Cardiometabolic Consequences of the Loss of Ovarian Function

Prior treatment

• Use of glucocorticoids (inhaled, oral, topical) or drugs that affect glucocorticoid metabolism (e.g., ketoconazole) in the last 3 months;
• Smoking or Tobacco use within the previous 12 months;

Other illness

• Known hypersensitivity to study medications;
• Preexisting or active cardiac, renal, or hepatic disease: past or current history of these diseases or conditions;
• Active or chronic infection: inflammation associated with active or chronic infections impair vascular function;
• History of venous thromboembolic event (VTE): safety reasons, estradiol therapy can increase the risk of VTE;
• History of breast cancer or other estrogen-dependent neoplasm: estradiol therapy is contraindicated;

Lab values

• Diabetic or fasted glucose \>126 mg/dL;

Other

• Body mass index (BMI) \>35 kg/m2;
• Weight change \>5 kg in the last 3 months;
• Excess alcohol consumption, defined as \>14 drinks per week by self-report;
• Depressive symptoms, defined as a CES-D score \>16;
• Resting blood pressure \>150/90 mmHg;
• Thyroid dysfunction, defined as an ultrasensitive TSH \<0.5 or \>5.0 mU/L; volunteers with abnormal TSH values will be reconsidered for participation in the study after follow-up evaluation by the PCP with initiation or adjustment of thyroid hormone replacement;
• Severe low bone mass or osteoporosis, defined as a hip or lumbar spine T-score \<-2.0: safety reasons, women who are randomized to the ovarian suppression plus placebo group could see a decrease in bone mineral density due to the suppression of estrogen;

• Age criteria of 20-45 years: the investigators are determining the effects of ovarian suppression on adiposity and vascular in premenopausal women;
• Premenopausal defined as normal menstrual cycle function defined as no more than 1 missed cycle in the previous year: irregular menstrual or missed menstrual cycles could indicate that women are anovulatory and/or perimenopause;
• Not pregnant or planning to become pregnant;
• Not lactating in the last 3 months;
• Serum FSH \<10 IU/L measured during days 1-10 of the menstrual cycle: to ensure the woman is premenopausal and not perimenopausal;
• Not on hormonal contraception in the last 3 months;
• Sedentary or recreationally active (\<2 days/wk vigorous exercise);
• No use of medications that might influence vascular function (i.e., antihypertensives, lipid lowering medications, blood thinners);
• No use of antioxidant supplements or chronic NSAIDs or be willing to go off them for 4 weeks prior to enrollment in the study;