Use of Fertility Drugs and Risk of Ovarian Cancer: Danish Population Based Cohort Study - Editorial comment

Since the late 1970s, the possible increased risk of ovarian cancer in women taking fertility drugs has received much public attention and raised patient anxiety. Three epidemiological studies published between 1992 and 1996 reported that fertility drugs increased risks of ovarian cancer. Although a large number of subsequent epidemiological studies found no strong association between use of fertility drugs and risk of ovarian cancer, most of these studies had methodologic problems. This population-based cohort study assessed the possible association between use of fertility drugs and overall risk of ovarian cancer among 54,362 Danish women who attended infertility clinics between 1963 and 1998. Data on the reproductive history for all infertile women with ovarian cancer in the cohort after enrollment and for those in the subcohort was obtained from the Danish National Birth Registry, the Danish Cancer Registry, and the Danish Registry of Pathology. The median year for enrollment was 1989. The median age at the initial evaluation for infertility was 30 years, and the median age at the end of follow-up was 47 years. A total of 156 women with invasive epithelial ovarian cancer (cases) were included in the analysis. A subcohort of 1241 women who were randomly selected during follow-up in 2006 served as the comparison group. The median follow-up was 16 years and 25% of the cases were followed for more than 23 years. The overall risk of ovarian cancer was examined in 4 groups of fertility drugs (gonadotropins, clomiphene, human chorionic gonadotropin, and gonadotropin releasing hormone). Cox regression analysis was used to adjust risk ratios for potential confounding factors. The overall risk of ovarian cancer was not significantly affected by use of gonadotropins (adjusted rate ratio [aRR], 0.83; 95% confidence interval [CI], 0.50-1.37), clorniphene (aRR, 1.14; 95% CI, 0.79-1.64), human chorionic gonadotropin (aRR, 0.89; 95% CI, 0.62-1.29), or gonadotropin releasing hormone (aRR, 0.80; 95% CI, 0.42-1.51). For all 4 groups of fertility drugs, the risk of ovarian cancer was not affected by the number of cycles of use, length of follow-up since first use of drug, or parity. These findings are consistent with those of most previous epidemiological studies and provide additional evidence for the absence of a strong association between use of fertility drugs and overall risk of ovarian cancer.