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. 2025 Oct 4.
doi: 10.1007/s00198-025-07679-8. Online ahead of print.

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

Maarten J Beekman  1 , Lara Terra  1 , Anniek Stuursma  2 , Bernadette A M Heemskerk-Gerritsen  3 , Jeanine E Roeters van Lennep  4 , Marc van Beurden  5 , Lena C van Doorn  6 , Joanne A de Hullu  7 , Eleonora B L van Dorst  8 , Constantijne H Mom  9 , Brigitte F M Slangen  10 , Christina Mitea  11 , Riemer H J A Slart  12 , Miranda M Snoeren  13 , Marcel P Stokkel  14 , Hein J Verberne  15 , Bart de Keizer  16 , Catharina M Korse  17 , Katja N Gaarenstroom  18 , Klaartje van Engelen  19 , Lizet E van der Kolk  20 , J Margriet Collée  21 , Marijke R Wevers  22 , Margreet G E M Ausems  23 , Lieke P V Berger  24 , Encarna B Gomez Garcia  25 , Christi J van Asperen  26 , Maartje J Hooning  3 , Angela H E M Maas  27 , Marian J E Mourits  2 , Flora E van Leeuwen #  1 , M Carola Zillikens #  28
Affiliations

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

Maarten J Beekman et al. Osteoporos Int. .

Abstract

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 > .

Keywords: Bone Mineral Density; DXA; Early Menopause; Epidemiology; Estrogen.

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Conflict of interest statement

Declarations. Ethics approval: This study was conducted according to the standards of Good Clinical Practice, in agreement with the principles of the Declaration of Helsinki and with the Dutch law as stated in the Medical Research Involving Human Subjects Act (WMO). The study has been approved in writing by the Institutional Review Board of the AVL/NKI to be conducted in all nine University Medical Centers and the Antoni van Leeuwenhoek. Consent to participate: All participants included in this study signed informed consent. Conflict of interest: MB, LT, AS, BH, JR, MvB, LvD, JdH, EvD, CM, BS, CM, RS, MS, MS, HV, BdK, CK, KG, KvE, LvdK, MC, MW, MA, LB, EG, CvA, MH, AM, MM, FvL and CZ declare that they have no conflict of interest.

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