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In this issue of the Journal, Woodson et al. (1) present findings on the role of hormone replacement therapy (HRT) and the risk of adenoma recurrence from a prospective study nested in the Polyp Prevention Trial (PPT). Their re- sults show that current HRT use is not associated with re- currence of adenomatous polyps. However, the investigators did observe a statistically significant interaction by age. Among women aged 62 years and older, an inverse association between HRT use and the risk of adenoma recurrence was shown (odds ratio (OR) 0.58; 95% confidence interval (CI) 0.35 to 0.97), whereas among women aged less than 62 years, an increased risk was observed (OR 1.99; 95% CI 1.11 to 3.55). There was also a suggestion of a negative association between HRT use and the risk of distal adenomas and a positive association between HRT use and the risk of proximal adeno- mas. The results of the study by Woodson et al. (1) do not support the majority of the published literature regarding HRT use and colorectal cancer. For example, when compared with never use, ever use of HRT is associated with a 20% reduction in the risk of colon cancer, and current use is associated with a 30% re- duction in risk (2). The few existing case-control studies (3-5) regarding adenoma prevalence also support an inverse associa- tion between HRT use and the risk of colorectal adenoma. The results of the study by Woodson et al. (1) are, however, sup- ported by those of the Nurses' Health Study (6), a prospective study of 21 153 women who underwent a colonoscopy or sig- moidoscopy for screening purposes and in whom 838 women had distal adenomatous polyps during 14 years of follow-up. In the Nurses' Health Study (6), no association was observed be- tween current HRT use and the relative risk (RR) of adenomas (RR 0.91; 95% CI 0.77 to 1.08). However, there was a statistically significant inverse association between HRT use and the risk of adenomas 1 cm or larger in size (RR 0.74; 95% CI 0.55 to 0.99). It was not possible to test the same hypothesis in the PPT (1) because of the small number of large recurrent adenomas. Because the study by Woodson et al. (1) was nested within a trial of adenoma recurrence, a common study design for colo- rectal cancer chemoprevention, the study population comprises individuals with a history of adenomatous polyps. After a clean- out colonoscopy for the removal of potentially missed polyps, participants were followed for 3 years, at which time they un- derwent an end-point colonoscopy for the detection of additional adenomas. In the present study, enrollment was restricted to women in whom an adenomatous polyp had already formed. However, at baseline or enrollment, approximately 40% of the women had developed an adenoma while receiving HRT. Thus, an argument can be made that these are women who had already undergone the initiation-phase of carcinogenesis and, further- more, that HRT was not highly protective against the formation of a baseline adenoma.

Hormone Replacement Therapy and Adenoma Recurrence: Implications for Its Role in Colorectal Cancer Risk