Managing Menopausal Symptoms and Associated Clinical Issues in Breast Cancer Survivors.

Objective: Review evidence to guide management of menopausal signs and symptoms in women after breast cancer and make recommendations accordingly. Evidence: Randomized controlled clinical trials, observational studies, evidence-based guidelines, and expert opinion from professional societies. Background: Symptoms and clinical problems associated with estrogen depletion-sleep disorders, vulvovaginal atrophy (VVA), vasomotor symptoms (VMS), mood changes, depressive symptoms, cardiovascular disease, osteopenia, and osteoporosis-confront the estimated 9.3 million breast cancer survivors globally. Recommendations: Following breast cancer, women should not generally be treated with menopausal hormone therapy or tibolone but should optimize lifestyle. Women with moderate to severe symptoms may benefit from mind-brain behavior or nonhormone, pharmacologic therapy. The selective serotonin/noradrenaline reuptake inhibitors and gabapentenoid agents improve VMS and quality of life. For osteoporosis, nonhormonal agents are available. Treatment of VVA remains an area of unmet need. Low-dose vaginal estrogen is absorbed in small amounts with blood levels remaining within the normal postmenopausal range but could potentially stimulate occult breast cancer cells, and although poorly studied, is not generally advised, particularly for those on aromatase inhibitors. Intravaginal dehydroepiandrosterone and oral ospemiphene have been approved to treat dyspareunia, but safety after breast cancer has not been established. Vaginal laser therapy is being used for VVA but efficacy from sham-controlled studies is lacking. Therapies undergoing development include lasofoxifene, neurokinin B inhibitors, stellate ganglion blockade, vaginal testosterone, and estetrol. Conclusions: Nonhormone options and therapies are available for treatment of estrogen depletion symptoms and clinical problems after a diagnosis of breast cancer. Individualization of treatment is essential.