Simon, James A.

Abstract The objective of The North American Menopause Society (NAMS) and The International Society for the Study of Women's Sexual Health (ISSWSH) Expert Consensus Panel was to create a point of care algorithm for treating genitourinary syndrome of menopause (GSM) in women with or at high risk for breast cancer. The consensus recommendations will assist healthcare providers in managing GSM with a goal of improving the care and quality of life for these women. The Expert Consensus Panel is comprised of a diverse group of 16 multidisciplinary experts well respected in their fields. The panelists individually conducted an evidence-based review of the literature in their respective areas of expertise. They then met to discuss the latest treatment options for genitourinary syndrome of menopause (GSM) in survivors of breast cancer and review management strategies for GSM in women with or at high risk for breast cancer, using a modified Delphi method. This iterative process involved presentations summarizing the current literature, debate, and discussion of divergent opinions concerning GSM assessment and management, leading to the development of consensus recommendations for the clinician. Genitourinary syndrome of menopause is more prevalent in survivors of breast cancer, is commonly undiagnosed and untreated, and may have early onset because of cancer treatments or risk-reducing strategies. The paucity of evidence regarding the safety of vaginal hormone therapies in women with or at high risk for breast cancer has resulted in avoidance of treatment, potentially adversely affecting quality of life and intimate relationships. Factors influencing decision-making regarding treatment for GSM include breast cancer recurrence risk, severity of symptoms, response to prior therapies, and personal preference. We review current evidence for various pharmacologic and nonpharmacologic therapeutic modalities in women with a history of or at high risk for breast cancer and highlight the substantial gaps in the evidence for safe and effective therapies and the need for future research. Treatment of GSM is individualized, with nonhormone treatments generally being first line in this population. The use of local hormone therapies may be an option for some women who fail nonpharmacologic and nonhormone treatments after a discussion of risks and benefits and review with a woman's oncologist. We provide consensus recommendations for an approach to the management of GSM in specific patient populations, including women at high risk for breast cancer, women with estrogen-receptor positive breast cancers, women with triple-negative breast cancers, and women with metastatic disease.

INTRODUCTION: Elagolix, an oral gonadotropin-releasing hormone antagonist, with and without add-back therapy, was evaluated in premenopausal women with heavy menstrual bleeding (HMB; greater than 80 mL/month menstrual blood loss [MBL]) associated with uterine fibroids (UF). METHODS: This double-blind, randomized, placebo-controlled, parallel group study evaluated the efficacy and safety of 6 months of treatment in 2 cohorts, with four arms/cohort: elagolix alone as 300 mg twice daily in cohort 1 (C1) and 600 mg once daily in cohort 2, and in both cohorts, placebo, elagolix with add-back therapy of estradiol (E2)/norethindrone acetate (NETA), low dose 0.5 mg E2/0.1 mg NETA (LDA), or standard dose 1.0 mg E2/0.5 mg NETA (SDA). The primary endpoint was the percentage of women with less than 80 mL MBL assessed by the alkaline-hematin-method and at least 50% reduction in MBL from baseline to the last 28 days of treatment. Adverse events (AE), changes in bone mineral density (BMD) and quality of life (QoL) were assessed. RESULTS: In C1, 259 women were randomized and treated; 80% completed treatment. C1 responses for the primary endpoint were 92% in elagolix alone, 85% elagolix+LDA, 79% elagolix+SDA, and 27% placebo (all p < .001 vs. placebo). Add-back therapy attenuated hot flushes and lumbar spine BMD decreases in a dose-dependent manner; there were no statistically significant differences in BMD between elagolix+SDA and placebo at month 6. All elagolix treatments were associated with improved QoL. Results were similar in C2. CONCLUSION: Elagolix with or without add-back significantly reduced MBL in UF-associated HMB. Hot flushes and BMD decreases were reduced by add-back in a dose-dependent manner.