The influence of endocrine factors on colorectal tumor development remains unclear. We performed a meta-analysis of studies of the association between the use of menopausal hormones and colon cancer in women, published up to December 1996. We derived summary measures of relative risk (RR) by fitting both fixed and random effects models. We also performed analyses by tumor location to the right or left colon, as well as by recency and duration of use. Heterogeneity was assessed according to study design, chronology, or other criteria. Overall, the 20 independent estimates of the association between ever use of menopausal hormones and colon cancer led to a summary RR of 0.85, (0.73, 0.99), using a random effects model. There was substantial heterogeneity among studies. The suggested protective effect of hormones was estimated to be stronger in studies published since 1990 [RR: 0.83, (0.66, 1.04), versus 0.93, (0.78, 1.10), for those published previously]. The estimated RRs were lower among current or recent users [RR: 0.69, (0.52, 0.91)] and among users of more than 5 years [RR: 0.73, (0.53, 1.02)] as compared with short-term users [RR: 0.88, (0.64, 1.21)]. The current state of knowledge suggests a 0-25% risk reduction among ever users of hormone replacement therapy. Inadequate assessment of exposure, poor control of confounding factors, and changing patterns of use over time might have contributed to the slow emergence of this association postulated almost two decades ago. Additional large studies are needed to replicate this finding and explain the exact mechanism of this putative protective effect.

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