IJE Advance Access originally published online on March 31, 2006
International Journal of Epidemiology 2006 35(3):740; doi:10.1093/ije/dyl061
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Response: Response to the Stampfer commentary
Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK
* Corresponding author. E-mail: joe.kim{at}lshtm.ac.uk
We thank Dr Stampfer for his helpful comments.1 We agree with his interpretation that unmeasured confounding is unlikely to be the only explanation for the HRT controversy given the available evidence in literature. However, we disagree with his remarks concerning our definition of the term ‘initiation,’ where he suggests we have used ‘misleading terminology’ to direct the reader into believing that our definition of HRT initiation concerns lifetime exposure, rather than exposure purely within the narrower timeframe of observation within our study.
In our original submission to the IJE,2 analyses were restricted to age of women at the time of MI, but at the request of the IJE reviewers we subsequently analysed the data also according to age at initiation. The reviewers clearly viewed this additional set of analyses to be of value for helping to resolve the HRT controversy, and neither the IJE reviewers nor the editors raised any concerns regarding our use of the term ‘initiation.’
As the basis for his criticism, Dr Stampfer states that ‘probably the large majority of these women were not beginning HT use then, since most women first begin hormone use around the time of menopause.’ Further examination of the data contradicts such a claim: the distribution of time to first HRT treatment after study entry is widespread. In fact, only 520 (13%) of the women on HRT began their use within 60 days of entering the study, suggesting they were users of HRT at the start of their observation period. The vast majority of the remaining 87% were probably starting HRT at the time of their first recorded prescription. The average duration from the start of observation until the first prescription for HRT was 17 months.
We now present a further analysis (Table 1) that excludes all exposed individuals who had HRT treatment within 1 year of the date of entry into the study (n = 1710). These new results are compatible with our original findings, both leading to the conclusion that the apparent protective effect of HRT on MI occurrence increases with age of initiation. It is unusual for women to have an interruption of over a year in taking HRT, making it highly likely that virtually all exposed women in this analysis were starting HRT for the first time. This analysis really should satisfy Dr Stamper's concerns regarding time of HRT initiation.
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We do observe a higher than expected number of women in older age groups starting HRT. However, we see no reason why our prescription data should be incorrect. Perhaps the uptake of HRT in older age groups occurs because of the increasing awareness of HRT in the UK by both post-menopausal women and their primary care physicians in more recent years, whereby the option of HRT was not considered by them ten or more years earlier when they entered menopause.
So it appears that the dog does have four legs after all: there is no evidence to suggest that HRT initiation at earlier ages is more beneficial than initiating therapy at a later age.
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1 Stamfer MJ. Commentary: Hormones, heart disease and the definition of hormone ‘initiation’ Int J Epidemiol 2006;35:738–39.
2 Kim J, Evans S, Smeeth L, Pocock S. Hormone replacement therapy and acute myocardial infarction: a large observational study exploring the influence of age Int J Epidemiol 2006;35:731–38.
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