Estrogen, HDL, and Coronary Heart Disease in Women

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Stefania lamon-Fava, Tufts University
ClinicalTrials.gov Identifier:
NCT00083824
First received: June 2, 2004
Last updated: March 3, 2014
Last verified: January 2008
  Purpose

To clarify the effects of estrogen, with or without progestin, on high density lipoprotein (HDL) in postmenopausal women.


Condition Intervention Phase
Cardiovascular Diseases
Coronary Disease
Heart Diseases
Coronary Arteriosclerosis
Drug: Estrogens, Conjugated (USP)
Drug: Medroxyprogesterone 17-Acetate
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Health Services Research
Official Title: Estrogen, HDL, and Coronary Heart Disease in Women

Resource links provided by NLM:


Further study details as provided by Tufts University:

Primary Outcome Measures:
  • HDL subpopulation distribution and composition [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    To assess the effect of hormonal replacement therapy on HDL subpopulation profile and HDL composition in postmenopausal women with established CHD


Secondary Outcome Measures:
  • Remnant lipoprotein cholesterol [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    To assess the effect of hormonal replacement therapy on remnant lipoprotein cholesterol levels in postmenopausal women with established CHD


Enrollment: 309
Study Start Date: March 2004
Study Completion Date: February 2007
Primary Completion Date: February 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Sugar Pill
Placebo
Experimental: Estrogens, Conjugated (USP)
Conjugated Equine Estrogen 0.625 mg/day for 3 years, drug
Drug: Estrogens, Conjugated (USP)
0.625 mg/day QID for 3 years
Other Name: Premarin
Experimental: Medroxyprogesterone 17-acetate
Conjugated Equine Estrogen 0.625 mg/day plus Medroxyprogesterone Acetate 2.5 mg/day
Drug: Estrogens, Conjugated (USP)
0.625 mg/day QID for 3 years
Other Name: Premarin
Drug: Medroxyprogesterone 17-Acetate
2.5 mg/day QID for 3 years
Other Name: Provera

Detailed Description:

BACKGROUND:

Coronary heart disease (CHD) is the leading cause of death and disability in postmenopausal women in the United States. Low plasma levels of high-density lipoprotein cholesterol (HDL-C) are a well-established risk factor for CHD. Elevated plasma triglyceride (TG) levels are also a risk factor for CHD in women. HDL particles are heterogeneous in composition (containing apo A-I only, LpAI, or apo A-I and apo A-II, LpAIAII) and charge and size (preBeta1, preBeta2, alpha1-3, preAlpha1-4). Different HDL subpopulations have different physiological functions and therefore may vary in their anti-atherogenic potential. Changes in alpha1 HDL subpopulations are a predictor of coronary disease progression in men. Hormonal replacement therapy (HRT) increases plasma levels of HDL-C, but has adverse effects on TG and C-reactive protein (CRP) levels. While observational studies had indicated a protective role of HRT in CHD, recent intervention studies have shown no CHD protection with the use of HRT. Our preliminary data indicate that there is a large inter-individual variability in HDL subpopulations and TG-rich lipoprotein remnants response to HRT.

The study uses the Estrogen Replacement and Atherosclerosis (ERA) trial which offers a unique opportunity to clarify the effects of estrogen with or without progestin on HDL and its subpopulation and TG-rich particles, and the effect of genetic polymorphisms on the response of these parameters to HRT. In addition, the ERA study will allow testing of the hypothesis that HRT may be of benefit to those postmenopausal women who experience large increases in HDL subpopulations (regardless of their overall effect on HDL cholesterol), without significant changes in TG levels. In addition, by looking at the TG and remnants of TG-rich lipoproteins, this study will enable a dissection of the beneficial and the adverse effects of HRT. The ERA population consists of 309 postmenopausal women who have established CHD and have participated in a randomized, placebo controlled, double-blind study of the effects of placebo (n-105), estrogen (n=100), and estrogen plus progestin (n=104) on the progression of coronary atherosclerosis, as assessed by quantitative coronary angiography. The trial showed no difference in coronary atherosclerosis progression across treatment groups after a mean follow-up of 3.2 years.

DESIGN NARRATIVE:

The study will clarify the effects of estrogen, with or without progestin, on HDL and its subpopulations and on lipoprotein remnants. It will also examine the impact of changes in HDL subpopulations and in lipoprotein remnants during HRT on progression of coronary atherosclerosis. These studies will be conducted in participants in the Estrogen Replacement and Atherosclerosis (ERA) trial, a randomized, placebo-controlled study of HRT and progression of atherosclerosis in postmenopausal women with CHD (n=309), in whom baseline and follow-up angiographic measurements of coronary artery diameter have been obtained. The following HDL parameters will be measured: preBeta1, preBeta2, alpha1-3, preAlpha1-4 HDL subpopulations by 2dGE, LpAI and LpAIAII in plasma and apo C-III in HDL and total plasma by immuno-electrophoresis, lipoprotein remnants by an immunoseparation method, and polymorphisms at gene loci involved in HDL metabolism (lipoprotein lipase, hepatic lipase, cholesteryl ester transfer protein, scavenger receptor B1, and ATPA1 receptor). Hypotheses tested are: 1) these HDL parameters and lipoprotein remnants will be significantly associated with severity of CHD at baseline; and 2) HRT-related changes in these parameters will predict coronary atherosclerosis progression in the ERA participants.

  Eligibility

Ages Eligible for Study:   55 Years to 80 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

age >55 years without natural menses for at least 5 years or a serum FSH levels >40 IU/L without natural menses for at least 1 y or bilateral oophorectomy documented coronary artery disease

Exclusion criteria:

history of breast or endometrial carcinoma history of deep-vein thrombosis or pulmonary embolism previous or planned coronary bypass gallstones fasting TG levels >400 mg/dl uncontrolled diabetes uncontrolled hypertension serum creatinine >2 mg/dl a >70% stenosis of the left main coronary artery.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00083824

Locations
United States, Massachusetts
HNRCA at Tufts University
Boston, Massachusetts, United States, 02111
Sponsors and Collaborators
Tufts University
Investigators
Principal Investigator: Stefania Lamon-Fava Tufts University
Study Director: David M Herrington, MD Wake Forest School of Medicine
  More Information

Publications:

Responsible Party: Stefania lamon-Fava, Associate Professor, Tufts University
ClinicalTrials.gov Identifier: NCT00083824     History of Changes
Other Study ID Numbers: 1253, R01HL070081
Study First Received: June 2, 2004
Last Updated: March 3, 2014
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Arteriosclerosis
Atherosclerosis
Cardiovascular Diseases
Coronary Artery Disease
Coronary Disease
Heart Diseases
Myocardial Ischemia
Arterial Occlusive Diseases
Vascular Diseases
Estrogens
Estrogens, Conjugated (USP)
Medroxyprogesterone
Medroxyprogesterone Acetate
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Contraceptive Agents
Contraceptive Agents, Female
Contraceptive Agents, Male
Contraceptives, Oral
Contraceptives, Oral, Synthetic
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014