------|-------------|-----| | Weight loss | -18.2% | +1.3% (gain) | | Waist reduction | -14.8 cm | -2.1 cm | | Total testosterone | Significant increase | Significant increase | | Free testosterone | Increased | Increased | | Erectile function (IIEF) | Improved | Improved | | Sperm production | Preserved | Suppressed | | Natural production | Restored | Replaced |
The headline: Tirzepatide produced comparable testosterone improvement with dramatically better weight loss and preserved fertility.
Lead researcher Dr. Rossella Cannarella called GLP-1s "a safer and more sustainable option" for obesity-related hypogonadism.
Testosterone Outcomes Compared
Both approaches raise testosterone. But the quality of that increase differs.
TRT Testosterone
- Immediate, predictable increase
- Levels depend on dose administered
- Natural production shuts down (LH and FSH drop to near zero)
- Testes often shrink from disuse
- Requires ongoing treatment indefinitely
- Stopping leads to crash below baseline (until recovery, if it occurs)
GLP-1 Testosterone
- Gradual increase as weight drops
- The ENDO 2025 study showed 53% → 77% of men achieving normal T (>300 ng/dL)
- Average increase: 312 → 368 ng/dL
- Natural production restored (LH and FSH increase)
- Testicular function preserved
- Stopping may maintain gains if weight is maintained
The GLP-1 approach takes longer but restores function rather than replacing it.
Fertility: The Dealbreaker
This is where the comparison isn't even close.
TRT and fertility: - Exogenous testosterone suppresses LH and FSH - Without these signals, testes stop producing sperm - Sperm count often drops to zero within months - 90% of men become azoospermic (no sperm) on TRT - Recovery after stopping takes 6-18 months, if it happens at all - Some men never recover fertility
GLP-1 and fertility: - No suppression of LH or FSH - Sperm production continues normally - A Ljubljana study showed semaglutide actually improved sperm morphology by 17% - The same study showed TRT decreased sperm concentration by 61% - Fertility fully preserved throughout treatment
If you want kids — now or potentially in the future — this ends the debate. GLP-1s preserve and may improve fertility. TRT tanks it.
Weight and Body Composition
TRT is often marketed with the implication it helps with weight loss. The reality is more complicated.
TRT effects on weight: - May increase lean mass (muscle) - Does not typically reduce fat mass significantly - Some men gain weight on TRT - The ENDO comparison showed +1.3% weight gain in TRT group - Does not address underlying metabolic dysfunction
GLP-1 effects on weight: - Substantial fat loss (15-25% of body weight) - Some lean mass loss (mitigated by training/protein) - Dramatically reduces visceral fat specifically - Improves metabolic markers across the board - Addresses root cause of obesity-related low T
If your low testosterone is caused by obesity, TRT doesn't fix the obesity. You'll still be overweight with all the associated health risks — you'll just have artificially normal testosterone while being overweight.
GLP-1s address both problems simultaneously.
Cardiovascular Implications
Heart disease is the leading killer of men. Both treatments have cardiovascular implications.
TRT cardiovascular concerns: - FDA black box warning for cardiovascular risks - Some studies show increased heart attack/stroke risk - May increase hematocrit (thickened blood) - May worsen sleep apnea initially - Long-term cardiovascular data is mixed/concerning
GLP-1 cardiovascular benefits: - SELECT trial: 20% reduction in cardiovascular events - FDA-approved cardiovascular indication - Reduces blood pressure - Improves lipid profile - Treats sleep apnea (Zepbound approved for OSA) - Strong long-term outcome data
For men with cardiovascular risk factors — which includes most men with obesity — the GLP-1 cardiovascular profile is dramatically better.
Side Effect Comparison
TRT side effects: - Acne - Oily skin - Hair loss (if genetically prone) - Testicular atrophy - Gynecomastia (breast tissue growth) - Polycythemia (high red blood cells) — requires blood donation - Mood changes - Sleep apnea worsening - Prostate concerns (controversial but monitored)
GLP-1 side effects: - Nausea (common, usually temporary) - Vomiting - Diarrhea - Constipation - Injection site reactions - Gallbladder issues (rare) - Pancreatitis (rare)
GLP-1 side effects are mostly GI-related and typically fade with time. TRT side effects are hormonal and persistent for the duration of treatment.
Cost Comparison
TRT monthly costs: - Testosterone cypionate (generic injectable): $30-100 - Testosterone gels (AndroGel): $400-600 - Testosterone pellets: $500-1,000 (every 3-6 months) - Monitoring labs: $100-300 per quarter
GLP-1 monthly costs: - Wegovy Pill: $149-299 (promotional) - LillyDirect Zepbound: ~$550 - Wegovy injectable: $1,300+ (retail) - With good insurance: $25-100 copay
TRT is generally cheaper, especially with injectable testosterone. But the cost calculation changes when you factor in: - Long-term cardiovascular risks - Fertility preservation value - Metabolic benefits of weight loss - Reduced need for other medications (blood pressure, etc.)
Who Should Choose TRT
TRT remains the right choice for:
Primary hypogonadism: If your testes don't produce testosterone due to injury, genetic conditions, or other non-obesity causes, weight loss won't help. You need replacement.
Severe hypogonadism: Men with testosterone under 200 ng/dL may need faster intervention than GLP-1s can provide.
Already lean with low T: If you're not overweight and have low testosterone, the obesity-driven mechanism isn't your problem.
Post-fertility completion: Men who've definitively completed their families may be comfortable with the fertility tradeoff.
GLP-1 non-responders: Men who've tried GLP-1s, lost weight, and still have low testosterone despite weight loss.
Who Should Choose GLP-1
GLP-1s are likely better for:
Obesity with low T: If your low testosterone is caused by obesity (functional hypogonadism), treating the cause makes more sense than masking the symptom.
Men wanting children: Fertility preservation is non-negotiable for many men.
Cardiovascular risk: The SELECT trial cardiovascular benefits are substantial and unmatched by TRT.
Men who want natural function: Restoring your body's own production feels different than replacing it externally.
Multiple metabolic issues: GLP-1s improve blood pressure, cholesterol, blood sugar, sleep apnea — the whole metabolic package.
The Combination Question
Can you take both?
Some clinics offer GLP-1s + TRT together. The logic: get the weight loss benefits while maintaining testosterone during the loss phase, then potentially transition off TRT as natural production recovers.
There's no clinical trial data on this combination. Mechanistically, it could work, but it's unproven territory. And if you're on TRT, your natural production is suppressed — you won't see the testosterone restoration benefits of GLP-1s until you stop TRT.
An alternative: GLP-1s + HCG or enclomiphene. These maintain testicular function while you lose weight, without fully replacing testosterone. Some men use this as a bridge.
The Decision Framework
Start with GLP-1s if: - BMI ≥30 or BMI ≥27 with metabolic issues - You suspect your low T is obesity-related - Fertility is a consideration - You have cardiovascular risk factors - You prefer restoring natural function
Consider TRT if: - GLP-1s haven't normalized testosterone despite significant weight loss - You have primary hypogonadism (non-obesity cause) - Testosterone is severely low (<200 ng/dL) - You've completed your family - Time is critical (TRT works faster)
The 6-month test: Try GLP-1s for 6 months. Lose significant weight. Recheck testosterone. If it's normalized, you may not need TRT at all. If it's still low despite weight loss, TRT remains an option.
The Bottom Line
For men with obesity-related low testosterone, GLP-1s offer advantages TRT can't match: - Treats the cause, not just the symptom - Preserves and may improve fertility - Proven cardiovascular protection - Restores natural hormone production - Addresses multiple metabolic issues simultaneously
TRT has its place — but that place is narrower than the marketing suggests. Most men with obesity and low T would be better served by losing the weight first and seeing what their natural testosterone does.
The research supports GLP-1s as first-line treatment for functional hypogonadism. TRT can remain an option if GLP-1s aren't enough — but most men won't need it.
Related Articles: - 77% of Men Normalized Testosterone on GLP-1s — Without TRT - Can You Take GLP-1s and TRT Together? - Low T and Obesity: The Vicious Cycle GLP-1s Can Break
Last updated: January 2026
Medical disclaimer: This content is for informational purposes only and does not constitute medical advice. Consult an endocrinologist or urologist for personalized testosterone management.