Health After eaRly Menopause Due to Oophorectomy

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.

Rationale: Women at high genetic risk of ovarian cancer are advised to undergo risk-reducing salpingo-oophorectomy (RRSO) at ages 35-45 years. Currently, in the Netherlands \~500 women/ year opt for RRSO, which minimizes ovarian cancer risk and may decrease breast cancer (BC) risk as well, due to reduced gonadal hormone levels. Besides favorable effects of RRSO on ovarian cancer and, potentially, BC risk, RRSO induces immediate menopause, which may have unfavorable long-term health consequences. Early menopause has been associated with increased risks of cardiovascular disease (CVD), lower bone mineral density (BMD), cognitive impairment, and decreased quality of life. Current evidence regarding these health effects is mainly based on women with a natural early menopause, and it is unknown whether these results hold for women undergoing RRSO at early premenopausal ages.

Objective: The investigators will investigate long-term health effects of premenopausal RRSO on (subclinical) cardiovascular status, BMD, cognition and quality of life.

Study design: the investigators will assess long-term health effects of RRSO in a cross-sectional study, among 500 women who underwent premenopausal RRSO compared to 250 women of the same age without RRSO (or with RRSO after age 55). Eligible women will be invited to participate in a screening program assessing cardiovascular status, bone mineral density, cognitive functioning and quality of life.

Study population: Women are eligible for the premenopausal RRSO group if:

* RRSO before the age of 45 years;
* RRSO was done 10 or more years ago; Women are eligible for the comparison group without premenopausal RRSO if the participant did not undergo RRSO before the age of 55 years, and did not have a natural or therapy induced menopause before age 50.

Primary study outcome: To study long-term effects of premenopausal RRSO on:

* (subclinical) CVD
* BMD
* Cognition

Secondary study outcome: To study long-term effects of premenopausal RRSO on:

* Quality of life
* Urogenital problems
* Cardiovascular risk factors

Furthermore, the investigators will examine the influence of age at RRSO, time since RRSO, hormone replacement therapy (HRT), carrier ship of a BRCA1 or BRCA2 mutation and BC history on the outcome.

The obtained knowledge will assist physicians in counselling women with high ovarian cancer risk and help them to make well-informed decisions.

Eligibility Criteria:
Inclusion Criteria:

* RRSO before age 45
* RRSO after age 55
* no RRSO

Exclusion Criteria:

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