Pharmacogenetic Study of Different Hormone Therapies in Recent Menopause Women

Study Overview
=================
Brief Summary
-----------------
This is cross-over, randomized clinical trial, with objective to evaluate the effects of low-dose oral hormone therapy and non-oral hormone therapy on endothelial function markers (fibrinogen, von Willebrand factor, c-reactive protein), natriuretic peptide and on anthropometric, metabolic and hormonal variables in early and healthy postmenopausal women and analyzing polymorphisms in the estrogen receptor gene and FTO polymorphisms Patients will be randomized to receive oral hormone treatment or non-oral hormone treatment The investigators hypothesis is that a different genotypes in the receptor estrogen gene and FTO may have an influences on treatment response in metabolic markers and cardiovascular risk

Official Title
-----------------
Polymorphisms in Genes Encoding the Estrogen Metabolism Enzymes and Effects of Hormone Therapy for Oral Low Dose or Not Oral on Variables Related Endothelial Function, Inflammation and Metabolic Profile in Patients in Recent Menopause Study Pharmacogenetic

Conditions
-----------------
Postmenopause

Intervention / Treatment
-----------------
* Drug: Estradiol and Progesterone
* Drug: Estradiol and Drospirenone


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: last menstrual period between 6 months and 3 years before the beginning of the study plus FSH levels higher than 35 IU/L; age between 42 and 58 years; no use of any medication known to interfere with hormonal, glucose, or lipoprotein levels in the past 3 months; no use of steroidal or no steroidal anti-inflammatory drugs in the last 15 days. Exclusion criteria: patients with diabetes, previous hysterectomy, endometrial thickness >0.5cm, history of cancer, thromboembolism, or established cardiovascular disease

Ages Eligible for Study
-----------------
Minimum Age: 42 Years
Maximum Age: 58 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Non-oral hormone therapy<br>3 mg/day intranasal estradiol daily or 1,5 mg/day transdermal estradiol and 200 mg/day vaginal micronized progesterone for 14 days/month | Drug: Estradiol and Progesterone<br>* 3 mg/day intranasal estradiol daily or 1,5 mg/day transdermal estradiol and 200 mg/day vaginal micronized progesterone for 14 days/month<br>|
| Active Comparator: oral homone therapy<br>estradiol 1mg and drospirenone 2 mg/day | Drug: Estradiol and Drospirenone<br>* oral estradiol 1mg and drospirenone 2 mg/day<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Polymorphisms of estrogen receptor | Influence of 4 polymorphisms (PVUII, ALUI, RSAI and BSTUI) on the effect of different treatment regimens. Change from Baseline in weight, waist circumference, BMI, systolic and diastolic blood pressure, fasting glucose, glucose at 120 min, Fasting insulin, HOMA, Cholesterol, HDL-c, LDL-c, Triglycerides, Von Willebrand Factor, Fibrinogen, Testosterone and C-reactive protein at six months. | six months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Polymorphisms in the fat mass-and obesity-associated (FTO) gene | Influence of 2 polymorphisms (rs9939609 and rs8050136) on the effect of different treatment regimens. Change from Baseline in weight, waist circumference, BMI, systolic and diastolic blood pressure, fasting glucose, glucose at 120 min, Fasting insulin,HOMA, Cholesterol, HDL-c, LDL-c, Triglycerides, Von Willebrand Factor, Fibrinogen, Testosterone and C-reactive protein at six months. | Six Months |