Primary Objective: To study long-term effects of premenopausal risk-reducing salpingo-oophorectomy (RRSO) on - cardiovascular status- bone mineral density- cognitionSecondary Objective: To study long-term effects of premenopausal RRSO on - quality…
ID
Source
Brief title
Condition
- Other condition
- Menopause related conditions
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Health condition
Botgezondheid
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
We will assess long-term physical and mental health of 500 women who underwent
premenopausal RRSO compared to 250 women of the same age without RRSO (or RRSO
after the age of 55) in a cross sectional retrospective cohort study on
- (subclinical)Cardiovascular disease
- Bone mineral density
- Cognitive functioning
Secondary outcome
Secondary parameters will be differences in the following factors between women
with premenopausal RRSO and women without premenopausal RRSO:
- Quality of life
- Sexual functioning
- Urogenital problems
Background summary
Women at high genetic risk of ovarian cancer (OC) 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 OC risk and may
decrease breast cancer (BC) risk as well, due to reduced gonadal hormone
levels. Besides favorable effects of RRSO on OC and, potentially, BC risk, RRSO
induces immediate menopause, which may have unfavorable 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 (QoL). 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.
Study objective
Primary Objective:
To study long-term effects of premenopausal risk-reducing salpingo-oophorectomy
(RRSO) on
- cardiovascular status
- bone mineral density
- cognition
Secondary Objective:
To study long-term effects of premenopausal RRSO on
- quality of life
- urogenital problems
- cardiovascular risk factors
Subgroup analysis of the effect of RRSO on CVD, BMD, cognition and Quality of
life will be performed according to:
- age at RRSO
- time since RRSO
- hormone replacement therapy
- BRCA1/2 mutation carrier ship
- breast cancer history
Study design
a cross-sectional study of women with premenopausal RRSO compared to women of
the same age without premenopausal RRSO. We will invite them to participate in
a screening program assessing cardiovascular status, bone mineral density,
cognitive functioning and quality of life.
we will assess the long-term effects of premenopausal RRSO on cardiovascular
status, bone mineral density and several aspects of quality of life in a
subgroup of women who underwent RRSO > 10 years ago and a comparison group. In
this study women will be invited for a medical assessment. During this medical
assessment the coronary artery score (CAC score) will be calculated as an
indication of (sub)clinical atherosclerosis as will the Pulse Wave Velocity
(PWV). Also the Advanced glycation end products (AGEs) will be calculated using
autofluorescence of the skin and the breast arterial calcification (BAC) score
will be calculated using mammograms. The length and weight of patients will be
measured as will the blood pressure and some specific cardiac enzymes in the
blood. For the calculation of the BMD a DEXA scan and some specific markers in
the blood will be tested. Cognitive function will be assessed using an online
test recently developed and for the QoL a questionnaire is filled in. We select
500 women with premenopausal RRSO and 250 women without RRSO of RRSO after 55
years of age.
multivariate linear regression analyses will be performed. Adjustment for
confounders (lifestyle factors, reproductive factors, medication use) will be
made. Analyses will be performed separately in women with and without BC
history (treatment as a confounding factor). Subgroup analyses are planned
according to HRT use (type, duration and timing of use), BRCA1/BRCA2 mutation
status, age at RRSO, time since RRSO
Women recruited from the UMCG are able to specify whether they want to fill in
an online questionnaire or a paper questionnaire. The questionnaire includes
questions that are relevant for assessment of osteoporosis and fracture risk,
such as fracture history, corticosteroid use, calcium and vitamin D intake,
duration of HRT use, physical activity and questions on lifestyle.
We will send two reminders to all eligible non-responding women, one after one
month, and one two months after the initial invitation. Women who do not want
to participate can send their refusal on the same reply form. A pre-stamped
envelope will be enclosed in the envelope containing the invitation letter and
information folder. Women willing to participate will be scheduled for a visit
in the UMCG. If possible, the DEXA scan will be performed on the same day.
Travel and parking cost of participants will be reimbursed if necessary.
Participants are able to withdraw from the study at any time for any reason.
Study burden and risks
The cardiovascular and fracture risk assessment will be performed consecutively
in one morning or afternoon. All medical tests combined will take 2.5 hours.
Test results will be discussed and when medical care is warranted (e.g.
increased blood glucose or hypertension) patients will be referred to their
general practitioner (e.g. in case of hypertension) or medical specialist if
specialized care is indicated (e.g. a cardiologist in case of suspected
impaired cardiac function as measured by ECG or NT-proBNP-level). They will be
offered standard of care according to the clinical practice guidelines and the
guidelines from the European Society for Cardiology. If the test results
implicate no further treatment, participants will not be informed about their
results.
Assessment of neurocognitive functioning in the current study will take place
at home, 1-3 weeks after the study visit in the hospital, to prevent
overburdening of participants before the study visit when they are already
asked to complete a questionnaire on general health, risk factors and quality
of life
We will assess generic HRQOL the SF-36 Health Survey. All raw scale scores
were linearly converted to a 0 to 100 scale, with higher scores indicating
higher levels of QOL. We will assess cancer-specific distress with the 7-item
Intrusion subscale of the Impact of Events Scale, with the frequency of
intrusive thoughts about the increased risk of developing breast/ovarian cancer
as the stressor. Cancer worries will be measured with 5 items adapted from
Lerman. Self-perceived cancer risk will be assessed with 2 items used in
previous studies. To assess endocrine symptoms we will employ the 18-item
FACT-ES and the Hot Flush rating Scale (HFRS). The Sexual Activity
Questionnaire (SAQ) will be used to measure sexual functioning. Urogenital
problems will be evaluated using the Urogenital Distress Inventory (UDI-6) and
Incontinence Impact Questionnaire (IIQ-7).
Plesmanlaan 121 Plesmanlaan 121
Amsterdam 1066 CX
NL
Plesmanlaan 121 Plesmanlaan 121
Amsterdam 1066 CX
NL
Listed location countries
Age
Inclusion criteria
Female patients
High genetic risk of ovarian cancer
Risk reducing salpingo-oophorectomy before the age of 46, or (for control
group):
High genetic risk for ovarian cancer
Natural menopause after age of 50 years
No RRSO before 55 years of age
No treatment induced menopause before 50 years of age
Exclusion criteria
For both groups:
History of gynecological cancer at time of RRSO
History of cancer at time of testing for BRCA-1 / BRCA-2
Ovariectomy for other reasons in patient history
Cystectomy in patients history
Metastatic disease
Other serious comorbidity, psychiatric disorders, which would interfere with a
clinic visit
Not enough understanding of the Dutch language
Non-bioresorbable cardiac stent
Younger age than 55 years
Premature Ovarian Insufficiency
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT03835793 |
| CCMO | NL63554.031.17 |