TY - JOUR
T1 - Long-term effects of premenopausal risk-reducing salpingo-oophorectomy on bone mineral density
AU - Beekman, Maarten J.
AU - Terra, Lara
AU - Stuursma, Anniek
AU - Heemskerk-Gerritsen, Bernadette A.M.
AU - van Lennep, Jeanine E.Roeters
AU - van Beurden, Marc
AU - van Doorn, Lena C.
AU - de Hullu, Joanne A.
AU - van Dorst, Eleonora B.L.
AU - Mom, Constantijne H.
AU - Slangen, Brigitte F.M.
AU - Mitea, Christina
AU - Slart, Riemer H.J.A.
AU - Snoeren, Miranda M.
AU - Stokkel, Marcel P.
AU - Verberne, Hein J.
AU - de Keizer, Bart
AU - Korse, Catharina M.
AU - Gaarenstroom, Katja N.
AU - van Engelen, Klaartje
AU - van der Kolk, Lizet E.
AU - Collée, J. Margriet
AU - Wevers, Marijke R.
AU - Ausems, Margreet G.E.M.
AU - Berger, Lieke P.V.
AU - Garcia, Encarna B.Gomez
AU - van Asperen, Christi J.
AU - Hooning, Maartje J.
AU - Maas, Angela H.E.M.
AU - Mourits, Marian J.E.
AU - van Leeuwen, Flora E.
AU - Zillikens, M. Carola
N1 - Funding Information:
The Dutch Cancer Society (KWF) and the Maarten van der Weijden foundation granted us with the funding for this project, registered under grant 10164. The funding body had no role in the design of the study, collection, analysis or interpretation of data or in writing the article.
Publisher Copyright:
© The Author(s) 2025.
PY - 2025/11
Y1 - 2025/11
N2 - Summary: 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 (ß -0.88, 95% CI, -1.10,-0.66 for LS; ß -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 >
AB - Summary: 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 (ß -0.88, 95% CI, -1.10,-0.66 for LS; ß -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 >
KW - Bone Mineral Density
KW - DXA
KW - Early Menopause
KW - Epidemiology
KW - Estrogen
U2 - 10.1007/s00198-025-07679-8
DO - 10.1007/s00198-025-07679-8
M3 - Article
SN - 0937-941X
VL - 36
SP - 2307
EP - 2317
JO - Osteoporosis International
JF - Osteoporosis International
IS - 11
ER -