Oophorectomy, Estrogen Therapy and Cardiovascular Disease Risk in Young Women

Impact of Individualized Estrogen Therapy on Cardiovascular Disease Risk Parameters in Young Women After Bilateral Oophorectomy: A Randomized Controlled Trial

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.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Risk Reduction
• Intervention / Treatment: Drug: Estradiol 100 Micrograms Patch; Drug: Estradiol Patch

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.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55902
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard replacement therapy regimen; 100 mcg transdermal estradiol patch (or equivalent oral dose)	Drug: Estradiol 100 Micrograms Patch; Standard
Active Comparator: Titrated replacement therapy regimen; Transdermal estradiol patch (or equivalent oral dose) titrated to achieve pre-menopausal estradiol level	Drug: Estradiol Patch; Individualized
No Intervention: Timed Control Group; Healthy age-matched subjects not on hormone therapy

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Blood Pressure Reactivity to Isometric Hand Grip Exercise	Change in mean blood pressure in response to isometric hand grip exercise (30% maximum voluntary contraction)	Baseline, 6 months, and 12 months
Mean Blood Pressure Reactivity to Cold Stress	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)	Baseline, 6 months, and 12 months
Changes in Whole Body Fat	Measurements of whole-body fat using Dual energy x-ray absorptiometry (DXA)	Baseline and 12 months

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Ekta Kapoor, MBBS, Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2019
• Primary Completion (Actual): August 28, 2023
• Study Completion (Actual): August 28, 2023

Study Registration Dates

• First Submitted: January 17, 2019
• First Submitted That Met QC Criteria: January 23, 2019
• First Posted (Actual): January 24, 2019

Study Record Updates

• Last Update Posted (Actual): October 23, 2024
• Last Update Submitted That Met QC Criteria: October 1, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Cardiovascular Disease; Hormone therapy; Pre-menopausal Oophorectomy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Contraceptive Agents, Hormonal; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Reproductive Control Agents; Contraceptive Agents, Female; Contraceptive Agents; Estrogens; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Estradiol; Polyestradiol phosphate
• Other Study ID Numbers: 18-007999

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No