Opinion ID: 1381810
Heading Depth: 2
Heading Rank: 4

Heading: The Women's Health Initiative Study

Text: The WHI study began in 1991. The study consisted of multiple components, one of which was an evaluation of the use of estrogen and progestin in postmenopausal women. Primarily, this component evaluated whether estrogen and progestin use decreased the incidence of cardiovascular disease. Secondarily, the study assessed numerous safety issues, including the risk of breast cancer. The study was organized as a randomized placebo-controlled trial, meaning that one group of women received the drugs and the other a placebo. The average age of the participants was sixty-three, and it included women who were already on hormone replacement therapy, as well as women who began treatment at the start of the study. The study had a predetermined stopping point if the incidence of breast cancer exceeded a certain point. In 2002, three years short of its scheduled completion, the NIH terminated the study, finding an unacceptably high incidence of invasive breast cancer among the participants. In July 2002, the initial results of the WHI study were published in the Journal of the American Medical Association. The study reported a relative risk of breast cancer of 1.24 over 5.6 years of estrogen and progestin use. Stated differently, the estrogen plus progestin group was twenty-four percent more likely to develop breast cancer than the control group. This result was consistent with estimates from pooled epidemiological data. Wyeth's Dr. Constantine described the relative risk of increased incidence of breast cancer as small and Scroggin's medical expert, Dr. Don Austin, described it as slightly elevated. The study also found that the risk of breast cancer decreased after stopping the hormone therapy. These initial results, however, contained variables not accounted for in the 1.24 relative risk. Dr. Austin testified that the 1.24 number was misleading, particularly for women using hormone replacement therapy for long periods of time. He noted that although randomized clinical trials assist in showing causal relationships, they may not be accurate in reporting the size of the risk. The 1.24 relative risk was based on the intent to treat group, meaning the women who had signed up to participate in the study, but it did not account for those who had dropped out during the course of the study. According to the WHI, all of the women had been enrolled for 3.5 years, with an average enrollment of 5.2 years, and a maximum enrollment of 8.5 years. Forty-two percent of estrogen plus progestin users and thirty-eight percent of the placebo group ceased participating during the course of the study. The initial WHI results, however, calculated the relative risk as if these women had remained in the study. In 2006, Dr. Garnet Anderson, who had worked on the WHI study, published a report that accounted for these variables. When she accounted for confounding variables, the relative risk was 1.96. She found that women who had been taking hormone replacement therapy prior to commencement of the study had a relative risk of 2.78 and that women who were taking the medication for more than five years had a relative risk of 2.5. When Dr. Anderson analyzed only the women who remained in the study and adhered to the treatment, she found a relative risk of 3.56. Dr. Austin testified that the true value is somewhere between 1.18 and 10.73, but the best estimate is 3.56. Dr. Colditz asserted that the relative risk is somewhere between 2.0 and 4.0 depending on use and duration. Both Dr. Colditz and Dr. Austin agreed that estrogen plus progestin use causes breast cancer. Additionally, the IARC has classified estrogen plus progestin as a carcinogen of the breast.