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ABSTRACT
Aim: Oral contraceptive use influences the risk for certain cancers; however, few studies have examined any link with risk of central nervous system tumors. We investigated the association between hormonal contraceptive use and glioma risk among premenopausal women in a population-based setting.

Methods: Using national administrative and health registries in Denmark to conduct a nationwide case–control study, we identified all women ages 15 to 49 years with a first-time diagnosis of histologically verified glioma between 2000 and 2009. Each case was age-matched to eight population controls using risk set sampling. Based on prescription data, exposure until 2 years prior to the index date was categorized according to hormonal contraceptive type, i.e., combined estrogen–progestagen or progestagen-only, and duration of use (<1, 1 to <5, =5 years). We used conditional logistic regression to compute odds ratios (ORs) with 95% confidence intervals (CIs) for glioma associated with hormonal contraceptive use, adjusting for potential confounders.

Results: We identified 317 cases and 2,126 controls. Ever use of hormonal contraceptive was associated with an OR of 1.5 (95% CI: 1.2-2.0) and the OR increased with duration of use (long-term, =5 years: OR, 1.9; 95% CI: 1.2–2.9). The association between long-term hormonal contraceptive use and glioma risk was most pronounced for progestagen-only therapy (OR, 2.4; 95% CI: 1.1–5.1), especially when this regimen constituted the sole hormonal contraceptive therapy (OR, 4.1; 95% CI: 0.8–20.8).

Conclusion: Long-term hormonal contraceptive use may increase the risk of glioma.

Funding for Study
This study was supported by grants from the Danish Cancer Society (grant no. R56-A2879), Odense University Hospital, and the University of Southern Denmark. The funding sources had no role in the design, analysis, and interpretation of the results. Thus, the authors were independent from the funding sources.

What is already known
Studies of glioma risk associated with use of hormonal contraceptives are limited by their focus on postmenopausal women and, typically, self-reported drug information.
Prospectively collected data on the association between hormonal contraceptive use and glioma risk among younger women are scarce.

What this study adds
In this Danish registry-based study, we found that ever use of hormonal contraceptives was associated with a moderately increased risk of glioma among younger women.
A nearly two-fold increased risk of glioma was observed among long-term users of hormonal contraceptives.

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/bcp.12535
[Pharmacoepidemiology, British Journal of Clinical Pharmacology, Hormonal contraceptive use and risk of glioma among younger women a nationwide case-control study,
DOI: 10.1111/bcp.12535 http://onlinelibrary.wiley.com/doi/10.1111/bcp.12535/abstract]