SAN FRANCISCO — New research suggests tirzepatide could be a game-changer for men with obesity-related metabolic hypogonadism.
Tirzepatide shows significant promise in treating metabolic hypogonadism in obese men, outperforming traditional testosterone therapy in a recent study.
- Tirzepatide led to greater weight loss and improved testosterone levels compared to testosterone replacement therapy (TRT) or no treatment.
- The drug also showed promise in improving erectile dysfunction in men with obesity and hypogonadism.
- Experts suggest tirzepatide could shift treatment strategies for metabolic hypogonadism, addressing root causes.
Could tirzepatide be a superior treatment for metabolic hypogonadism in obese men?
A study of 83 men found that those treated with tirzepatide for two months experienced more significant weight loss, increased natural testosterone production, and better erectile function compared to those receiving transdermal testosterone or no treatment. The findings were presented at ENDO 2025: The Endocrine Society Annual Meeting and also published in Reproductive Biology and Endocrinology.
“Tirzepatide offers a dual benefit, substantial weight loss and restoration of gonadal function in obese men,” said lead study author Rossella Cannarella, MD, of the University of Catania, Italy. “This may change first-line management strategies for metabolic hypogonadism, encouraging a shift away from immediate testosterone supplementation in select patients.”
Cannarella noted that unlike TRT, which can suppress the body’s natural hormone production, tirzepatide appears to restore the axis function. This offers an alternative that targets the underlying metabolic issues rather than just replacing testosterone.
Olena Klindukhova, MD, assistant professor at the Medical College of Wisconsin, echoed this sentiment. “Having patients achieve weight loss will improve their physiologic, natural production of testosterone. This gives us more validation.” She added that from an endocrinologist’s perspective, she would personally favor GLP-1 medications like tirzepatide over testosterone for suitable patients.
Tirzepatide’s Edge in Hormonal and Metabolic Improvements
Participants were divided into three groups: 28 received tirzepatide (escalating from 2.5 mg to 5 mg over two months), 30 received no pharmacological treatment, and 25 received transdermal testosterone. All were advised to follow a low-calorie diet and engage in daily brisk walking.
At the study’s start, all men had erectile dysfunction (ED), with scores on the International Index of Erectile Function (IIEF-5) between 5 and 12, indicating at least moderate ED. The group receiving no treatment had higher baseline waist circumference, while the tirzepatide group had higher scores on the Binge Eating Scale (BES), greater lean mass percentage, and higher luteinizing hormone (LH) levels.
After two months, the tirzepatide group demonstrated significantly greater improvements in body weight (an 8.1% reduction), BMI, waist circumference, fat mass, and BES scores compared to the other groups. The tirzepatide group also showed a better increase in lean mass than the lifestyle-only group.
While all groups saw reductions in insulin resistance, the pharmacological treatment groups experienced more significant decreases. The increase in IIEF-5 scores was higher in the tirzepatide group compared to the lifestyle-only group and also higher, though not significantly, than the testosterone group.
Crucially, tirzepatide treatment resulted in significantly higher levels of LH, follicle-stimulating hormone (FSH), and total testosterone compared to both other groups, with a notable decrease in 17β-estradiol (E₂). The testosterone group showed only minor changes, including a slight rise in E₂ levels.
Maja Stefanovic-Racic, MD, PhD, from the University of Pittsburgh School of Medicine, expressed impressment with tirzepatide’s impact on ED. “We know that especially in obese men, adding testosterone often does not improve ED at all. This may relate to endothelial function outside of weight.”
Cannarella also pointed out that tirzepatide’s benefits may extend beyond weight loss. “While weight loss undoubtedly plays a major role, the magnitude and speed of hormonal recovery — along with increases in gonadotropins (LH, FSH) and SHBG [sex hormone-binding globulin] — suggest that tirzepatide may exert additional regulatory effects on the hypothalamic-pituitary-gonadal axis.”
