Dr. Steve Narod, of the Women's College Research Institute, Toronto, agreed. “[The risk] might be thought of as small, but enormous numbers of women have been exposed,” he wrote in an accompanying commentary” (Lancet 2007 [Epub doi:10.1016/S0140-6736(07)60535-2]).
Study Controversial From the Start
There's no doubt that the Million Women Study has been directly responsible for the dramatic decrease in British and European hormone therapy prescriptions, experts say. But they also point out that criticism has dogged this enormous epidemiologic study every step of the way. Since 2003, critics have charged that a flawed methodology makes MWs' conclusions almost impossible to accept.
Critical response began with the first MWS publication in 2003. The Lancet published several letters questioning its methodology in the same issue that carried the breast cancer study (Lancet 2003;362:1330–1).
British epidemiologist Richard Farmer is one of several researchers who have repeatedly challenged the investigation's methodology. “Both [the breast cancer and endometrial cancer] studies have the same serious design flaws and there are important aspects of the published reports that are inconsistent,” wrote Dr. Farmer, emeritus professor of epidemiology at the University of Surrey (England) (Climacteric 2005;8:210–3).
Dr. Farmer and his colleague, Dr. M. Whitehead reported in 2004 that the study's design flaws “render the results largely uninterpretable because built-in biases have affected risk estimates” (Endoc. 2004;24:187–93).
Nevertheless, the Million Women Study carried the same national and international impact as did the U.S. Women's Health Initiative. Immediately after the first MWS publication, Britain's drug regulatory agency, the Committee on Safety of Medicines, announced that the data confirmed an HT duration-dependent increase in the risk of breast cancer, and advised counseling patients of that risk.
MWS significantly influenced HT prescribing patterns in the United Kingdom and throughout Europe. In the Netherlands, for instance, the publication of WHI was followed by a modest decrease in prescribing of HT. But after publication of the initial MWS results, rates dropped precipitously (Br. J. Clin. Pharm. 2005;60:641–7).
The study's main flaw is that HT use is based entirely based on recall—a notoriously unreliable source of information, said Dr. James Fiorica, director of gynecologic oncology at Sarasota Memorial Hospital, Fla., and a member of the speakers' board at Wyeth Pharmaceuticals, which manufactures the HT drugs Prempro and Premarin.
“MWS was questionnaire based,” he said in an interview. “This gives you no idea of compliance, or how long these women were really on hormones. It's easy to attribute cancer risk to a drug, but very hard to draw these conclusions based on a questionnaire.”
Dr. Wulf Utian, executive director of the North American Menopause Society, said the MWS ovarian cancer data won't change any of the HT prescribing recommendations included in the group's recent position statement. “The Million Women Study data are absolutely riddled with methodological problems; most serious investigators are not certain how to interpret these data,” Dr. Utian said in an interview. “The only conclusion we can draw from this study is that, clearly, we do not have all the answers. HT carries both potential benefit and potential risk, but in most instances, these absolute risks are rare.”
Treatment decisions should be based on a women's individual risk profile, he said. “If a woman of low risk and high need is prescribed HT she has little to fear. On the other hand, a woman of high risk and weak indication for HT would be better off to concentrate on healthy living and other more appropriate remedies for her problem.”