GLP-1 Receptor Agonists Naturally Restore Testosterone Levels in Men with Obesity and Type 2 Diabetes
核心洞察
A retrospective study of 110 men with obesity (搜索) or Type 2 diabetes (搜索) found that GLP-1 receptor (搜索) agonists like semaglutide and tirzepatide can naturally restore testosterone levels over 18 months of treatment.
Roughly half of the participants had low to low-normal testosterone at baseline, with most achieving normal levels after treatment without requiring testosterone replacement therapy.
The findings suggest men on existing testosterone therapy may need dose adjustments or discontinuation when starting weight loss medications, as natural hormone production recovers with improved metabolic health.
Popular weight loss medications including semaglutide and tirzepatide can help reverse low testosterone (搜索) levels in men with obesity (搜索) or Type 2 diabetes (搜索), according to new research presented at ENDO 2025, the Endocrine Society (搜索)'s annual meeting in San Francisco.
Researchers at SSM Health St. Louis University Hospital (搜索) analyzed electronic health records of 110 men with obesity (搜索) or Type 2 diabetes (搜索) to monitor testosterone changes while taking GLP-1 receptor (搜索) agonists. The study measured testosterone levels before medication initiation and for 18 months after starting treatment, with participants having a mean age of 54.
Study Findings and Clinical Implications
Roughly half of the men had low to low-normal testosterone at baseline, with most reaching normal levels after treatment. "The increases we observed were more modest than what you would typically see with testosterone replacement therapy," said lead author Dr. Shellsea Portillo Canales, endocrinologist at SSM Health St. Louis University Hospital (搜索). "However, they occurred naturally, without testosterone replacement therapy (TRT), and likely reflect the body recovering its normal hormone production as weight and insulin resistance improved."
The findings highlight important clinical considerations for men already receiving testosterone therapy. According to Portillo, these patients require close monitoring of testosterone levels after starting weight loss medications, as some may need dose reductions or complete discontinuation of testosterone supplements when levels normalize naturally.
Expert Perspectives on Treatment Approach
Dr. Susan Spratt, professor of medicine at Duke University School of Medicine, emphasized the clinical significance of natural testosterone restoration. "It would be better to treat obesity (搜索) or diabetes and naturally increase testosterone than to prescribe testosterone — which has known risks," said Spratt, who was not involved in the study.
Testosterone replacement therapy carries multiple risks including worsening sleep apnea (搜索), acne, prostate or breast enlargement, increased prostate cancer (搜索) growth, reduced sperm counts, testicular shrinkage, and elevated clot risk, according to Mayo Clinic data cited in the research.
Metabolic-Hormonal Connection
Dr. Fatima Cody Stanford, obesity (搜索) medicine physician scientist at Massachusetts General Hospital and Harvard Medical School, noted the dual therapeutic benefit. "The findings from this study highlight an important intersection between metabolic health and hormonal balance," Stanford said. "This dual benefit underscores the potential of these medications to enhance overall health outcomes, including reproductive health, in this population."
Normal testosterone levels range between 300 to 1,000 nanograms per deciliter. Testosterone naturally declines with age, starting around the late 30s to early 40s, with levels dropping to approximately 65% of young adult averages by age 75, according to Portillo.
Study Limitations and Future Research
The retrospective study design presents several limitations. The findings do not prove causation between GLP-1 receptor (搜索) agonists and increased testosterone levels, as researchers analyzed existing medical records rather than conducting a randomized clinical trial. Additionally, testosterone levels were not monitored after medication discontinuation.
"If weight is regained, testosterone levels could potentially drop again," Portillo noted. The research team plans to submit their findings to a medical journal for peer review.
Clinical Context and Overtreatment Concerns
Spratt highlighted the importance of distinguishing between normal testosterone levels that increase within the normal range versus low testosterone (搜索) levels that normalize. "However, treating low normal testosterone without a known cause is controversial and has increased in the past decade likely due to direct-to-consumer marketing," she said.
Truly low testosterone (搜索) levels are most concerning clinically, as they can reduce bone density, muscle mass, hemoglobin levels, and libido. Excess abdominal fat is known to decrease testosterone in men by interfering with hormone signals from the brain to the testicles.
"Fortunately, weight loss, whether through lifestyle changes or medications, can reverse it in many cases," Portillo concluded, supporting the potential for GLP-1 therapies to address both metabolic and hormonal dysfunction simultaneously.