Tamoxifen, clomiphene, and letrozole are primary pharmacological options for inducing ovulation in polycystic ovary syndrome (PCOS). Given the high clinical prevalence of PCOS, a comprehensive characterization of the adverse drug event (ADE) profiles associated with these treatments is essential.
Methods
We performed disproportionality analyses using FAERS data to detect ADE signals at the Preferred Term (PT) and System Organ Class (SOC) levels via four established algorithms (ROR, PRR, BCPNN, and EBGM). A drug-ADE network was constructed to visualize these associations.
Results
Of 21,730 identified PCOS-related reports, letrozole predominated (n=17,185), followed by tamoxifen (n=4465) and clomiphene (n=80). Most cases involved women aged 18-65 years (weight: 50-100 kg), primarily from the United States. Letrozole-related reports increased steadily, peaking at 2323 cases in 2021, while tamoxifen and clomiphene counts remained comparatively low. At the PT level, fatigue was a common signal for both tamoxifen and letrozole. Notably, malignant tumor progression, fatigue, and arthralgia emerged as shared signals across all three agents. At the SOC level, ADEs for tamoxifen and letrozole were frequently categorized under neoplasms; letrozole was specifically linked to hematological disorders (e.g, neutropenia). In contrast, clomiphene exhibited stronger associations with psychiatric and gastrointestinal events.
Conclusion
Distinct safety signals characterize these three primary PCOS treatments. These pharmacological variations underscore the necessity of personalized medicine; treatment selection must be tailored to the patient's specific risk profile, with targeted clinical monitoring for relevant ADEs to optimize therapeutic outcomes.
PMID 42524428 42524428 DOI 10.2147/IJWH.S586660 10.2147/IJWH.S586660 Zhang et al. 2026, Zhang 2026
Keywords
adverse events, clomiphene, food and drug administration adverse event reporting system, letrozole, polycystic ovary syndrome, tamoxifen
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