Conditions: Obesity
Keywords: hormone therapy obesity postmenopause disease /disorder proneness /risk insulin sensitivity /resistance metabolic syndrome women's health
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 79
Healthy volunteers: yes

Brief summary:
The purpose of this study is to evaluate potential mechanisms by which estradiol deficiency accelerates fat gain and abdominal fat accumulation in women.

Detailed description:
Many factors contribute to the current epidemic of obesity. Although estrogen status is not commonly recognized as a determinant of obesity risk in women, there is strong evidence from large randomized controlled trials that estradiol (E2)-based hormone therapy (HT) reduces weight gain by about 40% in postmenopausal women. Importantly, there is also strong evidence that E2 reduces abdominal fat accumulation, a fundamental component of the Metabolic Syndrome. Some studies suggest risks of HT outweigh the benefits for some women. However, this does not negate the importance of learning the mechanisms by which E2 influences energy balance and fat patterning.

This study uses gonadotropin releasing hormone (GnRH) analog therapy to determine the effects of chronic (5-month) sex hormone suppression on resting energy expenditure (REE), altered hypothalamic-pituitary-adrenal (HPA) axis activity, and fat gain.

It is hypothesized that REE will be reduced in response to chronic sex hormone suppression, promoting fat gain. It is also hypothesized that stress-induced hypothalamic-pituitary-adrenal (HPA)axis activity will be amplified during sex hormone suppression; altered HPA axis activity leading to cortisol excess causes abdominal fat accumulation. Finally, it is hypothesized that E2 add-back therapy will lessen these responses.

Participants will be randomized so that half of the women in each treatment arm will participate in an exercise training program, consisting of progressive resistance exercise to prevent the decline in fat-free mass (FFM) and the increase in fat mass that has been observed in young women in response to GnRH analog therapy.

Arms:
arm 1: GnRH agonist + placebo arm 2: GnRH agonist + placebo + exercise arm 3: GnRH agonist + Estradiol arm 4: GnRH agonist + Estradiol + exercise

Interventions: intervention 1: leuprolide acetate intervention 2: Estradiol Transdermal intervention 3: progressive resistance exercise training
Intervention descriptions: intervention 1: 3.75 mg for depot suspension delivered by monthly intramuscular injection for 5 months intervention 2: 0.075 mg patch per day for 5 months intervention 3: 45 minute exercise sessions 4 times per week for 5 months

Protocol document: