Researchers are trying to assess the appropriate dose of estrogen for decreasing the risk of cardiovascular disease in women who have removal of their ovaries at a young age, before the age of 46 years.

Baseline Study Visit: Subjects will report for the Baseline Study Day in an 8 hour fasting state (water only) and refrain from heavy exercise, caffeine, and alcohol for 24 hours. The participant will undergo study specific procedures including a urine pregnancy test if they are of child bearing potential. Participants will also complete a set of questionnaires. After the completion of the study tests, participants will be offered a meal.

Participants scheduled for surgery to remove their ovaries: after the surgery subjects will be randomized to one of two groups. They will receive the standard dose of the hormone (estrogen) patch, generally prescribed to patients after removal both ovaries. Or sent home on the standard dose hormone patch, hormone levels will be tested every 3-4 weeks, and patch dose adjusted until the estrogen level is reached that results in the hormone levels of a young woman before menopause. In order to check hormones, subjects will be able to choose to have a lab kit sent to them and have the draw done locally, or can come in person.

Participants will also receive a second hormone prescription if they have an intact uterus to protect the lining of the uterus from the effects of using estrogen alone.

6-Month Study Visit: Subjects will be asked to come back and repeat most of the study specific tests from the baseline study visit that will take about 5 hours.

1-Year Study Visit: Subjects will be asked to come back for the final visit and will repeat all the study tests done at baseline visit. This visit will take about 5 hours.

Control Group: Healthy subjects serving as controls to see how measures change over time will not undergo a surgery or be given estrogen. These healthy subjects will return after the baseline visit to repeat study visits at 6 and 12-months.

Inclusion Criteria:

• Premenopausal women undergoing (or completion of a) bilateral oophorectomy for non-malignant diagnoses at Mayo Clinic, Rochester; or premenopausal women not undergoing the procedure for the timed control group
• Currently between the ages of 21- 45 years
• Able to participate fully in all aspects of the study
• Able to understand and sign the informed consent.

Exclusion Criteria:

• History of hepatic, renal, or hematological diseases
• History of venous thromboembolism; peripheral vascular disease; coronary artery disease; stroke/neurovascular disease
• Chemotherapy or radiation therapy in the preceding 3 months
• Current tobacco use
• Current use of medication that alters autonomic or vascular function (e.g. tricyclic antidepressants, α-blockers, β-blockers, etc.) or aromatase inhibitor/tamoxifen therapy
• Contra-indication to estrogen use
• Current or previous diagnosis of breast and endometrial cancer
• For Timed Controls: Are currently pregnant or lactating, or are of child-bearing potential or are likely to become pregnant during the study and unwilling to use contraception; Acceptable forms include:Barrier methods (such as a condom or diaphragm) used with a spermicide (a foam, cream, or gel that kills sperm), Copper Intra Uterine Device, Hysterectomy, Tubal ligation, Abstinence (no sex)
• Any condition or factor judged by the investigator to preclude participation in the study

12 months