Hormone replacement therapy in gynecologic cancer: oncologic safety and alternative therapies

Recent advances in surgery and new therapies have greatly improved outcomes for gynecologic cancers, leading to more long-term survivors and a stronger focus on quality of life. Treatments such as surgery, radiation, and chemotherapy often cause iatrogenic menopause, leading to reduced quality of life and long-term health consequences. Hormone replacement therapy is the most effective option for managing menopausal symptoms. However, its use in patients with gynecologic cancer remains controversial because of concerns regarding oncologic safety. We conducted a comprehensive literature review evaluating the safety of hormone replacement therapy in survivors of endometrial, ovarian, cervical, vulvar, and vaginal cancers and uterine sarcomas, as well as in patients with hereditary cancer syndromes. Systemic hormone replacement therapy is safe in women with low-risk, early-stage endometrial cancer, most ovarian cancer sub-types, cervical cancer regardless of histology, and vulvar or vaginal cancers. However, contra-indications exist in specific scenarios such as advanced or non-endometrioid endometrial cancer, uterine sarcomas, and certain ovarian cancer sub-types (granulosa-cell tumors). In these cases, both non-systemic hormonal and non-hormonal alternatives have shown efficacy in managing menopausal symptoms. Hormonal therapies for genitourinary syndrome of menopause, including vaginal estrogens, ospemifene, and vaginal dehydroepiandrosterone, have demonstrated efficacy in relieving symptoms and improving urogenital health. Non-hormonal approaches, such as vaginal moisturizers, lubricants, and vaginal laser therapy, can also provide symptom relief. Non-hormonal therapies proven effective for managing vasomotor symptoms and sleep disturbances include cognitive behavioral therapy, clinical hypnosis, gabapentin, fezolinetant, and selective serotonin or serotonin-norepinephrine re-uptake inhibitors. Personalized treatment decisions should be guided by cancer type, recurrence risk, patient preferences, and quality-of-life considerations. It is essential to balance oncologic safety with symptom relief and long-term health outcomes in this growing population of cancer survivors.