Postmenopausal Hormone Therapy and the 'Healthy User' Effect


Synopsis: The benefits of postmenopausal hormone therapy are not explained by the healthy user effect.

Source: MacLennan AH, et al. Climacteric 1998;1:42-49.

Maclennan and colleagues from australia surveyed more than 3000 women in south Australia on three occasions in 1991, 1993, and 1995. Current use of postmenopausal hormone therapy in this population increased by 57% over this period of time. Ever use of postmenopausal hormone therapy in women older than 50 years in this population increased from 26.7% in 1991 to 40.5% in 1995. This increase in prevalence was accompanied by a doubling in compliance, with the median length of time increasing from 24 to 60 months for women older than the age of 50. In comparing health variables among users and non-users, there was no evidence to support the suggestion that healthy women are more likely to be users of postmenopausal hormone therapy. Of interest was a 28.8% increased use of mammography by users compared to non-users.


This article is of interest because, in the absence of randomized clinical trial data, critics have suggested that the benefits of postmenopausal hormone therapy in observational studies are due to self selection, specifically because healthier women choose to take hormone therapy. It is certainly true that in several studies, hormone users have been documented to be a little bit healthier. However, this study suggests that this notion is derived from studies involving populations that have had a low prevalence of hormone therapy use. Thus, use has been largely among women who are more educated, informed, and better off economically and, thus, are probably leading healthier lifestyles. With the increasing prevalence of hormone therapy in this Australian population, it is likely that more and more women with medical risk factors are choosing to use hormone therapy. The lack of support for the healthy user effect in the Australian study is supported by analysis of the Nurses' Health Study. Investigators in the Nurses' Health Study find that the differences between users and non-users are not sufficient to explain the major cardiovascular benefit of postmenopausal estrogen treatment.

Another finding of note is a 30% difference in the use of mammography comparing users to non-users. This has been observed in other studies ranging from a 14% difference in the Nurses' Health Study to a 50% difference in the Kaiser program in California. This difference in the use of mammography can yield a detection/surveillance bias in observational studies dealing with the risk of breast cancer. Earlier detection can yield better outcome and lower mortality rates.

Only data from randomized clinical trials will ultimately provide definitive answers to these puzzling questions. Results will not be available from the Women's Health Initiative in the United States until after 2007 and from the Women's International Study of Long Duration Oestrogen after Menopause (WISDOM) in Europe until after 2011. Until then, these data from this report indicate that patients and physicians have a growing confidence in postmenopausal therapy as reflected by increasing prevalence and compliance rates. (Dr. Speroff is Professor of Obstetrics and Gynecology, Oregon Health Sciences University, Portland.)