Ovulation induction and risk of endometrial cancer: A pilot study

Objective: To determine whether women with endometrial carcinoma are more likely to have been exposed to fertility drugs, in particular clomiphene, than healthy population controls. Study design: A nationwide case-control, pilot study. About 128 living women 35-64 years old, with a histologicaly confirmed diagnosis of endometrial carcinoma that was first diagnosed and reported to The Israel Cancer Registry between 1 January 1989 and 31 December 1992 were enrolled. The controls were 255 women from the same dialing areas selected by random digit dialing. A variety of demographic and clinical parameters were compared between cases and controls. A multivariate logistic model, controlling for age, was used to assess the independent effects of factors found to be significantly associated with endometrial cancer on univariate analysis. Results: About 7 women with endometrial carcinoma (5.5%) and 10 healthy controls (3.9%) reported that they had used any fertility drug (crude odds ratio (OR) 1.4; 95% confidence interval (CI) 0.47-4.2). Use of fertility drugs did not meet the criteria for entry into the logistic model. The following parameters were found to be independently associated with endometrial cancer controlling for age, European-American background OR = 2.2, (95% CI 1.3-3.7, P = 0.004); nulliparity OR = 2.7 (95% CI 1.1-6.5, P = 0.03); history of infertility OR = 1.8 (95% CI 1.0-3.3, P = 0.05); BMI ≥ 27 OR = 2.3 (95% CI 1.4-3.9, P = 0.001). The use of oral contraceptives and IUD were found to be protective, OR = 0.29 and 0.37, respectively, (95% CI 0.14-0.61, P = 0.001 and 0.19-0.70, P = 0.003, respectively). Conclusions: We found no evidence that the use of ovulation induction agents, including clomiphene citrate, are associated with a higher risk of endometrial carcinoma. The association between infertility drugs and endometrial carcinoma should be examined in other, larger studies.