Estrogen replacement therapy and endometrial cancer risk: unresolved issues. The Endometrial Cancer Collaborative...

To clarify several unresolved issues regarding the relationship of estrogens to endometrial cancer risk.

We conducted a hospital-based case-control study involving 300 menopausal women newly diagnosed with epithelial endometrial cancer and 207 population controls matched to the cases for age, race, and residence.

Estrogen use significantly increased endometrial cancer risk (adjusted relative risk [RR] 3.0, 95% confidence interval [CI] 1.7-5.1). Although both short- and long-term use appeared to elevate the risk of early-stage tumors, an effect of estrogens on late-stage tumors was observed only for long-term use (RR 2.1, 95% CI 0.7-6.4). A small proportion of women reported having used progestogens simultaneously with estrogens, which was associated with a lower risk (RR 1.8) than use of estrogens alone (RR 3.4). Although the highest risks were for recent users of estrogens, persistent excess risks were seen even for those who had discontinued use of 5 or more years. There were no striking relationships according to the type of estrogen or regimen used, and associations with dose were inconsistent, although women who used low-dose preparations exclusively had the lowest risk. Estrogen injections or creams, used by only 5.9 and 5.1% of the subjects, respectively, were not significant risk factors after adjustment for estrogen pill use. Women who were thin or who smoked cigarettes appeared to be most adversely affected by estrogen use. Estrogen users failed to experience the protective effect normally associated with oral contraceptive use.

The effect of estrogens on endometrial cancer risk appears to vary both by usage patterns and by patient characteristics.