To detect the adverse drug event (ADE) signals of fezolinetant and estradiol to provide references for rational drug use in treatment of vasomotor symptoms (VMS) in women during menopause.

The ADE signals of fezolinetant and estradiol from the FDA Adverse Event Reporting System (FAERS) database were mined from the third-party data platform OpenVigil 2.1. The reporting odds ratio (ROR) and proportional reporting ratio (PRR) methods were adopted to analyze and compare the risk signals of the two drugs.

A total of 72 255 adverse event reports (1 616 cases of fezolinetant and 70 639 cases of estradiol) were mined. After standardized screening, 344 cases of fezolinetant-related ADE were detected, and 33 positive signals were detected (menopausal symptoms, elevated liver function test values and postmenopausal bleeding, etc.), involving 11 system organ classification (SOC, all kinds of examinations, systemic diseases and various reactions at the administration site, and gastrointestinal system diseases, etc.). In 3 540 estradiol-associated ADE, 557 positive signals were detected (necrosis of uterine fibroids, testicular mixed germ cell tumors and pseudo-precocious puberty, etc.), covering 26 SOC classes (systemic diseases and various reactions at the administration site, product issues, and reproductive system and breast diseases, etc.). This study identified the following new potential risk signals: new ADE related to brain fog, dysarthria, oral discomfort and palpitations were discovered for fezolinetant; the SOC related to the estradiol group included benign, malignant and tumors of unknown nature, as well as those in the nervous, urinary and gastrointestinal systems.

The major adverse events of fezolinetant were associated with abnormal liver function indicators and gastrointestinal system diseases, while estradiol related ADE were associated with product use, reproductive system and breast diseases. The treatment of menopausal patients with vasomotor and other symptoms should be individualized and adverse drug reactions should be monitored.