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

Maarten J. Beekman; Lara Terra; Anniek Stuursma; Bernadette A.M. Heemskerk-Gerritsen; Jeanine E.Roeters van Lennep; Marc van Beurden; Lena C. van Doorn; Joanne A. de Hullu; Eleonora B.L. van Dorst; Constantijne H. Mom; Brigitte F.M. Slangen; Christina Mitea; Riemer H.J.A. Slart; Miranda M. Snoeren; Marcel P. Stokkel; Hein J. Verberne; Bart de Keizer; Catharina M. Korse; Katja N. Gaarenstroom; Klaartje van Engelen; Lizet E. van der Kolk; J. Margriet Collée; Marijke R. Wevers; Margreet G.E.M. Ausems; Lieke P.V. Berger; Encarna B.Gomez Garcia; Christi J. van Asperen; Maartje J. Hooning; Angela H.E.M. Maas; Marian J.E. Mourits; Flora E. van Leeuwen; M. Carola Zillikens

doi:10.1007/s00198-025-07679-8

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

Maarten J. Beekman
, Lara Terra
, Anniek Stuursma
, Bernadette A.M. Heemskerk-Gerritsen
, Jeanine E.Roeters van Lennep
, Marc van Beurden
, Lena C. van Doorn
, Joanne A. de Hullu
, Eleonora B.L. van Dorst
, Constantijne H. Mom
, Brigitte F.M. Slangen
, Christina Mitea
, Riemer H.J.A. Slart
, Miranda M. Snoeren
, Marcel P. Stokkel
, Hein J. Verberne
, Bart de Keizer
, Catharina M. Korse
, Katja N. Gaarenstroom
, Klaartje van Engelen

Lizet E. van der Kolk, J. Margriet Collée, Marijke R. Wevers, Margreet G.E.M. Ausems, Lieke P.V. Berger, Encarna B.Gomez Garcia, Christi J. van Asperen, Maartje J. Hooning, Angela H.E.M. Maas, Marian J.E. Mourits, Flora E. van Leeuwen, M. Carola Zillikens^*

^*Corresponding author for this work

Netherlands Cancer Institute
University Medical Centre Groningen
Erasmus University Rotterdam
Radboud University Medical Center
Utrecht University
Amsterdam UMC
Maastricht University
Leiden University
University of Groningen

Research output: Contribution to journal › Article › Academic › peer-review

3 Citations (Scopus)

19 Downloads (Pure)

Abstract

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 (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.

Original language	English
Pages (from-to)	2307-2317
Number of pages	11
Journal	Osteoporosis International
Volume	36
Issue number	11
DOIs	https://doi.org/10.1007/s00198-025-07679-8
Publication status	Published - Nov 2025

Bibliographical note

Publisher Copyright:
© The Author(s) 2025.

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Long-term effects of premenopausal risk-reducing salpingo-oophorectomy on bone mineral densityFinal published version, 1.09 MBLicence: CC BY-NC

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Beekman, M. J., Terra, L., Stuursma, A., Heemskerk-Gerritsen, B. A. M., van Lennep, J. E. R., van Beurden, M., van Doorn, L. C., de Hullu, J. A., van Dorst, E. B. L., Mom, C. H., Slangen, B. F. M., Mitea, C., Slart, R. H. J. A., Snoeren, M. M., Stokkel, M. P., Verberne, H. J., de Keizer, B., Korse, C. M., Gaarenstroom, K. N., ... Zillikens, M. C. (2025). Long-term effects of premenopausal risk-reducing salpingo-oophorectomy on bone mineral density. Osteoporosis International, 36(11), 2307-2317. https://doi.org/10.1007/s00198-025-07679-8

@article{0a119edbb8334ae497e54ec1ff778d35,

title = "Long-term effects of premenopausal risk-reducing salpingo-oophorectomy on bone mineral density",

abstract = "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 (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.",

author = "Beekman, \{Maarten J.\} and Lara Terra and Anniek Stuursma and Heemskerk-Gerritsen, \{Bernadette A.M.\} and \{van Lennep\}, \{Jeanine E.Roeters\} and \{van Beurden\}, Marc and \{van Doorn\}, \{Lena C.\} and \{de Hullu\}, \{Joanne A.\} and \{van Dorst\}, \{Eleonora B.L.\} and Mom, \{Constantijne H.\} and Slangen, \{Brigitte F.M.\} and Christina Mitea and Slart, \{Riemer H.J.A.\} and Snoeren, \{Miranda M.\} and Stokkel, \{Marcel P.\} and Verberne, \{Hein J.\} and \{de Keizer\}, Bart and Korse, \{Catharina M.\} and Gaarenstroom, \{Katja N.\} and \{van Engelen\}, Klaartje and \{van der Kolk\}, \{Lizet E.\} and Coll{\'e}e, \{J. Margriet\} and Wevers, \{Marijke R.\} and Ausems, \{Margreet G.E.M.\} and Berger, \{Lieke P.V.\} and Garcia, \{Encarna B.Gomez\} and \{van Asperen\}, \{Christi J.\} and Hooning, \{Maartje J.\} and Maas, \{Angela H.E.M.\} and Mourits, \{Marian J.E.\} and \{van Leeuwen\}, \{Flora E.\} and Zillikens, \{M. Carola\}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2025",

month = nov,

doi = "10.1007/s00198-025-07679-8",

language = "English",

volume = "36",

pages = "2307--2317",

journal = "Osteoporosis International",

issn = "0937-941X",

publisher = "Springer Science+Business Media",

number = "11",

}

Beekman, MJ, Terra, L, Stuursma, A, Heemskerk-Gerritsen, BAM, van Lennep, JER, van Beurden, M, van Doorn, LC, de Hullu, JA, van Dorst, EBL, Mom, CH, Slangen, BFM, Mitea, C, Slart, RHJA, Snoeren, MM, Stokkel, MP, Verberne, HJ, de Keizer, B, Korse, CM, Gaarenstroom, KN, van Engelen, K, van der Kolk, LE, Collée, JM, Wevers, MR, Ausems, MGEM, Berger, LPV, Garcia, EBG, van Asperen, CJ, Hooning, MJ, Maas, AHEM, Mourits, MJE, van Leeuwen, FE & Zillikens, MC 2025, 'Long-term effects of premenopausal risk-reducing salpingo-oophorectomy on bone mineral density', Osteoporosis International, vol. 36, no. 11, pp. 2307-2317. https://doi.org/10.1007/s00198-025-07679-8

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

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 (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.

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 (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.

UR - https://www.scopus.com/pages/publications/105017880356

U2 - 10.1007/s00198-025-07679-8

DO - 10.1007/s00198-025-07679-8

M3 - Article

C2 - 41045325

AN - SCOPUS:105017880356

SN - 0937-941X

VL - 36

SP - 2307

EP - 2317

JO - Osteoporosis International

JF - Osteoporosis International

IS - 11

ER -

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

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