The purpose of this study is to determine if estrogen or testosterone can affect cortisol levels and where fat builds up in our bodies.

Subjects will be studied 3 or 4 times on the inpatient unit of the Oregon Clinical and Translational Research Center. During each visit, testing will include measuring the amount of whole body fat and fat in the stomach area, muscle, and liver; levels of cortisol in the blood, urine, and fat tissue (taken from a biopsy); how well insulin works (insulin sensitivity).

• Obesity
• Menopause

• Drug: Placebo injection
  Normal saline injection IM monthly for 4 months
  Other Name: Normal Saline
• Drug: Depo Lupron/Aromatase inhibitor
  Depo Lupron injection 7.5mg IM monthly for 8 months, with addition of testosterone gel and aromatase inhibitor months 4-8.
  Other Names:

  • Depo-Lupron
  • Testim 1% gel
  • Anastrozole
  • Arimidex
• Drug: Depo Lupron/placebo
  Depo Lupron injection 7.5mg IM monthly for 8 months, with addition of testosterone gel and placebo months 4-8.
  Other Names:

  • Depo-Lupron
  • Testim 1% gel
  • Placebo capsules
• Drug: placebo
  Placebo Cream 1ml applied twice daily for four months
  Other Name: Placebo cream
• Drug: Estrogen cream
  Estrogen cream 1 ml twice daily, dose titrated to maintain estradiol level between 60 and 280 pg/ml.
  Other Name: Estradiol cream

• 1: Placebo Comparator
  Men on placebo injections for 4 months
  Intervention: Drug: Placebo injection
• 2: Active Comparator
  Men who receive Depo Lupron for 4 months, then are replaced with testosterone and aromatase inhibitor for 4 months.
  Intervention: Drug: Depo Lupron/Aromatase inhibitor
• 3: Active Comparator
  Men who receive Depo Lupron for 4 months, then are replaced with testosterone and placebo for 4 months.
  Intervention: Drug: Depo Lupron/placebo
• 4: Placebo Comparator
  Women on placebo cream
  Intervention: Drug: placebo
• 5: Active Comparator
  Women on estrogen cream
  Intervention: Drug: Estrogen cream

Inclusion Criteria:

• 40 postmenopausal women (age 40-62) and 30 men (age 18-45) will be recruited if they are healthy, at their lifetime maximal weight, have been weight stable for at least six months prior to entry, have a BMI between 19 and 39.9 kg/m2, and be willing to commit to not making significant changes to their diet or daily activities while enrolled in the study.

Exclusion Criteria:

• Subjects will be excluded for potential confounders on body weight, cortisol production rates, sex steroid metabolism, or contraindications to strong magnetic fields:

  1. Age less than 18 to exclude those who might be experiencing alterations in cortisol production or weight as a result of adolescent growth
  2. Subjects who exercise > 30 minutes/day, 3 times a week
  3. Smokers
  4. Heavy alcohol drinkers (> 2 drinks/ day)
  5. Subjects with medical diagnosis including diabetes, heart disease, and cancer
  6. Subjects with psychiatric illness (i.e., depression, psychosis, bipolar, schizophrenia; or are taking medications for these disorders)
  7. BMI 40 kg/m2, since obesity influences levels of sex steroids and sex hormone binding globulin; or body weight > 136 kg (300 lbs), since this is the weight limit for the DEXA and MR machines
  8. Presence of metal in the body such as body piercing, shrapnel, cardiac pacemakers or aneurysm clips
  9. Endocrine diseases affecting body composition, such as untreated hypothyroidism or Cushing's syndrome, will be excluded by history and physical examination, or by laboratory evaluation if necessary.
• Women with a contraindication to estrogen use will also be excluded, including: an estrogen dependent malignancy, active thrombophlebitis, history of deep venous thrombosis, hypertriglyceridemia, untreated hypertension, cardiovascular disease, migraine headaches, or current tobacco use.
• Women with frequent hot flashes or disrupted sleep will also be excluded since they will be unlikely to tolerate randomization to placebo and continued symptoms and altered sleep cycles will independently affect cortisol secretion patterns.
• All volunteers will have had a normal mammogram within the previous 12 months.
• Any subject with previously unevaluated postmenopausal bleeding will not be included and, instead, will be referred to a physician for evaluation.
• Women who underwent surgical menopause (bilateral ovariectomy) must be at least one year out from their surgery before considered eligible so as to allow weight stabilization after the procedure.
• Men will have had a prostate exam by their primary health provider within the previous year or by the PI at the time of screening for this study.
• Any subjects taking a blood thinning medication or with an abnormal exam will not be included and, instead, will be referred to a physician for evaluation