Hormonal contraception and lymphoma risk in Danish women aged 15-49 years: a nationwide cohort study

Lymphomas occur less frequently in women than men, but the causes remain unclear. Given the immunomodulatory potential of female hormones, hormonal contraceptive use could influence lymphoma risk, yet existing research is inconclusive.

We investigated the relationship between contemporary hormonal contraceptive use and lymphoma risk in a nationwide Danish cohort of women aged 15-49 years (1995-2021). Women with prior cancer, hysterectomy, oophorectomy, or sterilization were excluded. Data on hormonal contraceptive use, lymphomas, and confounders were retrieved from national registries. Incidence rate ratios with 95% confidence intervals (CIs) were estimated for any hormonal contraceptive use and lymphoma risk, including lymphoma subtypes, contraceptive types, duration of use, and time since last use. All statistical tests were 2-sided.

During 24.5 million person-years of follow-up, 1777 lymphomas (686 Hodgkin, 1091 non-Hodgkin) occurred among 1 957 490 women. Ever-using hormonal contraception was associated with reduced lymphoma risk (incidence rate ratio = 0.84, 95% CI = 0.75 to 0.94), with similar incidence rate ratios across lymphoma types. This was driven by current or recent use of both combined products (incidence rate ratio = 0.80, 95% CI = 0.70 to 0.91) and progestin-only products (incidence rate ratio = 0.81, 95% CI = 0.67 to 0.97), especially oral combined and nonoral progestin-only products. Risk decreased with longer use, with the lowest risk for use more than 10 years (incidence rate ratio = 0.53, 95% CI = 0.33 to 0.85), but no long-term sustained protective effect was seen after cessation.

The findings indicate that hormonal contraceptive use may have a role in lymphoma etiology and confer protective effects, underscoring the need to explore hormonal pathways in a preventive and therapeutic context.