Update on Hormone Replacement: Sorting Out the Options for Preventing Coronary Artery Disease and Osteoporosis

, Ohio State University

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Effect of HRT on Various Organ Systems

Cardiovascular system. Recent observational epidemiological studies have strongly suggested that estrogen replacement therapy (ERT) in women can reduce cardiovascular deaths significantly.[6] The marked reduction in cardiovascular mortality alone lends strong support for considering estrogen replacement in the majority of older women, particularly those who have atherosclerosis or who are at high risk foratherosclerotic heart disease.[7]

Oral, conjugated equine estrogens decrease total cholesterol and low-density lipoproteins (LDL)--the "badcholesterol" that builds up in blood vessels--and they increase high-density lipoproteins (HDL)--the "good cholesterol" that removes cholesterol from blood vessels. But conjugated estrogens can elevate triglycerides.Transdermal estradiol also decreases both total cholesterol and LDL cholesterol, but does not increase triglycerides. Elevated triglyceride levels are usually inversely related to HDL-cholesterol level and are an established risk factor for CAD in women.

The Postmenopausal Estrogen/Progestin Intervention Trial (PEPI) demonstrated that oral conjugated equine estrogens significantly lower LDL-cholesterol even when medroxyprogesterone acetate (MPA) or micronized progesterone is added to the regimen.[8] Of the 4 regimens studied, continuous conjugated estrogen 0.625mg without any progestin had the most favorable effect on raising HDL cholesterol; however, the high rate of endometrial hyperplasia (10% per year) makes unopposed estrogen an unacceptable regimen for women with an intact uterus. All of the 4 regimens lowered LDL-cholesterol and lowered fibrinogen levels without elevating blood pressure or detectably altering post-challenge insulin levels. The favorable lipid changes associated with HRT are only a small part of the cardiovascular benefit. Estradiol relaxes smooth muscle and has a direct beneficial effect on vessel wall physiology and endothelial function. Other suspected benefits of estradiol on the vascular system include endothelium-dependent vasodilation, a favorable impact the clotting mechanism by decreasing fibrinogen, inhibition of lipoprotein oxidation, and inhibition of foam formation associated with atherosclerosis.

The breast. The effect of estrogen replacement on the breast is somewhat controversial. Estrogen is a trophic growth hormone and therefore may promote the growth of a preexisting breast cancer. A meta-analysis of the major breast cancer studies does not show an increased risk of breast cancer in users of ERT versus those who have never used ERT.[9] The lack of consistency in studies that examine the relationship between breast cancer risk and HRT may actually be reassuring to the clinician and patient. After many epidemiological studies, there is no clear, definitive evidence showing that HRT raises the risk of breast cancer.[10]

Women with a family history of premenopausal breast cancer, particularly in a first-degree relative (mother, sister, daughter), are at increased risk for breast cancer. However, this risk is not thought to be further increased by the use of HRT. In terms of breast cancer risk, women can be assured of the safety of short-term HRT (less than 5 years of use). Long-term HRT may slightly increase the risk of breast cancer, but the data that suggest this association are neither compelling nor consistent.

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