial support to her institution during the conduct of the study. Dr. Desai reported no relevant financial disclosures. 
 

A version of this article appeared on Medscape.com.

Primary aldosteronism (PA) is a frequently overlooked yet common cause of secondary hypertension, presenting significant risk for cardiovascular morbidity and mortality.

But fewer than 4% of at-risk patients receive the recommended screening for PA, leaving a substantial gap in early detection and management, according to Adina F. Turcu, MD, MS, associate professor in endocrinology and internal medicine at University of Michigan Health in Ann Arbor. 

In response to this clinical challenge, Dr. Turcu and her colleagues developed a best-practice advisory (BPA) to identify patients who were at risk for PA and embedded it into electronic health record at University of Michigan ambulatory clinics. Her team found that use of the tool led to increased rates of screening for PA, particularly among primary care physicians.

Over a 15-month period, Dr. Turcu and her colleagues tested the BPA through a quality improvement study, identifying 14,603 unique candidates for PA screening, with a mean age of 65.5 years and a diverse representation of ethnic backgrounds. 

Notably, 48.1% of these candidates had treatment-resistant hypertension, 43.5% exhibited hypokalemia, 10.5% were younger than 35 years, and 3.1% had adrenal nodules. Of these candidates, 14.0% received orders for PA screening, with 70.5% completing the recommended screening within the system, and 17.4% receiving positive screening results. 

The study, conducted over 6 months in 2023, targeted adults with hypertension and at least one of the following: Those who took four or more antihypertensive medications, exhibited hypokalemia, were younger than age 35 years, or had adrenal nodules. Patients previously tested for PA were excluded from the analysis. 

The noninterruptive BPA was triggered during outpatient visits with clinicians who specialized in hypertension. The advisory would then offer an order set for PA screening and provide a link to interpretation guidance for results. Clinicians had the option to use, ignore, or decline the BPA.

“Although we were hoping for broader uptake of this EHR-embedded BPA, we were delighted to see an increase in PA screening rates to 14% of identified candidates as compared to an average of less than 3% in retrospective studies of similar populations, including in our own institution prior to implementing this BPA,” Dr. Turcu told this news organization.

Physician specialty played a crucial role in the utilization of the BPA. Internists and family medicine physicians accounted for the majority of screening orders, placing 40.0% and 28.1% of these, respectively. Family practitioners and internists predominantly used the embedded order set (80.3% and 68.9%, respectively).

“Hypertension often gets treated rather than screening for [causes of] secondary hypertension prior to treatment,” said Kaniksha Desai, MD, clinical associate professor and endocrinology quality director at Stanford University School of Medicine, Stanford, California, who was not involved in the research. But “primary hyperaldosteronism is a condition that can be treated surgically and has increased long term cardiovascular consequences if not identified. While guidelines recommend screening at-risk patients, this often can get lost in translation in clinical practice due to many factors, including time constraints and volume of patients.” 

Patients who did vs did not undergo screening were more likely to be women, Black, and younger than age 35 years. Additionally, the likelihood of screening was higher among patients with obesity and dyslipidemia, whereas it was lower in those with chronic kidney disease and established cardiovascular complications.

According to Dr. Turcu, the findings from this study suggest that noninterruptive BPAs, especially when integrated into primary care workflows, hold promise as effective tools for PA screening.

When coupled with artificial intelligence to optimize detection yield, these refined BPAs could significantly contribute to personalized care for hypertension, the investigators said. 

“Considering that in the United States almost one in two adults has hypertension, such automatized tools become instrumental to busy clinicians, particularly those in primary care,” Dr. Turcu said. “Our results indicate a promising opportunity to meaningfully improve PA awareness and enhance its diagnosis.” 

Dr. Turcu reported receiving grants from the National Heart, Lung, and Blood Institute and Doris Duke Foundation, served as an investigator in a CinCor Pharma clinical trial, and received financial support to her institution during the conduct of the study. Dr. Desai reported no relevant financial disclosures. 
 

A version of this article appeared on Medscape.com.

To assess thyroid function, clinicians typically determine blood levels of thyroid-stimulating hormone (TSH) and thyroxine (T4) and do not directly measure triiodothyronine (T3).

However, findings from a large observational study of a US sample of adults with normal thyroid function suggested that subclinical variation in the hypothalamic-pituitary-thyroid (HPT)–axis effector hormone T3 “is an important and overlooked factor linking socioeconomic forces, human biology, and aging,” researchers reported.

The study, with lead author Ralph I. Lawton, an MD-PhD student at Harvard Medical School, Boston, was published online on January 4, 2024, in Proceedings of the National Academy of Sciences. In this national sample of healthy adults older than 20, free T3 was negatively related to household income. At age 40 and older, free T3 was significantly linked to being employed. Among adults from age 51 to 80, free T3 levels were inversely related to mortality.

“It is important to note that the more typically measured biomarkers for thyroid function (T4 and TSH) are poorly linked to free T3 levels,” Dr. Lawton and colleagues wrote.

The ratio of TSH:T4 explained only 1.7% of variation in T3 levels, they noted, which suggested that TSH and T4 may not be accurate surrogates of free T3. Thus, “direct measurement of free T3 is likely vital to properly stratify the effects of HPT-axis variation,” they maintained. “Improved methods for measurement [of T3] and further investigation of the role of free T3 in clinical conditions may be high yield,” according to the researchers.

Further studies of the relationship between the action of deiodinase in converting T4 to T3 and social forces and aging could elucidate critical biology. “New therapeutics targeting T3/T4 ratios,” they suggested, “may be more beneficial for a significant cohort of older individuals [with hypothyroidism] currently treated with levothyroxine [(LT4)].”
 

‘Cherry on Top’

“I think this is a really important paper,” thyroidology expert Antonio Bianco, MD, PhD, professor of medicine, The University of Chicago, who was not involved with this research, told this news organization.

His research group and others “have slowly been providing evidence of the relevance of measuring T3 levels,” he said. “This paper is sort of a cherry on top. It is really the most recent strong evidence that looking at T3 levels in plasma is really important. We need to do a better job at developing a much more precise assay for T3,” he said, “because now we know T3 is a very important parameter that endocrinologists should be looking for. We know that about 20 million Americans have hypothyroidism, and are being treated with T4 (levothyroxine),” Dr. Bianco continued.

“As endocrinologists, we believe that if you treat someone with levothyroxine, you normalize T3 levels. However, many times, with standard of care with levothyroxine, T3 levels are not normalized.”
 

Larger Variations in T3

Thyroid hormones (TSH, free T4, and free T3) influence many aspects of human physiology and behavior, but it is not known how variations in these levels in a population free of thyroid disease are associated with mortality and socioeconomic factors.

The researchers analyzed data from 7626 adults over age 20 up to age 80 who participated in the National Health and Nutrition Examination Survey during 2007-2012 and had blood tests to determine TSH, free T4, and free T3 and were not being actively treated for thyroid conditions. Among the 3603 older adults (over age 50), there were 981 deaths up until the end of 2019. TSH levels were not linked to mortality, but increasing levels of free T3 and decreasing levels of free T4 were protective for mortality (hazard ratios, 0.88 and 1.26, respectively; P < .01).

There was a robust negative relationship between household income and employment and free T3 but no relationship between these factors and T4. There was a much larger variation across age in levels of free T3 than in levels of TSH or free T4. Free T4 and free T3 diverged at older ages, when free T4 increased and free T3 continually decreased.

Older adults with symptoms of hypothyroidism may have high free T4 levels despite low free T3, the researchers noted.

“In a nonclinical sample representative of the US population,” they summarized, “we find that free T3 is much more strongly related to all domains studied — age, sex, seasonality, household income, employment, and longevity — than the other molecules of the HPT axis.”

This work was supported by the Burroughs Wellcome Fund Career at Scientific Interface award, a Brain and Behavior Research Foundation young investigator award, the Howard Hughes Medical Institute, the National Institute of Aging, and the National Institute of General Medical Sciences. Dr. Bianco served as a consultant for AbbVie, Avion Pharmaceuticals, Synthonics, Synthion, and Thyron and recently published the book Rethinking Hypothyroidism: Why Treatment Must Change and What Patients Can Do.
 

A version of this article appeared on Medscape.com.

To assess thyroid function, clinicians typically determine blood levels of thyroid-stimulating hormone (TSH) and thyroxine (T4) and do not directly measure triiodothyronine (T3).

However, findings from a large observational study of a US sample of adults with normal thyroid function suggested that subclinical variation in the hypothalamic-pituitary-thyroid (HPT)–axis effector hormone T3 “is an important and overlooked factor linking socioeconomic forces, human biology, and aging,” researchers reported.

The study, with lead author Ralph I. Lawton, an MD-PhD student at Harvard Medical School, Boston, was published online on January 4, 2024, in Proceedings of the National Academy of Sciences. In this national sample of healthy adults older than 20, free T3 was negatively related to household income. At age 40 and older, free T3 was significantly linked to being employed. Among adults from age 51 to 80, free T3 levels were inversely related to mortality.

“It is important to note that the more typically measured biomarkers for thyroid function (T4 and TSH) are poorly linked to free T3 levels,” Dr. Lawton and colleagues wrote.

The ratio of TSH:T4 explained only 1.7% of variation in T3 levels, they noted, which suggested that TSH and T4 may not be accurate surrogates of free T3. Thus, “direct measurement of free T3 is likely vital to properly stratify the effects of HPT-axis variation,” they maintained. “Improved methods for measurement [of T3] and further investigation of the role of free T3 in clinical conditions may be high yield,” according to the researchers.

Further studies of the relationship between the action of deiodinase in converting T4 to T3 and social forces and aging could elucidate critical biology. “New therapeutics targeting T3/T4 ratios,” they suggested, “may be more beneficial for a significant cohort of older individuals [with hypothyroidism] currently treated with levothyroxine [(LT4)].”
 

‘Cherry on Top’

“I think this is a really important paper,” thyroidology expert Antonio Bianco, MD, PhD, professor of medicine, The University of Chicago, who was not involved with this research, told this news organization.

His research group and others “have slowly been providing evidence of the relevance of measuring T3 levels,” he said. “This paper is sort of a cherry on top. It is really the most recent strong evidence that looking at T3 levels in plasma is really important. We need to do a better job at developing a much more precise assay for T3,” he said, “because now we know T3 is a very important parameter that endocrinologists should be looking for. We know that about 20 million Americans have hypothyroidism, and are being treated with T4 (levothyroxine),” Dr. Bianco continued.

“As endocrinologists, we believe that if you treat someone with levothyroxine, you normalize T3 levels. However, many times, with standard of care with levothyroxine, T3 levels are not normalized.”
 

Larger Variations in T3

Thyroid hormones (TSH, free T4, and free T3) influence many aspects of human physiology and behavior, but it is not known how variations in these levels in a population free of thyroid disease are associated with mortality and socioeconomic factors.

The researchers analyzed data from 7626 adults over age 20 up to age 80 who participated in the National Health and Nutrition Examination Survey during 2007-2012 and had blood tests to determine TSH, free T4, and free T3 and were not being actively treated for thyroid conditions. Among the 3603 older adults (over age 50), there were 981 deaths up until the end of 2019. TSH levels were not linked to mortality, but increasing levels of free T3 and decreasing levels of free T4 were protective for mortality (hazard ratios, 0.88 and 1.26, respectively; P < .01).

There was a robust negative relationship between household income and employment and free T3 but no relationship between these factors and T4. There was a much larger variation across age in levels of free T3 than in levels of TSH or free T4. Free T4 and free T3 diverged at older ages, when free T4 increased and free T3 continually decreased.

Older adults with symptoms of hypothyroidism may have high free T4 levels despite low free T3, the researchers noted.

“In a nonclinical sample representative of the US population,” they summarized, “we find that free T3 is much more strongly related to all domains studied — age, sex, seasonality, household income, employment, and longevity — than the other molecules of the HPT axis.”

This work was supported by the Burroughs Wellcome Fund Career at Scientific Interface award, a Brain and Behavior Research Foundation young investigator award, the Howard Hughes Medical Institute, the National Institute of Aging, and the National Institute of General Medical Sciences. Dr. Bianco served as a consultant for AbbVie, Avion Pharmaceuticals, Synthonics, Synthion, and Thyron and recently published the book Rethinking Hypothyroidism: Why Treatment Must Change and What Patients Can Do.
 

A version of this article appeared on Medscape.com.

To assess thyroid function, clinicians typically determine blood levels of thyroid-stimulating hormone (TSH) and thyroxine (T4) and do not directly measure triiodothyronine (T3).

However, findings from a large observational study of a US sample of adults with normal thyroid function suggested that subclinical variation in the hypothalamic-pituitary-thyroid (HPT)–axis effector hormone T3 “is an important and overlooked factor linking socioeconomic forces, human biology, and aging,” researchers reported.

The study, with lead author Ralph I. Lawton, an MD-PhD student at Harvard Medical School, Boston, was published online on January 4, 2024, in Proceedings of the National Academy of Sciences. In this national sample of healthy adults older than 20, free T3 was negatively related to household income. At age 40 and older, free T3 was significantly linked to being employed. Among adults from age 51 to 80, free T3 levels were inversely related to mortality.

“It is important to note that the more typically measured biomarkers for thyroid function (T4 and TSH) are poorly linked to free T3 levels,” Dr. Lawton and colleagues wrote.

The ratio of TSH:T4 explained only 1.7% of variation in T3 levels, they noted, which suggested that TSH and T4 may not be accurate surrogates of free T3. Thus, “direct measurement of free T3 is likely vital to properly stratify the effects of HPT-axis variation,” they maintained. “Improved methods for measurement [of T3] and further investigation of the role of free T3 in clinical conditions may be high yield,” according to the researchers.

Further studies of the relationship between the action of deiodinase in converting T4 to T3 and social forces and aging could elucidate critical biology. “New therapeutics targeting T3/T4 ratios,” they suggested, “may be more beneficial for a significant cohort of older individuals [with hypothyroidism] currently treated with levothyroxine [(LT4)].”
 

‘Cherry on Top’

“I think this is a really important paper,” thyroidology expert Antonio Bianco, MD, PhD, professor of medicine, The University of Chicago, who was not involved with this research, told this news organization.

His research group and others “have slowly been providing evidence of the relevance of measuring T3 levels,” he said. “This paper is sort of a cherry on top. It is really the most recent strong evidence that looking at T3 levels in plasma is really important. We need to do a better job at developing a much more precise assay for T3,” he said, “because now we know T3 is a very important parameter that endocrinologists should be looking for. We know that about 20 million Americans have hypothyroidism, and are being treated with T4 (levothyroxine),” Dr. Bianco continued.

“As endocrinologists, we believe that if you treat someone with levothyroxine, you normalize T3 levels. However, many times, with standard of care with levothyroxine, T3 levels are not normalized.”
 

Larger Variations in T3

Thyroid hormones (TSH, free T4, and free T3) influence many aspects of human physiology and behavior, but it is not known how variations in these levels in a population free of thyroid disease are associated with mortality and socioeconomic factors.

The researchers analyzed data from 7626 adults over age 20 up to age 80 who participated in the National Health and Nutrition Examination Survey during 2007-2012 and had blood tests to determine TSH, free T4, and free T3 and were not being actively treated for thyroid conditions. Among the 3603 older adults (over age 50), there were 981 deaths up until the end of 2019. TSH levels were not linked to mortality, but increasing levels of free T3 and decreasing levels of free T4 were protective for mortality (hazard ratios, 0.88 and 1.26, respectively; P < .01).

There was a robust negative relationship between household income and employment and free T3 but no relationship between these factors and T4. There was a much larger variation across age in levels of free T3 than in levels of TSH or free T4. Free T4 and free T3 diverged at older ages, when free T4 increased and free T3 continually decreased.

Older adults with symptoms of hypothyroidism may have high free T4 levels despite low free T3, the researchers noted.

“In a nonclinical sample representative of the US population,” they summarized, “we find that free T3 is much more strongly related to all domains studied — age, sex, seasonality, household income, employment, and longevity — than the other molecules of the HPT axis.”

This work was supported by the Burroughs Wellcome Fund Career at Scientific Interface award, a Brain and Behavior Research Foundation young investigator award, the Howard Hughes Medical Institute, the National Institute of Aging, and the National Institute of General Medical Sciences. Dr. Bianco served as a consultant for AbbVie, Avion Pharmaceuticals, Synthonics, Synthion, and Thyron and recently published the book Rethinking Hypothyroidism: Why Treatment Must Change and What Patients Can Do.
 

A version of this article appeared on Medscape.com.

Women with autoimmune disease are more likely to have perinatal depression (PND), according to findings from a new study that also suggested the reverse relationship is true: Women with a history of PND have a higher risk of developing autoimmune disease.

The research, published online on January 9, 2024, in Molecular Psychiatry, was led by Emma Bränn, PhD, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.

The researchers used data from the Swedish Medical Birth Register and identified all women who had given birth in Sweden between 2001 and 2013. Out of the group of approximately 815,000 women and 1.3 million pregnancies, just more than 55,000 women had been diagnosed with depression during their pregnancy or within a year after delivery.

The researchers then compared the incidence of 41 autoimmune diseases in women who had and did not have PND. They controlled for factors including genetic makeup and childhood environment.

Results indicated that women with autoimmune disease were 30% more likely to have PND (odds ratio, 1.30; 95% CI, 1.25-1.35). Conversely, women with PND were 30% more likely than women with no PND to develop an autoimmune disease (hazard ratio, 1.30; 95% CI, 1.25-1.36).

A sibling comparison helped confirm the results by controlling for some shared genetic and early life environmental factors related to the household in which sisters grew up.
 

Potential Shared Biological Mechanisms

The association was independent of psychiatric comorbidities, suggesting there may be shared biological mechanisms.

Dr. Bränn told this news organization that the research team wanted to do the study because previous research has shown involvement of the immune system in depression, with similarities in both the symptoms of immune system–activated diseases and depression and the molecular pathways activated by the immune system.

“Adding on top of the tremendous changes in the immune system that we see in the body of the woman during the perinatal period, we hypothesized that autoimmune diseases could be associated to perinatal depression,” she said. “This had also been shown in some previous literature but not to the extent as what we have investigated in this paper.”

She said their results help make a case for counseling women at several points in healthcare interactions — before and after conception and childbirth — and in rheumatology visits to inform women with autoimmune diseases who are contemplating motherhood of the association with developing PND. The results may also demonstrate a need for monitoring women in these groups for depression or autoimmune disease.

Fred Miller, MD, PhD, retired Scientist Emeritus of the Environmental Autoimmunity Group at the National Institute of Environmental Health Sciences, who was not part of the study, said the results seem plausible as they build on early work that demonstrated selected associations between autoimmune conditions and mental illness.

“These associations may be the result of shared genetic and environmental risk factors, including stress, hormonal changes, medications, and the proinflammatory states that can lead to both,” he said.

The novelty, he said, is in the relatively strong associations of PND with autoimmune disease overall and with specific autoimmune diseases.
 

Strong Link Found With Multiple Sclerosis (MS)

According to the paper, a significant positive bidirectional link was found for autoimmune thyroid disease, psoriasis, MS, ulcerative colitis, and celiac disease.

Researchers found a particularly strong association — double the risk in both directions — between PND and MS.

Dr. Miller said though it is unclear from this study why the association of PND with MS was stronger than with other autoimmune diseases, people with MS are known to be at a high risk for depression in general. That may come from greater shared genetic and environmental risk factors, he added.

Additionally, MS is one of the more common autoimmune diseases, he noted, so the population is larger for study.

He said he was surprised the researchers didn’t investigate medication use because medications used in depression have immunologic effects and medications used in autoimmune diseases could have effects on mental conditions.

The study has implications for clinicians in a wide variety of specialties, Dr. Miller noted.

“It suggests that caregivers be more alert to the signs of developing autoimmune disease in women with perinatal depression and to the signs of developing perinatal depression in those with autoimmune disease,” Dr. Miller said, “so that appropriate screening, diagnostics, and interventions may be undertaken.”

The researchers say they will continue to examine the long-term effects of depression during pregnancy and in the year after childbirth.

“Depression during this sensitive period can have serious consequences for both the mother and the baby,” Dr. Bränn said. “We hope that our results will help decision-makers to steer funding toward maternal healthcare so that more women can get help and support in time.”

The study was financed by Karolinska Institute, Forte (the Swedish Research Council for Health, Working Life and Welfare), the Swedish Research Council, and the Icelandic Research Fund.

The researchers and Dr. Miller reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Women with autoimmune disease are more likely to have perinatal depression (PND), according to findings from a new study that also suggested the reverse relationship is true: Women with a history of PND have a higher risk of developing autoimmune disease.

The research, published online on January 9, 2024, in Molecular Psychiatry, was led by Emma Bränn, PhD, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.

The researchers used data from the Swedish Medical Birth Register and identified all women who had given birth in Sweden between 2001 and 2013. Out of the group of approximately 815,000 women and 1.3 million pregnancies, just more than 55,000 women had been diagnosed with depression during their pregnancy or within a year after delivery.

The researchers then compared the incidence of 41 autoimmune diseases in women who had and did not have PND. They controlled for factors including genetic makeup and childhood environment.

Results indicated that women with autoimmune disease were 30% more likely to have PND (odds ratio, 1.30; 95% CI, 1.25-1.35). Conversely, women with PND were 30% more likely than women with no PND to develop an autoimmune disease (hazard ratio, 1.30; 95% CI, 1.25-1.36).

A sibling comparison helped confirm the results by controlling for some shared genetic and early life environmental factors related to the household in which sisters grew up.
 

Potential Shared Biological Mechanisms

The association was independent of psychiatric comorbidities, suggesting there may be shared biological mechanisms.

Dr. Bränn told this news organization that the research team wanted to do the study because previous research has shown involvement of the immune system in depression, with similarities in both the symptoms of immune system–activated diseases and depression and the molecular pathways activated by the immune system.

“Adding on top of the tremendous changes in the immune system that we see in the body of the woman during the perinatal period, we hypothesized that autoimmune diseases could be associated to perinatal depression,” she said. “This had also been shown in some previous literature but not to the extent as what we have investigated in this paper.”

She said their results help make a case for counseling women at several points in healthcare interactions — before and after conception and childbirth — and in rheumatology visits to inform women with autoimmune diseases who are contemplating motherhood of the association with developing PND. The results may also demonstrate a need for monitoring women in these groups for depression or autoimmune disease.

Fred Miller, MD, PhD, retired Scientist Emeritus of the Environmental Autoimmunity Group at the National Institute of Environmental Health Sciences, who was not part of the study, said the results seem plausible as they build on early work that demonstrated selected associations between autoimmune conditions and mental illness.

“These associations may be the result of shared genetic and environmental risk factors, including stress, hormonal changes, medications, and the proinflammatory states that can lead to both,” he said.

The novelty, he said, is in the relatively strong associations of PND with autoimmune disease overall and with specific autoimmune diseases.
 

Strong Link Found With Multiple Sclerosis (MS)

According to the paper, a significant positive bidirectional link was found for autoimmune thyroid disease, psoriasis, MS, ulcerative colitis, and celiac disease.

Researchers found a particularly strong association — double the risk in both directions — between PND and MS.

Dr. Miller said though it is unclear from this study why the association of PND with MS was stronger than with other autoimmune diseases, people with MS are known to be at a high risk for depression in general. That may come from greater shared genetic and environmental risk factors, he added.

Additionally, MS is one of the more common autoimmune diseases, he noted, so the population is larger for study.

He said he was surprised the researchers didn’t investigate medication use because medications used in depression have immunologic effects and medications used in autoimmune diseases could have effects on mental conditions.

The study has implications for clinicians in a wide variety of specialties, Dr. Miller noted.

“It suggests that caregivers be more alert to the signs of developing autoimmune disease in women with perinatal depression and to the signs of developing perinatal depression in those with autoimmune disease,” Dr. Miller said, “so that appropriate screening, diagnostics, and interventions may be undertaken.”

The researchers say they will continue to examine the long-term effects of depression during pregnancy and in the year after childbirth.

“Depression during this sensitive period can have serious consequences for both the mother and the baby,” Dr. Bränn said. “We hope that our results will help decision-makers to steer funding toward maternal healthcare so that more women can get help and support in time.”

The study was financed by Karolinska Institute, Forte (the Swedish Research Council for Health, Working Life and Welfare), the Swedish Research Council, and the Icelandic Research Fund.

The researchers and Dr. Miller reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Women with autoimmune disease are more likely to have perinatal depression (PND), according to findings from a new study that also suggested the reverse relationship is true: Women with a history of PND have a higher risk of developing autoimmune disease.

The research, published online on January 9, 2024, in Molecular Psychiatry, was led by Emma Bränn, PhD, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.

The researchers used data from the Swedish Medical Birth Register and identified all women who had given birth in Sweden between 2001 and 2013. Out of the group of approximately 815,000 women and 1.3 million pregnancies, just more than 55,000 women had been diagnosed with depression during their pregnancy or within a year after delivery.

The researchers then compared the incidence of 41 autoimmune diseases in women who had and did not have PND. They controlled for factors including genetic makeup and childhood environment.

Results indicated that women with autoimmune disease were 30% more likely to have PND (odds ratio, 1.30; 95% CI, 1.25-1.35). Conversely, women with PND were 30% more likely than women with no PND to develop an autoimmune disease (hazard ratio, 1.30; 95% CI, 1.25-1.36).

A sibling comparison helped confirm the results by controlling for some shared genetic and early life environmental factors related to the household in which sisters grew up.
 

Potential Shared Biological Mechanisms

The association was independent of psychiatric comorbidities, suggesting there may be shared biological mechanisms.

Dr. Bränn told this news organization that the research team wanted to do the study because previous research has shown involvement of the immune system in depression, with similarities in both the symptoms of immune system–activated diseases and depression and the molecular pathways activated by the immune system.

“Adding on top of the tremendous changes in the immune system that we see in the body of the woman during the perinatal period, we hypothesized that autoimmune diseases could be associated to perinatal depression,” she said. “This had also been shown in some previous literature but not to the extent as what we have investigated in this paper.”

She said their results help make a case for counseling women at several points in healthcare interactions — before and after conception and childbirth — and in rheumatology visits to inform women with autoimmune diseases who are contemplating motherhood of the association with developing PND. The results may also demonstrate a need for monitoring women in these groups for depression or autoimmune disease.

Fred Miller, MD, PhD, retired Scientist Emeritus of the Environmental Autoimmunity Group at the National Institute of Environmental Health Sciences, who was not part of the study, said the results seem plausible as they build on early work that demonstrated selected associations between autoimmune conditions and mental illness.

“These associations may be the result of shared genetic and environmental risk factors, including stress, hormonal changes, medications, and the proinflammatory states that can lead to both,” he said.

The novelty, he said, is in the relatively strong associations of PND with autoimmune disease overall and with specific autoimmune diseases.
 

Strong Link Found With Multiple Sclerosis (MS)

According to the paper, a significant positive bidirectional link was found for autoimmune thyroid disease, psoriasis, MS, ulcerative colitis, and celiac disease.

Researchers found a particularly strong association — double the risk in both directions — between PND and MS.

Dr. Miller said though it is unclear from this study why the association of PND with MS was stronger than with other autoimmune diseases, people with MS are known to be at a high risk for depression in general. That may come from greater shared genetic and environmental risk factors, he added.

Additionally, MS is one of the more common autoimmune diseases, he noted, so the population is larger for study.

He said he was surprised the researchers didn’t investigate medication use because medications used in depression have immunologic effects and medications used in autoimmune diseases could have effects on mental conditions.

The study has implications for clinicians in a wide variety of specialties, Dr. Miller noted.

“It suggests that caregivers be more alert to the signs of developing autoimmune disease in women with perinatal depression and to the signs of developing perinatal depression in those with autoimmune disease,” Dr. Miller said, “so that appropriate screening, diagnostics, and interventions may be undertaken.”

The researchers say they will continue to examine the long-term effects of depression during pregnancy and in the year after childbirth.

“Depression during this sensitive period can have serious consequences for both the mother and the baby,” Dr. Bränn said. “We hope that our results will help decision-makers to steer funding toward maternal healthcare so that more women can get help and support in time.”

The study was financed by Karolinska Institute, Forte (the Swedish Research Council for Health, Working Life and Welfare), the Swedish Research Council, and the Icelandic Research Fund.

The researchers and Dr. Miller reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Medicare will now cover the use of an AI-based test for prostate cancer that can predict which men will benefit from potentially disabling androgen deprivation therapy.

The Centers for Medicare & Medicare Services (CMS) on January 1 approved the payment rate for ArteraAI as a clinical diagnostic laboratory test. The test is the first that can both predict therapeutic benefit and prognosticate long-term outcomes in localized prostate cancer. 

Daniel Spratt, MD, chair of radiation oncology at UH Seidman Cancer Center in Cleveland, who has been involved in researching ArteraAI, told this news organization that the test improves risk stratification or prognostication over standard clinical and pathologic tools, such as prostate-specific antigen, Gleason score, and T-stage, or risk groupings such as those from the National Comprehensive Cancer Network (NCCN).

“Medicare approval allows this test to reach more patients without the financial burden of covering the test out of pocket. The test is found among other tests in NCCN guidelines as a tool to improve risk stratification and personalization of treatment,” said Dr. Spratt, who serves on the network’s prostate cancer panel.

ArteraAI combines a patient’s standard clinical and pathologic information into an algorithm, alongside a digitized image analysis of the patients’ prostate biopsy. The result is a score that estimates a patient’s risk of developing metastasis or dying from prostate cancer.

Dr. Spratt was the lead author of article last June in NEJM Evidence that validated ArteraAI. He said ArteraAI is 80% accurate as a prognostic test compared with 65% accuracy using NCCN stratification systems. 

The AI test spares about two thirds of men with intermediate-risk prostate cancer who are starting radiation therapy from androgen deprivation and its side effects, such as weight gain, breast enlargement, hot flashes, heart disease, and brain problems, Dr. Spratt added. 

Andre Esteva, CEO and co-founder of San Francisco-based ArteraAI, said, “After someone is diagnosed with localized prostate cancer, deciding on a treatment can feel very overwhelming as there are so many factors to consider. During this time, knowledge is power, and having detailed, personalized information can increase confidence when making these challenging decisions. The ArteraAI Prostate Test was developed with this in mind and can predict whether a patient will benefit from hormone therapy and estimate long-term outcomes.”

Bruno Barrey is one of Dr. Spratt’s patients. Barrey, a robotics engineer from suburban Detroit who was transitioning from active surveillance with Gleason 3+4 intermediate-risk prostate cancer to radiation therapy, said, “I was concerned about the side effects from androgen-deprivation therapy. I was relieved that the AI test allowed me to avoid hormone therapy.”

Dr. Spratt reported working with NRG Oncology, a clinical trials group funded by the National Cancer Institute, and as an academic collaborator with ArteraAI. 

A version of this article appeared on Medscape.com.

Medicare will now cover the use of an AI-based test for prostate cancer that can predict which men will benefit from potentially disabling androgen deprivation therapy.

The Centers for Medicare & Medicare Services (CMS) on January 1 approved the payment rate for ArteraAI as a clinical diagnostic laboratory test. The test is the first that can both predict therapeutic benefit and prognosticate long-term outcomes in localized prostate cancer. 

Daniel Spratt, MD, chair of radiation oncology at UH Seidman Cancer Center in Cleveland, who has been involved in researching ArteraAI, told this news organization that the test improves risk stratification or prognostication over standard clinical and pathologic tools, such as prostate-specific antigen, Gleason score, and T-stage, or risk groupings such as those from the National Comprehensive Cancer Network (NCCN).

“Medicare approval allows this test to reach more patients without the financial burden of covering the test out of pocket. The test is found among other tests in NCCN guidelines as a tool to improve risk stratification and personalization of treatment,” said Dr. Spratt, who serves on the network’s prostate cancer panel.

ArteraAI combines a patient’s standard clinical and pathologic information into an algorithm, alongside a digitized image analysis of the patients’ prostate biopsy. The result is a score that estimates a patient’s risk of developing metastasis or dying from prostate cancer.

Dr. Spratt was the lead author of article last June in NEJM Evidence that validated ArteraAI. He said ArteraAI is 80% accurate as a prognostic test compared with 65% accuracy using NCCN stratification systems. 

The AI test spares about two thirds of men with intermediate-risk prostate cancer who are starting radiation therapy from androgen deprivation and its side effects, such as weight gain, breast enlargement, hot flashes, heart disease, and brain problems, Dr. Spratt added. 

Andre Esteva, CEO and co-founder of San Francisco-based ArteraAI, said, “After someone is diagnosed with localized prostate cancer, deciding on a treatment can feel very overwhelming as there are so many factors to consider. During this time, knowledge is power, and having detailed, personalized information can increase confidence when making these challenging decisions. The ArteraAI Prostate Test was developed with this in mind and can predict whether a patient will benefit from hormone therapy and estimate long-term outcomes.”

Bruno Barrey is one of Dr. Spratt’s patients. Barrey, a robotics engineer from suburban Detroit who was transitioning from active surveillance with Gleason 3+4 intermediate-risk prostate cancer to radiation therapy, said, “I was concerned about the side effects from androgen-deprivation therapy. I was relieved that the AI test allowed me to avoid hormone therapy.”

Dr. Spratt reported working with NRG Oncology, a clinical trials group funded by the National Cancer Institute, and as an academic collaborator with ArteraAI. 

A version of this article appeared on Medscape.com.

Medicare will now cover the use of an AI-based test for prostate cancer that can predict which men will benefit from potentially disabling androgen deprivation therapy.

The Centers for Medicare & Medicare Services (CMS) on January 1 approved the payment rate for ArteraAI as a clinical diagnostic laboratory test. The test is the first that can both predict therapeutic benefit and prognosticate long-term outcomes in localized prostate cancer. 

Daniel Spratt, MD, chair of radiation oncology at UH Seidman Cancer Center in Cleveland, who has been involved in researching ArteraAI, told this news organization that the test improves risk stratification or prognostication over standard clinical and pathologic tools, such as prostate-specific antigen, Gleason score, and T-stage, or risk groupings such as those from the National Comprehensive Cancer Network (NCCN).

“Medicare approval allows this test to reach more patients without the financial burden of covering the test out of pocket. The test is found among other tests in NCCN guidelines as a tool to improve risk stratification and personalization of treatment,” said Dr. Spratt, who serves on the network’s prostate cancer panel.

ArteraAI combines a patient’s standard clinical and pathologic information into an algorithm, alongside a digitized image analysis of the patients’ prostate biopsy. The result is a score that estimates a patient’s risk of developing metastasis or dying from prostate cancer.

Dr. Spratt was the lead author of article last June in NEJM Evidence that validated ArteraAI. He said ArteraAI is 80% accurate as a prognostic test compared with 65% accuracy using NCCN stratification systems. 

The AI test spares about two thirds of men with intermediate-risk prostate cancer who are starting radiation therapy from androgen deprivation and its side effects, such as weight gain, breast enlargement, hot flashes, heart disease, and brain problems, Dr. Spratt added. 

Andre Esteva, CEO and co-founder of San Francisco-based ArteraAI, said, “After someone is diagnosed with localized prostate cancer, deciding on a treatment can feel very overwhelming as there are so many factors to consider. During this time, knowledge is power, and having detailed, personalized information can increase confidence when making these challenging decisions. The ArteraAI Prostate Test was developed with this in mind and can predict whether a patient will benefit from hormone therapy and estimate long-term outcomes.”

Bruno Barrey is one of Dr. Spratt’s patients. Barrey, a robotics engineer from suburban Detroit who was transitioning from active surveillance with Gleason 3+4 intermediate-risk prostate cancer to radiation therapy, said, “I was concerned about the side effects from androgen-deprivation therapy. I was relieved that the AI test allowed me to avoid hormone therapy.”

Dr. Spratt reported working with NRG Oncology, a clinical trials group funded by the National Cancer Institute, and as an academic collaborator with ArteraAI. 

A version of this article appeared on Medscape.com.

TOPLINE:

Testosterone replacement therapy in middle-aged and older men with hypogonadism does not increase the risk for high-grade or any prostate cancer, new data confirmed.

METHODOLOGY:

• The relationship between testosterone replacement therapy and prostate cancer risk remains unclear.
• Epidemiologic studies have shown inconsistent findings, and clinical trials have not examined prostate safety. As a result, guidelines generally advise against testosterone replacement therapy in men with a history of or increased risk for prostate cancer.
• The current placebo-controlled, double-blind, parallel-group randomized study included 5204 men, ages 45-80, who had two fasting testosterone concentrations < 300 ng/dL, one or more hypogonadal symptoms, and a history of cardiovascular disease or increased . Patients were randomly assigned 1:1 to receive either testosterone replacement therapy or placebo.
• The primary prostate safety endpoint was incident high-grade prostate cancer (Gleason score 4 + 3 or higher).
• Secondary endpoints included incidence of any prostate cancer, acute urinary retention, invasive procedure for , , and new pharmacologic treatment for lower urinary tract symptoms.

TAKEAWAY:

• The incidence of high-grade prostate cancer did not differ significantly between groups. Over a mean follow-up of 33 months, only 0.19% (5 of 2596 participants) in the testosterone replacement therapy group and 0.12% (3 of 2602) in the placebo group were diagnosed with high-grade disease (hazard ratio [HR], 1.62; P = .51).
• The rate of any prostate cancer also did not differ significantly between the testosterone vs placebo groups (0.46% vs 0.42%; HR, 1.07; P = .87).
• The rates of acute urinary retention (0.77% vs 0.61%; HR, 1.25; P = .50), invasive procedures for benign prostatic hyperplasia (0.89% vs 0.46%; HR, 1.91; P = .07), prostate biopsy (0.62% vs 0.54%; HR, 1.13; P = .74), or new treatment for lower urinary tract symptoms (3.89% vs 3.34%; HR, 1.16; P = .32) did not differ significantly between the testosterone vs placebo groups.
• Compared with placebo, testosterone therapy did increase prostate-specific antigen (PSA) levels, but the differences were small and did not increase after 12 months.

IN PRACTICE:

In a population of middle-aged and older men with hypogonadism, “the incidences of high-grade or any prostate cancer and other prostate events were low and did not differ significantly between testosterone- and placebo-treated men,” the authors concluded. “The study’s findings will facilitate a more informed appraisal of the potential prostate risks of testosterone replacement therapy.”

SOURCE:

This study, led by Shalender Bhasin, MB, BS, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, was published online in JAMA Network Open.

LIMITATIONS:

These study findings do not apply to men with known prostate cancer, higher PSA values, or those without confirmed hypogonadism. The study design did not include prostate imaging or other biomarker tests after PSA testing, which may have affected the decision to perform a biopsy. Also, the rates of treatment discontinuation and loss to follow-up were high.

DISCLOSURES:

This study was funded by a consortium of testosterone manufacturers led by AbbVie Inc., with additional financial support from Endo Pharmaceuticals, Acerus Pharmaceuticals Corporation, and Upsher-Smith Laboratories. Bhasin, Lincoff, and Khera reported receiving grants and consulting and personal fees from various sources. The remaining authors disclosed no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Testosterone replacement therapy in middle-aged and older men with hypogonadism does not increase the risk for high-grade or any prostate cancer, new data confirmed.

METHODOLOGY:

• The relationship between testosterone replacement therapy and prostate cancer risk remains unclear.
• Epidemiologic studies have shown inconsistent findings, and clinical trials have not examined prostate safety. As a result, guidelines generally advise against testosterone replacement therapy in men with a history of or increased risk for prostate cancer.
• The current placebo-controlled, double-blind, parallel-group randomized study included 5204 men, ages 45-80, who had two fasting testosterone concentrations < 300 ng/dL, one or more hypogonadal symptoms, and a history of cardiovascular disease or increased . Patients were randomly assigned 1:1 to receive either testosterone replacement therapy or placebo.
• The primary prostate safety endpoint was incident high-grade prostate cancer (Gleason score 4 + 3 or higher).
• Secondary endpoints included incidence of any prostate cancer, acute urinary retention, invasive procedure for , , and new pharmacologic treatment for lower urinary tract symptoms.

TAKEAWAY:

• The incidence of high-grade prostate cancer did not differ significantly between groups. Over a mean follow-up of 33 months, only 0.19% (5 of 2596 participants) in the testosterone replacement therapy group and 0.12% (3 of 2602) in the placebo group were diagnosed with high-grade disease (hazard ratio [HR], 1.62; P = .51).
• The rate of any prostate cancer also did not differ significantly between the testosterone vs placebo groups (0.46% vs 0.42%; HR, 1.07; P = .87).
• The rates of acute urinary retention (0.77% vs 0.61%; HR, 1.25; P = .50), invasive procedures for benign prostatic hyperplasia (0.89% vs 0.46%; HR, 1.91; P = .07), prostate biopsy (0.62% vs 0.54%; HR, 1.13; P = .74), or new treatment for lower urinary tract symptoms (3.89% vs 3.34%; HR, 1.16; P = .32) did not differ significantly between the testosterone vs placebo groups.
• Compared with placebo, testosterone therapy did increase prostate-specific antigen (PSA) levels, but the differences were small and did not increase after 12 months.

IN PRACTICE:

In a population of middle-aged and older men with hypogonadism, “the incidences of high-grade or any prostate cancer and other prostate events were low and did not differ significantly between testosterone- and placebo-treated men,” the authors concluded. “The study’s findings will facilitate a more informed appraisal of the potential prostate risks of testosterone replacement therapy.”

SOURCE:

This study, led by Shalender Bhasin, MB, BS, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, was published online in JAMA Network Open.

LIMITATIONS:

These study findings do not apply to men with known prostate cancer, higher PSA values, or those without confirmed hypogonadism. The study design did not include prostate imaging or other biomarker tests after PSA testing, which may have affected the decision to perform a biopsy. Also, the rates of treatment discontinuation and loss to follow-up were high.

DISCLOSURES:

This study was funded by a consortium of testosterone manufacturers led by AbbVie Inc., with additional financial support from Endo Pharmaceuticals, Acerus Pharmaceuticals Corporation, and Upsher-Smith Laboratories. Bhasin, Lincoff, and Khera reported receiving grants and consulting and personal fees from various sources. The remaining authors disclosed no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Testosterone replacement therapy in middle-aged and older men with hypogonadism does not increase the risk for high-grade or any prostate cancer, new data confirmed.

METHODOLOGY:

• The relationship between testosterone replacement therapy and prostate cancer risk remains unclear.
• Epidemiologic studies have shown inconsistent findings, and clinical trials have not examined prostate safety. As a result, guidelines generally advise against testosterone replacement therapy in men with a history of or increased risk for prostate cancer.
• The current placebo-controlled, double-blind, parallel-group randomized study included 5204 men, ages 45-80, who had two fasting testosterone concentrations < 300 ng/dL, one or more hypogonadal symptoms, and a history of cardiovascular disease or increased . Patients were randomly assigned 1:1 to receive either testosterone replacement therapy or placebo.
• The primary prostate safety endpoint was incident high-grade prostate cancer (Gleason score 4 + 3 or higher).
• Secondary endpoints included incidence of any prostate cancer, acute urinary retention, invasive procedure for , , and new pharmacologic treatment for lower urinary tract symptoms.

TAKEAWAY:

• The incidence of high-grade prostate cancer did not differ significantly between groups. Over a mean follow-up of 33 months, only 0.19% (5 of 2596 participants) in the testosterone replacement therapy group and 0.12% (3 of 2602) in the placebo group were diagnosed with high-grade disease (hazard ratio [HR], 1.62; P = .51).
• The rate of any prostate cancer also did not differ significantly between the testosterone vs placebo groups (0.46% vs 0.42%; HR, 1.07; P = .87).
• The rates of acute urinary retention (0.77% vs 0.61%; HR, 1.25; P = .50), invasive procedures for benign prostatic hyperplasia (0.89% vs 0.46%; HR, 1.91; P = .07), prostate biopsy (0.62% vs 0.54%; HR, 1.13; P = .74), or new treatment for lower urinary tract symptoms (3.89% vs 3.34%; HR, 1.16; P = .32) did not differ significantly between the testosterone vs placebo groups.
• Compared with placebo, testosterone therapy did increase prostate-specific antigen (PSA) levels, but the differences were small and did not increase after 12 months.

IN PRACTICE:

In a population of middle-aged and older men with hypogonadism, “the incidences of high-grade or any prostate cancer and other prostate events were low and did not differ significantly between testosterone- and placebo-treated men,” the authors concluded. “The study’s findings will facilitate a more informed appraisal of the potential prostate risks of testosterone replacement therapy.”

SOURCE:

This study, led by Shalender Bhasin, MB, BS, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, was published online in JAMA Network Open.

LIMITATIONS:

These study findings do not apply to men with known prostate cancer, higher PSA values, or those without confirmed hypogonadism. The study design did not include prostate imaging or other biomarker tests after PSA testing, which may have affected the decision to perform a biopsy. Also, the rates of treatment discontinuation and loss to follow-up were high.

DISCLOSURES:

This study was funded by a consortium of testosterone manufacturers led by AbbVie Inc., with additional financial support from Endo Pharmaceuticals, Acerus Pharmaceuticals Corporation, and Upsher-Smith Laboratories. Bhasin, Lincoff, and Khera reported receiving grants and consulting and personal fees from various sources. The remaining authors disclosed no conflicts of interest.

A version of this article appeared on Medscape.com.

Prophylactic treatment with zoledronic acid (ZA) in individuals at high genetic risk for Paget disease of the bone (PDB) can prevent the development or progression of the condition, according to a new study. The authors argued that the positive results from the trial suggest that individuals with a familial history of PDB should undergo genetic screening.

“If it’s positive, you should be able to have a bone scan and take it from there,” senior author Stuart Ralston, MBChB, MD, professor of rheumatology at the University of Edinburgh (Scotland), said in an interview.

Dr. Ralston

PDB is a chronic skeletal growth disorder that affects an estimated 1-3 million people in the United States and is most prevalent in individuals over 65 years old. Symptoms of the disease may not present until later stages when there is already skeletal damage that cannot be resolved by medications. Earlier intervention in individuals who have not yet shown signs of the condition could potentially halt disease progression, Dr. Ralston said.

Genetics plays a substantial role in PDB, especially pathogenic variants of the gene SQSTM1. An estimated 40%-50% of people with a familial history of PDB have these variants, according to the study, which are associated with earlier PDB onset and more severe disease.

However, it was unclear if early interventions in these higher-risk individuals may result in better health outcomes.

In this new study, published on December 20, 2023, in Annals of the Rheumatic Diseases, researchers recruited participants through family members already diagnosed with PDB who received treatment at outpatient clinics. Over 1400 individuals with PDB underwent genetic testing for pathogenic SQSTM1 variants. If they tested positive, their first-degree relatives — primarily children — were offered the same genetic test. In total, 350 relatives tested positive for these pathogenic SQSTM1 variants, and of these individuals, 222 agreed to participate in the trial.

At the beginning of the study, all participants received a radionuclide bone scan to screen for bone lesions. They also underwent testing for the bone resorption marker type I collagen C-terminal telopeptides (CTX) and the bone formation marker procollagen type I amino-terminal propeptide (P1NP).

Participants were then randomized to receive either a single intravenous infusion of 5 mg of ZA or placebo treatment. Researchers followed up with participants annually for a median of 84 months (7 years), and then baseline assessments were repeated.

A total of 90 individuals in the ZA treatment group and 90 individuals in the placebo group completed the trial.

Participants were, on average, 50 years old at the beginning of the study. In the ZA group, nine individuals had lesions detected in bone scans at baseline, compared with just one at the study’s end. In the placebo group, 12 individuals had detectable lesions at baseline, compared with 11 individuals at the study’s end.

While the proportion of individuals with lesions was similar between the two groups, there were about twice as many lesions overall in the placebo group, compared with the ZA group (29 vs 15), which researchers said was by chance. All but two lesions disappeared in the ZA group, compared with 26 lesions remaining in the placebo group (P < .0001).

“The bone scan reversal of abnormalities was amazing,” said Ralston, where eight of nine patients with lesions in the ZA group “had their bone scan evidence completely wiped out,” he said. “That’s a very powerful result.”

Both CTX and P1NP concentrations fell in the ZA group at 12 months and remained significantly lower than the placebo group throughout the study (P < .0001 for each).

Overall, the researchers reported that eight individuals in the placebo group and no individuals in the ZA group had a poor outcome, defined as new bone lesions or lesions that were unchanged or progressed (odds ratio, 0.08; P = .003). Two individuals in the placebo group developed lesions during the study, compared with none in the ZA group, but this difference was not statistically significant.

Importantly, there were no differences in adverse events between the two groups.

While only a small number of people in the study had legions — around 9% of participants — the effect of ZA is “dramatic,” Linda A. Russell, MD, director of the Osteoporosis and Metabolic Bone Health Center at the Hospital for Special Surgery in New York City, told this news organization.

While clinicians primarily diagnose PDB with X-rays or an alkaline phosphatase blood test, testing for SQSTM1 is a new way to understand if someone is at higher risk for the disease, she said.

“Now, it seems like [the test] is fairly easily available, so probably it’s something we can begin to incorporate into our armamentarium,” Dr. Russell said.

Individuals who test positive for pathogenic variants of SQSTM1 could then get a bone scan, while those who tested negative may not need any additional testing, she added.

Dr. Ralston and coauthors noted that the effect size shown in this study is similar to that of studies examining adjuvant bisphosphonate therapy for postmenopausal women with early breast cancer. That practice, they write, is now a part of the standard of care.

“We believe that a similar approach is now justified in people with a family history of PDB who test positive for SQSTM1 mutations,” they wrote.

However, it is not clear if all individuals with pathogenic SQSTM1 should receive ZA treatment or if treatment should be given to only those with bone lesions.

“Future research to gather the views of people with a family history of PDB will help to inform the most appropriate way forward,” the authors wrote.

The UK Medical Research Council and Arthritis Research UK funded the trial. Zoledronic acid and a placebo were supplied by Novartis. Dr. Ralston reported funding to his institution from Kyowa Kirin, UCB, the Paget’s Association, and the Royal Osteoporosis Society. Some coauthors reported financial relationships with pharmaceutical companies outside the trial. Dr. Russell had no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Prophylactic treatment with zoledronic acid (ZA) in individuals at high genetic risk for Paget disease of the bone (PDB) can prevent the development or progression of the condition, according to a new study. The authors argued that the positive results from the trial suggest that individuals with a familial history of PDB should undergo genetic screening.

“If it’s positive, you should be able to have a bone scan and take it from there,” senior author Stuart Ralston, MBChB, MD, professor of rheumatology at the University of Edinburgh (Scotland), said in an interview.

Dr. Ralston

PDB is a chronic skeletal growth disorder that affects an estimated 1-3 million people in the United States and is most prevalent in individuals over 65 years old. Symptoms of the disease may not present until later stages when there is already skeletal damage that cannot be resolved by medications. Earlier intervention in individuals who have not yet shown signs of the condition could potentially halt disease progression, Dr. Ralston said.

Genetics plays a substantial role in PDB, especially pathogenic variants of the gene SQSTM1. An estimated 40%-50% of people with a familial history of PDB have these variants, according to the study, which are associated with earlier PDB onset and more severe disease.

However, it was unclear if early interventions in these higher-risk individuals may result in better health outcomes.

In this new study, published on December 20, 2023, in Annals of the Rheumatic Diseases, researchers recruited participants through family members already diagnosed with PDB who received treatment at outpatient clinics. Over 1400 individuals with PDB underwent genetic testing for pathogenic SQSTM1 variants. If they tested positive, their first-degree relatives — primarily children — were offered the same genetic test. In total, 350 relatives tested positive for these pathogenic SQSTM1 variants, and of these individuals, 222 agreed to participate in the trial.

At the beginning of the study, all participants received a radionuclide bone scan to screen for bone lesions. They also underwent testing for the bone resorption marker type I collagen C-terminal telopeptides (CTX) and the bone formation marker procollagen type I amino-terminal propeptide (P1NP).

Participants were then randomized to receive either a single intravenous infusion of 5 mg of ZA or placebo treatment. Researchers followed up with participants annually for a median of 84 months (7 years), and then baseline assessments were repeated.

A total of 90 individuals in the ZA treatment group and 90 individuals in the placebo group completed the trial.

Participants were, on average, 50 years old at the beginning of the study. In the ZA group, nine individuals had lesions detected in bone scans at baseline, compared with just one at the study’s end. In the placebo group, 12 individuals had detectable lesions at baseline, compared with 11 individuals at the study’s end.

While the proportion of individuals with lesions was similar between the two groups, there were about twice as many lesions overall in the placebo group, compared with the ZA group (29 vs 15), which researchers said was by chance. All but two lesions disappeared in the ZA group, compared with 26 lesions remaining in the placebo group (P < .0001).

“The bone scan reversal of abnormalities was amazing,” said Ralston, where eight of nine patients with lesions in the ZA group “had their bone scan evidence completely wiped out,” he said. “That’s a very powerful result.”

Both CTX and P1NP concentrations fell in the ZA group at 12 months and remained significantly lower than the placebo group throughout the study (P < .0001 for each).

Overall, the researchers reported that eight individuals in the placebo group and no individuals in the ZA group had a poor outcome, defined as new bone lesions or lesions that were unchanged or progressed (odds ratio, 0.08; P = .003). Two individuals in the placebo group developed lesions during the study, compared with none in the ZA group, but this difference was not statistically significant.

Importantly, there were no differences in adverse events between the two groups.

While only a small number of people in the study had legions — around 9% of participants — the effect of ZA is “dramatic,” Linda A. Russell, MD, director of the Osteoporosis and Metabolic Bone Health Center at the Hospital for Special Surgery in New York City, told this news organization.

While clinicians primarily diagnose PDB with X-rays or an alkaline phosphatase blood test, testing for SQSTM1 is a new way to understand if someone is at higher risk for the disease, she said.

“Now, it seems like [the test] is fairly easily available, so probably it’s something we can begin to incorporate into our armamentarium,” Dr. Russell said.

Individuals who test positive for pathogenic variants of SQSTM1 could then get a bone scan, while those who tested negative may not need any additional testing, she added.

Dr. Ralston and coauthors noted that the effect size shown in this study is similar to that of studies examining adjuvant bisphosphonate therapy for postmenopausal women with early breast cancer. That practice, they write, is now a part of the standard of care.

“We believe that a similar approach is now justified in people with a family history of PDB who test positive for SQSTM1 mutations,” they wrote.

However, it is not clear if all individuals with pathogenic SQSTM1 should receive ZA treatment or if treatment should be given to only those with bone lesions.

“Future research to gather the views of people with a family history of PDB will help to inform the most appropriate way forward,” the authors wrote.

The UK Medical Research Council and Arthritis Research UK funded the trial. Zoledronic acid and a placebo were supplied by Novartis. Dr. Ralston reported funding to his institution from Kyowa Kirin, UCB, the Paget’s Association, and the Royal Osteoporosis Society. Some coauthors reported financial relationships with pharmaceutical companies outside the trial. Dr. Russell had no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Prophylactic treatment with zoledronic acid (ZA) in individuals at high genetic risk for Paget disease of the bone (PDB) can prevent the development or progression of the condition, according to a new study. The authors argued that the positive results from the trial suggest that individuals with a familial history of PDB should undergo genetic screening.

“If it’s positive, you should be able to have a bone scan and take it from there,” senior author Stuart Ralston, MBChB, MD, professor of rheumatology at the University of Edinburgh (Scotland), said in an interview.

Dr. Ralston

PDB is a chronic skeletal growth disorder that affects an estimated 1-3 million people in the United States and is most prevalent in individuals over 65 years old. Symptoms of the disease may not present until later stages when there is already skeletal damage that cannot be resolved by medications. Earlier intervention in individuals who have not yet shown signs of the condition could potentially halt disease progression, Dr. Ralston said.

Genetics plays a substantial role in PDB, especially pathogenic variants of the gene SQSTM1. An estimated 40%-50% of people with a familial history of PDB have these variants, according to the study, which are associated with earlier PDB onset and more severe disease.

However, it was unclear if early interventions in these higher-risk individuals may result in better health outcomes.

In this new study, published on December 20, 2023, in Annals of the Rheumatic Diseases, researchers recruited participants through family members already diagnosed with PDB who received treatment at outpatient clinics. Over 1400 individuals with PDB underwent genetic testing for pathogenic SQSTM1 variants. If they tested positive, their first-degree relatives — primarily children — were offered the same genetic test. In total, 350 relatives tested positive for these pathogenic SQSTM1 variants, and of these individuals, 222 agreed to participate in the trial.

At the beginning of the study, all participants received a radionuclide bone scan to screen for bone lesions. They also underwent testing for the bone resorption marker type I collagen C-terminal telopeptides (CTX) and the bone formation marker procollagen type I amino-terminal propeptide (P1NP).

Participants were then randomized to receive either a single intravenous infusion of 5 mg of ZA or placebo treatment. Researchers followed up with participants annually for a median of 84 months (7 years), and then baseline assessments were repeated.

A total of 90 individuals in the ZA treatment group and 90 individuals in the placebo group completed the trial.

Participants were, on average, 50 years old at the beginning of the study. In the ZA group, nine individuals had lesions detected in bone scans at baseline, compared with just one at the study’s end. In the placebo group, 12 individuals had detectable lesions at baseline, compared with 11 individuals at the study’s end.

While the proportion of individuals with lesions was similar between the two groups, there were about twice as many lesions overall in the placebo group, compared with the ZA group (29 vs 15), which researchers said was by chance. All but two lesions disappeared in the ZA group, compared with 26 lesions remaining in the placebo group (P < .0001).

“The bone scan reversal of abnormalities was amazing,” said Ralston, where eight of nine patients with lesions in the ZA group “had their bone scan evidence completely wiped out,” he said. “That’s a very powerful result.”

Both CTX and P1NP concentrations fell in the ZA group at 12 months and remained significantly lower than the placebo group throughout the study (P < .0001 for each).

Overall, the researchers reported that eight individuals in the placebo group and no individuals in the ZA group had a poor outcome, defined as new bone lesions or lesions that were unchanged or progressed (odds ratio, 0.08; P = .003). Two individuals in the placebo group developed lesions during the study, compared with none in the ZA group, but this difference was not statistically significant.

Importantly, there were no differences in adverse events between the two groups.

While only a small number of people in the study had legions — around 9% of participants — the effect of ZA is “dramatic,” Linda A. Russell, MD, director of the Osteoporosis and Metabolic Bone Health Center at the Hospital for Special Surgery in New York City, told this news organization.

While clinicians primarily diagnose PDB with X-rays or an alkaline phosphatase blood test, testing for SQSTM1 is a new way to understand if someone is at higher risk for the disease, she said.

“Now, it seems like [the test] is fairly easily available, so probably it’s something we can begin to incorporate into our armamentarium,” Dr. Russell said.

Individuals who test positive for pathogenic variants of SQSTM1 could then get a bone scan, while those who tested negative may not need any additional testing, she added.

Dr. Ralston and coauthors noted that the effect size shown in this study is similar to that of studies examining adjuvant bisphosphonate therapy for postmenopausal women with early breast cancer. That practice, they write, is now a part of the standard of care.

“We believe that a similar approach is now justified in people with a family history of PDB who test positive for SQSTM1 mutations,” they wrote.

However, it is not clear if all individuals with pathogenic SQSTM1 should receive ZA treatment or if treatment should be given to only those with bone lesions.

“Future research to gather the views of people with a family history of PDB will help to inform the most appropriate way forward,” the authors wrote.

The UK Medical Research Council and Arthritis Research UK funded the trial. Zoledronic acid and a placebo were supplied by Novartis. Dr. Ralston reported funding to his institution from Kyowa Kirin, UCB, the Paget’s Association, and the Royal Osteoporosis Society. Some coauthors reported financial relationships with pharmaceutical companies outside the trial. Dr. Russell had no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

There’s no question that glucagon-like peptide 1 (GLP-1) agonists represent a major advance in the treatment of obesity for patients with or without diabetes. In clinical trials, participants lost 15%-20% of their body weight, depending on the drug.

But studies also have shown that once people stop taking these drugs — either by choice, because of shortage, or lack of access — they regain most, if not all, the weight they lost.

Arguably more frustrating is the fact that those who continue on the drug eventually reach a plateau, at which point, the body seemingly stubbornly refuses to lose more weight. Essentially, it stabilizes at its set point, said Fatima Cody Stanford, MD, MPH, MPA, MBA, an obesity medicine physician at Massachusetts General Hospital and associate professor at Harvard Medical School in Boston.
 

‘Tug of War’

Every study of weight loss drugs done over the past 40 years or so shows a plateau, Dr. Stanford told this news organization. “If you look at the phentermine/topiramate studies, there’s a plateau. If you look at the bupropion/naltrexone studies, there’s a plateau. Or if we look at bariatric surgery, there’s a plateau. And it’s the same for the newer GLP-1 drugs.”

The reason? “It really depends on where the body gets to,” Dr. Stanford said. “The body knows what it needs to do to maintain itself, and the brain knows where it’s supposed to be. And when you lose weight and reach what you feel is a lower set point, the body resists.”

When the body goes below its set point, the hunger hormone ghrelin, which is housed in the brain, gets reactivated and gradually starts to reemerge, she explained. GLP-1, which is housed in the distal portion of the small intestine and in the colon, also starts to reemerge over time.

“It becomes kind of a tug of war” between the body and whatever weight loss strategy is being implemented, from drugs to surgery to lifestyle changes, Dr. Stanford said. “The patient will start to notice changes in how their body is responding. Usually, they’ll say they don’t feel like the treatment is working the same. But the treatment is working the same as it’s always been working — except their body is now acclimated to it.”

Anne L. Peters, MD, CDE, professor and clinical scholar, Keck School of Medicine of the University of Southern California, and director, agreed that in the simplest terms, a plateau occurs because “the body becomes more and more used to” the weight loss intervention.

However, when you lose weight, you lose both fat mass and lean body mass, and lean body mass is the metabolically active part of your body, explained Dr. Peters. “That’s what burns and basically makes up your basal metabolic rate.”

With weight loss, the metabolism slows down, she said. If patients need 2000 calories a day to survive at a certain weight and then lose 50 pounds, they may then need only a 1000 calories a day. “With any obesity treatment, you reach a point at which your metabolic rate and your daily caloric requirements become equal, and you stop losing weight, even though your daily caloric requirement is less than it was when your weight was higher.”
 

Managing the Plateau

Several strategies can be used to help patients break through a plateau. One is to try multiple weight loss agents with different targets — something often done in the real world, Dr. Stanford said. “You don’t see this in the studies, which are focused on just one drug, but many of our patients are on combination therapy. They’re on a GLP-1 drug plus phentermine/topiramate plus metformin, and more. They’re usually on three, four, five drugs, similar to what we would see with resistant hypertension.”

If a patient plateaus on a GLP-1 drug, Dr. Stanford might add phentermine. When the patient reaches a plateau on phentermine, she would switch again to another agent. “The goal is to use agents that treat different receptors in the brain,” she said. “You would never use two GLP-1 agonists; you would use the GLP-1, and then something that treats norepinephrine, for example.”

At the same time, Dr. Peters noted, “try to get them off the drugs that cause weight gain, like insulin and sulfonylurea agents.”

Tapering the GLP-1 dose can also help, Dr. Peters said. However, she added, “If I’m using a GLP-1 drug for type 2 diabetes, it’s different than if I’m using it just for weight loss. With type 2 diabetes, if you taper too much, the blood sugar and weight will go back up, so you need to reach a balance.”

Dr. Peters has successfully tapered patients from a 2-mg dose down to 1 mg. She has also changed the strategy for some — ie, the patient takes the drug every other week instead of every week. “I even have a patient or two who just take it once a month and that seems to be enough,” she said. “You want to help them be at the dose that maintains their weight and keeps them healthy with the least possible medication.”

Emphasizing lifestyle changes is also important, she said. Although resistance training won’t necessarily help with weight loss, “it’s critical to maintaining lean body mass. If people keep losing and regaining weight, they’re going to lose more and more lean body mass and gain the weight back primarily as fat mass. So, their exercise should include about half aerobic activity and half resistance training.”
 

Long-term Journey

Setting appropriate expectations is a key part of helping patients accept and deal with a plateau. “This is long-term, lifelong journey,” Dr. Stanford said. “We need to think about obesity as a complex, multifactorial chronic disease, like we think about hypertension or type 2 diabetes or hyperlipidemia.”

Furthermore, and in keeping with that perspective, emerging evidence is demonstrating that GLP-1 drugs also have important nonglycemic benefits that can be achieved and maintained, Dr. Peters said. “Obviously weight loss matters, and weight loss is good for you if you’re overweight or obese. But now we know that GLP-1 drugs have wonderful benefits for the heart as well as renal function.” These are reasons to continue the drugs even in the face of a plateau.

One of Dr. Peters’ patients, a physician with type 2 diabetes, had “fought with her weight her whole life. She’s been on one or another GLP-1 drug for more than 15 years, and while none seem to impact her weight, she’s gone from having relatively poorly controlled to now beautifully controlled diabetes,” Dr. Peters said. “Even if she hasn’t lost, she’s maintained her weight, a benefit since people tend to gain weight as they get older, and she hasn’t gained.”

Another patient was disabled, on oxygen, and had recurrent pulmonary embolisms. “She weighed 420 pounds, and I put her on semaglutide because she was too sick to be considered for bariatric surgery.” When that didn’t work, Dr. Peters switched her to tirzepatide, gradually increasing the dose; the patient lost 80 pounds, her emboli are gone, she can walk down the street, and went back to work.

“Part of why she could do that is that she started exercising,” Dr. Peters noted. “She felt so much better from the drug-related weight loss that she began to do things that help enhance weight loss. She became happier because she was no longer homebound.”

This points to another element that can help patients break through a plateau over time, Dr. Peters said — namely, behavioral health. “The more people lose weight, the more they feel better about themselves, and that may mean that they take better care of themselves. The psychological part of this journey is as important as anything else. Not everyone has the same response to these agents, and there are all sorts of issues behind why people are overweight that physicians can’t ignore.

“So, in addition to managing the drugs and lifestyle, it’s important to make sure that people access the behavioral health help they need, and that once they break through a plateau, they don’t develop an eating disorder or go to the opposite extreme and become too thin, which has happened with some of my patients,” she said. “We need to remember that we’re not just giving patients a miraculous weight loss. We’re helping them to be healthier, mentally as well as physically.”

Dr. Stanford disclosed that she had been a consultant for Calibrate, GoodRx, Pfizer, Eli Lilly, Boehringer Ingelheim, Gelesis, Vida Health, Life Force, Ilant Health, Melli Cell, and Novo Nordisk. Dr. Peters disclosed that she had been a consultant for Vertex, Medscape Medical News, and Lilly; received funding from Abbott and Insulet; and had stock options in Omada Health.

A version of this article appeared on Medscape.com.

There’s no question that glucagon-like peptide 1 (GLP-1) agonists represent a major advance in the treatment of obesity for patients with or without diabetes. In clinical trials, participants lost 15%-20% of their body weight, depending on the drug.

But studies also have shown that once people stop taking these drugs — either by choice, because of shortage, or lack of access — they regain most, if not all, the weight they lost.

Arguably more frustrating is the fact that those who continue on the drug eventually reach a plateau, at which point, the body seemingly stubbornly refuses to lose more weight. Essentially, it stabilizes at its set point, said Fatima Cody Stanford, MD, MPH, MPA, MBA, an obesity medicine physician at Massachusetts General Hospital and associate professor at Harvard Medical School in Boston.
 

‘Tug of War’

Every study of weight loss drugs done over the past 40 years or so shows a plateau, Dr. Stanford told this news organization. “If you look at the phentermine/topiramate studies, there’s a plateau. If you look at the bupropion/naltrexone studies, there’s a plateau. Or if we look at bariatric surgery, there’s a plateau. And it’s the same for the newer GLP-1 drugs.”

The reason? “It really depends on where the body gets to,” Dr. Stanford said. “The body knows what it needs to do to maintain itself, and the brain knows where it’s supposed to be. And when you lose weight and reach what you feel is a lower set point, the body resists.”

When the body goes below its set point, the hunger hormone ghrelin, which is housed in the brain, gets reactivated and gradually starts to reemerge, she explained. GLP-1, which is housed in the distal portion of the small intestine and in the colon, also starts to reemerge over time.

“It becomes kind of a tug of war” between the body and whatever weight loss strategy is being implemented, from drugs to surgery to lifestyle changes, Dr. Stanford said. “The patient will start to notice changes in how their body is responding. Usually, they’ll say they don’t feel like the treatment is working the same. But the treatment is working the same as it’s always been working — except their body is now acclimated to it.”

Anne L. Peters, MD, CDE, professor and clinical scholar, Keck School of Medicine of the University of Southern California, and director, agreed that in the simplest terms, a plateau occurs because “the body becomes more and more used to” the weight loss intervention.

However, when you lose weight, you lose both fat mass and lean body mass, and lean body mass is the metabolically active part of your body, explained Dr. Peters. “That’s what burns and basically makes up your basal metabolic rate.”

With weight loss, the metabolism slows down, she said. If patients need 2000 calories a day to survive at a certain weight and then lose 50 pounds, they may then need only a 1000 calories a day. “With any obesity treatment, you reach a point at which your metabolic rate and your daily caloric requirements become equal, and you stop losing weight, even though your daily caloric requirement is less than it was when your weight was higher.”
 

Managing the Plateau

Several strategies can be used to help patients break through a plateau. One is to try multiple weight loss agents with different targets — something often done in the real world, Dr. Stanford said. “You don’t see this in the studies, which are focused on just one drug, but many of our patients are on combination therapy. They’re on a GLP-1 drug plus phentermine/topiramate plus metformin, and more. They’re usually on three, four, five drugs, similar to what we would see with resistant hypertension.”

If a patient plateaus on a GLP-1 drug, Dr. Stanford might add phentermine. When the patient reaches a plateau on phentermine, she would switch again to another agent. “The goal is to use agents that treat different receptors in the brain,” she said. “You would never use two GLP-1 agonists; you would use the GLP-1, and then something that treats norepinephrine, for example.”

At the same time, Dr. Peters noted, “try to get them off the drugs that cause weight gain, like insulin and sulfonylurea agents.”

Tapering the GLP-1 dose can also help, Dr. Peters said. However, she added, “If I’m using a GLP-1 drug for type 2 diabetes, it’s different than if I’m using it just for weight loss. With type 2 diabetes, if you taper too much, the blood sugar and weight will go back up, so you need to reach a balance.”

Dr. Peters has successfully tapered patients from a 2-mg dose down to 1 mg. She has also changed the strategy for some — ie, the patient takes the drug every other week instead of every week. “I even have a patient or two who just take it once a month and that seems to be enough,” she said. “You want to help them be at the dose that maintains their weight and keeps them healthy with the least possible medication.”

Emphasizing lifestyle changes is also important, she said. Although resistance training won’t necessarily help with weight loss, “it’s critical to maintaining lean body mass. If people keep losing and regaining weight, they’re going to lose more and more lean body mass and gain the weight back primarily as fat mass. So, their exercise should include about half aerobic activity and half resistance training.”
 

Long-term Journey

Setting appropriate expectations is a key part of helping patients accept and deal with a plateau. “This is long-term, lifelong journey,” Dr. Stanford said. “We need to think about obesity as a complex, multifactorial chronic disease, like we think about hypertension or type 2 diabetes or hyperlipidemia.”

Furthermore, and in keeping with that perspective, emerging evidence is demonstrating that GLP-1 drugs also have important nonglycemic benefits that can be achieved and maintained, Dr. Peters said. “Obviously weight loss matters, and weight loss is good for you if you’re overweight or obese. But now we know that GLP-1 drugs have wonderful benefits for the heart as well as renal function.” These are reasons to continue the drugs even in the face of a plateau.

One of Dr. Peters’ patients, a physician with type 2 diabetes, had “fought with her weight her whole life. She’s been on one or another GLP-1 drug for more than 15 years, and while none seem to impact her weight, she’s gone from having relatively poorly controlled to now beautifully controlled diabetes,” Dr. Peters said. “Even if she hasn’t lost, she’s maintained her weight, a benefit since people tend to gain weight as they get older, and she hasn’t gained.”

Another patient was disabled, on oxygen, and had recurrent pulmonary embolisms. “She weighed 420 pounds, and I put her on semaglutide because she was too sick to be considered for bariatric surgery.” When that didn’t work, Dr. Peters switched her to tirzepatide, gradually increasing the dose; the patient lost 80 pounds, her emboli are gone, she can walk down the street, and went back to work.

“Part of why she could do that is that she started exercising,” Dr. Peters noted. “She felt so much better from the drug-related weight loss that she began to do things that help enhance weight loss. She became happier because she was no longer homebound.”

This points to another element that can help patients break through a plateau over time, Dr. Peters said — namely, behavioral health. “The more people lose weight, the more they feel better about themselves, and that may mean that they take better care of themselves. The psychological part of this journey is as important as anything else. Not everyone has the same response to these agents, and there are all sorts of issues behind why people are overweight that physicians can’t ignore.

“So, in addition to managing the drugs and lifestyle, it’s important to make sure that people access the behavioral health help they need, and that once they break through a plateau, they don’t develop an eating disorder or go to the opposite extreme and become too thin, which has happened with some of my patients,” she said. “We need to remember that we’re not just giving patients a miraculous weight loss. We’re helping them to be healthier, mentally as well as physically.”

Dr. Stanford disclosed that she had been a consultant for Calibrate, GoodRx, Pfizer, Eli Lilly, Boehringer Ingelheim, Gelesis, Vida Health, Life Force, Ilant Health, Melli Cell, and Novo Nordisk. Dr. Peters disclosed that she had been a consultant for Vertex, Medscape Medical News, and Lilly; received funding from Abbott and Insulet; and had stock options in Omada Health.

A version of this article appeared on Medscape.com.

There’s no question that glucagon-like peptide 1 (GLP-1) agonists represent a major advance in the treatment of obesity for patients with or without diabetes. In clinical trials, participants lost 15%-20% of their body weight, depending on the drug.

But studies also have shown that once people stop taking these drugs — either by choice, because of shortage, or lack of access — they regain most, if not all, the weight they lost.

Arguably more frustrating is the fact that those who continue on the drug eventually reach a plateau, at which point, the body seemingly stubbornly refuses to lose more weight. Essentially, it stabilizes at its set point, said Fatima Cody Stanford, MD, MPH, MPA, MBA, an obesity medicine physician at Massachusetts General Hospital and associate professor at Harvard Medical School in Boston.
 

‘Tug of War’

Every study of weight loss drugs done over the past 40 years or so shows a plateau, Dr. Stanford told this news organization. “If you look at the phentermine/topiramate studies, there’s a plateau. If you look at the bupropion/naltrexone studies, there’s a plateau. Or if we look at bariatric surgery, there’s a plateau. And it’s the same for the newer GLP-1 drugs.”

The reason? “It really depends on where the body gets to,” Dr. Stanford said. “The body knows what it needs to do to maintain itself, and the brain knows where it’s supposed to be. And when you lose weight and reach what you feel is a lower set point, the body resists.”

When the body goes below its set point, the hunger hormone ghrelin, which is housed in the brain, gets reactivated and gradually starts to reemerge, she explained. GLP-1, which is housed in the distal portion of the small intestine and in the colon, also starts to reemerge over time.

“It becomes kind of a tug of war” between the body and whatever weight loss strategy is being implemented, from drugs to surgery to lifestyle changes, Dr. Stanford said. “The patient will start to notice changes in how their body is responding. Usually, they’ll say they don’t feel like the treatment is working the same. But the treatment is working the same as it’s always been working — except their body is now acclimated to it.”

Anne L. Peters, MD, CDE, professor and clinical scholar, Keck School of Medicine of the University of Southern California, and director, agreed that in the simplest terms, a plateau occurs because “the body becomes more and more used to” the weight loss intervention.

However, when you lose weight, you lose both fat mass and lean body mass, and lean body mass is the metabolically active part of your body, explained Dr. Peters. “That’s what burns and basically makes up your basal metabolic rate.”

With weight loss, the metabolism slows down, she said. If patients need 2000 calories a day to survive at a certain weight and then lose 50 pounds, they may then need only a 1000 calories a day. “With any obesity treatment, you reach a point at which your metabolic rate and your daily caloric requirements become equal, and you stop losing weight, even though your daily caloric requirement is less than it was when your weight was higher.”
 

Managing the Plateau

Several strategies can be used to help patients break through a plateau. One is to try multiple weight loss agents with different targets — something often done in the real world, Dr. Stanford said. “You don’t see this in the studies, which are focused on just one drug, but many of our patients are on combination therapy. They’re on a GLP-1 drug plus phentermine/topiramate plus metformin, and more. They’re usually on three, four, five drugs, similar to what we would see with resistant hypertension.”

If a patient plateaus on a GLP-1 drug, Dr. Stanford might add phentermine. When the patient reaches a plateau on phentermine, she would switch again to another agent. “The goal is to use agents that treat different receptors in the brain,” she said. “You would never use two GLP-1 agonists; you would use the GLP-1, and then something that treats norepinephrine, for example.”

At the same time, Dr. Peters noted, “try to get them off the drugs that cause weight gain, like insulin and sulfonylurea agents.”

Tapering the GLP-1 dose can also help, Dr. Peters said. However, she added, “If I’m using a GLP-1 drug for type 2 diabetes, it’s different than if I’m using it just for weight loss. With type 2 diabetes, if you taper too much, the blood sugar and weight will go back up, so you need to reach a balance.”

Dr. Peters has successfully tapered patients from a 2-mg dose down to 1 mg. She has also changed the strategy for some — ie, the patient takes the drug every other week instead of every week. “I even have a patient or two who just take it once a month and that seems to be enough,” she said. “You want to help them be at the dose that maintains their weight and keeps them healthy with the least possible medication.”

Emphasizing lifestyle changes is also important, she said. Although resistance training won’t necessarily help with weight loss, “it’s critical to maintaining lean body mass. If people keep losing and regaining weight, they’re going to lose more and more lean body mass and gain the weight back primarily as fat mass. So, their exercise should include about half aerobic activity and half resistance training.”
 

Long-term Journey

Setting appropriate expectations is a key part of helping patients accept and deal with a plateau. “This is long-term, lifelong journey,” Dr. Stanford said. “We need to think about obesity as a complex, multifactorial chronic disease, like we think about hypertension or type 2 diabetes or hyperlipidemia.”

Furthermore, and in keeping with that perspective, emerging evidence is demonstrating that GLP-1 drugs also have important nonglycemic benefits that can be achieved and maintained, Dr. Peters said. “Obviously weight loss matters, and weight loss is good for you if you’re overweight or obese. But now we know that GLP-1 drugs have wonderful benefits for the heart as well as renal function.” These are reasons to continue the drugs even in the face of a plateau.

One of Dr. Peters’ patients, a physician with type 2 diabetes, had “fought with her weight her whole life. She’s been on one or another GLP-1 drug for more than 15 years, and while none seem to impact her weight, she’s gone from having relatively poorly controlled to now beautifully controlled diabetes,” Dr. Peters said. “Even if she hasn’t lost, she’s maintained her weight, a benefit since people tend to gain weight as they get older, and she hasn’t gained.”

Another patient was disabled, on oxygen, and had recurrent pulmonary embolisms. “She weighed 420 pounds, and I put her on semaglutide because she was too sick to be considered for bariatric surgery.” When that didn’t work, Dr. Peters switched her to tirzepatide, gradually increasing the dose; the patient lost 80 pounds, her emboli are gone, she can walk down the street, and went back to work.

“Part of why she could do that is that she started exercising,” Dr. Peters noted. “She felt so much better from the drug-related weight loss that she began to do things that help enhance weight loss. She became happier because she was no longer homebound.”

This points to another element that can help patients break through a plateau over time, Dr. Peters said — namely, behavioral health. “The more people lose weight, the more they feel better about themselves, and that may mean that they take better care of themselves. The psychological part of this journey is as important as anything else. Not everyone has the same response to these agents, and there are all sorts of issues behind why people are overweight that physicians can’t ignore.

“So, in addition to managing the drugs and lifestyle, it’s important to make sure that people access the behavioral health help they need, and that once they break through a plateau, they don’t develop an eating disorder or go to the opposite extreme and become too thin, which has happened with some of my patients,” she said. “We need to remember that we’re not just giving patients a miraculous weight loss. We’re helping them to be healthier, mentally as well as physically.”

Dr. Stanford disclosed that she had been a consultant for Calibrate, GoodRx, Pfizer, Eli Lilly, Boehringer Ingelheim, Gelesis, Vida Health, Life Force, Ilant Health, Melli Cell, and Novo Nordisk. Dr. Peters disclosed that she had been a consultant for Vertex, Medscape Medical News, and Lilly; received funding from Abbott and Insulet; and had stock options in Omada Health.

A version of this article appeared on Medscape.com.

To lose weight, patients with obesity may be more interested in semaglutide products, but the glucagon-like peptide I agonists, such as Ozempic injections and Rybelsus tablets, are not yet cost-effective, according to a modeling study that compared the drugs with surgery and endoscopy.

Sleeve gastrectomy (SG) for moderate to severe (class II/III) obesity and the less invasive endoscopic sleeve gastroplasty (ESG) for mild (class I) obesity were both cost effective strategies to reduce obesity, the researchers report.

“SG should be offered as the first-line treatment for class II and class III obesity,” write Monica Saumoy, MD, of the Center for Digestive Health, Penn Medicine Princeton Medical Center, Plainsboro, N.J., and coauthors. “ESG is an effective and cost-effective nonsurgical treatment for class I, class II and class III obesity, and more efforts are needed to ensure that patients have access to this procedure.

Penn Medicine

“While semaglutide is highly effective for weight loss, and there is substantial patient interest, it is not currently cost-effective due to its high cost,” they add. “With methods to reduce semaglutide’s annual cost, it may provide an effective and cost-effective method to reduce the morbidity related to obesity.”

The study was published in Gut.
 

Cost Concerns

One in two Americans will likely be obese by 2030, according to current models, and nearly one in four adults will be severely obese.

Several weight-loss therapies exist to treat obesity. Evidence shows bariatric surgery is effective in reducing weight, metabolic comorbidities, and mortality in people with obesity compared with lifestyle intervention alone, but surgery has risks, adverse events, and poor national uptake. Patients are likely more interested in less invasive options, the authors write.

Recent trials have reported effective weight loss from less invasive options. A five-year follow-up of the randomized controlled MERIT trial found that ESG was associated with a 13.6% total body weight loss for people with mild to moderate obesity.

On the pharmaceutical front, other randomized controlled trials have shown that semaglutide is linked with as much as 17% total body weight loss at two years. Also, recent guidance from the American Gastroenterological Association (AGA) states that long-term treatment with a semaglutide is the preferred strategy for weight loss.

“However, concerns about the cost and the cost-effectiveness of these [less invasive] interventions have limited their usage in the USA,” the study authors write.

The aim of the study was to perform a cost-effectiveness analysis comparing SG, ESG, semaglutide, and lifestyle interventions (LI) for patients with obesity in class I (defined as BMI 30-34.9 kg/m²), class II (35-29.9 kg/m²), and class III (>40kg/m²) obesity.

Researchers used a state-transition, semi-Markov microsimulation model to analyze the effectiveness of ESG, SG, semaglutide, and LI in a simulated 40-year-old with three different base-case scenarios of class I, II, or III obesity. They then performed a detailed threshold and sensitivity analysis to change the cost of treatment modalities and the semaglutide adherence rate. Outcome measures included a willingness-to-pay threshold of US $100,000/quality-adjusted life years (QALY) and incremental cost-effectiveness ratios (ICERs).
 

Cost-Effectiveness of Treatments

When the treatment modalities were compared with each other, findings showed that for class I obesity, ESG was cost effective (US $4,105/QALY). For class II and III obesity, SG was cost-effective as well (US $5,883/QALY) and (US $7,821/QALY), respectively.

In all classes of obesity, SG and ESG were cost-effective compared with LI. Semaglutide was not cost-effective compared with LI for class I, II, and III obesity (ICER US $508,414/QALY, $420,483/QALY, and $350,637/QALY, respectively).

“For semaglutide to be cost-effective when compared with ESG, it would have to cost less than US $1,879 (class III), US $1,204 (class II), or US $297 (class I) annually,” the authors note.

The authors addressed recent guidelines to consider bariatric surgery in all obese patients. They recommend SG remain the standard of care for patients with severe obesity.

But national projections show that SG would address only 0.5% of life-years lost due to obesity.

“Barring a dramatic increase in patient adherence, bariatric surgery will not likely successfully mitigate the harm from the obesity epidemic,” they write.

“ESG may fill this gap and provide an additional option for patients with obesity as it demonstrated sustained weight loss at 2-5 years.” While insurance coverage is limited, they write, “our model demonstrates that payer coverage for ESG would provide an alternative tool to combat the obesity epidemic as part of a multidisciplinary approach.”

Semaglutide shows sustained weight loss in trials for up to two years but has a substantial annual cost, the authors note.

At lower prices, semaglutide can make a “major impact on the obesity pandemic as it can be prescribed in multiple healthcare settings and due to increased patient interested in non-invasive obesity treatment,” they write.

One limitation to the study is a lack of long-term data available for ESG and semaglutide. Authors were also not able to use a lifetime horizon because of a lack of long-term weight loss.

One study author reports financial relationships with BSC, Cook Medical, Surgical Intuitive, and Olympus America. Another author reports relationships with ACI, AGA-Varia, BSC, Dark Canyon Labs, Endiatx, Medtronic, Olympus, Virgo Systems; equity: AGA-Varia, Dark Canyon Labs, Endiatx, EndoSound, and Virgo Systems. The rest of the authors have no conflicts to disclose.

To lose weight, patients with obesity may be more interested in semaglutide products, but the glucagon-like peptide I agonists, such as Ozempic injections and Rybelsus tablets, are not yet cost-effective, according to a modeling study that compared the drugs with surgery and endoscopy.

Sleeve gastrectomy (SG) for moderate to severe (class II/III) obesity and the less invasive endoscopic sleeve gastroplasty (ESG) for mild (class I) obesity were both cost effective strategies to reduce obesity, the researchers report.

“SG should be offered as the first-line treatment for class II and class III obesity,” write Monica Saumoy, MD, of the Center for Digestive Health, Penn Medicine Princeton Medical Center, Plainsboro, N.J., and coauthors. “ESG is an effective and cost-effective nonsurgical treatment for class I, class II and class III obesity, and more efforts are needed to ensure that patients have access to this procedure.

Penn Medicine

“While semaglutide is highly effective for weight loss, and there is substantial patient interest, it is not currently cost-effective due to its high cost,” they add. “With methods to reduce semaglutide’s annual cost, it may provide an effective and cost-effective method to reduce the morbidity related to obesity.”

The study was published in Gut.
 

Cost Concerns

One in two Americans will likely be obese by 2030, according to current models, and nearly one in four adults will be severely obese.

Several weight-loss therapies exist to treat obesity. Evidence shows bariatric surgery is effective in reducing weight, metabolic comorbidities, and mortality in people with obesity compared with lifestyle intervention alone, but surgery has risks, adverse events, and poor national uptake. Patients are likely more interested in less invasive options, the authors write.

Recent trials have reported effective weight loss from less invasive options. A five-year follow-up of the randomized controlled MERIT trial found that ESG was associated with a 13.6% total body weight loss for people with mild to moderate obesity.

On the pharmaceutical front, other randomized controlled trials have shown that semaglutide is linked with as much as 17% total body weight loss at two years. Also, recent guidance from the American Gastroenterological Association (AGA) states that long-term treatment with a semaglutide is the preferred strategy for weight loss.

“However, concerns about the cost and the cost-effectiveness of these [less invasive] interventions have limited their usage in the USA,” the study authors write.

The aim of the study was to perform a cost-effectiveness analysis comparing SG, ESG, semaglutide, and lifestyle interventions (LI) for patients with obesity in class I (defined as BMI 30-34.9 kg/m²), class II (35-29.9 kg/m²), and class III (>40kg/m²) obesity.

Researchers used a state-transition, semi-Markov microsimulation model to analyze the effectiveness of ESG, SG, semaglutide, and LI in a simulated 40-year-old with three different base-case scenarios of class I, II, or III obesity. They then performed a detailed threshold and sensitivity analysis to change the cost of treatment modalities and the semaglutide adherence rate. Outcome measures included a willingness-to-pay threshold of US $100,000/quality-adjusted life years (QALY) and incremental cost-effectiveness ratios (ICERs).
 

Cost-Effectiveness of Treatments

When the treatment modalities were compared with each other, findings showed that for class I obesity, ESG was cost effective (US $4,105/QALY). For class II and III obesity, SG was cost-effective as well (US $5,883/QALY) and (US $7,821/QALY), respectively.

In all classes of obesity, SG and ESG were cost-effective compared with LI. Semaglutide was not cost-effective compared with LI for class I, II, and III obesity (ICER US $508,414/QALY, $420,483/QALY, and $350,637/QALY, respectively).

“For semaglutide to be cost-effective when compared with ESG, it would have to cost less than US $1,879 (class III), US $1,204 (class II), or US $297 (class I) annually,” the authors note.

The authors addressed recent guidelines to consider bariatric surgery in all obese patients. They recommend SG remain the standard of care for patients with severe obesity.

But national projections show that SG would address only 0.5% of life-years lost due to obesity.

“Barring a dramatic increase in patient adherence, bariatric surgery will not likely successfully mitigate the harm from the obesity epidemic,” they write.

“ESG may fill this gap and provide an additional option for patients with obesity as it demonstrated sustained weight loss at 2-5 years.” While insurance coverage is limited, they write, “our model demonstrates that payer coverage for ESG would provide an alternative tool to combat the obesity epidemic as part of a multidisciplinary approach.”

Semaglutide shows sustained weight loss in trials for up to two years but has a substantial annual cost, the authors note.

At lower prices, semaglutide can make a “major impact on the obesity pandemic as it can be prescribed in multiple healthcare settings and due to increased patient interested in non-invasive obesity treatment,” they write.

One limitation to the study is a lack of long-term data available for ESG and semaglutide. Authors were also not able to use a lifetime horizon because of a lack of long-term weight loss.

One study author reports financial relationships with BSC, Cook Medical, Surgical Intuitive, and Olympus America. Another author reports relationships with ACI, AGA-Varia, BSC, Dark Canyon Labs, Endiatx, Medtronic, Olympus, Virgo Systems; equity: AGA-Varia, Dark Canyon Labs, Endiatx, EndoSound, and Virgo Systems. The rest of the authors have no conflicts to disclose.

To lose weight, patients with obesity may be more interested in semaglutide products, but the glucagon-like peptide I agonists, such as Ozempic injections and Rybelsus tablets, are not yet cost-effective, according to a modeling study that compared the drugs with surgery and endoscopy.

Sleeve gastrectomy (SG) for moderate to severe (class II/III) obesity and the less invasive endoscopic sleeve gastroplasty (ESG) for mild (class I) obesity were both cost effective strategies to reduce obesity, the researchers report.

“SG should be offered as the first-line treatment for class II and class III obesity,” write Monica Saumoy, MD, of the Center for Digestive Health, Penn Medicine Princeton Medical Center, Plainsboro, N.J., and coauthors. “ESG is an effective and cost-effective nonsurgical treatment for class I, class II and class III obesity, and more efforts are needed to ensure that patients have access to this procedure.

Penn Medicine

“While semaglutide is highly effective for weight loss, and there is substantial patient interest, it is not currently cost-effective due to its high cost,” they add. “With methods to reduce semaglutide’s annual cost, it may provide an effective and cost-effective method to reduce the morbidity related to obesity.”

The study was published in Gut.
 

Cost Concerns

One in two Americans will likely be obese by 2030, according to current models, and nearly one in four adults will be severely obese.

Several weight-loss therapies exist to treat obesity. Evidence shows bariatric surgery is effective in reducing weight, metabolic comorbidities, and mortality in people with obesity compared with lifestyle intervention alone, but surgery has risks, adverse events, and poor national uptake. Patients are likely more interested in less invasive options, the authors write.

Recent trials have reported effective weight loss from less invasive options. A five-year follow-up of the randomized controlled MERIT trial found that ESG was associated with a 13.6% total body weight loss for people with mild to moderate obesity.

On the pharmaceutical front, other randomized controlled trials have shown that semaglutide is linked with as much as 17% total body weight loss at two years. Also, recent guidance from the American Gastroenterological Association (AGA) states that long-term treatment with a semaglutide is the preferred strategy for weight loss.

“However, concerns about the cost and the cost-effectiveness of these [less invasive] interventions have limited their usage in the USA,” the study authors write.

The aim of the study was to perform a cost-effectiveness analysis comparing SG, ESG, semaglutide, and lifestyle interventions (LI) for patients with obesity in class I (defined as BMI 30-34.9 kg/m²), class II (35-29.9 kg/m²), and class III (>40kg/m²) obesity.

Researchers used a state-transition, semi-Markov microsimulation model to analyze the effectiveness of ESG, SG, semaglutide, and LI in a simulated 40-year-old with three different base-case scenarios of class I, II, or III obesity. They then performed a detailed threshold and sensitivity analysis to change the cost of treatment modalities and the semaglutide adherence rate. Outcome measures included a willingness-to-pay threshold of US $100,000/quality-adjusted life years (QALY) and incremental cost-effectiveness ratios (ICERs).
 

Cost-Effectiveness of Treatments

When the treatment modalities were compared with each other, findings showed that for class I obesity, ESG was cost effective (US $4,105/QALY). For class II and III obesity, SG was cost-effective as well (US $5,883/QALY) and (US $7,821/QALY), respectively.

In all classes of obesity, SG and ESG were cost-effective compared with LI. Semaglutide was not cost-effective compared with LI for class I, II, and III obesity (ICER US $508,414/QALY, $420,483/QALY, and $350,637/QALY, respectively).

“For semaglutide to be cost-effective when compared with ESG, it would have to cost less than US $1,879 (class III), US $1,204 (class II), or US $297 (class I) annually,” the authors note.

The authors addressed recent guidelines to consider bariatric surgery in all obese patients. They recommend SG remain the standard of care for patients with severe obesity.

But national projections show that SG would address only 0.5% of life-years lost due to obesity.

“Barring a dramatic increase in patient adherence, bariatric surgery will not likely successfully mitigate the harm from the obesity epidemic,” they write.

“ESG may fill this gap and provide an additional option for patients with obesity as it demonstrated sustained weight loss at 2-5 years.” While insurance coverage is limited, they write, “our model demonstrates that payer coverage for ESG would provide an alternative tool to combat the obesity epidemic as part of a multidisciplinary approach.”

Semaglutide shows sustained weight loss in trials for up to two years but has a substantial annual cost, the authors note.

At lower prices, semaglutide can make a “major impact on the obesity pandemic as it can be prescribed in multiple healthcare settings and due to increased patient interested in non-invasive obesity treatment,” they write.

One limitation to the study is a lack of long-term data available for ESG and semaglutide. Authors were also not able to use a lifetime horizon because of a lack of long-term weight loss.

One study author reports financial relationships with BSC, Cook Medical, Surgical Intuitive, and Olympus America. Another author reports relationships with ACI, AGA-Varia, BSC, Dark Canyon Labs, Endiatx, Medtronic, Olympus, Virgo Systems; equity: AGA-Varia, Dark Canyon Labs, Endiatx, EndoSound, and Virgo Systems. The rest of the authors have no conflicts to disclose.