Midlife Cholesterol Study

Cardiovascular Disease Clinical Trial

Official title:

Mentored Patient Oriented Research Career Development Award

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00361075
• Other study ID #: 5K23RR016067-05
• Status: Completed
• Phase: Phase 4
• First received: August 3, 2006
• Last updated: November 4, 2014
• Start date: July 1998
• Est. completion date: May 2005

Study information

• Verified date: November 2014
• Source: Northwestern University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: May 2005
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 47 Years to 55 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Cardiovascular Disease
• Cardiovascular Diseases
• Menopause
• Postmenopause
• Premenopause

Intervention

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

Locations

Country	Name	City	State
United States	Northwestern University	Chicago	Illinois
United States	University of Washington	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Northwestern University	University of Washington

Country where clinical trial is conducted

United States, 

References & Publications (2)

Carr MC, Hokanson JE, Deeb SS, Purnell JQ, Mitchell ES, Brunzell JD. A hepatic lipase gene promoter polymorphism attenuates the increase in hepatic lipase activity with increasing intra-abdominal fat in women. Arterioscler Thromb Vasc Biol. 1999 Nov;19(11):2701-7. — View Citation

Carr MC, Kim KH, Zambon A, Mitchell ES, Woods NF, Casazza CP, Purnell JQ, Hokanson JE, Brunzell JD, Schwartz RS. Changes in LDL density across the menopausal transition. J Investig Med. 2000 Jul;48(4):245-50. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	LDL particle size and density
Secondary	Total body adiposity (Dexa scans)
Secondary	Intra-abdominal fat (CT scans)
Secondary	Lipid Profile
Secondary	Inflammatory Factors
Secondary	Adipocytokines