In situ and invasive cervical carcinoma in a cohort of infertile women

Objective: To assess the risk of cervical neoplasia associated with the use of ovulation-inducing agents such as clomiphene citrate (CC). Design: Case-cohort study. Setting: Infertility clinics in Seattle, Washington. Patients: A cohort of 3,837 women evaluated for infertility at some time during 1974-1985. Main Outcome Measure: Computer linkage with a population-based tumor registry was used to identify women diagnosed with cervical cancer before January 1, 1992. Data regarding infertility testing and treatment were abstracted from medical records for women who developed cancer and a randomly selected subcohort. Results: Thirty-six women in the cohort developed in situ or invasive cervical cancer in comparison with an expected number of 67.8 cases (standardized incidence ratio = 0.5, 95% confidence interval [CI] 0.4 to 0.7). Infertile women with fallopian tube abnormalities were at an increased risk of cervical cancer relative to women whose infertility was believed to be due to other causes. The risk among women who had taken CC was reduced relative to infertile women who had not used this drug (relative risk = 0.4, 95% CI 0.2 to 0.8). This association was present both in women with and without tubal abnormalities. However, the size of the reduction in risk was not influenced by duration of use. Conclusions: The hypothesis that use of antiestrogenic agents, such as CC, can lead to a reduced risk of cervical neoplasia warrants testing in other studies.