Cardiovascular Risks Associated With Celecoxib and Rofecoxib Dose/Drugs continued...
Postmenopausal female hormone supplements
Several observational studies have suggested a decreased risk of colon cancer among users of postmenopausal female hormone supplements.[67,68,69,70] For rectal cancer, most studies have observed no association or a slightly elevated risk.[71,72,73]
The Women's Health Initiative (WHI) trial examined, as a secondary endpoint, the effect of combined estrogen and progestin therapy and estrogen-only therapy on CRC incidence and mortality. Among women in the combined estrogen plus progestin group of the WHI, an extended follow-up (mean, 11.6 years) confirmed that fewer CRC were diagnosed in the combined hormone therapy group than in the placebo group (HR = 0.72; 95% CI, 0.56-0.94); the CRCs in women in the combined group were more likely to have lymph node involvement than the CRCs in women in the placebo group (50.5% vs. 28.6%; P < .001) and were classified at higher stages (regional and distant) (68.8% vs. 51.4%; P = .003). The number of CRC deaths in the combined group was higher than in the placebo group (37 vs. 27 deaths), but the difference was not statistically significant (HR = 1 .29; 95% CI, 0.78-2.11).
The estrogen-only intervention component of the WHI was conducted among women who had a hysterectomy, with CRC incidence included as a secondary trial endpoint. CRC incidence was not decreased among women who had taken estrogens; after a median of 7.1 years of follow-up, 58 invasive cancers occurred in the estrogen arm compared with 53 invasive cancers in the placebo arm (HR = 1.12; 95% CI, 0.77-1.63). Tumor stage and grade were similar in the two groups; deaths after CRC were 34% in the hormone group compared with 30% in the placebo group (HR = 1.34; 95% CI, 0.58-3.19).
An analysis of data from the National Polyp Study (NPS), 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 NPS 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.