Oophorectomy, Estrogen Therapy and Cardiovascular Disease Risk in Young Women

Sponsor

Mayo Clinic (Other)

Overall Status

Recruiting

CT.gov ID

NCT03815929

Collaborator

(none)

Enrollment

Location

Arms

55.6

Anticipated Duration (Months)

1.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cardiovascular Risk Reduction	Drug: Estradiol 100 Micrograms Patch Drug: Estradiol Patch	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Intervention Model Description:

Subject be placed into three different study arms. Subjects undergoing surgery will be randomized to receive either standard hormone therapy or individualized hormone therapy. These arms will be compared against each other as well as a third arm of healthy timed-control subjectsSubject be placed into three different study arms. Subjects undergoing surgery will be randomized to receive either standard hormone therapy or individualized hormone therapy. These arms will be compared against each other as well as a third arm of healthy timed-control subjects

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Mar 15, 2019

Anticipated Primary Completion Date :

Aug 1, 2023

Anticipated Study Completion Date :

Nov 1, 2023

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Change in Endothelial function [Baseline, 6 months, and 12 months]
Brachial artery flow mediated dilation using ultrasonography to measure any endothelium dysfunction occurring over 12 months.
Change in cerebral vascular reactivity [Baseline, 6 months, and 12 months]
Changes to the middle cerebral artery blood flow velocity measured using a Multigon Trans-Cranial Doppler sonogram probe monitoring with three stepwise end-tidal carbon dioxide elevations of constant concentration levels with 3 minutes at each level is compared over planned time frames.

Secondary Outcome Measures

Change in Arterial tonometry [Baseline, 6 months, and 12 months]
Arterial stiffness is recorded through high-fidelity pressure waveforms and compared at planned time frames
Changes in maximal Voluntary Contraction of the non-dominant arm [Baseline, 6 months, and 12 months]
Isometric handgrip exercise squeezing a transducer with goal of consistently maintaining a moderate workload average over 5 attempts and compared over time.
Changes to the index of baroreflex sensitivity [Baseline, 6 months, and 12 months]
Colder pressor test immersing hand up to wrist in ice water while changes in blood pressure and heart rate are monitored and compared over time frames.
Changes in measurements of whole body and regional fat and fat-free mass [Baseline and 12 months]
Measurements will be taken using Dual energy x-ray absorptiometry (DXA) scans and compared over time and between the groups.

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 45 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

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