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Estrogen, HDL, and Coronary Heart Disease in Women

This study has been completed.
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Stefania lamon-Fava, Tufts University Identifier:
First received: June 2, 2004
Last updated: April 19, 2016
Last verified: April 2016
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 Drug: Placebo Phase 2 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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 Stefania lamon-Fava, Tufts University:

Primary Outcome Measures:
  • HDL subpopulation distribution and composition [ Time Frame: 1 year ]
    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 ]
    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
Drug: Placebo
2 pills/day QID for 3 years
Other Name: Sugar Pill
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:


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.


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.


Ages Eligible for Study:   55 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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.

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Please refer to this study by its identifier: NCT00083824

United States, Massachusetts
HNRCA at Tufts University
Boston, Massachusetts, United States, 02111
Sponsors and Collaborators
Tufts University
National Heart, Lung, and Blood Institute (NHLBI)
Principal Investigator: Stefania Lamon-Fava Tufts University
Study Director: David M Herrington, MD Wake Forest University
  More Information


Responsible Party: Stefania lamon-Fava, Associate Professor, Tufts University Identifier: NCT00083824     History of Changes
Other Study ID Numbers: 1253
R01HL070081 ( U.S. NIH Grant/Contract )
Study First Received: June 2, 2004
Last Updated: April 19, 2016

Additional relevant MeSH terms:
Cardiovascular Diseases
Heart Diseases
Coronary Disease
Coronary Artery Disease
Myocardial Ischemia
Vascular Diseases
Arterial Occlusive Diseases
Estrogens, Conjugated (USP)
Medroxyprogesterone Acetate
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Contraceptives, Oral, Synthetic
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents
Reproductive Control Agents
Contraceptive Agents, Male
Antineoplastic Agents, Hormonal
Antineoplastic Agents processed this record on August 23, 2017