Comparison of Vascular Findings Between Symptomatic and Asymptomatic Postmenopausal Women Before and During Hormone Therapy (HRT)

Study Overview
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Brief Summary
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Recent large randomized, placebo-controlled studies assessing the health effects of HT question the overall benefits of long term HT, especially with respect to cardiovascular disease. However, recently menopausal women with severe hot flushes were mostly excluded from these trials. This was unfortunate since vasomotor symptoms may reflect different vascular sensitivity to estrogen or its deficiency, and therefore, the vascular responses to HT in women with and without hot flushes can differ. Aims of the present project are to compare vascular, cardiac and sympathetic function in recently menopausal women with or without severe vasomotor symptoms in a randomized placebo controlled clinical trial investigate vascular response to oral and trans-dermal HT.

Detailed Description
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We recruit 160 healthy postmenopausal women between ages 48-55. Eighty women must have severe vasomotor symptoms (at least seven severe or moderate hot flush attacks per day) whereas 80 comparators must be symptomless (no hot flushes). Thorough vascular function and risk factor assessments will be done, including clinical assessment of autonomic nervous system, endothelial function measurements, 24-hour ECG and blood pressure evaluation, and lipid and various other vascular surrogate marker measurements. In the first part of the study we compare these baseline measurements between women with or without severe vasomotor symptoms. In the second part of the study the women are randomized to receive placebo, oral estrogen, oral estrogen plus progestin or transdermal estrogen for 6 months. After the treatments the baseline assessments are repeated.

Official Title
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Comparison of Vascular Findings Between Symptomatic and Asymptomatic Postmenopausal Women Before and During Hormone Therapy: A Randomized, Placebo-controlled Prospective Study

Conditions
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Postmenopausal Vasomotor Symptoms, Cardiovascular Disease

Intervention / Treatment
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* Drug: 17-b-estradiol
* Drug: 17-b-estradiol + medroxyprogeterone acetate
* Drug: 17-b-estradiol hemihydrate
* Drug: placebo pill + gel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Postmenopausal women between ages 48-55 Minimum of 6 months and maximum of 36 months from last menstrual period Postmenopausal status of these women will be confirmed by level of FSH that should exceed 30 U/l Eighty women must have severe vasomotor symptoms (at least seven severe or moderate hot flush attacks per day) whereas eighty comparators must be symptomless Exclusion Criteria: smoking hysterectomy dyslipidemia overt hypertension (blood pressure > 140/90) diabetes any regular medication HT in the previous 3 months body mass index over 27

Ages Eligible for Study
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Minimum Age: 48 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2<br>Postmenopausal women with severe vasomotor symptoms | Drug: 17-b-estradiol<br>* 2mg oral daily for 6 months<br>Drug: 17-b-estradiol + medroxyprogeterone acetate<br>* 2mg E2 + 5mg MPA daily for 6 months<br>* Other names: Indivina;Drug: 17-b-estradiol hemihydrate<br>* 1 mg skin gel daily for 6 months<br>* Other names: Divigel;Drug: placebo pill + gel<br>* placebo daily for 6 months<br>|
| Experimental: 1<br>Postmenopausal women without vasomotor symptoms | Drug: 17-b-estradiol<br>* 2mg oral daily for 6 months<br>Drug: 17-b-estradiol + medroxyprogeterone acetate<br>* 2mg E2 + 5mg MPA daily for 6 months<br>* Other names: Indivina;Drug: 17-b-estradiol hemihydrate<br>* 1 mg skin gel daily for 6 months<br>* Other names: Divigel;Drug: placebo pill + gel<br>* placebo daily for 6 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vascular function |  | 0 and 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiac and sympathetic function |  | 0 and 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Postmenopausal vasomotor symptoms, Hot flush, Vascular function, Cardiac function, Cardiovascular risk factor