When recruitment for the Women's Health Initiative (WHI) began in 1993, hormone therapy (HT) was prescribed for a variety of reasons that ranged from the management of menopausal symptoms to the prevention of chronic disease, and the WHI focused on documenting the risks and benefits of HT use for chronic disease prevention. In 2004, one of the first publications from the WHI reported the balance of risks and benefits during active intervention with unopposed estrogen among women with previous hysterectomy.1 Based on data collected through the end of the trial's intervention phase, women randomly assigned to estrogen had a significantly increased risk of stroke and reduced risk of hip fracture and possibly breast cancer compared with women receiving placebo. There was no overall effect of estrogen on a global index of risks and benefits1 including coronary heart disease. These findings were revolutionary and changed practice.2,3
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