Ozempic and TRT Together: What the Research Actually Shows

Search for how GLP-1 medications and testosterone therapy relate to each other and you get nine results: seven clinic and telehealth pages, a Reddit thread and a YouTube video. Not one peer-reviewed source on the first page.

The underlying literature is thinner than any of those pages suggest — but it is not empty, and one part of it is unusually clear.

A note on names before anything else. Almost none of the research here is a study of Ozempic specifically. The direct trials used semaglutide, liraglutide or tirzepatide, and the testosterone regimens differ between studies too — an injection in one, a transdermal gel in another. "Ozempic and TRT" is how people search it; it is not what was measured.

The Short Answer

Direct evidence on combining a GLP-1 medication with testosterone therapy is extremely limited. One 2026 pilot study included ten men in total, and a 2026 review states plainly that "no randomized trials have directly evaluated the combined effects of GLP-1 RAs and TRT," concluding that the available evidence "does not support routine combined therapy."

Two small head-to-head trials suggest the two approaches affect weight, testosterone, pituitary hormones, semen parameters and sexual symptoms differently — highlighting different strengths rather than identifying a winner.

Exogenous testosterone clearly suppresses sperm production. That is on the FDA label and in two society guidelines. The GLP-1 studies have not shown the same hormonal suppression.

Neither the AUA nor the EAU guideline, in the versions reviewed for this article, gives any recommendation on GLP-1 medications in this context.

The Difference That Is Genuinely Well Established

This is the sharpest distinction between the two, and it is documented in FDA labelling and in two society guidelines.

Exogenous testosterone suppresses sperm production

Testosterone taken from outside the body signals the brain to stop instructing the testicles to make their own. The pituitary hormones LH and FSH fall, intratesticular testosterone falls with them, and sperm production is impaired.

The AUA guideline quantifies it: 200 mg of testosterone enanthate weekly has been shown to decrease intratesticular testosterone levels by 94% within three weeks of starting.

The FDA label for AndroGel states that "with large doses of exogenous androgens… spermatogenesis may be suppressed through feedback inhibition of pituitary FSH possibly leading to adverse effects on semen parameters including sperm count," and that "testis disorder, testicular atrophy, and oligospermia have been identified during use." It adds a sentence worth reading twice: "With either type of use, the impact on fertility may be irreversible."

The guidance follows from that. The AUA's Statement 23 is a Strong Recommendation at Grade A: "Exogenous testosterone therapy should not be prescribed to men who are currently trying to conceive." Statement 16, also Strong and Grade A, says the long-term impact on sperm production should be discussed with any man interested in future fertility. The EAU states it as a Strong recommendation too: do not use testosterone therapy "for the treatment of male infertility and in males wishing to be fathers."

What is known about recovery — and what is not

Sperm production usually returns after stopping, and the best data come from an integrated analysis of 30 male hormonal contraception studies published in The Lancet, covering 1,549 men. Median time for sperm to recover to 20 million per mL was 3.4 months (95% CI 3.2–3.5), with recovery in 67% of men by six months, 90% by twelve, and effectively all by twenty-four.

That reassuring figure comes with a condition that matters enormously. Those were healthy men with normal testosterone and normal semen parameters, enrolled as contraceptive volunteers. The AUA says so directly: given that reproductive profile, "the spermatogenesis results might not be generalizable to patients with testosterone deficiency." It goes further — "there are no high-quality reports detailing the recovery of spermatogenesis for either testosterone deficient or infertile males who have used exogenous testosterone," and some infertile men "may never recover."

So three things are true at once: recovery is usual, its timing is variable, and neither the trial population nor the label supports promising it to a man with hypogonadism or existing fertility problems.

A Cochrane review of 33 trials found that the proportion of men reaching azoospermia "varied widely" and declined to pool the results, so no single percentage figure for that is defensible.

Where GLP-1 medications differ

A 2026 systematic review in the Journal of Sexual Medicine covering ten studies and 639 men found that total testosterone rose during GLP-1 treatment while LH and FSH were preserved or increased.

That hormonal pattern differs from exogenous testosterone therapy, which suppresses pituitary gonadotropins through negative feedback.

A hormone pattern is not a fertility outcome, and the distinction matters. The GLP-1 studies have not shown the gonadotropin suppression characteristic of exogenous testosterone, and one small randomised trial reported improved sperm morphology — but the same 2026 review describes the semen-parameter evidence as limited and heterogeneous. Nothing here establishes GLP-1 medications as fertility-preserving treatments.

The Two Head-to-Head Trials

Both are small, both are open-label, and both come from the same Slovenian research group. Neither is practice-changing. Together they are the only direct comparison that exists.

Semaglutide versus testosterone undecanoate

A 2025 randomised open-label trial in Diabetes, Obesity and Metabolism assigned 25 men with type 2 diabetes, obesity and functional hypogonadism to semaglutide 1 mg weekly or intramuscular testosterone undecanoate 1000 mg every 10–12 weeks, for 24 weeks.

• Semaglutide group: morphologically normal sperm rose from 2% to 4% (p = 0.012)
• Testosterone group: sperm concentration and total sperm number decreased significantly
• Both groups: total testosterone rose, and hypogonadism symptom scores improved
• Erectile function on the IIEF-15: improved only in the testosterone group

That last line is the one a page selling either intervention would be tempted to leave out. Twenty-five men, open-label, 24 weeks — this is hypothesis-generating in both directions.

Liraglutide versus testosterone gel

A 2019 prospective randomised open-label study in Endocrine Connections assigned 30 obese men who had responded poorly to lifestyle measures to liraglutide 3.0 mg daily or 50 mg of 1% transdermal testosterone gel daily, for 16 weeks.

• Total testosterone: rose in both, but more than twice as much on testosterone — +5.9 ± 7.2 nmol/L against +2.6 ± 3.5 nmol/L
• LH and FSH: rose significantly on liraglutide (p < 0.001 for the between-treatment effect)
• Weight: 7.9 ± 3.8 kg lost on liraglutide against 0.9 ± 4.5 kg on testosterone

And sexual symptoms improved in both arms, which is easy to miss and important to report. Self-rated libido rose from 1.0 to 2.2 on testosterone (p = 0.003) and from 1.1 to 1.8 on liraglutide (p = 0.003). Weekly morning erections rose in both, as did weekly ejaculations. None of the three between-arm comparisons was statistically significant — p = 0.762 for libido, 0.550 for morning erections, 0.204 for ejaculations.

Two caveats belong with those numbers, and the authors supply the first themselves. The sexual measures were ad hoc self-reports — libido scored 1 to 3, and participants counting their own erections and ejaculations — in an unblinded trial. The paper's limitations section states: "Libido and sexual function were not measured with validated tools, and therefore could be inaccurate."

Second, the Aging Males' Symptoms scale — a validated questionnaire covering sexual, psychological and somatic symptoms — was reported as a total score only, and it improved significantly on testosterone (p = 0.002) but not on liraglutide (p = 0.157). The between-group difference was not significant either.

The authors' own reading of the liraglutide result is worth quoting, because it proposes a mechanism nobody markets: sexual symptoms improved "despite only a modest rise of total testosterone," and they hypothesised that "psychosocial factors related to improved body image due to significant weight reduction" might be involved.

What the two trials together show

They do not produce a single verdict, and they did not measure sexual function the same way.

In the 2019 liraglutide study, sexual symptoms improved in both arms on non-validated self-report, with no significant difference between them. In the 2025 semaglutide study, using the validated IIEF-15, the improvement appeared only in the testosterone arm.

What is consistent across both: testosterone therapy raises testosterone more; the GLP-1 raises the pituitary hormones and removes considerably more weight. They are not doing the same job.

Has Anyone Studied Taking Both?

Almost not at all — and this is the honest centre of the article.

A 2026 pilot study followed ten men with obesity and functional hypogonadism who had lost less than 5% of their weight after at least three months on tirzepatide. Five continued tirzepatide alone; five added testosterone undecanoate. Over six months the combination group showed greater weight and fat-mass reduction, higher lean body mass, lower insulin resistance and a higher IIEF-5 score.

Five men per arm. The published description does not say the allocation was randomised. The participants were a highly selected subgroup — people for whom tirzepatide had already underperformed. There was no fertility endpoint. And the authors report that physical activity nearly doubled in the combination arm, which they themselves cite as contributing to the outcomes — an uncontrolled difference in an unblinded ten-man study.

The authors' own language is appropriately tentative: their findings "suggest" the approach "may" optimise weight-loss quality.

That is the only direct published combination study we could identify. A 2026 review of the question puts it plainly: "no randomized trials have directly evaluated the combined effects of GLP-1 RAs and TRT… The available evidence suggests a biologically plausible interaction but does not support routine combined therapy."

A search of the published literature returns fewer than thirty records on the combination in men at all, most of them concerning polycystic ovary syndrome or animal work.

Both Guidelines Emphasise Lifestyle — But Not in the Same Way

Two things are worth reporting here, and the second is a genuine absence.

The EAU is firmer than the AUA

The EAU makes it a Strong recommendation: "improve lifestyle and reduce weight (e.g. obesity); withdraw, when possible, concomitant drugs that can impair testosterone production; treat comorbidities, before starting testosterone therapy." Its reasoning is that in obesity-associated hypogonadism the suppression is functional and potentially reversible, so "weight loss and lifestyle changes should be the first approach for all men with hypogonadism that are overweight or obese." It notes that the testosterone increase from diet and exercise is small, at 1 to 2 nmol/L, and that most weight lost is regained within three to five years.

The AUA does not set the same hierarchy. Its lifestyle statement is a Conditional Recommendation at Grade B — all men with testosterone deficiency should be counselled on lifestyle modification — with the caveat that "improvements in total testosterone levels might not be clinically meaningful." It suggests reassessment before starting therapy in mild deficiency specifically, and elsewhere endorses weight-loss programmes "concurrent with testosterone therapy" rather than instead of it.

The EAU separately advises, as a Weak recommendation, against using testosterone therapy "to reduce weight and enhance cardio-metabolic status."

Neither guideline addresses GLP-1 medications

We searched the full text of both the AUA testosterone deficiency guideline and the EAU male hypogonadism chapter for every relevant term — GLP-1, semaglutide, liraglutide, tirzepatide, incretin — and found no matches in either.

Stated carefully: in the current versions reviewed for this article, neither guideline provides recommendations on GLP-1 receptor agonists in this context. Guidelines are revised, so that may change. What it means today is that no professional body has issued guidance on this question, and anyone presenting a confident answer is going beyond what any guideline supports.

Cardiovascular Safety, Reported Narrowly

A reader comparing two long-term interventions will ask about cardiovascular risk, and one large trial answers half the question.

TRAVERSE, published in the New England Journal of Medicine in 2023, randomised 5,246 men aged 45–80 with hypogonadism and either existing cardiovascular disease or high risk of it, to daily transdermal testosterone gel or placebo. A primary cardiovascular event occurred in 7.0% on testosterone against 7.3% on placebo — hazard ratio 0.96 (95% CI 0.78–1.17).

TRAVERSE found testosterone therapy noninferior to placebo for major adverse cardiovascular events in the population studied. Noninferiority is a specific and limited claim: it is not evidence of cardiovascular benefit, and it applies to men resembling those enrolled.

The investigators also observed a higher incidence of atrial fibrillation, acute kidney injury and pulmonary embolism in the testosterone group. The trial was funded by the manufacturer of the gel studied, and several company employees are among its authors.

We have deliberately not set that against a corresponding figure for GLP-1 medications. Comparing cardiovascular outcomes across two drug classes requires the relevant trials to be read directly, and that comparison is outside what this article has verified.

What None of This Can Tell an Individual

Low testosterone has causes that have nothing to do with body weight, and a single low reading is not a diagnosis. The AUA requires two total testosterone measurements taken on separate occasions, both in the early morning, together with symptoms or signs, before the diagnosis is made — a Strong Recommendation at Grade A.

Whether either intervention is appropriate for a particular man, whether fertility is a consideration now or later, and whether anything should be combined are clinical judgements that depend on facts no article has access to. Related reading: Does Losing Weight Increase Testosterone? What the Meta-Analyses Show, Does Ozempic Cause Erectile Dysfunction? and Low Libido in Men: Causes, Testosterone and Treatment Options.

Decisions about starting, stopping, continuing or combining any prescribed medication belong to the clinician who prescribed it. Nothing in this article is a reason to change how a medication is taken, and this article does not describe a protocol, a sequence or a combination for anyone to follow.

Frequently Asked Questions

Can you take Ozempic and TRT at the same time?

That question has almost no direct evidence behind it. The only published study of the combination we could identify is a 2026 pilot with ten men, five per arm, in a selected group for whom tirzepatide had already underperformed, with no fertility endpoint and a large uncontrolled difference in physical activity between arms. A 2026 review states that no randomised trials have evaluated the two together and that current evidence "does not support routine combined therapy." Neither the AUA nor the EAU guideline addresses GLP-1 medications in this context. This is a decision for a prescribing clinician, not one this literature can answer.

Can GLP-1 medications replace TRT?

No evidence supports treating them as interchangeable. They are used for different indications — GLP-1 medications for metabolic and weight-management purposes, testosterone therapy for appropriately diagnosed testosterone deficiency — and the small comparative trials show different effects on weight, pituitary hormones, semen parameters and testosterone concentrations. Whether addressing weight first changes whether testosterone therapy is needed is a clinical question, and the EAU guideline does recommend lifestyle and weight measures before starting testosterone in obesity-associated hypogonadism.

Can TRT prevent muscle loss on a GLP-1 medication?

Biologically plausible, not established. Testosterone can increase lean mass in men with confirmed hypogonadism, and weight loss on GLP-1 medications can include some loss of fat-free mass. But no randomised trial has shown that testosterone therapy specifically prevents GLP-1-related lean-mass loss. The 2026 ten-man pilot reported better lean-mass outcomes with tirzepatide plus testosterone — five men per arm, unblinded, with physical activity nearly doubling in that group, which is far too small and too confounded to establish the effect.

Does Ozempic raise testosterone like TRT does?

Not to the same degree. Systematic reviews generally report increases in total testosterone during GLP-1 therapy in men with obesity or metabolic dysfunction. But in the only randomised comparison reporting both, testosterone therapy raised total testosterone by 5.9 ± 7.2 nmol/L against 2.6 ± 3.5 nmol/L on liraglutide — more than twice as much.

Does TRT affect fertility?

Yes, and this is the best-established fact in this area. Exogenous testosterone suppresses LH and FSH and reduces intratesticular testosterone — by 94% within three weeks at 200 mg of testosterone enanthate weekly, according to the AUA — which impairs sperm production. The AUA states as a Strong, Grade A recommendation that testosterone therapy should not be prescribed to men currently trying to conceive, and the FDA label for AndroGel warns that the impact on fertility may be irreversible.

Is TRT-related infertility reversible?

Usually, but the reassuring numbers come from the wrong population. An analysis of 1,549 healthy men in contraceptive studies found a median 3.4 months to sperm recovery and 90% recovering within a year. The AUA states explicitly that those results may not generalise to men with testosterone deficiency, that there are no high-quality reports on recovery in that group, and that some infertile men may never recover. Timing is also variable between individuals.

Do GLP-1 medications affect sperm?

The evidence is limited. In the one randomised comparison measuring it, the semaglutide group's proportion of morphologically normal sperm rose from 2% to 4% (p = 0.012) over 24 weeks in 25 men, while sperm concentration and total number decreased in the testosterone group. A 2026 systematic review describes the semen-parameter evidence across this literature as limited and heterogeneous. This is not a basis for treating a GLP-1 as a fertility treatment.

Which is better for erections?

There is not enough direct evidence to declare one superior, and the two trials disagree. In the 2025 semaglutide-versus-testosterone trial, IIEF-15 scores improved only in the testosterone group. In the earlier liraglutide-versus-testosterone trial, self-reported sexual symptoms improved in both groups with no significant difference between them — though those measures were not validated instruments, as the authors note. Both studies were small and open-label.

Should I lose weight before starting testosterone therapy?

The two guidelines differ in emphasis. The EAU makes it a Strong recommendation to improve lifestyle and reduce weight before starting testosterone therapy, because obesity-associated suppression may be reversible. The AUA is more conditional, advising counselling and reassessment in mild deficiency, noting that testosterone improvements from lifestyle change might not be clinically meaningful, and elsewhere endorsing weight-loss programmes alongside testosterone therapy rather than before it.

Is testosterone therapy safe for the heart?

The largest trial found it noninferior to placebo for major adverse cardiovascular events. TRAVERSE randomised 5,246 men with cardiovascular disease or high risk of it and found events in 7.0% on testosterone against 7.3% on placebo, hazard ratio 0.96 (95% CI 0.78–1.17). Noninferiority is not evidence of benefit, and the investigators observed more atrial fibrillation, acute kidney injury and pulmonary embolism in the testosterone group.

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References

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2. Jensterle M, Podbregar A, Goricar K, Gregoric N, Janez A. Effects of liraglutide on obesity-associated functional hypogonadism in men. Endocrine Connections. 2019;8(3):195–202. PMID 30707677.
3. Deameh MG, Ramez M, Rowaiee R, et al. Effects of GLP-1 receptor agonists on male reproductive hormones, semen parameters, and metabolic outcomes: a systematic review. Journal of Sexual Medicine. 2026;23(2):qdaf381. PMID 41498523.
4. Seminara G, Leuzzi M, Meduri L, Greco EA, Aversa A. Effects of testosterone undecanoate as add-on therapy in obese hypogonadal men that are late responders to tirzepatide: a pilot study. Minerva Endocrinology. 2026;51(2):104–117. PMID 41801155.
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6. EAU Guidelines on Sexual and Reproductive Health: Male Hypogonadism. European Association of Urology.
7. Liu PY, Swerdloff RS, Christenson PD, Handelsman DJ, Wang C. Rate, extent, and modifiers of spermatogenic recovery after hormonal male contraception: an integrated analysis. The Lancet. 2006;367(9520):1412–1420. PMID 16650651.
8. Lincoff AM, Bhasin S, Flevaris P, et al. Cardiovascular Safety of Testosterone-Replacement Therapy. New England Journal of Medicine. 2023;389(2):107–117. PMID 37326322.
9. AndroGel 1.62% (testosterone gel) — U.S. Prescribing Information. DailyMed, U.S. National Library of Medicine. Sections 5.8 and 8.3.
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This article is provided for general educational purposes only and is not a substitute for individualized medical advice, diagnosis or treatment. It reports published research and does not recommend starting, stopping, continuing or combining any medication, and does not describe any dosing protocol. The comparative trials described are small and open-label, and the combination of these treatments has not been evaluated in a randomised trial. Questions about a prescribed medication should be discussed with the clinician who prescribed it. AmalfiDuo Journal articles are written by AmalfiDuo Editorial and are not medically reviewed — see our Editorial Policy.

Ozempic® and Wegovy® are trademarks of Novo Nordisk A/S. AndroGel® is a trademark of AbbVie Inc. AmalfiDuo is not affiliated with or endorsed by the owners or manufacturers of these brands.