Although several studies have found an association between the use of oral contraceptives and an increased risk of cervical cancer, little is known about whether similar risks exist when estrogen is used for postmenopausal hormone replacement therapy. Parazzini and colleagues conducted a case-control study to determine whether the use of hormone replacement therapy is associated with an increased risk of cervical cancer.

The study included 645 women from 40 to 75 years of age who were hospitalized between 1981 and 1993 because of histologically confirmed invasive cervical cancer. Control patients included 749 women of the same age admitted for trauma or orthopedic, surgical and dental conditions. None of the women in the control group were admitted because of gynecologic conditions, and none had undergone hysterectomy. Extensive data were obtained from all study participants through the use of structured questionnaires that evaluated lifestyle, risk factors for cervical and other cancers, history of screening for cervical cancer and use of oral contraceptives or hormone replacement therapy.

Estrogen use was reported by 40 women with cervical cancer and 86 women in the control group, for an odds ratio of 0.5 (95 percent confidence interval: 0.3 to 0.8), indicating a possible protective effect. The odds of having cervical cancer fell with the duration of estrogen use. The authors calculated the odds ratio to be 0.6 (0.4 to 1.1) for use of less than 12 months' duration and 0.5 (0.2 to 1.0) for use of 12 months' duration or more when compared with women who had never received estrogen therapy. Protection tended to be stronger in women with 10 or more years of estrogen use and in women who started estrogen therapy before 50 years of age.

Although the use of estrogen replacement therapy in this population was low, the authors conclude that use of exogenous estrogens does not appear to increase the risk of cervical cancer and may have a protective effect. The biologic explanation for this effect is not clear. Some of the differences may be attributable to factors such as the increased use of screening and the lower number of sexual partners reported by women in the control group. However, these results confirm those of an earlier, Swedish study and provide some indication that estrogen replacement therapy does not increase the risk of cervical cancer.