Postmenopausal female hormone supplements
Several observational studies have suggested a decreased risk of colon cancer among users of postmenopausal female hormone supplements.[63,64,65,66] For rectal cancer, most studies have observed no association or a slightly elevated risk.[67,68,69]
In the Women's Health Initiative (WHI) Trial, 16,608 postmenopausal women aged 50 to 79 years were randomly assigned to a combination of conjugated equine estrogens (0.625 mg/day) plus medroxyprogesterone (2.5 mg/day) or placebo. There were 43 invasive CRCs in the hormone group and 72 in the placebo group (HR = 0.56; 95% CI, 0.38-0.81; P = .003). The invasive CRCs in the hormone group were similar in histologic features and grade to those in the placebo group but with a greater number of positive lymph nodes (mean � standard deviation 3.24 � 4.1 vs. 0.8 � 1.7; P = .002) and were more advanced (regional or metastatic disease; 76.2% vs. 48.5%; P = .004).
An analysis of data from the National Polyp Study, with external, historical controls, has commonly been cited to show a reduction of 76% to 90% in the subsequent incidence of CRC after colonoscopic polypectomy compared with three nonconcurrent, historical control groups. This study may be biased in several ways that inflate the apparent efficacy of polyp removal; the main problem is that potential enrollees in the National Polyp Study were excluded if they had CRC at their baseline examination. Because no such exclusions (or baseline colonoscopy examinations) were done in the three comparison groups, persons who had CRC at baseline would be counted as having incident CRC in subsequent follow-up. Although adjustments were attempted, it is not possible to know the magnitude of the impact of this problem on the result because it is not known how long CRC may be present without causing symptoms.
Other evidence about the benefit of sigmoidoscopy screening (at which time both polyps and early cancer would be removed) suggests that the impact of endoscopic screening, at least on the left side of the colon, is substantial and prolonged. In an RCT, 170,000 persons were randomly assigned to one-time sigmoidoscopy versus usual care. At sigmoidoscopy, polyps were removed and cancer was detected and referred for treatment. Based on sigmoidoscopy findings, persons were considered to have low risk if they had normal exams or only one or two small (<1 cm) tubular adenomas; such persons were not referred either for colonoscopy workup, or for colonoscopic surveillance. In a follow-up of 10 years, the left-sided CRC incidence in the low-risk group (about 95% of attendees were low risk) was 0.02% to 0.04% per year-a very low risk of CRC compared with average risk. The cause of reduced risk-whether due to detection and removal of large polyps or small ones, or selection of individuals at lower risk-is yet unclear. The natural history of large polyps is not well known, but some evidence suggests that such lesions become clinical CRC at a rate of approximately 1% per year. As a result of the strong data about the impact of endoscopy on the left colon, evidence from multiple studies has raised questions about the ability of endoscopy to reduce CRC mortality in the right colon.[74,75,76] Thus, it is unclear what the overall impact of endoscopy (e.g., colonoscopy screening) is, and whether there may be a large difference in impact on the left side of the colon compared with the right side.