Postmenopausal Hormone Therapy Reduces the Risk of Colorectal Cancer

Abstract & Commentary

Synopsis: Current use of postmenopausal hormone therapy provides substantial protection against colorectal cancer.

Source: Grodstein F, et al. Am J Med 1999;106: 574-582.

Grodstein and associates performed a meta-analysis of the 18 published epidemiologic reports that have examined the association between postmenopausal hormone therapy and the risk of colorectal cancer. Overall, there was a 20% reduction in the risk of colon cancer and a 19% decrease in the risk of rectal cancer whenever users of postmenopausal hormone therapy were compared with never users. Nine studies indicated a similar benefit for both proximal and distal colon cancers. Greater protection was associated with current use compared with ever use. A summary of 10 studies with information on timing of hormone use indicated a 34% reduced risk of colorectal cancer in current users. The protection was substantially lost within several years after discontinuing hormone use, and by five years a benefit was no longer apparent. Surprisingly, there was no indication that protection was affected by duration of use. Although data were limited, there was no indication that the effect was influenced by the addition of a progestational agent to treatment regimens. These estimates were unaffected by various adjustments to correct for possible differences between hormone users and nonusers (such as body mass index, aspirin use, and smoking).

Comment by Leon Speroff, MD

In the latest cancer statistics for U.S. women, colorectal cancer accounts for 11.2% of all cancers, third in prevalence after breast (29.7%) and lung cancers (13.3%), and 9.8% of cancer deaths, compared with 24.8% from lung cancer and 16.1% from breast cancer.1 In both prevalence and mortality, colorectal cancer outranks the more familiar reproductive cancers (endometrial, ovarian, and cervical).

One can only speculate regarding the biologic mechanism for this protective effect of estrogen. Estrogen causes a decrease in bile acids, substances associated with promotion of colorectal cancer. Estrogen may maintain tumor suppression, either directly or indirectly by reducing mitogens such as insulin like growth factor.

An anti-estrogen can be expected to have opposite effects, and there is some evidence that tamoxifen is associated with a slight increase in the risk of colorectal cancer, raising concerns regarding the long-term effects of the selective estrogen receptor modulators (like raloxifene).

Although the results of the ongoing long-term randomized clinical trials will be necessary to confirm this effect of estrogen, the uniformity and agreement among the many observational studies make it legitimate to provide this information to our patients. Indeed, this is a little-publicized effect of estrogen even among healthcare providers. I believe it is appropriate and important to include this possible benefit in our discussions regarding the use of postmenopausal hormones. This is especially important to elderly women considering hormone therapy for the first time.


1. American Cancer Society,

The following statements are true regarding postmenopausal hormone therapy and the risk of colorectal cancer except:

a. Although colorectal cancer is more prevalent than cancers of the uterus and ovaries, it is a less common cause of cancer mortality.

b. Protection against colorectal cancer is limited to current and recent use of postmenopausal estrogen therapy.

c. There is no evidence that adding a progestin influences the risk of colorectal cancer.

d. The protective effect of estrogen is apparent throughout the length of the lower GI tract.