Health After eaRly Menopause Due to Oophorectomy

NCT03835793 | Unknown DMC

• 1 other identifier: M18HAR
• Study Type: observational
• Target: 750
• Locations: 1 country
• Sites: 1

Brief Summary

Risk-Reducing Salpingo-Oophorectomy (RRSO) at the age of 35 to 45 years is recommended for women with a high genetic risk for ovarian cancer. While this procedure decreases the risk of ovarian cancer by 80-96%, it also results in an immediate menopause. Current research on potential adverse effects of premenopausal risk-reducing salpingo-oophorectomy, such as increased risk of cardiovascular disease, compromised bone health, cognitive dysfunction and reduced quality of life, is limited, mostly due to short follow up. The investigators will conduct a multicenter cross-sectional study nested in a cohort of BRCA mutation carriers from 8 Dutch centers for hereditary cancer. Eligible participants are women who underwent RRSO before the age of 45. The participants will be frequency-matched on current age with women above the age of 55 without RRSO or with RRSO after the age of 55. Participants will complete an online questionnaire containing various questions about lifestyle, medical history, risk factors for cardiovascular disease, bone health, cognition and quality of life. Participants will be asked to visit one of the participating hospitals for a blood test, a cardiovascular assessment and a DEXA scan for determining bone mineral density. Afterwards participants will be requested to perform the online Amsterdam Cognition Scale.

Conditions

Surgical Menopause; BRCA1 Mutation; BRCA2 Mutation; Cardiovascular Diseases; Bone Mineral Density; Cognitive Decline; Quality of Life; Menopause Surgical

Keywords

long-term; premature ovarian insufficiency

Outcome Measures

Primary Outcomes (9)

• What is the prevalence of atherosclerotic diseases in women with RRSO compared to women with a high genetic risk of ovarian cancer with a natural menopause as assessed by coronary artery calcium scoring in agatston units

  Due to the lack of estrogen we expect more atherosclerotic diseases.

  4 years

• What is the prevalence of atherosclerotic diseases in women with RRSO compared to women with a high genetic risk of ovarian cancer with a natural menopause as assessed by pulse wave velocity in meters/second

  Due to the lack of estrogen we expect more atherosclerotic diseases.

  4 years

• What is the prevalence of atherosclerotic diseases in women with RRSO compared to women with a high genetic risk of ovarian cancer with a natural menopause as assessed by high-sensitive CRP in miligram/liter

  Due to the lack of estrogen we expect more atherosclerotic diseases.

  4 years

• What is the prevalence of atherosclerotic diseases in women with RRSO compared to women with a high genetic risk of ovarian cancer with a natural menopause as assessed by high-sensitive cardial Troponine T in microgram/liter

  Due to the lack of estrogen we expect more atherosclerotic diseases.

  4 years

• What is the prevalence of osteoporosis in women with a premenopausal RRSO compared to women with a high genetic risk of ovarian cancer with a natural menopause as assessed by dual-energy X-ray absoptiometry in T- and Z-scores

  Loss of estrogen can result in more activity of osteoclasts and less activity of osteoblasts, The DXA-scan is corrected for age, with lower values representing a worse outcome

  4 years

• What is the prevalence of osteoporosis in women with a premenopausal RRSO compared to women with a high genetic risk of ovarian cancer with a natural menopause as assessed by instant vertebral assessment

  Loss of estrogen can result in more activity of osteoclasts and less activity of osteoblasts

  4 years

• What is the prevalence of osteoporosis in women with a premenopausal RRSO compared to women with a high genenetic risk of ovarian cancer with a natural menopause as assessed by beta-CTX in picogram/mililiter

  Loss of estrogen can result in more activity of osteoclasts and less activity of osteoblasts

  4 years

• What is the prevalence of osteoporosis in women with a premenopausal RRSO compared to women with a high genenetic risk of ovarian cancer with a natural menopause as assessed by P1NP in miligram/liter

  Loss of estrogen can result in more activity of osteoclasts and less activity of osteoblasts

  4 years

• What is the prevalence of cognitive decline in women with RRSO compared to women with a natural menopause as assessed by the Amsterdam Cognition Scan

  There are some studies suggesting that an early menopause has an influence on cognition

  4 years

Secondary Outcomes (7)

• Quality of life after a premenopausal RRSO compared to women from families with a high genetic risk of ovarian cancer with a natural menopause as assessed by validated questionnaires such as the SF-36

  4 years

• Quality of life after a premenopausal RRSO compared to women from families with a high genetic risk of ovarian cancer with a natural menopause as assessed by validated questionnaires such as the EORTC-QLQ BR23.

  4 years

• Quality of life after a premenopausal RRSO compared to women from families with a high genetic risk of ovarian cancer with a natural menopause as assessed by validated questionnaires such as the FACT-ES

  4 years

• What is the prevalence of urogenital problems in women with a RRSO compared to women with a natural menopause as assessed by validated questionnaires such as the SAQ

  4 years

• What is the prevalence of urogenital problems in women with a RRSO compared to women with a natural menopause as assessed by validated questionnaires such as the UDI-6

  4 years

Other Outcomes (1)

• What is the effect of premenopausal RRSO on risk of (contralateral) breast cancer and breast cancer-specific survival as assessed in a prospective setting within a well established cohort.

  4 years

Study Arms (2)

Early-RRSO

* RRSO before the age of 45 years * RRSO was done 10 or more years ago

Diagnostic Test: CAC-score

Late-/non-RRSO group

* Natural menopause ≥ 50 years of age * No RRSO ≤ age of 55 * No treatment-induced menopause ≤ 50 years of age

Diagnostic Test: CAC-score

Interventions

CAC-score DIAGNOSTIC_TEST

Testing for possible unfavourable health effects of early surgical menopause

Also known as: Blood sampling, DXA-scan, Vertebral Fracture Assessment, Online cognition test (Amsterdam Cognition Scale), Quality of life questionnaire

Early-RRSO; Late-/non-RRSO group

Eligibility Criteria

• Age: 55 Years+
• Gender Eligibility Details: In order to be eligible the ovaries have been removed.
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Women are eligible if they underwent RRSO before age 45 and the RRSO was done 10 or more years ago (early RRSO group) and women are eligible as control group if they did not undergo RRSO, or underwent RRSO after age 55 while reaching natural menopause after the age of 50 years. The comparison group will be frequency-matched with the RRSO group on categories of calendar year of birth, and breast cancer history. For each patient with breast cancer, the investigators will perform individual matching accounting for age at breast cancer diagnosis and carrier status. For the early RRSO group the investigators select women who underwent RRSO at least 10 years ago and are currently older than 55 years because the investigators expect subclinical atherosclerosis not to manifest earlier.

You may qualify if:

• RRSO before age 45
• RRSO after age 55
• no RRSO

You may not qualify if:

• metastatic disease
• Premature ovarian insufficiency
• Physical or mental problems interfering with a outpatient visit
• nonbioabsorbable cardiac stent
• insufficient understanding of the Dutch language

Sponsors & Collaborators

• The Netherlands Cancer Institute: lead
• Dutch Cancer Society: collaborator
• Erasmus Medical Center: collaborator
• Radboud University Medical Center: collaborator

Study Sites (1)

Netherlands Cancer Institute - Antoni van Leeuwenhoek

Amsterdam, 1066CX, Netherlands

Location

Related Publications (4)

• 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, Collee JM, Wevers MR, Ausems MGEM, Berger LPV, Garcia EBG, van Asperen CJ, Hooning MJ, Maas AHEM, Mourits MJE, van Leeuwen FE, Zillikens MC. Long-term effects of premenopausal risk-reducing salpingo-oophorectomy on bone mineral density. Osteoporos Int. 2025 Nov;36(11):2307-2317. doi: 10.1007/s00198-025-07679-8. Epub 2025 Oct 4.

  PMID: 41045325 DERIVED

• Beekman MJ, Terra L, Roeters van Lennep JE, Heemskerk-Gerritsen BAM, van Beurden M, van Doorn HC, de Hullu JA, van Dorst EBL, Mom CH, Slangen BFM, Mourits MJE, Gaarenstroom KN, van Engelen K, van der Kolk LE, Collee JM, Wevers MR, Ausems MGEM, Berger LPV, Gomez Garcia EB, van Asperen CJ, Hooning MJ, van Leeuwen FE, Maas AHEM. No increased arterial stiffness after premenopausal risk-reducing salpingo-oophorectomy (RRSO). Maturitas. 2025 Jun;197:108265. doi: 10.1016/j.maturitas.2025.108265. Epub 2025 Apr 11.

  PMID: 40262388 DERIVED

• Terra L, Beekman MJ, Engelhardt EG, Heemskerk-Gerritsen BAM, van Beurden M, Roeters van Lennep JE, van Doorn HC, de Hullu JA, Van Dorst EBL, Mom CH, Slangen BFM, Gaarenstroom KN, van der Kolk LE, Collee JM, Wevers MR, Ausems MGEM, Van Engelen K, van de Beek I, Berger LPV, van Asperen CJ, Gomez Garcia EB, Maas AHEM, Hooning MJ, Aaronson NK, Mourits MJE, van Leeuwen FE. Sexual functioning more than 15 years after premenopausal risk-reducing salpingo-oophorectomy. Am J Obstet Gynecol. 2023 Apr;228(4):440.e1-440.e20. doi: 10.1016/j.ajog.2022.11.1289. Epub 2022 Nov 17.

  PMID: 36403862 DERIVED

• Terra L, Hooning MJ, Heemskerk-Gerritsen BAM, van Beurden M, Roeters van Lennep JE, van Doorn HC, de Hullu JA, Mom C, van Dorst EBL, Mourits MJE, Slangen BFM, Gaarenstroom KN, Zillikens MC, Leiner T, van der Kolk L, Collee M, Wevers M, Ausems MGEM, van Engelen K, Berger LP, van Asperen CJ, Gomez-Garcia EB, van de Beek I, Rookus MA, Hauptmann M, Bleiker EM, Schagen SB, Aaronson NK, Maas AHEM, van Leeuwen FE. Long-Term Morbidity and Health After Early Menopause Due to Oophorectomy in Women at Increased Risk of Ovarian Cancer: Protocol for a Nationwide Cross-Sectional Study With Prospective Follow-Up (HARMOny Study). JMIR Res Protoc. 2021 Jan 22;10(1):e24414. doi: 10.2196/24414.

  PMID: 33480862 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Optional for studyparticipants is to collect and store DNA in a blood Biobank.

MeSH Terms

Conditions

Cardiovascular Diseases; Cognitive Dysfunction; Primary Ovarian Insufficiency

Interventions

Blood Specimen Collection; Absorptiometry, Photon

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Radiography; Diagnostic Imaging; Densitometry; Photometry; Chemistry Techniques, Analytical

Study Officials

• Flora E van Leeuwen, Phd

  NKI-AvL

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2018
• First Posted: February 11, 2019
• Study Start: February 11, 2019
• Primary Completion: September 30, 2021
• Study Completion: January 1, 2022
• Last Updated: September 14, 2020

Record last verified: 2020-09

Locations

NL (1)