Midlife Cholesterol Study

Northwestern University

Status and phase

Completed

Phase 4

Conditions

Premenopause

Menopause

Postmenopause

Cardiovascular Disease

Treatments

Drug: transdermal estradiol patch (Vivelle), oral estrogen (Estrace), progesterone (Prometrium)

Study type

Interventional

Funder types

Other

Identifiers

NCT00361075

5K23RR016067-05

Details and patient eligibility

About

The postmenopausal state is associated with an increase risk for heart disease. Much of this increase in risk may be due to the loss of estrogen (the main female hormone) and the effect of this loss on lipids (blood fats). This loss of estrogen is often treated by estrogen replacement therapy. Estrogen replacement therapy seems to have a beneficial effect on lipid levels. The purpose of this research study is to understand 1) how menopause affects lipids and 2) how hormone replacement therapy effects the lipid metabolism of postmenopausal women.

Full description

Women with the Metabolic Syndrome (central obesity, insulin resistance, and dyslipidemia) are at especially high risk for coronary heart disease (CHD). The prevalence of the Metabolic Syndrome increases with menopause and may partially explain the acceleration in CHD after menopause. Menopause is associated with increased central adiposity, insulin resistance, dyslipidemia (hypertriglyceridemia, increased low density lipoprotein (LDL), reduced high density lipoprotein (HDL) and small dense LDL particles), and increased thrombotic/inflammatory states, but there are no studies investigating the mechanisms that mediate these changes. The objectives of the proposed project are to investigate the emergence of the features of the Metabolic Syndrome in women followed prospectively through the menopause and determine if these features can be reversed with transdermal estrogen. We hypothesize that the increase in central adiposity with menopause will be a major contributor to the increased prevalence of the Metabolic Syndrome with menopause. This is the first prospective study to investigate the 1) effects of menopause and 2) estrogen replacement therapy (ERT) (oral vs. transdermal) on features of the Metabolic Syndrome. We will determine if the increase in central (intraabdominal)fat with menopause is associated with changes in lipids, insulin resistance, adipocytokines, and fibrinolytic/inflammatory markers. We will then determine if these changes can be reversed with transdermal ERT, as compared to oral ERT, which has pharmacologic effects on the liver.

Sex

Female

Ages

47 to 55 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Have demonstrated an interest to participate in the ERT trial
Be premenopausal (have menstrual period in previous three months) prior to start of observational arm
Prior to start of interventional arm (ERT), the women must be postmenopausal (have not had a menstrual cycle in the past twelve months and FSH >30)
Be between the ages of 47 and 55
Not be taking any form of estrogen replacement
Have an intact uterus and at least one ovary and normal screening mammogram in the 12 months prior to starting ERT

Exclusion criteria

Body mass index (kg/m2) greater than 40 kg/m2
History of diabetes mellitus or fasting >110 mg/dl at screening
Abnormal fasting LDL or triglyceride
Use of lipid lowering medications, beta-blockers, birth control pills
Active liver disease (recent history of active hepatitis, jaundice, scleral icterus, and/or elevated liver function tests
History of breast, endometrial or ovarian cancer
History of thrombotic disorder (past history of pulmonary embolus or deep venous thrombosis) or known history of CAD