Risk of colorectal cancer after use of fertility drugs-results from a large Danish population-based cohort of women with infertility

OBJECTIVE: To study the association between use of fertility drugs and colorectal cancer among women with infertility.

DESIGN: Population-based cohort study.

SETTING: Not applicable.

PATIENT(S): The study cohort was obtained from the Danish Infertility Cohort and consisted of all women with infertility aged 20-45 years living in Denmark during 1995-2017.

INTERVENTION(S): Information on the use of specific types of fertility drugs, colorectal cancer diagnoses, covariates, and vital status were obtained from the Danish Infertility Cohort and Danish national registers.

MAIN OUTCOME MEASURE(S): Cox proportional hazard models adjusted for potential confounders were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for colorectal cancer overall and rectal and colon cancer separately.

RESULTS(S): Among 148,036 women in the final study cohort, 205 women were diagnosed with colorectal cancer. Ever use of clomiphene citrate (CC) was associated with a lower rate of colorectal cancer (unadjusted HR, 0.67; 95% CI, 0.51-0.89; adjusted HR, 0.68; 95% CI, 0.50-0.93). However, the lower rate was only seen among women who first used CC >8 years ago (unadjusted HR, 0.56; 95% CI, 0.41-0.76; adjusted HR, 0.52; 95% CI, 0.36-0.75). No marked associations were found between the use of any of other types of fertility drugs and colorectal cancer. The results for colon and rectal cancer analyzed separately were similar, except for a suggestion of a decreased risk of rectal cancer associated with the use of gonadotropins (adjusted HR, 0.46; 95% CI, 0.20-1.08).

CONCLUSION(S): Among women with infertility, the use of most types of fertility drugs was not associated with colorectal cancer. However, CC may decrease the risk of colorectal cancer and gonadotropins might decrease the risk of rectal cancer, but we cannot rule out that these findings may be more related to the underlying conditions in these women or are chance findings. Consequently, the results from this study should be investigated further in large epidemiological studies.