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Health After eaRly Menopause Due to Oophorectomy (HARMOny)

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ClinicalTrials.gov Identifier: NCT03835793
Recruitment Status : Not yet recruiting
First Posted : February 11, 2019
Last Update Posted : February 11, 2019
Sponsor:
Collaborators:
Dutch Cancer Society
Erasmus Medical Center
Radboud University
Information provided by (Responsible Party):
The Netherlands Cancer Institute

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.


Condition or disease Intervention/treatment
Surgical Menopause BRCA1 Mutation BRCA2 Mutation Cardiovascular Diseases Bone Mineral Density Cognitive Decline Quality of Life Menopause Surgical Diagnostic Test: CAC-score

Detailed 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.


Study Type : Observational
Estimated Enrollment : 750 participants
Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Favourable and Unfavourable Health Effects of Risk-Reducing Salpingo-Oophorectomy in Women With a High Genetic Risk of Ovarian Cancer
Estimated Study Start Date : February 21, 2019
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : October 1, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Menopause

Group/Cohort Intervention/treatment
Early-RRSO
  • RRSO before the age of 45 years
  • RRSO was done 10 or more years ago
Diagnostic Test: CAC-score
Testing for possible unfavourable health effects of early surgical menopause
Other Names:
  • Blood sampling
  • DXA-scan
  • Vertebral Fracture Assessment
  • Online cognition test (Amsterdam Cognition Scale)
  • Quality of life questionnaire

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
Testing for possible unfavourable health effects of early surgical menopause
Other Names:
  • Blood sampling
  • DXA-scan
  • Vertebral Fracture Assessment
  • Online cognition test (Amsterdam Cognition Scale)
  • Quality of life questionnaire




Primary Outcome Measures :
  1. 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 [ Time Frame: 4 years ]
    Due to the lack of estrogen we expect more atherosclerotic diseases.

  2. 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 [ Time Frame: 4 years ]
    Due to the lack of estrogen we expect more atherosclerotic diseases.

  3. 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 [ Time Frame: 4 years ]
    Due to the lack of estrogen we expect more atherosclerotic diseases.

  4. 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 [ Time Frame: 4 years ]
    Due to the lack of estrogen we expect more atherosclerotic diseases.

  5. 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 [ Time Frame: 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

  6. 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 [ Time Frame: 4 years ]
    Loss of estrogen can result in more activity of osteoclasts and less activity of osteoblasts

  7. 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 [ Time Frame: 4 years ]
    Loss of estrogen can result in more activity of osteoclasts and less activity of osteoblasts

  8. 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 [ Time Frame: 4 years ]
    Loss of estrogen can result in more activity of osteoclasts and less activity of osteoblasts

  9. 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 [ Time Frame: 4 years ]
    There are some studies suggesting that an early menopause has an influence on cognition


Secondary Outcome Measures :
  1. 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 [ Time Frame: 4 years ]
    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

  2. 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. [ Time Frame: 4 years ]
    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

  3. 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 [ Time Frame: 4 years ]
    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. 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 [ Time Frame: 4 years ]

    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


  5. 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 [ Time Frame: 4 years ]

    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


  6. 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 [ Time Frame: 4 years ]

    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


  7. 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. [ Time Frame: 4 years ]
    Are some risk factors for cardiovascular disease more prevalent in women with a premenopausal RRSO


Other Outcome Measures:
  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. [ Time Frame: 4 years ]
    we will study the effect of RRSO on BC, contralateral breast cancer and ovarian cancer risk and prognosis after BC/ovarian cancer


Biospecimen Retention:   Samples With DNA
Optional for studyparticipants is to collect and store DNA in a blood Biobank.


Information from the National Library of Medicine

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Ages Eligible for Study:   55 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   In order to be eligible the ovaries have been removed.
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.
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03835793


Contacts
Contact: van Leeuwen, PhD +31 20 512 2024 f.v.leeuwen@nki.nl
Contact: Terra +31 20 512 9081 l.terra@nki.nl

Locations
Netherlands
Netherlands Cancer Institute - Antoni van Leeuwenhoek Not yet recruiting
Amsterdam, Netherlands, 1066CX
Contact: Flora E van Leeuwen, PhD         
Sponsors and Collaborators
The Netherlands Cancer Institute
Dutch Cancer Society
Erasmus Medical Center
Radboud University
Investigators
Principal Investigator: Flora E van Leeuwen, Phd NKI-AvL

Responsible Party: The Netherlands Cancer Institute
ClinicalTrials.gov Identifier: NCT03835793     History of Changes
Other Study ID Numbers: M18HAR
First Posted: February 11, 2019    Key Record Dates
Last Update Posted: February 11, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by The Netherlands Cancer Institute:
long-term
premature ovarian insufficiency

Additional relevant MeSH terms:
Cardiovascular Diseases
Cognitive Dysfunction
Cognition Disorders
Neurocognitive Disorders
Mental Disorders