Cardiovascular disease is the leading cause of mortality among women in the United States. The number of deaths from diseases of the circulatory system in women in the United States is greater than the number who die from cancers of the breast, reproductive tract, and maternal morbidity combined. It is only during the reproductive years that more women die from malignancy than from cardiovascular disease. This is reversed past 60 years of age.
The endocrine influences of factors thought to be contributors to the risk of cardiovascular disease have been studied extensively. The literature is vast and has been well summarized in several recent reviews. Unopposed estrogen raises the serum level of high-density lipoprotein cholesterol, especially the HDL2 subfraction, and lowers the serum level of low-density lipoprotein cholesterol.6 Other less well-studied factors that may influence cardiovascular health during treatment with estrogen, with or without progestin, include beneficial effects on the circulation, blood pressure, coagulation, and fibrinol-ysis.7,8 Estrogen also has vasodilating properties mediated by the generation of prostacyclin in the cell membrane.
Many epidemiological studies have found that postmenopausal women who use estrogen are at a much lower risk for coronary disease than are nonusers. Observational studies suggest a 50 percent reduction in the risk of coronary heart disease among healthy post-menopausal women taking oral estrogen.9
In 1981, Henderson and colleagues recruited over 8,000 women from a retirement community in Laguna Hills, California called Leisure World. This is a stable community and very few individuals were lost to follow-up. Of this cohort, 57 percent reported estrogen use, 14 percent were current users at the time of the questionnaire, and 43 percent reported previous use. The incidence of mortality from acute myocardial infarction was statistically lower among current users and those who had used estrogen in the past compared to nonusers. The relative risk was 0.59, with the 95 percent confidence interval (CI) of 0.42 to 0.82.
Hunt10 reported on a cohort of 4,544 women who had taken hormone replacement therapy continuously for at least 1 year at the time of recruitment. When compared with the general female population, mortality rates for ischemic heart disease among the cohort were significantly lower, with a relative risk of 0.41 and a 95 percent CI of 0.2 to 0.61. Bush11 evaluated a cohort of 2,270 women, 593 of whom were estrogen users. The age-adjusted relative risk of death from cardiovascular disease was 0.34, with the 95 percent CI of 0.12-0.81.
Stampfer12 evaluated postmenopausal estrogen therapy and cardiovascular disease in the Nurses' Health Study, with a 10-year follow-up. Women currently using post-menopausal hormone therapy accounted for 21.8 percent of the total follow-up time of 337,854 person-years. There was a reduction in the age-adjusted relative risk of fatal cardiovascular disease among current hormone users. In the same study, the age-adjusted risk of major coronary artery disease among current estrogen users was about half that of women who had never used estrogen, with a relative risk of 0.51 p < .0001. For former users, the age-adjusted relative risk (RR) was 0.91. When this was adjusted for other risk factors, the relative risk was 0.83. The relative risk of fatal cardiovascular disease was decreased in both current and former users.
The above studies were all based on post-menopausal estrogen use only. Given the fact that current medical recommendations call for the addition of a progestin to estrogen therapy in nonhysterectomized women, there is the valid concern that progestin therapy may negate the benefits gained by estrogen (Table 15-1).
The investigators in the Postmenopausal Estrogen/Progestin Interventions (PEPI) trial examined this issue.13 They found, as had been confirmed in numerous previous studies, that unopposed estrogen decreased the risk factors for cardiovascular disease. However, estrogen given with medroxyprogesterone acetate or micronized progesterone hormone-replacement therapy (HRT) was associated with lower fibrinogen levels and improved lipoprotein profiles. No adverse effects on the rate of car diovascular incidents were observed for HRT over ERT.
Grodstein14 evaluated the effect of combined estrogen and progestin use and the risk of cardiovascular disease in the Nurses' Health Study. Among the 59,337 women enrolled, there were 770 casualties of myocardial infarction or deaths from coronary artery disease. There was a marked decrease in the risk of major coronary artery disease among women who took estrogen with progestin compared to that for women who did not use hormones. The multivariate-adjusted relative risk was 0.39, with the 95 percent CI of 0.19 to 0.78.
Postmenopausal women are at risk for loss of cancellous bone in the vertebrae and other long bones, which places them at increased risk for fracture. Bone mineral density decreases rapidly within 5 years of menopause due to estrogen deficiency. This ultimately results in microarchitectural deterioration and a progressive increased fracture risk. Postmenopausal untreated women may lose 35 percent of their cortical bone and up to 50 percent of their tra-becular bone. It is estimated that 1.2 million major fractures per year in the United States in women are related to osteoporosis. Fifteen percent of postmenopausal women will suffer wrist fractures, and an even larger number will incur spinal compression fractures. Compression fractures of the vertebral bones may result in loss of stature, pulmonary restriction, and
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