Human menopausal gonadotropin and the risk of epithelial ovarian cancer

Objective: To determine whether women with epithelial ovarian cancer are more likely to have been exposed to fertility drugs, and in particular hMG, than healthy population controls. Design: A nationwide case-control study. Patients: Two hundred living women 36 to 64 years of age, with a histologically confirmed diagnosis of primary invasive or borderline epithelial ovarian cancer that was first diagnosed and reported to the Israel Cancer Registry between January 1, 1990 and September 1, 1993 were enrolled. There were 164 (82%) invasive and 36 (18%) borderline epithelial ovarian tumors among the 200 cases. The controls were 408 women from the same dialing areas selected by random digit dialing. Cases and controls were interviewed using a standard questionnaire. A multivariate logistic model was used to assess the association of fertility drug use and ovarian cancer, controlling for variables found to be statistically associated with this outcome on univariate analysis. Results: Twenty-four women with epithelial ovarian cancer (12%) and 29 healthy controls (7.1%) reported that they had used any fertility drug (adjusted odds ratio [OR] 1.31; 95% confidence interval [CI] 0.63 to 2.74). Among cases and controls, respectively, 22 and 24 reported that they had used hMG alone or in combination with clomiphene citrate (adjusted OR 1.42, 95% CI 0.65 to 3.12), and 11 and 6 reported that they had used hMG alone (adjusted OR 3.19, 95% CI 0.86 to 11.82). The risk was increased particularly in the subgroup of women with borderline ovarian tumors who had used hMG (adjusted OR 9.38, 95% CI 1.66 to 52.08). Conclusions: We conclude that the use of ovulation induction agents, in particular hMG, may increase the risk of epithelial ovarian tumors.