GLP-1 drugs, menstrual changes: FAERS 2026

A pharmacovigilance study published on 9 July 2026 in Obstetrics and Gynecology found that semaglutide produced the broadest pattern of menstrual safety signals among three GLP-1 receptor agonists examined, while tirzepatide generated narrower signals and liraglutide produced none^[1]. The research, by Connor Frey and Mahyar Etminan, analysed FDA Adverse Event Reporting System (FAERS) data through March 2026 in female patients aged 12 to 55.

What the study found

Using disproportionality analysis and Bayesian statistical methods on FAERS reports, the authors identified signals for specific menstrual events associated with each drug. Semaglutide showed disproportionate reporting across five outcomes: heavy menstrual bleeding, intermenstrual bleeding, menstrual clots, oligomenorrhea (infrequent periods), and anovulatory cycles (cycles where ovulation does not occur). Tirzepatide generated signals for two outcomes: intermenstrual bleeding and menstrual clots. Liraglutide showed no significant signals for any of the menstrual outcomes examined^[1].

The authors concluded that the findings may support including menstrual health in clinical counselling for reproductive-aged patients starting these medications.

What FAERS data can and cannot tell you

FAERS is a voluntary reporting system. Healthcare providers, patients, and manufacturers submit adverse event reports, but reporting is inconsistent and selective. A disproportionality signal means that a particular adverse event appears more often in reports for a given drug than you would expect based on background reporting across all drugs in the database. It does not establish causation^[1]. Several biases can inflate or deflate signals: semaglutide is the most widely prescribed GLP-1 agonist and carries the highest media and patient awareness, which can drive higher voluntary reporting rates for any outcome.

A second FAERS-based analysis published in May 2026 in Diabetes, Metabolism Research and Reviews, by Lee and Kim, reached broadly similar conclusions: semaglutide showed elevated reporting odds for reproductive and hormonal disorders including polycystic ovary syndrome associations, while tirzepatide demonstrated lower reporting odds for several of those outcomes. The two studies were independent and used overlapping but not identical methodologies.

The weight-loss mechanism and menstrual cycles

GLP-1 receptor agonists produce significant weight loss, and weight loss itself is a well-established disruptor of the hypothalamic-pituitary-ovarian axis. Rapid caloric restriction or fat-mass reduction can alter sex hormone levels, luteinizing hormone pulsatility, and ovulation. Whether the menstrual changes reported in FAERS reflect the drug's direct pharmacology, the downstream effect of weight loss, or some combination of both is not resolved by this study^[2].

A separate body of literature examines GLP-1 receptor agonists in women with polycystic ovary syndrome (PCOS), where the drugs have shown some benefit. A 2026 meta-analysis by Lu and colleagues in Diabetes, Obesity and Metabolism, covering seven randomised controlled trials and 330 women with PCOS, found that liraglutide significantly increased menstrual frequency compared with control treatments alongside reductions in BMI and insulin resistance^[3]. That is the opposite direction from the FAERS signals for heavier or irregular bleeding on semaglutide, and it illustrates how context matters: women with PCOS often start with irregular or absent cycles, so regularisation looks like a benefit, while women with normal cycles who develop irregularities represent a different outcome.

Differential signals across the drug class

The Frey and Etminan paper adds weight to a pattern emerging in 2025 and 2026 pharmacovigilance literature: GLP-1 receptor agonists are not pharmacologically identical in their off-target effects even where they share a primary mechanism. Semaglutide is a GLP-1 monoagonist. Tirzepatide is a dual GIP and GLP-1 receptor agonist. Liraglutide is an older GLP-1 monoagonist with a shorter half-life and lower tissue exposure at currently used doses. The structural and pharmacokinetic differences plausibly explain differential signal patterns, but the mechanistic pathway linking any of these drugs to specific menstrual changes has not been characterised in human reproductive tissue studies^[4].

Reproductive safety beyond menstrual changes

A wider reproductive-safety concern is unintended pregnancy. A 2026 narrative review in the Journal of Clinical Medicine noted that GLP-1 receptor agonists may restore ovulatory function in women who had experienced anovulation, particularly those with obesity or PCOS, which could result in pregnancies in women not expecting to conceive. The same review flagged a possible reduction in oral contraceptive absorption during dose escalation, a concern also noted in the EU prescribing information for tirzepatide^[5]. The mechanism is the same gastric-emptying delay that underlies GI side effects: slower gastric transit may reduce peak concentrations of orally administered hormonal contraceptives.

A Danish nationwide cohort study published in Human Reproduction Open in March 2026, covering 756,636 singleton pregnancies, found that increased preterm birth risk was confined to women using GLP-1 receptor agonists for diabetes treatment, not for weight management^[6]. The authors interpreted that as evidence that underlying diabetes, rather than the drug itself, was the likely contributor to the preterm birth signal. Per-country regulatory status for semaglutide is on the drug's regulation pages.

What clinicians and patients should take from this

The Frey and Etminan study is a hypothesis-generating signal, not a definitive safety characterisation. Its clinical value is in prompting a conversation that has often been missing: reproductive-aged women starting semaglutide or tirzepatide for weight management or diabetes have rarely been counselled explicitly about potential menstrual changes, and they have sometimes been surprised by those changes in the absence of any prior warning.

The authors' recommendation that menstrual health be included in counselling for this patient group is consistent with 2026 guidance from a commentary in the Journal of Pediatric and Adolescent Gynecology, which similarly called for contraceptive counselling, menstrual monitoring, and discussion of reproductive goals when prescribing GLP-1 receptor agonists to adolescents^[7].

What is not yet known: the incidence rate in the clinical trial populations (FAERS gives signals, not frequencies); whether the signals persist at lower doses; whether dose de-escalation resolves the menstrual changes; and whether women who experience these changes go on to have any longer-term reproductive consequences. Those questions require prospective studies designed specifically to capture menstrual outcomes, which are typically not primary endpoints in obesity or diabetes trials.

If you are a reproductive-aged person taking semaglutide, tirzepatide, or liraglutide and have noticed changes in your menstrual cycle, that is a conversation for a clinician who knows your full history. This article is educational and does not constitute medical advice. The tirzepatide and semaglutide pages on this site cover the broader trial evidence, safety profiles, and regulatory status for each drug.