Tirzepatide Emerges as Superior Treatment for Obesity-Related Hypogonadism

Recent research presented at the ENDO 2025 annual meeting in San Francisco has indicated that tirzepatide may surpass traditional testosterone replacement therapy (TRT) in treating men with obesity and functional hypogonadism. The study, conducted by Dr. Rossella Cannarella, a research fellow in the Department of Clinical and Experimental Medicine at the University of Catania, involved 83 men diagnosed with obesity, insulin resistance, and functional hypogonadism. Over a two-month period, those receiving tirzepatide exhibited greater reductions in body weight and waist circumference, along with notable improvements in erectile dysfunction compared to their counterparts on TRT and those receiving no treatment.

The findings revealed that the tirzepatide group lost an average of 8.1% of their body weight, significantly outpacing the weight loss seen in the TRT group (-3.0%) and the lifestyle-only group (-2.4%). Additionally, the tirzepatide treatment led to increased endogenous testosterone levels and improvements in erectile function, as measured by the International Index of Erectile Function (IIEF-5) scores.

Dr. Cannarella emphasized the dual benefits of tirzepatide, stating, "Unlike TRT, which suppresses gonadotropins, tirzepatide appears to restore axis function. This offers an alternative for functional hypogonadism that addresses root metabolic causes rather than symptomatically replacing testosterone." This perspective is echoed by Dr. Olena Klindukhova, an assistant professor at the Medical College of Wisconsin, who remarked that the data supports the notion that weight loss can enhance natural testosterone production.

The study allocated participants into three groups based on individual preferences and health status: 28 men received tirzepatide (2.5 mg for the first month, increasing to 5 mg in the second), 30 men underwent no pharmacological treatment, and 25 men were administered transdermal testosterone. All participants adhered to a low-calorie diet and incorporated daily brisk walking into their routines.

At baseline, all subjects presented with erectile dysfunction, with scores indicating severe conditions across groups. Notably, participants in the tirzepatide group demonstrated higher baseline levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) alongside significant decreases in estradiol levels after treatment.

Dr. Maja Stefanovic-Racic, an associate professor of medicine at the University of Pittsburgh, underscored the significance of the findings, particularly how tirzepatide’s effects extend beyond weight loss to improve endothelial function and, consequently, erectile dysfunction. She stated, "If there’s a patient who is open to it, I would personally choose GLP-1 over testosterone."

The implications of this research are considerable, as they may prompt a reevaluation of treatment protocols for metabolic hypogonadism, particularly in obese men. With a growing body of evidence supporting the efficacy of tirzepatide in this domain, healthcare providers may soon shift towards prioritizing this medication over traditional testosterone therapies, offering patients a holistic approach to address both weight and hormonal health efficiently. The study's results were also published in the journal Reproductive Biology and Endocrinology, further solidifying the growing interest in tirzepatide as a multifaceted treatment option for men facing these health challenges.