Clinical Trials

Inclusion Criteria:

• 42-58 years of age at date of randomization.
• Menses absent for at least 6 months and no more than 36 months.
• Last spontaneous menses occurring after age 40.
• Good general health.
• Plasma FSH level ≥ 35 mIU/ml (µu/L) and E2 levels < 40 pg/ml or one of these two hormone criteria plus absence of menses for at least one year. (FSH and E2; FSH and E2 assays may be repeated once if out of range on initial evaluation).
• Normal mammogram within 1 year of randomization.

Exclusion Criteria:

• Use of estrogen- or progestin-containing medication or phytoestrogen containing supplements (e.g., soy concentrates or extracts) within 3 months of randomization; soy containing foods (e.g. tofu, soy milk) will be permissible.
• Use of selective estrogen receptor modulators (SERMs) such as Raloxifene, Tamoxifen, etc.
• Self reported, known BrCa positive genotype (KEEPS will not screen or advise screening for BrCa genes).
• Endometrial thickness > 5 mm by vaginal ultrasound, unless complex endometrial hyperplasia with or without atypia and endometrial cancer are excluded by biopsy.
• Iin utero exposure to diethylstilbestrol (DES) (maternal treatment) by self-report.
• Current smoking- more than 10 cigarettes/day by self report.
• Obesity- body mass index (weight in kg/height in meters^2) > 35.
• History of clinical CVD including myocardial infarction, angina, or congestive heart failure.
• History of cerebrovascular disease including stroke or transient ischemic attack (TIA).
• History of thromboembolic disease (deep vein thrombosis or pulmonary embolus).
• Coronary calcium score ≥ 50 units.
• History of untreated (no cholecystectomy) gallbladder disease.
• Ddyslipidemia – LDL cholesterol >190 mg/dl, or current NCEP criteria for statin treatment based on Framingham Risk Score, if personal physician prescribes and patient initiates lipid-lowering medication.
• Hypertriglyceridemia - triglycerides >400 mg/dl.
• Medications – current or recent (3 months) use of lipid lowering medications or supplements (e.g. statin, fibrate, > 500 mg/day of niacin, red rice yeast).
• Nut allergy (Prometrium® includes peanut oil).
• Uncontrolled hypertension – systolic BP >150 and/or diastolic BP > 95.
• Hysterectomy.
• History of, or prevalent, chronic diseases including any cancer (other than basal cell skin cancers), renal failure, cirrhosis, uncontrolled hypertension, diabetes mellitus, and endocrinopathies other than adequately treated thyroid disease.
• Known HIV infection and/or medications for HIV infection.
• Active severe clinical depression (BDS score > 17).
• Dementia (MMSE score < 23).
• Results of any safety laboratory test (chemistries, TSH, CBC, U/A) more than 20% above or below limits of normal for center laboratory at which value is measured, unless cleared by either a repeat value within acceptable limits or further medical screening by a qualified medical provider documenting absence of any other evidence of pathology predicted by the out-of-range laboratory value in question.