Postmenopausal bleeding associated with semaglutide: a diagnostic challenge

Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, is widely used for obesity and type 2 diabetes management, but its gynecological adverse effects have not been systematically described. We report a 58-year-old postmenopausal woman with new-onset vaginal bleeding six weeks after starting semaglutide for weight reduction, with onset following dose escalation to 0.5 mg weekly. Hemoglobin fell from 12.9 g/dL (Système International [SI]: 129 g/L) to 10.8 g/dL (SI: 108 g/L) (reference range, 12.0-16.0 g/dL [SI: 120-160 g/L]). The serum follicle-stimulating hormone (FSH) concentration was elevated at 68.4 mIU/mL (SI: 68.4 IU/L; reference, >25 IU/L postmenopausal), and estradiol was suppressed at 3.5 pg/mL (SI: 13 pmol/L; reference, <5.4 pg/mL [SI: <20 pmol/L]), consistent with stable postmenopausal status throughout, without hormonal reactivation (no return toward a premenopausal pattern). Endometrial malignancy, structural pathology, and coagulopathy were excluded. The Naranjo Adverse Drug Reaction Probability Scale score was 6 ("probable"). Bleeding resolved completely within five weeks of discontinuation. We propose that rapid semaglutide-induced adipose loss may transiently alter peripheral estrogen metabolism, destabilizing the endometrium despite unchanged hormone levels. This case highlights postmenopausal bleeding as a rare but clinically important adverse effect of GLP-1 receptor agonist therapy warranting malignancy-first evaluation.