Postmenopausal Estrogen Helps Prevent Atherosclerosis in Some Women

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The summary below is from the full report titled "Estrogen in the Prevention of Atherosclerosis. A Randomized, Double-Blind, Placebo- Controlled Trial." It is in the 4 December 2001 issue of Annals of Internal Medicine (volume 135, pages 939-953). The authors are HN Hodis, WJ Mack, RA Lobo, D Shoupe, A Sevanian, PR Mahrer, RH Selzer, C-R Liu, C-H Liu, and SP Azen, for the Estrogen in the Prevention of Atherosclerosis Trial Research Group.

What is the problem and what is known about it so far?

Sorting through the potential benefits and harms of postmenopausal hormone use can be confusing. For example, benefits include less osteoporosis (weakening of the bones) and fewer menopausal symptoms. Harms include small increases in risk for breast, uterine, and ovarian cancer and an increased risk for stroke and blood clots in the legs. Whether postmenopausal hormone use helps prevent heart disease is unclear. One recent study showed that therapy with a particular hormone (conjugated equine estrogen plus medroxyprogesterone, known by the brand name Prempo) for 1 to 3 years did not decrease repeated episodes of heart disease in older postmenopausal women who had known preexisting heart disease. Now physicians are uncertain about whether hormone use prevents atherosclerosis (narrowing of the arteries due to build up of fatty substances and cholesterol), particularly in healthy postmenopausal women without known heart disease.

Why did the researchers do this particular study?

To see whether hormone use (estrogen replacement therapy) prevents atherosclerosis in postmenopausal women who have never had heart disease or stroke.

Who was studied?

The study included 222 postmenopausal women older than 45 years of age. None had coronary artery disease, stroke, or cancer. All had high levels of the type of cholesterol that increases risk for heart disease (greater than 130 mg/dL of low-density lipoprotein, or LDL, cholesterol).

How was the study done?

Women were randomly assigned to receive estrogen (unopposed 17ß-estradiol) or dummy pills (placebo). Women and researchers were not told who got estrogen or dummy pills. All women received advice about low-fat diets. Women with very high LDL cholesterol levels (>160 mg/dL) were given cholesterol-lowering medicines. Every 6 months for 2 years, women had ultrasound tests of major arteries in their neck (carotid arteries). These tests measured the thickness of the inner part of the artery wall, which is where the fat and cholesterol are deposited in atherosclerosis. The researchers tested whether the thickness of the artery wall increased faster (which would indicate more atherosclerosis) in women given placebo than in those given estrogen hormones.

What did the researchers find?

Among women with high LDL cholesterol levels, atherosclerosis progressed less rapidly in those given hormones than in those given placebo. Among women with very high LDL cholesterol levels who were also taking cholesterol-lowering medicines, hormones did not seem to affect the rate of atherosclerosis progression. None of the women receiving hormones developed cancer or had blood clots in their legs or lungs.

What were the limitations of the study?

This study was too small to see whether estrogen use had any effect on clinical outcomes, such as heart attack or stroke, or such complications as blood clots and stroke.

What are the implications of the study?

Estrogen use in healthy postmenopausal women with high LDL cholesterol levels may prevent progression of atherosclerosis in some women who are not taking cholesterol-lowering medicines.