Health After eaRly Menopause Due to Oophorectomy

Cardiovascular Diseases Clinical Trial

— HARMOny  

Official title:

Favourable and Unfavourable Health Effects of Risk-Reducing Salpingo-Oophorectomy in Women With a High Genetic Risk of Ovarian Cancer

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT03835793
• Other study ID #: M18HAR
• Status: Enrolling by invitation
• Start date: February 11, 2019
• Est. completion date: January 1, 2022

Study information

• Verified date: September 2020
• Source: The Netherlands Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 750
• Est. completion date: January 1, 2022
• Est. primary completion date: September 30, 2021
• Gender: Female
• Age group: 55 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Diagnostic Test:
• CAC-score
Testing for possible unfavourable health effects of early surgical menopause

Locations

Country	Name	City	State
Netherlands	Netherlands Cancer Institute - Antoni van Leeuwenhoek	Amsterdam

Sponsors (4)

Lead Sponsor	Collaborator
The Netherlands Cancer Institute	Dutch Cancer Society, Erasmus Medical Center, Radboud University

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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.	we will study the effect of RRSO on BC, contralateral breast cancer and ovarian cancer risk and prognosis after BC/ovarian cancer	4 years
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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	How do women with a premenopausal RRSO experience their life. The SF-36 questionnaire ranges from 36 to 149, with higher values representing a worse outcome	4 years
Secondary	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.	How do women with a premenopausal RRSO experience their life. We measure the body image using the EORTC QLQ BR23, with ranges from 2 to 8, with higher values representing a worse outcome	4 years
Secondary	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	How do women with a premenopausal RRSO experience their life. The FACT-ES questionnaire ranges from 0 to 76, with higher values representing a worse outcome	4 years
Secondary	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	Have women with a premenopausal RRSO more urogenital complaints due to longer duration of estrogen deficiency.; The SAQ questionnaire scale has questions with different weights as described in Thirlaway et al. 1996	4 years
Secondary	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	Have women with a premenopausal RRSO more urogenital complaints due to longer duration of estrogen deficiency.; The UDI-6 questionnaire scale has a range from 0 to 18, with higher values representing a worse outcome	4 years
Secondary	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	Have women with a premenopausal RRSO more urogenital complaints due to longer duration of estrogen deficiency.; The IIQ-7 questionnaire scale has a range from 0 to 24, with higher values representing a worse outcome	4 years
Secondary	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.	Are some risk factors for cardiovascular disease more prevalent in women with a premenopausal RRSO	4 years