Hormone therapy for menopausal symptoms | BMJ

 Editorial

Hormone therapy for menopausal symptoms

BMJ 2012; 344 doi: 10.1136/bmj.e815 (Published 8 February 2012)

Cite this as: BMJ 2012;344:e815

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"Recent evaluations of the methods of key studies should not change how we advise wome.

A recently published and much publicised paper by Shapiro and colleagues, the last in a series of four, evaluated the effects of hormone therapy on the risk of breast cancer.1 

The authors of the four review articles applied epidemiological principles to the findings of two randomised placebo controlled studies from the Women’s Health Initiative (WHI; 27 347 women) and two observational studies—the Collaborative Reanalysis (53 865 women) and the Million Women Study (MWS). Shapiro and colleagues concluded in their fourth paper that the MWS had design defects, that it contained multiple biases, and that its findings were thus not robust enough to show that hormone therapy increased the risk of breast cancer.

All observational studies are inherently biased because subjects are not randomly assigned to treatment or control. Adjustment for confounders and careful design of observational studies help to reduce bias. However, because there is no independent variable, such studies can tell us only about association not causation.

The MWS was published in the Lancet in August 2003,2 and a flurry of letters was published in a print issue later that year, many …"

ecancernews: Researchers defend HRT breast cancer (The Million Women Study)study

Million Women Study Wrong, Group Says - in Endocrinology, Menopause from MedPage Today

"A study long used to establish causal links between hormone replacement therapy (HRT) and breast cancer is severely flawed, a group of epidemiologists have charged. The observational Million Women Study (MWS), conducted in the U.K., doesn't adequately satisfy several criteria for causality -- including information bias, detection bias, and biological plausibility -- and thus can't be used to conclude that HRT causes breast cancer, according to Samuel Shapiro, PhD, of the University of Cape Town in South Africa, and colleagues.
"HRT may or may not increase the risk of breast cancer, but the MWS did not establish that it does," they wrote in the Journal of Family Planning and Reproductive Healthcare.
Several experts not involved in the study, however, have emphasized that they're well aware of the limitations of observational studies such as the MWS, and that the totality of evidence thus far has shown a strong association between HRT and breast cancer....."

"The analysis of the Million Women Study is the latest in a series of four papers by the Shapiro group exploring the credibility of three studies -- the MWS, the Women's Health Initiative (WHI), and the collaborative reanalysis (CR) -- that causally linking HRT, particularly estrogen plus progestogen therapy, with breast cancer.
The earlier papers similarly found that neither the CR nor the WHI could satisfy criteria for establishing causality...."