Prevention of Obesity in Women Via Estradiol Regulation
Condition: Obesity
MeSH terms: Obesity
Intervention: leuprolide acetate; Estradiol Transdermal; progressive resistance exercise training
Intervention description: 3.75 mg for depot suspension delivered by monthly intramuscular injection for 5 months; 0.075 mg patch per day for 5 months; 45 minute exercise sessions 4 times per week for 5 months
Intervention MeSH terms: Leuprolide; Estradiol
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 79.0
Sex: Female
Minimum age: 18 Years
Maximum age: 49 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: hormone therapy; obesity; postmenopause; disease /disorder proneness /risk; insulin sensitivity /resistance; metabolic syndrome; women's health

Summary:

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

Eligibility criteria:

        Inclusion Criteria:

          -  Healthy premenopausal women, aged 18 to 49 years

          -  Regular menses (no missed cycles in previous year; cycle length 25-35 days)

          -  Positive luteinizing hormone test or a mid-luteal serum progesterone greater than 3
             ng/mL

          -  Nonsmokers

          -  Willing to receive all study interventions

          -  Physically able and willing to be randomized to participate in a supervised resistance
             exercise training program

        Exclusion Criteria:

          -  Already performing high-intensity resistance exercise training more than 1 day per
             week

          -  On diabetes medications

          -  Use of hormonal contraception in the past 3 months

          -  On oral or inhaled glucocorticoids

          -  Positive pregnancy test

          -  Intention to become pregnant or start hormonal contraceptive therapy during the period
             of study

          -  Lactation

          -  Hypersensitivity to extrinsic peptide hormones, mannitol, Gonadotropin-releasing
             hormone (GnRH), leuprolide acetate, benzyl alcohol (the vehicle for injection of
             leuprolide acetate), or transdermal patch

          -  Score greater than 16 on the Center for Epidemiologic Studies Depression Scale and
             Beck Depression Inventory-II score greater than 18, or clinician recommendation to
             exclude

          -  Severe osteopenia or osteoporosis (proximal femur or lumbar spine t scores < -2.0)

          -  BMI greater than 40 kg/m2, weight change of more than ± 2 kg in last 6 months, or
             weight-reduced by more than 5 kg from maximal body weight

          -  Abnormal vaginal bleeding

          -  History of breast cancer or other estrogen-dependent neoplasms

          -  History of venous thromboembolic events

          -  Moderate or severe renal impairment (creatinine clearance <50 mL/min by
             Cockcroft-Gault)

          -  Chronic hepatobiliary disease, defined as liver function tests (AST, ALT, alkaline
             phosphatase, total bilirubin) greater than 1.5 times the upper limit of normal

          -  Thyroid dysfunction, defined as ultra sensitive TSH less than 0.5 or greater than 5.0
             mU/L

          -  Uncontrolled hypertension, defined as resting BP greater than 150/90 mmHg

          -  Cardiovascular disease, including indicators of ischemic heart disease or serious
             arrhythmias at rest or during the graded exercise test; follow-up diagnostic testing
             to rule out cardiovascular disease by a cardiologist will be allowed

          -  Orthopedic or other problems that would interfere with participation in the exercise
             program