To explore the effect of HRT on women’s colorectal cancer risk, Dr. Gad Rennert at Carmel Hospital in Haifa and colleagues studied peri- and post-menopausal women who were participants in a population-based case-control study of incident colorectal cancer.
Included were 1234 women diagnosed with colorectal cancer between 1998 and 2006, and 1226 control subjects matched by age, residential area, and ethnic group. In both groups, the mean age was 70 years.
According to the paper in the Journal of Clinical Oncology, 230 women reported using HRT after age 45, representing 8.7% of patients and 12.3% of controls. Reported use of HRT was associated with an overall colorectal cancer risk reduction of 33% on univariate analysis.
“The associations were significantly stronger in sedentary women and a clear interaction was found with the use of aspirin, where a strong negative association between HRT and colorectal cancer risk was noted only among nonaspirin users who used HRT,” the authors state.
The authors also found that the negative association was significantly stronger among those who used oral preparations of combined estrogen-progestin rather than estrogen alone or transdermal patches.
From pharmacy records, the researchers observed that the risk was reduced mostly in past users (odds ratio, 0.50) rather than in those who had used hormones during the previous 2 years (odds ratio, 0.85).
In multivariate analysis adjusting for other prognostic factors, including the interactions of HRT with aspirin and sports activity, the negative association of HRT use with the occurrence of colorectal cancer remained significant at an OR of 0.37. (But, the authors note, the model includes “an interaction of HRT x aspirin, therefore the aspirin effect is in non-HRT users and the HRT effect is in non-aspirin users.”) However, the interaction of HRT x aspirin was associated with an odds ratio of 3.55, and HRT x sports was associated with an odds ratio of 2.25.
Dr. Rennert’s team theorizes that “progestins may increase the estrogenic effect of the conjugated estrogen leading to a combination that may be more biologically active in the colon than estrogen alone.”
In all postmenopausal women, aspirin use was associated with an overall colorectal cancer risk reduction of 44%. “However, the absence of the risk reduction effect of aspirin in HRT users and the differences in risk reduction with preparation-type call for further study to understand the causes for these phenomena and call for caution in indicating HRT for colorectal cancer prevention,” the researchers conclude.
J Clin Oncol 2009.