GLP-1 vs TRT: The Head-to-Head Comparison for Men

------|-------------|-----| | Weight loss | 18%+ | Often weight gain | | Waist circumference | Superior reduction | Modest change | | Testosterone increase | Natural recovery | External replacement | | Erectile function | Improved | Improved | | Fertility preserved | Yes | No — suppresses sperm | | HPT axis function | Restored | Suppressed |

Dr. Cannarella's conclusion: tirzepatide is "a safer and more sustainable option" for obesity-related low testosterone.

Understanding the Two Approaches

TRT: External Replacement

Testosterone replacement therapy provides external testosterone — through injections, gels, patches, or pellets. Your testosterone levels rise because you're adding hormone from outside your body.

How it works: - Inject/apply testosterone - Blood testosterone rises immediately - Brain senses adequate testosterone - Brain stops signaling testes to produce testosterone - Natural production shuts down - Testes shrink (testicular atrophy) - Sperm production crashes

You're not fixing low testosterone. You're replacing your body's production with external supply. Stop TRT, and you're often worse off than before because your HPT axis has been suppressed.

GLP-1s: Natural Restoration

GLP-1 medications help you lose fat — particularly visceral fat around your organs. This fat contains aromatase enzymes that convert testosterone to estrogen.

How it works: - Take GLP-1 medication - Appetite decreases, weight drops - Visceral fat reduces - Aromatase activity decreases - Less testosterone converted to estrogen - Natural testosterone levels rise - HPT axis function improves - Testes continue normal function

You're fixing the underlying problem (excess fat) rather than masking the symptom (low T). Your body's testosterone production recovers naturally.

Weight Loss: GLP-1s Win Decisively

TRT doesn't help you lose weight. In fact, it often causes weight gain — partly fluid retention, partly increased appetite.

Tirzepatide: - SURMOUNT trials: 20-22% weight loss average - ENDO 2025 comparison: 18%+ weight loss vs TRT

Semaglutide: - STEP trials: 15-17% weight loss average

TRT: - No significant weight loss effect - May cause fluid retention - Doesn't address obesity at all

If you're a man with obesity AND low testosterone, TRT treats one problem while potentially making the other worse. GLP-1s address both simultaneously.

Testosterone Outcomes: Both Work, Different Mechanisms

Both approaches raise testosterone. The mechanisms are completely different.

TRT testosterone increase: - Immediate and predictable - Directly proportional to dose - Requires ongoing treatment - Natural production suppressed

GLP-1 testosterone increase: - Gradual (months, not days) - Proportional to fat loss - May become self-sustaining - Natural production restored

The ENDO 2025 data showed 53% → 77% testosterone normalization in obese men on GLP-1s over 18 months. That's comparable to TRT outcomes — but through restoration rather than replacement.

Fertility: The Dealbreaker

This is where the comparison becomes stark.

TRT and fertility: - Suppresses FSH and LH (hormones that drive sperm production) - Sperm count typically crashes within weeks - Many men become functionally infertile on TRT - Recovery after stopping is uncertain and slow (months to years) - Some men never fully recover sperm production

GLP-1s and fertility: - Do not suppress FSH/LH - Sperm production continues normally - Ljubljana study: 17% improvement in normal sperm morphology - No fertility concerns during treatment - No recovery period needed

For men who want children — now or potentially in the future — this distinction is critical. TRT is effectively contraception. GLP-1s preserve and may improve fertility.

Sexual Function: Comparable Results

Both approaches improve erectile function in men with obesity-related low T.

The mechanism differs:

TRT improves erections through: - Direct testosterone increase - Improved libido - Psychological confidence

GLP-1s improve erections through: - Weight loss improving vascular function - Natural testosterone restoration - Reduced inflammation - Improved metabolic health

The ENDO 2025 comparison found comparable erectile function improvement between tirzepatide and TRT groups. You don't sacrifice sexual function by choosing GLP-1s.

Long-Term Sustainability

TRT long-term: - Lifelong treatment required - Stopping causes testosterone crash - HPT axis may not fully recover - Ongoing monitoring needed - Potential cardiovascular concerns (debated) - Prostate monitoring required

GLP-1 long-term: - Weight loss can become self-maintaining for some - Testosterone improvement persists with maintained weight loss - If you stop and regain weight, testosterone may drop again - No HPT axis suppression to recover from - Cardiovascular protection (SELECT trial: 20% risk reduction)

Neither approach is truly "one and done." But GLP-1s work with your biology rather than overriding it. If you maintain weight loss, your testosterone benefits can persist even if you eventually taper medication.

Cost Comparison

TRT costs: - Generic testosterone cypionate: $30-50/month - Testosterone gels: $200-500/month - Monitoring labs: $100-300 every 3-6 months - Ongoing indefinitely

GLP-1 costs: - Brand-name injectable: $1,000-1,400/month retail - Wegovy Pill: $149-299/month with programs - LillyDirect Zepbound: ~$550/month - Potentially time-limited (though most stay on long-term)

TRT is cheaper. But TRT doesn't address the obesity that's causing the low testosterone. You're saving money on testosterone while remaining obese with all its health consequences.

Who Should Choose TRT

TRT remains appropriate for:

Primary hypogonadism: When testes can't produce testosterone due to injury, genetic conditions, or other causes unrelated to obesity. Losing weight won't fix this.

Severe symptomatic hypogonadism: When testosterone is extremely low (<200 ng/dL) and symptoms are debilitating. GLP-1s work over months; severe cases may need faster intervention.

Failed GLP-1 response: If significant weight loss doesn't normalize testosterone, TRT may be added.

Post-GLP-1 optimization: Some men use TRT after reaching goal weight if testosterone remains suboptimal despite fat loss.

Who Should Choose GLP-1s First

GLP-1s should be first-line for:

Functional hypogonadism: Low testosterone caused by obesity. This is the majority of "low T" cases in middle-aged men.

Men who want children: TRT destroys fertility. GLP-1s preserve it.

Men with cardiovascular risk: GLP-1s provide proven cardioprotection. TRT's cardiovascular effects remain debated.

Men with obesity AND low T: GLP-1s address both problems. TRT only addresses one.

Younger men: Starting TRT in your 30s means decades of external hormone dependence. GLP-1s offer a less permanent intervention.

The Combination Approach

Some men use both — though this requires careful management.

GLP-1 + TRT scenarios: - Start GLP-1, add low-dose TRT if testosterone doesn't normalize - Start TRT for severe symptoms, add GLP-1 for weight management - Use HCG alongside TRT to preserve fertility while adding GLP-1 for weight

GLP-1 + Enclomiphene: - Enclomiphene (a SERM) stimulates natural testosterone production - Preserves fertility (unlike TRT) - Some telehealth providers offer this combination - Less data than TRT but growing interest

If you're already on TRT and want to try GLP-1s, don't stop TRT abruptly. Work with your provider on a transition plan — potentially tapering TRT as weight loss improves natural testosterone.

The Decision Framework

Start with GLP-1 if: - Your low T is likely obesity-related (functional hypogonadism) - You're overweight or obese (BMI ≥27) - Fertility matters to you - You have cardiovascular concerns - You prefer not to be on lifelong hormone replacement

Consider TRT if: - Primary testicular failure (not obesity-related) - Severely low T with debilitating symptoms - GLP-1 + significant weight loss didn't normalize testosterone - You've completed your family and fertility isn't a concern - Cost is the primary driver

Consider both if: - Severe symptoms requiring fast intervention + obesity requiring treatment - GLP-1s working for weight but testosterone still suboptimal

The Bottom Line

For most men with obesity and low testosterone, GLP-1s should be the first-line approach. They address the root cause (excess fat), preserve fertility, provide cardiovascular protection, and restore natural hormone production.

TRT has its place — particularly for primary hypogonadism or severe cases. But the reflexive "low T = TRT" approach is outdated. The ENDO 2025 data confirms what the physiology predicted: fixing obesity often fixes testosterone.

GLP-1s aren't just weight loss drugs. For men with functional hypogonadism, they're hormone restoration therapy that happens to also help you lose weight.

Last updated: January 2026

Medical disclaimer: This content is for informational purposes only and does not constitute medical advice. Both TRT and GLP-1 medications require physician supervision.