Vasomotor Symptoms and Endothelial Function-A Randomized Placebo-controlled Trial of Oral Micronized Progesterone (Prometrium®)
Trial Snapshot
- Phase
- Phase 2
- Enrollment
- 125
- Locations
- 1
- Primary Endpoint
- Vasomotor symptoms prospectively recorded in the final month of therapy by therapy assignment, with pre-therapy baseline vasomotor symptoms as a covariate.
Study Overview
Brief Summary
The primary purpose of this study is to determine the effects of a full dose (300 mg at hs) of oral micronized progesterone (OMP) on vasomotor symptoms [VMS] (hot flushes/night sweats), on forearm blood flow and on lipid levels and blood pressure in menopausal women without cardiovascular disease and with moderate to severe VMS.
The hypotheses are that progesterone will improve hot flushes, increase endothelium-dependent forearm blood flow and will decrease blood pressure without change in lipid levels.
Detailed Description
In this 4-month study, menopausal women are randomized to either placebo or oral micronized progesterone (Prometrium®). Participants maintain a daily diary to keep track of their vasomotor symptoms and other factors. Forearm blood flow will be assessed by venous occlusion plethysmography at baseline and after three months of therapy. Screening tests at baseline to rule out heart disease include measurement of blood pressure and heart rate, electrocardiogram (ECG) and blood tests - fasting blood glucose and lipid profile.
Collection of serum and plasma samples at baseline and end of therapy for analysis of cardiovascular markers (e.g., c-reactive protein) and clotting and fibrinolytic markers. Continued daily diary collection for one month after therapy discontinuation to look for possible rebound effects. Analysis of outcomes will be by analysis of covariates, with final value as the outcome, therapy as factor and baseline values as covariate.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 40 Years to 65 Years (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Menopausal women (final menstrual period one or more but less than 10 years before)
- •No evidence of vascular disease (normal BP; without diabetes mellitus; normal cholesterol levels and non-smoker for at least a year; and normal ECG.)
- •Moderate to severe VMS during the day and night.
Exclusion Criteria
- •Any menstruation in the preceding year.
- •History of hysterectomy without ovariectomy unless 60 years of age.
- •Use of ovarian hormone therapy (estrogen, progestin, progesterone or androgen) or selective estrogen receptor modulator (SERM) therapy (raloxifene or tamoxifen) in the preceding six months.
- •Body mass index (BMI) over 35 or less than
- •Mean of several pre-treatment blood pressures over 145/
- •Documented abnormal cholesterol; abnormal fasting capillary glucose; abnormal angiogram; ECG or exercise stress tests or a diagnosis of diabetes mellitus; or any history suggestive of angina.
Arms & Interventions
1
Oral micronized progesterone
Intervention: Oral Micronized Progesterone (Prometrium®) (Drug)
2
Placebo
Intervention: Placebo (Other)
Outcomes
Primary Outcomes
Vasomotor symptoms prospectively recorded in the final month of therapy by therapy assignment, with pre-therapy baseline vasomotor symptoms as a covariate.
Time Frame: Four months
Forearm blood flow by plethysmography prospectively measured before and after three months of therapy
Time Frame: Four months
Secondary Outcomes
- Lipid, blood pressure (BP), waist circumference and weight changes, measured at baseline and at the end of the study period(Four months)
- Other hormone-related quality of life measures on the Daily Menopause Diary®, especially self worth, sleep, and energy, recorded during the 4 months of the study.(Four months)
- Changes in two Quality of Life instruments - the Rand SF-36 and the Menopause-specific Quality of Life (MenQoL) questionnaires, measured at baseline and at the end of the study period(Four months)