Oophorectomy, Estrogen Therapy and Cardiovascular Disease Risk in Young Women

Phase 2

Completed

Conditions: Cardiovascular Risk Reduction

Interventions: Drug: Estradiol 100 Micrograms Patch
Drug: Estradiol Patch

Registration Number: NCT03815929

Lead Sponsor: Mayo Clinic

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 35

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard replacement therapy regimen	Estradiol 100 Micrograms Patch	100 mcg transdermal estradiol patch (or equivalent oral dose)
Titrated replacement therapy regimen	Estradiol Patch	Transdermal estradiol patch (or equivalent oral dose) titrated to achieve pre-menopausal estradiol level

Primary Outcome Measures

Name	Time	Method
Arterial Stiffness	Baseline, 6 months, and 12 months	Augmented pressure, a measure of arterial stiffness was recorded through high-fidelity pressure waveforms and compared at planned time frames

Secondary Outcome Measures

Name	Time	Method
Mean Blood Pressure Reactivity to Isometric Hand Grip Exercise	Baseline, 6 months, and 12 months	Change in mean blood pressure in response to isometric hand grip exercise (30% maximum voluntary contraction)
Mean Blood Pressure Reactivity to Cold Stress	Baseline, 6 months, and 12 months	Maximum change in mean blood pressure during 3-minute cold pressor test (immersing hand up to wrist in ice water while changes in blood pressure monitored)
Changes in Whole Body Fat	Baseline and 12 months	Measurements of whole-body fat using Dual energy x-ray absorptiometry (DXA)