Iatrogenic menopause and long-term health: a call for better evidence

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.

Iatrogenic Menopause After Treatment for Cervical Cancer

Female cancers, including breast and gynecological malignancies, are among the most prevalent oncological conditions worldwide. Advances in screening, diagnosis, and treatment have markedly improved survival, resulting in a growing population of female cancer survivors. Consequently, long-term health and quality of life have become essential aspects of comprehensive cancer care. Among survivorship issues, sleep disturbances-particularly insomnia-are highly prevalent and associated with adverse outcomes including mood and cognitive impairment, fatigue, immune and cardiometabolic dysregulation, and reduced adherence to therapy. Insomnia, defined as difficulty initiating or maintaining sleep or experiencing poor sleep quality with daytime impairment, affects 6-10% of the general population and is more common in women. In cancer survivors, poor sleep quality appears to be three times more frequent, reaching 62% in breast cancer survivors, although these data may be underestimated, especially for other cancer types, due to the small sample size and heterogeneity of the studies. The pathogenesis of insomnia in female cancer patients is multifactorial, involving cancer-related inflammation, hypothalamic-pituitary-adrenal axis dysregulation, neuroimmune alterations, treatment effects, psychological distress, and behavioral factors. Hormonal disruption plays a central role, as oncological treatments are often the cause of iatrogenic menopause, leading to vasomotor symptoms, mood and cognitive disturbances, sexual dysfunction, and genitourinary complaints, all contributing to sleep disruption. Importantly, estrogens and progesterone independently regulate sleep-wake pathways via central mechanisms, influencing sleep quality even in the absence of vasomotor symptoms. Management requires a multidisciplinary approach integrating oncology, gynecology, and sleep medicine. Cognitive Behavioral Therapy for Insomnia (CBT-I) is first-line, while pharmacologic options include benzodiazepines, Z-drugs, SSRIs/SNRIs, melatonin, or new medication like DORAs. Menopausal hormone therapy (MHT) should be considered for premature menopause management in selected women without contraindications, improving both vasomotor symptoms and sleep quality. Emerging neurokinin receptor (NK-R) antagonists show promise, and ongoing trials suggest significant potential even in breast cancer survivors.

Trends and clinical predictors in ovarian preservation in patients with low-risk endometrial cancer.