{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T19:36:10Z","timestamp":1772825770261,"version":"3.50.1"},"reference-count":10,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T00:00:00Z","timestamp":1654560000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>EGFR-TKI is widely used for EGFR-mutant NSCLC patients. Bleeding is reported as a neglected adverse effect induced by EGFR-TKI. Female patients with lung adenocarcinoma have a high frequency of EGFR mutations. This study investigated the effect of EGFR-TKI on the menstrual cycle, especially on bleeding, in women of childbearing age. The underlying mechanism was further investigated in a patient with severe bleeding. We retrospectively investigated the effects on menstrual cycle in premenopausal female NSCLC patients who underwent EGFR-TKI treatment during 2013 to 2019. Menstrual changes including cycle disorders and prolonged bleeding were investigated <jats:italic>via<\/jats:italic> questionnaire survey. EGFR signaling, ER, PR and tissue factor expression were analyzed in endometrium tissue obtained from a 43-year-old patient who suffered from continuous vaginal bleeding during treatment with erlotinib and osimertinib. Among 42 premenopausal female patients taking EGFR tyrosine kinase inhibitor, 69.05% patients experienced abnormal menstruation. In women with abnormal menstruation, 41.37% had profuse menstruation and 20.69% had irregular menstruation. In most cases, the abnormal vaginal bleeding stopped when suspending EGFR-TKI. The EGFR-TKI induced abnormal vaginal bleeding might be associated with low progesterone level, decreased EGFR activation and tissue factor (TF) expression in endometrial tissues. EGFR-TKI unusually induce abnormal vaginal bleeding in premenopausal female NSCLC patients, which may be attributed to progesterone\/EGFR\/TF signaling. Megestrol acetate may be an available and effective drug for the uncommon adverse effect.<\/jats:p>","DOI":"10.3389\/fonc.2022.805538","type":"journal-article","created":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T11:43:03Z","timestamp":1654602183000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Continuous Vaginal Bleeding Induced By EGFR-TKI in Premenopausal Female Patients With EGFR Mutant 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