Favourable and Unfavourable Health Effects of Risk-Reducing Salpingo-Oophorectomy in Women With a High Genetic Risk of Ovarian Cancer
试验速览
- 阶段
- 不适用
- 入组人数
- 750
- 试验地点
- 1
- 主要终点
- 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
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 55 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •RRSO before age 45
- •RRSO after age 55
排除标准
- •metastatic disease
- •Premature ovarian insufficiency
- •Physical or mental problems interfering with a outpatient visit
- •nonbioabsorbable cardiac stent
- •insufficient understanding of the Dutch language
结局指标
主要结局
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
时间窗: 4 years
Due to the lack of estrogen we expect more atherosclerotic diseases.
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
时间窗: 4 years
Loss of estrogen can result in more activity of osteoclasts and less activity of osteoblasts
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
时间窗: 4 years
Loss of estrogen can result in more activity of osteoclasts and less activity of osteoblasts
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
时间窗: 4 years
There are some studies suggesting that an early menopause has an influence on cognition
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
时间窗: 4 years
Due to the lack of estrogen we expect more atherosclerotic diseases.
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
时间窗: 4 years
Due to the lack of estrogen we expect more atherosclerotic diseases.
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
时间窗: 4 years
Due to the lack of estrogen we expect more atherosclerotic diseases.
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
时间窗: 4 years
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
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
时间窗: 4 years
Loss of estrogen can result in more activity of osteoclasts and less activity of osteoblasts
次要结局
- 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 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 cardiovascular risk factors in women with RRSO compared to women with a high genetic risk of ovarian cancer as assessed by a questionnaire.(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)
- 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)
- 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 IIQ-7(4 years)