# Leukemia in users of contemporary hormonal contraception: A nationwide registry-based cohort study among premenopausal women in Denmark

## TL;DR

A large Danish study found no link between modern hormonal contraceptives and leukemia risk in premenopausal women.

## Contribution

The study is the first to evaluate contemporary hormonal contraceptives and leukemia risk using nationwide data.

## Key findings

- Contemporary hormonal contraceptive use was not associated with leukemia risk.
- Results were consistent across contraceptive types, durations of use, and leukemia subtypes.
- The study found no evidence of increased risk despite long-term follow-up.

## Abstract

Sex hormones have been implicated in leukemogenesis, but evidence regarding hormonal contraceptive use and leukemia risk remains limited and primarily based on older formulations. Given the widespread use of contemporary hormonal contraceptives, clarification of this potential association is needed. This study examines the association between contemporary hormonal contraceptives and leukemia risk.

In a nationwide cohort design, we assessed associations between the use of contemporary hormonal contraceptives and the risk of leukemia based on a cohort of all women aged 15–49 years residing in Denmark from 1995 to 2021 with no previous cancer, hysterectomy, oophorectomy, or sterilization. Information on hormonal contraception use, leukemia diagnoses, and potential confounders (age, calendar year, education) was obtained from nationwide registries. Adjusted incidence rate ratios (IRRs) and 95% confidence intervals [CIs] were estimated for any leukemia, and specific types of leukemia, associated with any hormonal contraceptive use, current and recent use, and previous use, type of product used, duration, and time since last use. Among 1,957,490 pre-menopausal women followed for 24.5 million person-years (median 12.5 years, interquartile range: 5.9,20.5), 671 were diagnosed with leukemia. The incidence rate for leukemia among current and recent users was similar to that among women who had never used hormonal contraception: IRR 0.95 (95% CI [0.78,1.16]; p = 0.62). No association with different durations of use was found: 0–5 years; IRR 0.93 (95% CI [0.75,1.14]; p = 0.48), >5–10 years; IRR 1.16 (95% CI [0.84,1.61]; p = 0.37), >10 years; IRR 0.67 (95% CI [0.33,1.37]; p = 0.27); nor for time since last use: 0–5 years; IRR 1.01 (95% CI [0.78,1.29]; p = 0.96), >5–10 years; IRR 1.05 (95% CI [0.76,1.45]; p = 0.75), >10 years; IRR 0.88 (95% CI [0.60,1.29]; p = 0.52). Also, the IRRs for leukemia with use of different hormonal contraceptive types (e.g., combined products; IRR 0.91 (95% CI [0.73,1.14]; p = 0.42) and progestin-only products; IRR 1.05 (95% CI [0.78,1.40]; p = 0.75)), as well as for product-specific durations of use, were for the majority close to 1. The IRRs were similar for different types of leukemia. Main study limitations include small case numbers in some analyses; therefore, additional large-scale studies are warranted to reliably exclude weak associations.

Contemporary hormonal contraceptives were not associated with leukemia, independent of product used, duration of use, time since last use, and type of leukemia. While estimates were imprecise for some subgroups, the overall findings do not support an association.

Sex hormones have been implicated in the development of leukemia, but it is unclear whether hormonal contraceptive use is associated with leukemia risk.

No study has been identified evaluating the potential impact of hormonal contraceptive use on leukemia development in women of reproductive age in the context of the contemporary formulations predominantly in use.

Nearly 2 million Danish women aged 15–49 years were followed from 1995 to 2021 using Danish nationwide registry data. Women with prior cancer, hysterectomy, oophorectomy, or sterilization were excluded.

No association was found between contemporary hormonal contraceptive use and the risk of leukemia. Results were consistent across contraceptive types, durations of use, time since last use, and leukemia types.

These findings suggest that contemporary hormonal contraceptive use is not associated with the risk of leukemia in women of reproductive age, offering reassurance about the safety of modern hormonal contraceptives commonly used with respect to this specific cancer risk. However, weak associations cannot be ruled out, as our nationwide study lacks statistical precision to detect weak associations, given the relative rarity of leukemia.

Using Danish nationwide registry data of nearly 2 million women, Caroline H. Hemmingsen and colleagues evaluate the risk of leukemia among pre-menopausal women using contemporary hormonal contraceptives.