Units 6 and 7 researched and written by Vicki Meade

Published by Dowden Publishing Company, Montvale, NJ. Before publication, all material in this series was reviewed by medical experts.



A 53-year-old woman with a history of a hysterectomy for uterine myomas requests estrogen replacement therapy. The minimum required daily cardioprotective dose of estrogen for her is:

  1. 0.625 mg of conjugated equine estrogens (CEE)
  2. 0.02 mg of 17 ß-estradiol
  3. 0.035 mg of ethinyl estradiol
  4. 0.05 mg of mestranol


The majority of research into the cardioprotective effects of estrogen is based on 0.625 mg oral conjugated equine estrogens (CEE) taken daily, the regimen most widely employed in the United States. This dosage reduces the relative risk of coronary heart disease to 0.50. The vast majority of studies, however, have not compared specific preparations. The few studies that have compared dosages found a nonsignificant trend for greater protection from doses of 0.625 mg CEE daily versus doses of 1.25 mg or more, suggesting that higher dosages may have a diminishing effect on cardioprotection.

The central hypothesis explaining estrogen’s cardioprotective effect asserts that oral absorption and hepatic metabolism increase high-density lipoprotein (HDL) levels. Adding a progestin need not lower this level of protection, but it would confer no additional benefits in a patient who lacks a uterus. The same hepatic “first pass” mechanism that appears to confer the majority of cardioprotection also is responsible for potential risks, including hepatic synthesis of renin substrates that may be connected to blood pressure increases, as well as circulatory blood clotting factors that increase the relative risk of coronary and cerebrovascular thromboses. Natural estrogens appear to minimize the latter effects.