Over the last two decades, mortality rates for colorectal cancer in many developed countries have declined in women but not in men. A role of exogenous female hormones (i.e. oral contraceptives and hormone replacement therapy (HRT) in such different trends is possible. Seven cohort studies reported information on HRT use and colorectal cancer risk, for a total of over 2,400 cases. Most studies showed relative risks (RRs) around or below unity. A significant inverse association was found in two cohort investigations, including the largest one dealing with fatal colon cancer. Of 12 case-control studies, for a total of over 5,000 cases, five reported 20-40% significant risk reductions among ever-users of HRT. Two additional investigations showed moderate, non-significant inverse associations. Studies showing an inverse association between HRT use and colorectal cancer were among the largest and best controlled ones. The apparent protection tended to be stronger among recent users. Differences in RRs by duration of HRT use and anatomic subsite were not consistent, but the protective effect seemed stronger in most recent publications. Available studies support the possibility of an inverse association between colorectal cancer and HRT, but prevention and surveillance bias cannot be ruled out.
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