GLP-1 Drugs, Testosterone and Male Fertility: Where the Evidence Splits

Almost everything written about these drugs and reproduction is about women. The men’s evidence is thinner and it contains one genuinely surprising result: in a randomized comparison, semaglutide improved sperm morphology while testosterone replacement therapy significantly reduced sperm concentration and total count — even though both raised total testosterone.^[1] If you are on TRT and hoping to father a child, that is worth knowing. The erectile function evidence is messier, and points both ways.

Why weight matters here at all

Excess body fat lowers testosterone through a fairly well-understood route: fat tissue converts testosterone to estradiol, and the resulting signal suppresses the hormonal axis that tells the testes to produce more. The clinical name for the result is functional hypogonadism — low testosterone with no disease of the testes themselves.

The word doing the work is functional. It means the machinery is intact and the signal is being suppressed, which in turn means losing weight can reverse it. That is the mechanism through which any effective weight-loss drug could raise testosterone without acting on the hormone directly.

The trial that compared the two options

A randomized open-label trial put semaglutide against testosterone replacement therapy in 25 men with type 2 diabetes, obesity and functional hypogonadism — men who, in ordinary practice, would be offered TRT.^[1] Baseline sperm quality across the group was poor, below the fifth percentile of reference values.

Both treatments did the thing they were prescribed for. Only one of them did it without cost to fertility.

Erectile function: the evidence disagrees

Here the picture splits, and the honest thing is to show both halves.

• Against these drugs: a TriNetX database study of non-diabetic obese men aged 18 to 50 prescribed semaglutide for weight loss found an increased risk of a subsequent erectile dysfunction diagnosis, in men with no prior ED history.^[2] The authors note sexual dysfunction already appears in package inserts, and that nobody had quantified it.
• For them: a second TriNetX study in men with type 2 diabetes found tirzepatide associated with reduced ED risk against every comparator — risk ratio 0.70 against sitagliptin and 0.67 against injectable semaglutide.^[3]

Those are less contradictory than they first appear. Both studies place semaglutide worse than whatever it is compared with — the second finds tirzepatide better than semaglutide specifically. So a defensible reading is that the drugs may differ from one another, rather than that the class is uniformly good or bad.

A defensible reading is not a finding. Both are retrospective analyses of the same commercial database, in different populations, and neither randomized anything. Erectile dysfunction is also diagnosed when someone raises it, which makes it unusually sensitive to how often a man is seeing a doctor — and starting a new weight-loss drug means seeing one more often.

A diagnosis rate measures consultations as well as disease.

What the systematic review concludes

A 2026 systematic review in the Journal of Sexual Medicine gathered the randomized trials and cohort studies of GLP-1 drugs on male reproductive hormones, semen parameters and metabolic outcomes across liraglutide, semaglutide, dulaglutide and exenatide.^[4] Its summary is that emerging evidence suggests these drugs may improve male reproductive parameters, particularly in men with metabolic dysfunction.

“May” and “emerging” are the operative words, and they are the reviewers’ own. This is a field with a handful of small studies, not a settled answer.

What to take from it

• If low testosterone is the problem and weight is a driver, ask whether treating the weight is an alternative to treating the hormone, rather than assuming TRT is the only route.
• If fertility matters to you now or later, raise it before starting testosterone replacement. The fertility cost of TRT is well established and is not a reason to avoid it, only a reason to plan around it.
• If sexual function changes after starting a GLP-1, report it. The evidence is genuinely unsettled, which makes your prescriber’s judgment more important, not less.
• Do not read a 25-man trial as a treatment plan. It is a reason for a conversation and for larger studies.

For the corresponding questions on the other side, our preconception timing article covers the interval before a planned pregnancy, and the PCOS piece deals with the female fertility evidence.