Hot Flash as a Marker of Cardiovascular Risk in Recent Postmenopause: Effects of Non-hormonal Treatments

Study Overview
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Brief Summary
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Hot flashes, vasomotor symptoms that affect many postmenopausal women, are associated with cardiovascular disease and endothelial dysfunction. Estrogen therapy, associated or not with progestogens, is the standard treatment for vasomotor symptoms and improves the endothelial function of postmenopausal women with hot flushes, even those with cardiovascular risk factors, such as hypertension. It is not known whether hot flushes are a cause for the development of endothelial dysfunction or are markers of this dysfunction, evidenced by estrogen deficiency, thus representing primitive target organ (vessel) lesion. Paroxetine was approved by the FDA as a non hormonal treatment for menopausal hot flashes. In this double-blind randomized clinical trial, the vascular effects of paroxetine at a dose of 7.5 mg / day, compared to placebo, during 12 weeks are evaluated.

Detailed Description
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Paroxetine and placebo effects at baseline and after 12 weeks in endothelial, autonomic and pressure components of vascular function are evaluated. Non invasive venous occlusion plethysmography is used to study endothelial function; ambulatory blood pressure monitoring is used to study blood pressure variations during daytime and nocturnal descent; autonomic function is studied following sympathetic and parasympathetic parameters through heart rate variability. The effects of paroxetine and placebo are also evaluated on: daytime sleepiness (through Epworth Sleepiness Scale ), sleep quality (through Pittsburgh Sleep Quality Index), perceived stress (through Perceived Scale Stress). Biochemical and hormonal profiles including complete lipid profile, fasting glucose, insulin, estradiol, follicle stimulating hormone (FSH), luteinizing hormone (LH); inflammatory and oxidative stress markers are also studied.

Official Title
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Endothelial, Autonomic and Pressure Effects of Paroxetine in Recent Postmenopause Women With Hot Flashes: a Randomized Placebo Controlled Clinical Trial

Conditions
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Postmenopausal Flushing, Cardiovascular Risk Factor, Endothelial Dysfunction

Intervention / Treatment
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* Drug: Paroxetine
* Drug: Placebo oral capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Postmenopause Present hot flushes (note ≥ 3 on a scale of 0 to 10) Exclusion Criteria: > 10 years of hypoestrogenism Smoking Diabetes mellitus or altered fasting glycemia in use of oral hypoglycemic agents or insulin BMI ≥ 35 Kg / m2 Uncontrolled hypertension - blood pressure (BP) ≥ 140/90 mmHg Users of glucocorticoids, phytoestrogens, β-blockers, selective serotonin reuptake inhibitors (SSRIs), selective noradrenaline reuptake inhibitors (SNRIs), clonidine, gabapentin, pregabalin, cinnarizine, alphamethyldopa or any drugs with effects on the central nervous system; Uncompensated hypo or hyperthyroidism; Previous cardiovascular event history.

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 65 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 |
| --- | --- |
| Active Comparator: Paroxetine<br>Paroxetine 7,5 mg - 1 pill/day for 12 weeks | Drug: Paroxetine<br> <br> |
| Placebo Comparator: Placebo<br>Placebo oral capsule (corn starch) - 1 pill/day for 12 weeks | Drug: Placebo oral capsule<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endothelial function in non invasive venous occlusion plethysmography | Forearm blood flow (ml/min per 100 ml) | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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postmenopause, paroxetine, endothelial dysfunction, blood pressure, heart rate variability, sleep quality, perceived stress, sleepiness