Hormone replacement therapy in gynecologic cancer survivors: bridging the gap between evidence and clinical practice

Advances in gynecologic oncology have substantially improved survival, resulting in a rapidly growing population of long-term survivors. However, surgery, chemotherapy, and radiotherapy frequently induce iatrogenic menopause or exacerbate pre-existing menopausal symptoms, leading to impaired quality of life and increased long-term risks, including osteoporosis, cardiovascular disease, and sexual dysfunction. Despite increasing evidence supporting the oncologic safety of hormone replacement therapy in selected patients, its use remains inconsistent because of uncertainty regarding patient selection, timing, and safety. This review summarizes current evidence and international guideline recommendations to provide a practical framework for menopause management in gynecologic cancer survivors, including treatment eligibility, hormone replacement therapy initiation, regimen selection, duration of therapy, drug-drug interactions, and long-term follow-up. When oncologically appropriate, women with treatment-induced premature ovarian insufficiency should receive hormone replacement therapy until the average age of natural menopause. Hormone replacement therapy may be initiated immediately after surgical menopause, whereas ovarian recovery should be assessed following chemotherapy before confirming permanent ovarian insufficiency. In post-menopausal women, treatment should be individualized according to symptom burden using validated assessment tools. Trans-dermal estrogen is the preferred systemic formulation because of its more favorable thrombotic profile, and women with an intact uterus require combined estrogen-progestogen therapy. Potential interactions with contemporary anti-cancer therapies should also be considered. Hormone replacement therapy initiation should generally be deferred during chemotherapy or bevacizumab because of cumulative thrombotic risk. Although clinically relevant pharmacokinetic interactions with poly(adenosine diphosphate-ribose) polymerase inhibitors are unlikely, overlapping toxicities warrant careful monitoring. With immune checkpoint inhibitors, the principal challenge is distinguishing menopausal symptoms from immune-related endocrinopathies rather than avoiding hormone replacement therapy. Integrating menopause management into routine survivorship care is essential to optimize quality of life, minimize the long-term consequences of estrogen deficiency, and support comprehensive care for gynecologic cancer survivors.