Semaglutide's direct reproductive effects

A September 2026 paper in Molecular Metabolism by Sotzen et al. asks a question that weight-loss trial coverage rarely surfaces: does semaglutide affect reproductive systems directly, or are those effects simply a side-product of losing weight^[1]? The team from the University of Calgary and Pennsylvania State University answered by running semaglutide-treated rats alongside calorie-restricted controls matched for the same degree of weight loss. Whatever differed between the two groups could not be explained by weight change alone.

The short version: GLP-1 receptors are present in the ovaries and testes, and semaglutide produces sex-specific effects at those sites that go beyond what comparable calorie restriction achieves. In males, most of those effects were favourable. In females, the picture was more complicated.

What the researchers actually measured

The Sotzen team compared three groups: semaglutide-treated rats, weight-matched calorie-restricted controls, and ad-libitum-fed controls^[1]. Because the calorie-restriction group was matched to produce the same body-weight reduction as the drug group, any difference in reproductive markers between those two groups reflects a drug action rather than a weight-loss effect. That design is the key methodological contribution of the paper.

GLP-1 receptor expression was confirmed in both ovarian and testicular tissue. Testicular expression was notably higher than ovarian expression, which the authors note may partly explain why the male and female findings diverged.

Males: broadly positive findings

In male rats, semaglutide improved sperm quality relative to the weight-matched calorie-restricted group^[1]. The drug also attenuated the androgen reductions that calorie restriction typically produces: across all androgens measured, semaglutide-treated males maintained higher levels than their calorie-restricted, weight-matched counterparts. Structural improvements in testicular tissue were also observed.

This finding carries a practical implication worth flagging. Weight loss by calorie restriction alone can suppress testosterone and impair sperm parameters in men with obesity. If semaglutide produces comparable weight reduction while partially protecting against those hormonal drops, that is a meaningful distinction for men considering weight-loss treatment who are also thinking about fertility or androgen levels.

Females: decreased reproductive hormones

The female picture was less straightforward. Semaglutide-treated female rats showed decreases in progesterone and estradiol relative to controls^[1]. These are not the same as the androgen reductions seen after calorie restriction in males; they appear to be a more direct drug-tissue interaction at the ovary level. Structural changes in ovarian tissue were observed alongside the hormonal shifts.

This sits alongside a separate 2026 real-world cohort study from Taiwan (Wu et al., published in Reproductive Biology and Endocrinology) that found semaglutide pretreatment in women with overweight and obesity seeking fertility care was associated with reduced pregnancy and live birth rates compared to matched controls^[2]. The two studies are not directly comparable: Wu et al. studied women undergoing fertility treatment, Sotzen et al. studied healthy female rats. But together they reinforce the case for caution about reproductive assumptions when prescribing to women of reproductive age.

What this is not

This is rodent research. Extrapolating rat reproductive endocrinology to human fertility or hormone levels requires care: rat and human reproductive cycles differ substantially in length, hormonal regulation, and ovarian physiology. The findings are mechanistic groundwork, not clinical guidance.

The study also does not assess fertility outcomes. Observing lower progesterone and estradiol in female rats is not the same as showing impaired ovulation, failed implantation, or reduced pregnancy rates in the same animals. Those downstream questions need their own studies.

And for men, the findings are not an endorsement to use semaglutide as a fertility treatment. The study was conducted in otherwise healthy animals, not in men with infertility or hypogonadism. The clinical relevance of sperm-quality improvements in non-infertile rats is limited.

Where this lands

The paper is one of a wave of studies pushing the same basic question outward from weight loss into organ-level biology. Earlier in 2026, a review in Pharmacological Research looked at what GLP-1 and GIP agonists do inside fat cells and reached a similar conclusion: the drugs are doing things beyond calorie restriction, the mechanistic picture in humans is incomplete, and that gap matters for long-term prescription decisions.

For clinicians and patients, the practical upshot is that reproductive-system effects of semaglutide are not fully captured by its weight-loss profile, and that those effects differ by sex. The current guidance from regulators in countries where semaglutide is approved is that the drug should be discontinued if a patient becomes pregnant. For broader context on how semaglutide is regulated across jurisdictions, including where it is prescription-only and what the approved indications cover, see the peptide page.

What we do not know yet

Several unanswered questions follow from this paper. Whether the androgen-protective effect in males holds in human men at clinical semaglutide doses is unknown. Whether the progesterone and estradiol reductions in female rats translate to measurable hormonal changes in women on Wegovy or Ozempic doses is uncharacterised. Whether structural gonadal changes observed in rats are reversible after the drug is discontinued has not been tested. And whether the magnitude of the GLP-1 receptor expression difference between testis and ovary explains the sex divergence, or whether other tissue factors are involved, remains an open research question.