What Happens After Menopause (WHAM)? A Progress Report of a Prospective Controlled Study of Women After...

Surgical menopause, the removal of both ovaries prior to natural menopause, may impact short-and long-term physical and emotional health. An increasingly common cause of surgical menopause is risk-reducing salpingo-oophorectomy (RRSO) in those at high inherited risk of ovarian cancer. The WHAM (What Happens After Menopause?) study is the largest prospective controlled study of RRSO. It measured the effect of RRSO compared to controls on physical and mental health over 2 years, and the potential modifying effects of menopausal hormone therapy (MHT). WHAM consists of 104 premenopausal women with BRCA1/2 pathogenic variants undergoing RRSO and 102 age-matched comparators who retained their ovaries. Outcomes including sexual function, vasomotor symptoms, cognition, mood, cardiometabolic health and bone health were measured between baseline and 24 months. MHT uptake after RRSO and the impact of MHT on these outcomes were assessed. Findings of WHAM have been published in more than ten manuscripts. Key findings include that RRSO adversely affects sexual function, sleep, and mood compared to comparison women. After RRSO, vasomotor symptoms (VMS) are generally mild, peak at 3 months, and do not worsen by 24 months. MHT reduces but does not resolve VMS. Loss of bone density was observed at 24 months and was partially mitigated by MHT. Cardiometabolic health and cognition were largely maintained at 24 months. This manuscript summarises the published findings of WHAM. These unique data will enhance evidence-based care in surgical menopause and will support shared decision-making around RRSO, ensuring rapid translation of new evidence into clinical practice. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: registration no: ACTRN12615000082505; anzctr.org.au.