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
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.
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