In 2002, the Women's Health Initiative (WHI) randomized trial of placebo vs hormone therapy with estrogen and progestin was stopped early because of evidence of harm.1 Sales of combined estrogen-progestin plummeted 32% between the period immediately before the study's release and the analogous period 1 year later, as the WHI trial had shown that hormone therapy increased a woman's risk of breast cancer and myocardial infarction.2 The finding contradicted decades of case-control and observational cohort studies that had suggested that hormone therapy was associated with strong protective effects on the cardiovascular system. The WHI results also undermined a long and successful campaign by hormone replacement advocates to present hormone therapy as a panacea against heart disease, loss of femininity, and other perils of aging. In the scientific community, the WHI results became “exhibit 1” for critics of observational studies, who argued that this latest upheaval of conventional medical knowledge proved (once again) that only randomized studies can yield useful insights into cause and effect.