Female Sex Hormones, Insulin Resistance and Effects of Exercise in a Human Experimental Model of Menopause

Lead Sponsor

Rigshospitalet, Denmark

Source

Rigshospitalet, Denmark

Oversight Info

Has Dmc

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

Condition

Metabolic Syndrome

Intervention

Intervention Type

Behavioral

Intervention Name

exercise

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

Hormone treatment

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

Overall Official

Last Name	Role	Affiliation
Julie Abildgaard, MD	Principal Investigator	Centre of Inflammation and Metabolism

Overall Contact

Last Name

Julie Abildgaard, MD

Phone

+4535457190

Email

[email protected]

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

Condition Browse

Metabolic Syndrome

, Insulin Resistance

Number Of Arms

Intervention Browse

Mesh Term

Hormones

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.

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