Vasomotor Symptoms (VMS) Progesterone Study: Vasomotor Symptoms and Endothelial Function - Trial of Oral Micronized Progesterone

Phase 2

• Conditions: Menopause
• Interventions: Drug: Oral Micronized Progesterone (Prometrium®); Other: Placebo

• Registration Number: NCT00152438
• Lead Sponsor: University of British Columbia

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 Timeline

• Study Start: 2005-09
• Study First Submitted: 2005-09-08
• Study First Submitted QC: 2005-09-08
• Study First Posted: 2005-09-09
• Primary Completion: 2009-10
• Status Verified: 2011-09
• Last Update Submitted: 2011-09-20
• Last Update Posted: 2011-09-22
• Study Completion: 2012-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 125

Inclusion Criteria

1. Menopausal women (final menstrual period one or more but less than 10 years before)
2. No evidence of vascular disease (normal BP; without diabetes mellitus; normal cholesterol levels and non-smoker for at least a year; and normal ECG.)
3. Moderate to severe VMS during the day and night.

Exclusion Criteria

1. Any menstruation in the preceding year.
2. History of hysterectomy without ovariectomy unless 60 years of age.
3. 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.
4. Body mass index (BMI) over 35 or less than 20.
5. Mean of several pre-treatment blood pressures over 145/95.
6. 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Oral Micronized Progesterone (Prometrium®)	Oral micronized progesterone
2	Placebo	Placebo

Primary Outcome Measures

Name	Time	Method
Vasomotor symptoms prospectively recorded in the final month of therapy by therapy assignment, with pre-therapy baseline vasomotor symptoms as a covariate.	Four months
Forearm blood flow by plethysmography prospectively measured before and after three months of therapy	Four months

Secondary Outcome Measures

Name	Time	Method
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
Lipid, blood pressure (BP), waist circumference and weight changes, measured at baseline and at the end of the study period	Four months

Trial Locations

Locations (1)

Centre for Menstrual Cycle and Ovulation Research; 🇨🇦 Vancouver, British Columbia, Canada