What happens after menopause? (WHAM): A prospective controlled study of cognition 24 months after premenopausal risk-reducing salpingo-oophorectomy.

OBJECTIVE

Women with BRCA1/2 pathogenic variants considering risk-reducing bilateral oophorectomy (RRSO) may be concerned about potential effects of surgical menopause on cognition. Whether RRSO affects cognition and whether hormone therapy (HT) modifies this effect remains uncertain. This study aimed to prospectively measure the effect of premenopausal RRSO on cognition and the modifying effects of HT up to 24 months.

METHODS

The design was a prospective, multisite (4 sites in Australia), 24-month observational study. Participants were premenopausal BRCA1/2 carriers (n = 83) planning RRSO referred from gynecology-oncology and familial cancer centers and a premenopausal comparison group (n = 98) not planning oophorectomy or pregnancy who self-referred. Baseline data were collected within 8 weeks of eligibility screening, and RRSO was scheduled between baseline and 3 months. Of 687 screened, 181 were analysed. Cognitive performance (verbal learning and memory, psychomotor speed, fluency) was assessed at baseline, 3, 12 and 24 months with the a priori outcomes of verbal learning and memory.

RESULTS

After RRSO, 65 % initiated HT. In multivariable models of group differences in cognitive performance over time, RRSO and comparison groups showed similar performance improvements except for verbal learning. The RRSO group showed a small, statistically significant lower improvement in verbal learning vs comparisons, after adjustment for HT and other factors (p = 0.03). After RRSO, verbal learning was higher in HT users vs non-users (p = 0.04).

CONCLUSIONS AND RELEVANCE: Over 24 months RRSO minimally impacted cognition except for a small adverse effect on verbal learning, partly offset by HT.

TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (anzctr.org.au); Identifier #: ACTRN12615000082505; URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=363554&isReview=true.