Association between risk-reducing salpingooophorectomy and bone health in women with hereditary breast and ovarian cancer syndrome

OBJECTIVE: To explore any association between risk-reducing bilateral salpingooophorectomy (RRSO) and bone mineral density (BMD) and fracture risk among women with a germline likely pathogenic or pathogenic variant in genes causing hereditary breast and ovarian cancer. METHODS: Longitudinal prospective observational study. Clinical, biochemical, and BMD assessments were performed at study entry (V0) and after 18 months (V1). Four groups were compared: RRSO (RRSO in premenopause without hormone therapy [HT]), RRSO+HT (RRSO followed by HT), MEN (natural menopause with/without RRSO), and FERT (regular menstrual cycles not undergoing RRSO). RESULTS: One hundred four women were enrolled (52 BRCA1 germline likely pathogenic or pathogenic variant, 49 BRCA2, 3 other genes): 30 RRSO, 10 RRSO+HT, 29 MEN, 35 FERT. The V0 evaluation was performed at 2.85 ± 2.03 years from RRSO. At V0, no difference in lumbar spine (LS) and femoral neck BMD was detected comparing RRSO to RRSO+HT, MEN, and FERT. At V1 RRSO was associated with higher femoral neck BMD than MEN (P = 0.016), together with worse LS BMD than FERT (P = 0.045). The temporal decline of LS BMD in RRSO was more pronounced than MEN (P = 0.019). Calculated risk of fracture (Fracture Risk Assessment Tool [FRAX]) at V0 was lower in RRSO than MEN (P < 0.001), similar to RRSO+HT and FERT; at V1, FRAX was higher in RRSO than FERT (P = 0.014). CONCLUSIONS: RRSO was associated with greater and prolonged bone health decline in women ovariectomized at premenopausal age, not receiving HT. This high-risk population deserves long-term BMD monitoring, and HT mitigating effect might be considered.