• INCLUSION CRITERIA:

Patients with karyotypically normal spontaneous premature ovarian failure (as defined by screening protocol 91-CH-0127, i.e. women who have at least 4 months of amenorrhea, two FSH levels above 40 mIU/ml, at least one month apart, and a normal 46, XX karotype, diagnosed with premature ovarian failure prior to the age of 40) who are between the age of 18 and 42 years will be candidates.

EXCLUSION CRITERIA:

General:

Smokers (more than 2 cigarettes per day).

Alcohol users (more than 2 drinks of alcohol per day).

Body mass index (BMI, kg/m(2)) greater than or equal to 30 and less than or equal to 19.

Previous history of hip fracture or other active hip pathology.

Abnormalities of the hip precluding the assessment of bone mineral density.

Major dermatologic disorders, or a history of skin sensitivity to adhesive bandages, tape or transdermal matrix patches.

Hirsutism score greater than 8.

Acne score greater than 1.

Hysterectomy

Baseline free testosterone (FT) levels above the normal range (greater than 6.3 pg/ml in our current essay) and/or SHBG levels less than 36 nmol/L.

Medical use:

Any prior treatment in the past 6 months known to affect bone other than estrogen (i.e., calcitonin, biphosphonates, fluoride, anabolic steroids, testosterone, or herbal therapy that contains androstenedione, and DHEA).

Current and/or past use of: diuretics, anticoagulants (heparin, Coumadin), glucocorticoid drugs, gonadotropin-releasing hormone agonist or antagonist therapy, chemotherapy.

Medical history of:

Anorexia nervosa, hyperprolactinemia, insulin-dependent diabetes, Cushing's syndrome, gastrectomy, osteogenesis imperfecta, mastocytosis, rheumatoid arthritis, long-term parenteral nutrition, hemolytic anemia, hemochromatosis and thalassemia, ankylosing spondylitis, multiple myeloma, Vitamin D deficiency, Paget's disease, primary hyperparathyroidism, hyperthyroidism, hypothyroidism, any cancer or any other major illness.

Contraindications to hormone replacement therapy:

Thromboembolic event associated with previous estrogen use History of endometrial cancer or hyperplasia

History of breast cancer

Hypertriglyceridemia (fasting triglyceride levels greater than 500 mg/dL)

LDL greater than 190mg/dl

Patients taking "statins"

Serum Alkaline phosphatase greater than or equal to 2X the upper limit of normal

Serum GGT greather than or equal to 2X the upper limit of normal

Abnormal values on two or more hepatic panel tests

Undiagnosed Vaginal Bleeding

Known sensitivity to agents

Note: We will include patients with premature ovarian failure on antidepressant medications, since today's most common antidepressant medication (Prozac) does not have a major import on cognitive function. However, we will note whether they are on these medications.

CONTROL SELECTION CRITERIA:

Healthy non-pregnant regularly menstruating women (cycles between 21 and 35 days), non-smokers, non-alcohol users, under no medications, using non-hormonal contraceptive methods (i.e. barrier methods of contraception, or sterilization) and with no intention to conceive within the following 3 years.