Potential cardioprotection was based on generally supportive data on lipid levels in intermediate outcome clinical trials, trials in nonhuman primates, and a large body of observational studies suggesting a 40 % to 50 %
reduction in risk among users of either estrogen alone or, less frequently, combined estrogen and progestin.2 - 5 Hip fracture was designated as a secondary outcome, supported by observational data as well as clinical trials showing benefit for bone mineral
density.6, 7 Invasive
breast cancer was designated as a primary adverse outcome based on observational data.3, 8 Additional clinical outcomes chosen as secondary outcomes that may plausibly be affected by hormone therapy include other cardiovascular diseases; endometrial, colorectal, and other cancers; and other fractures.3, 6,9