Menstrual Clots and Heavy Bleeding Linked to Popular Weight-Loss Drugs

 GLP-1 receptor agonists (RAs), particularly semaglutide, are associated with disproportionate reporting of menstrual adverse events including heavy bleeding, intermenstrual bleeding, and menstrual clots in reproductive-aged female patients. Tirzepatide showed signals for intermenstrual bleeding and menstrual clots.

METHODOLOGY

• Researchers performed a disproportionality and Bayesian analysis using the FDA Adverse Event Reporting System (FAERS) database, collecting reports from database inception through March 2026, totaling 14,104,743 reports.
• Analysis was restricted to female patients aged 12-55 years, with total drug-associated reports numbering 4024 for liraglutide, 27,469 for tirzepatide, and 6060 for semaglutide.
• Investigators queried menstrual adverse events using Medical Dictionary for Regulatory Activities terminology, comparing GLP-1 RAs (semaglutide, liraglutide, and tirzepatide) against all other drugs in the FAERS database as the reference group.
• Two complementary statistical approaches were used: frequentist analysis calculating reporting odds ratio (ROR) with signals defined as the lower bound of the 95% CI for ROR exceeding 1, and Bayesian analysis generating a posterior ROR distribution with 95% credible intervals using 50,000 simulated samples.
• The study was conducted by researchers from the Department of Medicine at the University of British Columbia and Epilytics using publicly accessible pharmacovigilance data from physicians, patients, caregivers, and manufacturers.

TAKEAWAY

• Semaglutide showed signals for heavy menstrual bleeding (ROR, 3.51; 95% CI, 2.42-5.10; information component lower bound [ICo95], 1.25), intermenstrual bleeding (ROR, 2.91; 95% CI, 1.51-5.61; ICo95, 0.53), and menstrual clots (ROR, 31.63; 95% CI, 12.62-79.28; ICo95, 3.54).
• Tirzepatide generated signals for intermenstrual bleeding (ROR, 1.64; 95% CI, 1.09-2.48; ICo95, 0.09) and menstrual clots (ROR, 5.41; 95% CI, 1.96-14.96; ICo95, 0.82), while liraglutide produced no significant menstrual signals in the age-restricted cohort.
• Semaglutide also produced signals for oligomenorrhea (ROR, 3.09; 95% CI, 1.54-6.20; ICo95, 0.56), anovulatory cycle (ROR, 8.96; 95% CI, 2.20-36.51; ICo95, 0.87), and menstrual disorder (ROR, 2.54; 95% CI, 1.65-3.90; ICo95, 0.69).
• Amenorrhea, irregular menstruation, dysmenorrhea, and polymenorrhea showed no positive associations (ROR < 1 or ICo25 markedly below zero) for all three agents, with Bayesian analyses corroborating all frequentist findings.

IN PRACTICE

“The mechanistic basis for these findings is likely multifactorial and includes direct GLP-1 RA in endometrial tissue, weight-loss-driven alterations in estrogen metabolism, and downstream effects on coagulation pathways,” the authors of the study wrote.

SOURCE

The study was led by Connor Frey, MD, and Mahyar Etminan, PharmD, MSc, Department of Medicine, University of British Columbia and Epilytics, Vancouver, British Columbia, Canada. It was published online in Obstetrics & Gynecology.

LIMITATIONS

According to the authors, confounding by indication cannot be excluded because obesity independently affects menstrual regularity. FAERS data are subject to underreporting, variable report quality, and notoriety bias, which may affect the reliability of the findings. Some events had very low counts that resulted in unstable estimates, potentially limiting the precision of the statistical analyses. The researchers noted that these findings are based on pharmacovigilance data and cannot establish causality, requiring prospective epidemiologic studies to determine true incidence and risk.

DISCLOSURES

The authors reported no relevant conflicts of interest or potential conflicts of interest related to this study. No funding sources or research grants were disclosed in the study.

https://www.medscape.com/viewarticle/menstrual-clots-and-heavy-bleeding-linked-popular-weight-2026a1000nmn