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

Lead Sponsor: Rigshospitalet, Denmark

Source Rigshospitalet, Denmark
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 August 2015
Completion Date August 2018
Primary Completion Date August 2018
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
insulin sensitivity 1 year
Enrollment 48
Condition
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.

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

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

Last Name: Julie Abildgaard, MD

Phone: +4535457190

Email: [email protected]

Verification Date

August 2015

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
Arm Group

Label: training + HT

Type: Experimental

Description: training + HT

Label: training - HT

Type: Experimental

Description: training - HT

Label: -training + HT

Type: Placebo Comparator

Description: -training + HT

Label: - training - HT

Type: No Intervention

Description: - training - HT

Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Prevention

Masking: None (Open Label)

Source: ClinicalTrials.gov