Long-term effects of premenopausal risk-reducing salpingo-oophorectomy on bone mineral density

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Women at high familial risk for ovarian cancer are recommended to undergo risk-reducing salpingo-oophorectomy (RRSO), leading to surgical menopause and short-term bone loss. However, long-term studies and osteoporosis screening recommendations are lacking. Eighteen years after premenopausal RRSO, women had lower bone mineral density compared with women who underwent a postmenopausal RRSO. PURPOSE: To prevent ovarian cancer, BRCA1/2 germline pathogenic variant carriers are recommended to undergo premenopausal risk-reducing salpingo-oophorectomy (RRSO). Premenopausal RRSO leads to immediate menopause, which has been associated with an acute phase of rapid bone loss. However, data on long-term bone mineral density (BMD) is scarce and inconclusive. We aimed to investigate long-term BMD after premenopausal RRSO. METHODS: We conducted a cross-sectional study nested in a nationwide cohort of women at high familial risk of ovarian cancer. We compared 493 women who underwent premenopausal RRSO (≤ 45 years) with 228 women who underwent postmenopausal RRSO (≥ 54 years). BMD was assessed by Dual-Energy X-ray absorptiometry of the lumbar spine (LS) and femoral neck (FN). Age differences between the pre- and postmenopausal RRSO groups were accounted for using Z-scores. RESULTS: Median age at study visit was 59.2 years in the premenopausal RRSO group and 69.7 years in the postmenopausal RRSO group (P < 0.001), median time since premenopausal RRSO was 18.1 years (IQR 15.3-21.3). In multivariable regression analyses the BMD Z-scores of the LS and FN were significantly lower for the premenopausal compared with the postmenopausal RRSO group (β -0.88, 95% CI, -1.10,-0.66 for LS; β -0.51, 95% CI, -0.71,-0.31 for FN). Relative risks (RRs) of having a Z-score ≤ -1.0 were also higher in the premenopausal compared with the postmenopausal RRSO group (RR 2.35, 95% CI, 1.26-4.40 and RR 1.84, 95% CI, 1.08-3.13, respectively). CONCLUSION: Premenopausal RRSO appears to be associated with long-term lowering of BMD Z-scores, emphasizing the importance of counseling women about bone health after premenopausal RRSO. CLINICAL TRIAL REGISTRATION: The pre-registered clinical trial number is < NCT03835793 > .