Review study design to understand results

The Women’s Health Initiative (WHI) estrogen/progestin trial was designed to assess the major benefits and risks of hormone replacement therapy (HRT) with regard to coronary heart disease, venous thrombotic events, breast cancer, colon cancer, and fractures. Women participating in the WHI trial were randomized to receive an estrogen-progestin HRT regimen of conjugated equine estrogens (0.625 mg/day) and medroxyprogesterone acetate (2.5 mg/day) [Prempro, Wyeth Pharmaceuticals, Collegeville, PA] or placebo.

Limits for trends in adverse events were set prior to the start of the study, which allowed researchers to determine whether the trial would continue. To weigh the observed risks and benefits to the participants’ health, an independent data and safety monitoring board used a global index to sum up the designated health outcomes. Quality of life issues, such as reduction of hot flashes and reduction of vaginal dryness, were not part of the risk benefit analysis.

In 2000 and again in 2001, WHI investigators informed participants of a small increase in heart attacks, strokes, and blood clots in women taking hormones. (See the June 2000 issue of Contracep-tive Technology Update, p. 68, for a review of the 2000 update.) The advisory committee overseeing the study recommended continuing the trial since the actual number of women having any one of these events was small and did not cross the statistical boundary established to ensure participant safety.

However, during a May 2002 review, the data indicated for the first time that the number of cases of invasive breast cancer in the estrogen plus progestin group had crossed the boundary established as a signal of increased risk. The advisory committee examined the findings and recommended that the trial be halted. The WHI trial on estrogen use alone is continuing, as study authors report no increased risk for breast cancer in the estrogen-only study group.