Clinical trials in women with and without established CAD, however, have failed to con- firm a decrease in cardiovascular events with hormone therapy. In HERS (Heart and Estrogen/progesterone Replace- ment Study), 2763 postmenopausal women with CAD were randomized to therapy with 0.625 mg of conjugated estrogen plus 2.5 mg of medroxy progesterone acetate or placebo and were followed up for an average of 4.4 years. Despite an 11% lower level of LDL cholesterol and a 10% higher level of HDL cholesterol in the hormone therapy group, there was no difference in the composite primary endpoint of MI or IHD death, and an early increase in cardiovascular events was observed.811 In HERS-II, an unblinded follow-up study of HERS, the lack of benefit with estrogen/progestin therapy persisted at an average of 6.8 years.834 A subsequent angio- graphic study demonstrated a nonsignificant worsening of coronary stenoses in patients prescribed estrogen therapy.835 The Women s Health Initiative, a randomized controlled primary prevention trial, also found no evidence that estrogen protects against IHD.812 814 Thus, the weight of current scientific evidence suggests that estrogen/progestin therapy in postmenopausal women does not reduce the risk of vascular events or coronary deaths in secondary prevention. Women who are taking estrogen therapy and who have vascular disease can continue this therapy if it is prescribed for other well-established indications and if no better alternative ther- apies are appropriate, although the FDA recommends use in the lowest dose and shortest duration acceptable. There is, however, no basis for adding or continuing estrogens in postmenopausal women with clinically evident SIHD in an effort to prevent or retard progression of their atherosclerotic disease. 4.4.2.5.2. Vitamin C, Vitamin E, and Beta-Carotene. 