Cardiovascular Risk Reduction
Conditions
Keywords
Hormone therapy, Pre-menopausal Oophorectomy, Cardiovascular Disease
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.
Interventions
DRUGEstradiol 100 Micrograms Patch
Standard
DRUGEstradiol Patch
Individualized
Sponsors
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
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 subjects
Eligibility
Sex/Gender
FEMALE
Age
21 Years to 45 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Standard Replacement Therapy Regimen 100 mcg transdermal estradiol patch (or equivalent oral dose)
Estradiol 100 Micrograms Patch: Standard | 15 |
| Titrated Replacement Therapy Regimen Transdermal estradiol patch (or equivalent oral dose) titrated to achieve pre-menopausal estradiol level
Estradiol Patch: Individualized | 15 |
| Timed Control Group Healthy age-matched subjects not on hormone therapy | 5 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 1 | 0 |
| Overall Study | Physician Decision | 2 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Standard Replacement Therapy Regimen | Titrated Replacement Therapy Regimen | Timed Control Group | Total |
|---|---|---|---|---|
| Age, Customized < 20 years old | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized 21-45 years old | 15 Participants | 15 Participants | 5 Participants | 35 Participants |
| Age, Customized >46 years old | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race and Ethnicity Not Collected | — | — | — | 0 Participants |
| Region of Enrollment United States | 15 participants | 15 participants | 5 participants | 35 participants |
| Sex: Female, Male Female | 15 Participants | 15 Participants | 5 Participants | 35 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 | 0 / 5 |
| other Total, other adverse events | 3 / 15 | 11 / 15 | 0 / 5 |
| serious Total, serious adverse events | 2 / 15 | 2 / 15 | 0 / 5 |
Outcome results
Primary
Arterial Stiffness
Augmented pressure, a measure of arterial stiffness was recorded through high-fidelity pressure waveforms and compared at planned time frames
Time frame: Baseline, 6 months, and 12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard Replacement Therapy Regimen | Arterial Stiffness | 6 months augmented pressure | 12.7 mm Hg | Standard Deviation 6 |
| Standard Replacement Therapy Regimen | Arterial Stiffness | Baseline augmented pressure | 10.1 mm Hg | Standard Deviation 6.9 |
| Standard Replacement Therapy Regimen | Arterial Stiffness | 12 months augmented pressure | 12.9 mm Hg | Standard Deviation 6.7 |
| Titrated Replacement Therapy Regimen | Arterial Stiffness | 6 months augmented pressure | 16.8 mm Hg | Standard Deviation 6.4 |
| Titrated Replacement Therapy Regimen | Arterial Stiffness | Baseline augmented pressure | 14.8 mm Hg | Standard Deviation 4.3 |
| Titrated Replacement Therapy Regimen | Arterial Stiffness | 12 months augmented pressure | 17.3 mm Hg | Standard Deviation 7.2 |
| Timed Control Group | Arterial Stiffness | Baseline augmented pressure | 6.4 mm Hg | Standard Deviation 3.7 |
| Timed Control Group | Arterial Stiffness | 12 months augmented pressure | 6.5 mm Hg | Standard Deviation 4 |
| Timed Control Group | Arterial Stiffness | 6 months augmented pressure | 5.1 mm Hg | Standard Deviation 3.1 |
Secondary
Changes in Whole Body Fat
Measurements of whole-body fat using Dual energy x-ray absorptiometry (DXA)
Time frame: Baseline and 12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard Replacement Therapy Regimen | Changes in Whole Body Fat | Baseline total body fat | 30712 gm | Standard Deviation 12958 |
| Standard Replacement Therapy Regimen | Changes in Whole Body Fat | 12-month total body fat | 31868 gm | Standard Deviation 18020 |
| Titrated Replacement Therapy Regimen | Changes in Whole Body Fat | Baseline total body fat | 43363 gm | Standard Deviation 26212 |
| Titrated Replacement Therapy Regimen | Changes in Whole Body Fat | 12-month total body fat | 42660 gm | Standard Deviation 25938 |
| Timed Control Group | Changes in Whole Body Fat | Baseline total body fat | 199936 gm | Standard Deviation 14221 |
| Timed Control Group | Changes in Whole Body Fat | 12-month total body fat | 16735 gm | Standard Deviation 3114 |
Secondary
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)
Time frame: Baseline, 6 months, and 12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard Replacement Therapy Regimen | Mean Blood Pressure Reactivity to Cold Stress | 6-month mean blood pressure reactivity | 21 mm Hg | Standard Deviation 13 |
| Standard Replacement Therapy Regimen | Mean Blood Pressure Reactivity to Cold Stress | Baseline mean blood pressure reactivity | 22 mm Hg | Standard Deviation 10 |
| Standard Replacement Therapy Regimen | Mean Blood Pressure Reactivity to Cold Stress | 12-month mean blood pressure reactivity | 26 mm Hg | Standard Deviation 12 |
| Titrated Replacement Therapy Regimen | Mean Blood Pressure Reactivity to Cold Stress | 6-month mean blood pressure reactivity | 25 mm Hg | Standard Deviation 9 |
| Titrated Replacement Therapy Regimen | Mean Blood Pressure Reactivity to Cold Stress | Baseline mean blood pressure reactivity | 20 mm Hg | Standard Deviation 9 |
| Titrated Replacement Therapy Regimen | Mean Blood Pressure Reactivity to Cold Stress | 12-month mean blood pressure reactivity | 25 mm Hg | Standard Deviation 7 |
| Timed Control Group | Mean Blood Pressure Reactivity to Cold Stress | Baseline mean blood pressure reactivity | 20 mm Hg | Standard Deviation 8 |
| Timed Control Group | Mean Blood Pressure Reactivity to Cold Stress | 12-month mean blood pressure reactivity | 17 mm Hg | Standard Deviation 3 |
| Timed Control Group | Mean Blood Pressure Reactivity to Cold Stress | 6-month mean blood pressure reactivity | 18 mm Hg | Standard Deviation 5 |
Secondary
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)
Time frame: Baseline, 6 months, and 12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Standard Replacement Therapy Regimen | Mean Blood Pressure Reactivity to Isometric Hand Grip Exercise | 6-month mean blood pressure reactivity | 11.7 mm Hg | Standard Deviation 5 |
| Standard Replacement Therapy Regimen | Mean Blood Pressure Reactivity to Isometric Hand Grip Exercise | baseline mean blood pressure reactivity | 11.6 mm Hg | Standard Deviation 4.6 |
| Standard Replacement Therapy Regimen | Mean Blood Pressure Reactivity to Isometric Hand Grip Exercise | 12-month mean blood pressure reactivity | 16.2 mm Hg | Standard Deviation 7.1 |
| Titrated Replacement Therapy Regimen | Mean Blood Pressure Reactivity to Isometric Hand Grip Exercise | 6-month mean blood pressure reactivity | 15.3 mm Hg | Standard Deviation 5.3 |
| Titrated Replacement Therapy Regimen | Mean Blood Pressure Reactivity to Isometric Hand Grip Exercise | baseline mean blood pressure reactivity | 11.4 mm Hg | Standard Deviation 5.9 |
| Titrated Replacement Therapy Regimen | Mean Blood Pressure Reactivity to Isometric Hand Grip Exercise | 12-month mean blood pressure reactivity | 12.4 mm Hg | Standard Deviation 7.6 |
| Timed Control Group | Mean Blood Pressure Reactivity to Isometric Hand Grip Exercise | baseline mean blood pressure reactivity | 8.3 mm Hg | Standard Deviation 3.5 |
| Timed Control Group | Mean Blood Pressure Reactivity to Isometric Hand Grip Exercise | 12-month mean blood pressure reactivity | 13.9 mm Hg | Standard Deviation 9.9 |
| Timed Control Group | Mean Blood Pressure Reactivity to Isometric Hand Grip Exercise | 6-month mean blood pressure reactivity | 10.7 mm Hg | Standard Deviation 2.6 |