Female Sex Hormones, Insulin Resistance and Effects of Exercise in a Human Experimental Model of Menopause
Female Sex Hormones, Insulin Resistance and Effects of Exercise in a Human Experimental Model of Menopause
Sponsors
Source
Rigshospitalet, Denmark
Oversight Info
Has Dmc
No
Brief Summary
The main objective of this study is to investigate the role of female sex hormones in
relation to insulin resistance in a controlled human experimental model of menopause and to
explore whether exercise and/or hormone treatment (HT) can compensate for loss of endogenous
sex hormone production by maintaining insulin sensitivity and metabolic activity at a level
equivalent to what is seen in premenopausal women.
Loss of ovarian function is associated with an increased incidence of metabolic disease
including metabolic syndrome, type 2 diabetes and cardiovascular disease. This increased
disease incidence seems to be related to changes in body composition including decreased
skeletal muscle mass and increased visceral fat mass as well as decreased whole body fat
oxidation and energy expenditure. Regular physical activity decreases general mortality among
other things by increasing fat free mass and insulin sensitivity and hereby prevents
metabolic syndrome and cardiovascular disease - conditions seen with an increased incidence
after menopause and could therefore be a possible treatment.
In the present study the Investigators will assess the role of sex hormones in a model of
menopause where healthy women are undergoing planned bilateral oophorectomy due to risk of
hereditary ovary cancer. The use of this model makes it possible to control the time point
for loss of ovarian function and hereby investigate the timeframe and possible contributing
factors in a strictly controlled model. 48 premenopausal women will be included in the study.
The study is conducted in women who have already been offered surgical oophorectomy. The
first 2 months the study will be an observational cohort study. Hereafter the patients will
be allocated to one of four groups (n=12) in a randomized controlled trial, addressing the
effects of 6 months of exercise with or without HT. Type of surgery has been decided before
inclusion based on medical indications. The women will be offered HT according to national
guidelines, but the choice is up to them. Randomization applies only to the training
intervention.
Firstly the Investigators aim at investigating the role of endogenous female sex hormones and
HT in relation to insulin resistance, whole body fat oxidation and -energy expenditure,
changes in visceral fat mass and fat free mass after oophorectomy. Secondly, the
Investigators wish to study the molecular mechanisms behind the oophorectomy-induced insulin
resistance with a focus on insulin signaling in skeletal muscle and fat tissue. Lastly, the
investigators aim to explore whether exercise and/or HT can compensate for loss of endogenous
female sex hormone production by maintaining IS and metabolic activity, hereby preventing
future incidents of metabolic disease in relation to menopause.
All in all, this project will contribute with new knowledge concerning the question of how
endogenous female sex hormones affect insulin sensitivity and metabolic functioning and how
exercise may be used as a disease preventive modality for middle-aged women.
Overall Status
Unknown status
Start Date
2015-08-01
Completion Date
2018-08-01
Primary Completion Date
2018-08-01
Phase
N/A
Study Type
Interventional
Primary Outcome
Measure |
Time Frame |
insulin sensitivity |
1 year |
Enrollment
48
Condition
Intervention
Intervention Type
Behavioral
Intervention Name
Description
The exercise intervention will conduct the following training program 4 days/week for 6 months: endurance training consisting of supervised training on a bike ergometer for 20 min at 70% of maximal heart rate (HR) the first week, increased by 5 min each week until reaching 40 min. Then the intensity will be increased to 80% of max HR over the next month and recalculated every month.
Arm Group Label
training + HT
training - HT
Intervention Type
Drug
Intervention Name
Description
Continually estradiol and gestagens - tablets and patches or cyclic estradiol and gestagens - tablets or patches.
Including:
Drospirenon, Norethisteronacetat, Medroxyprogesteronacetat
Arm Group Label
training + HT
-training + HT
Eligibility
Criteria
Inclusion Criteria:
- women
- going through oophorectomy to prevent hereditary cancer
- premenopausal
Exclusion Criteria:
- infection during the last month
- chronic disease
- smoking
- alcohol > 14 servings/week
- hysterectomized
- premature menopause
- BMI > 30
Gender
Female
Minimum Age
18 Years
Maximum Age
55 Years
Healthy Volunteers
No
Overall Official
Last Name |
Role |
Affiliation |
Julie Abildgaard, MD |
Principal Investigator |
Centre of Inflammation and Metabolism |
Overall Contact
Verification Date
2015-08-01
Lastchanged Date
N/A
Firstreceived Date
N/A
Responsible Party
Responsible Party Type
Principal Investigator
Investigator Affiliation
Rigshospitalet, Denmark
Investigator Full Name
Anders Rasmussen Rinnov
Investigator Title
MD PhD
Has Expanded Access
No
Condition Browse
Number Of Arms
4
Intervention Browse
Mesh Term
Hormones
Arm Group
Arm Group Label
training + HT
Arm Group Type
Experimental
Description
training + HT
Arm Group Label
training - HT
Arm Group Type
Experimental
Description
training - HT
Arm Group Label
-training + HT
Arm Group Type
Placebo Comparator
Description
-training + HT
Arm Group Label
- training - HT
Arm Group Type
No Intervention
Description
- training - HT
Firstreceived Results Date
N/A
Firstreceived Results Disposition Date
N/A
Study Design Info
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Prevention
Masking
None (Open Label)
Study First Submitted
July 29, 2015
Study First Submitted Qc
August 14, 2015
Study First Posted
August 17, 2015
Last Update Submitted
August 14, 2015
Last Update Submitted Qc
August 14, 2015
Last Update Posted
August 17, 2015
Last Known Status
Not yet recruiting
ClinicalTrials.gov processed this data on December 13, 2019
Conditions
Conditions usually refer to a disease, disorder, syndrome, illness, or injury. In ClinicalTrials.gov,
conditions include any health issue worth studying, such as lifespan, quality of life, health risks, etc.
Interventions
Interventions refer to the drug, vaccine, procedure, device, or other potential treatment being studied.
Interventions can also include less intrusive possibilities such as surveys, education, and interviews.
Study Phase
Most clinical trials are designated as phase 1, 2, 3, or 4, based on the type of questions
that study is seeking to answer:
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.
In Phase 1 (Phase I) clinical trials, researchers test a new drug or treatment in a small group of people (20-80) for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
In Phase 2 (Phase II) clinical trials, the study drug or treatment is given to a larger group of people (100-300) to see if it is effective and to further evaluate its safety.
In Phase 3 (Phase III) clinical trials, the study drug or treatment is given to large groups of people (1,000-3,000) to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
In Phase 4 (Phase IV) clinical trials, post marketing studies delineate additional information including the drug's risks, benefits, and optimal use.
These phases are defined by the Food and Drug Administration in the Code of Federal Regulations.