ENDO 2025: 77% OF OBESE MEN NORMALIZED TESTOSTERONE ON GLP-1S

THE STUDY AT A GLANCE

Presented at ENDO 2025 (the Endocrine Society's annual meeting), this retrospective study from Saint Louis University followed 110 men with obesity who were prescribed GLP-1 receptor agonists. Researchers tracked testosterone levels over 18 months to answer the question men keep asking: what do these drugs actually do to hormones?

The results were unambiguous. Among men who started with low testosterone, the proportion achieving normal levels jumped from 53% to 77% after approximately 10% body weight loss. Total testosterone increased from an average of 312 ng/dL to 368 ng/dL — a clinically meaningful improvement of 56 ng/dL (P<.001).

Metric	Before GLP-1	After GLP-1	Change
Men with normal T	53%	77%	+24 pts
Total testosterone	312 ng/dL	368 ng/dL	+56 ng/dL
Weight loss achieved	—	~10%	—

WHY THIS HAPPENS: THE OBESITY-TESTOSTERONE CONNECTION

To understand why GLP-1s improve testosterone, you need to understand why obesity tanks it in the first place. The relationship between fat and hormones creates a vicious cycle:

Step 1: Fat tissue produces aromatase. This enzyme converts testosterone to estrogen. More body fat means more aromatase activity, which means less testosterone and more estrogen in circulation.

Step 2: Elevated estrogen suppresses the HPT axis. Your hypothalamus and pituitary gland sense the higher estrogen and respond by reducing signals to the testes to produce testosterone. This is called "functional hypogonadism" — your testes work fine, but they're not getting the signal to produce.

Step 3: Low testosterone promotes fat storage. Testosterone helps regulate fat distribution and metabolic rate. Lower levels make it easier to gain fat and harder to lose it, which increases aromatase activity, which further suppresses testosterone.

GLP-1s break this cycle by reducing fat mass, particularly visceral fat. Less fat means less aromatase, which means testosterone stops being converted to estrogen and the HPT axis can function normally again.

HOW THIS COMPARES TO TRT

The ENDO 2025 data gains additional significance when compared to testosterone replacement therapy (TRT). While TRT directly increases testosterone levels, it does so by suppressing your body's natural hormone production. Your testes essentially shut down.

GLP-1s work the opposite way. An Italian study presented at the same conference compared tirzepatide to transdermal testosterone in 83 men with obesity and erectile dysfunction:

• Tirzepatide increased gonadotropins (LH and FSH) — the hormones that signal testes to produce testosterone
• TRT suppressed these same hormones
• Both improved testosterone, but through completely different mechanisms
• Tirzepatide achieved better erectile function scores

This distinction matters enormously for fertility (TRT can cause infertility; GLP-1s don't) and for long-term hormonal health.

WHAT THIS MEANS FOR YOU

If you're an overweight or obese man with low testosterone symptoms — low energy, reduced libido, difficulty building muscle, brain fog — this research suggests GLP-1s may address the root cause rather than just the symptom.

Good Candidates for GLP-1 Approach

• Obese men with functional hypogonadism (low T caused by weight)
• Men who want to preserve fertility
• Men interested in addressing root cause rather than symptom management

TRT May Still Be Appropriate For

• Men with primary hypogonadism (testicular damage or genetic conditions)
• Men who aren't candidates for GLP-1 medications
• Men who've already lost significant weight without testosterone improvement

STUDY LIMITATIONS

• Retrospective design: Not a randomized controlled trial
• No control group: Before/after within same patients only
• Single center: All patients from Saint Louis University
• 18 months: Long-term data beyond this not yet available

That said, the effect size is large enough and the mechanism well-understood enough that the finding is considered robust.