Fertility treatment and risk of non-Hodgkin lymphoma - results from a Danish population-based cohort study

PURPOSE: To investigate the association between fertility drug use and non-Hodgkin lymphoma.

METHODS: This cohort study utilized data from the extensive Danish Infertility Cohort, comprising 148,036 women with fertility problems residing in Denmark between January 1, 1995 and December 31, 2017. The study cohort was linked to national registers to gather information on fertility drug use, cancer diagnoses, covariates, and emigration and vital status. Cox proportional hazard models were employed to calculate hazard ratios (HRs) and 95% confidence intervals for non-Hodgkin lymphoma (overall and for histologic subtypes), with adjustments for potential confounders.

RESULTS: Over a median follow-up of 11.3 years, 115 women were diagnosed with non-Hodgkin lymphoma. After adjustment for potential confounders, overall non-Hodgkin lymphoma rates were decreased following treatment with all specific types of fertility drugs analyzed being clomiphene citrate (HR 0.74; 95% CI 0.43-1.26), gonadotropins (HR 0.67; 95% CI 0.39-1.16), hCG (HR 0.69; 95% CI 0.41-1.17), GnRH receptor modulators (HR 0.58; 95% CI 0.33-1.03), and progesterone (HR 0.69; 95% CI 0.39-1.21). However, none of these associations were statistically significant implying that the results should be interpreted with great caution. Similar trends were seen for B-cell lymphomas. For most fertility drugs, we observed a tendency toward lower associations within the first 10 years after start of drug use.

CONCLUSION: The findings of this study do not indicate any strong associations between the use of fertility drugs and the risk of non-Hodgkin lymphoma. However, the relatively young age of the cohort at the end of follow-up underscores the need for an extended follow-up period to evaluate the long-term risk of non-Hodgkin lymphoma in women who have used fertility drugs.