Cardiovascular Complications

Estrogen replacement therapy is associated with an increased risk of thromboembolic disease, and alternative therapies for osteoporosis and cardiovascular protection are recommended for individuals with prior throm-boembolic episodes. The problems generally are more severe and/or more frequent when either of the synthetic estrogens, ethinyl estradiol or mestranol, is used. These preparations alter liver function more significantly than do the natural estrogens, such as the sulfate conjugates or esterified estrogens. Alterations in the synthesis of specific liver proteins, such as coagulation factors and fibrinogen, are implicated in the formation of thromboembolisms. Conjugated estrogens, tamox-ifen, clomiphene and raloxifene also increase the frequency of thromboembolic disease.

Current estimates are that oral contraceptive use doubles to triples the overall risk of thromboembolic disease. The increased use in recent years of oral contraceptives with lower estrogen content probably contributes to the decreased risk. However, the risk is greater in women who smoke, who are over age 35, or who are diabetic.

Mild hypertension and fluid retention frequently occur in oral contraceptive users. Systolic blood pressure is elevated 5 to 6 mm Hg; diastolic blood pressure increases are on the order of 1 to 2 mm Hg. Hypertension is not commonly a problem in postmenopausal women receiving conjugated estrogens.

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