Brain cancer and hormonal contraception


A recent Danish study reported that ever use of hormonal contraception was associated with a 50 percent increased risk of glioblastoma multiforme, a deadly form of cancer responsible for 80% of brain tumors.[1] Longer term use, ask at least 5 years, was associated with a 90 percent increased risk, compared to women who did not use hormonal contraceptives. The results received substantial media coverage, with a Time magazine headline stating “Birth control pill risks may now include brain cancer”[2] and CBS news broadcasting a similar banner.[3]

The case-control study drew from national Danish health and administrative registries on cancer and on pharmaceutical use. The researchers identified 317 women with glioma and matched them to 2,126 controls.

The greatest association occurred with progestin-only contraceptives, with an odds ratio of 2.5. For those women for whom progestin-only contraceptives were their solo method, the odds ratio was 4.1. These increased odds ratios may at first glance appear concerning, however, several factors place the study results in more balanced perspective.

First, glioma is rare, with only 0.17% incidence, or about a tenth the incidence of breast cancer. Even if there were a true doubling or quadrupling of risk, its incidence would still be rare.

Second, a meta-analysis 11 earlier case-control studies analyzing 4,860 cases failed to find a correlation, or found a trend toward the inverse, that the glioma risk decreased with use of hormonal contraceptives or hormone therapy.[4]

Third, although the cases were matched to controls in regard to age, schooling, parity, history of allergy or asthma, and use of hormone therapy, antidepressants, antihistamines, anti-asthma medications, and non-aspirin NSAIDS, the only established risk factors for glioma are radiation and rare genetic disorders.[5]

Fourth, case control studies are especially vulnerable to bias because so few confounding factors can be controlled. Generally, odd ratios of 4 or below might be regarded as “non-informative.”[6]

Fifth, the number of cases in some of the data cells was very low. For example, only 3 cases involved solo use of progestin-only contraceptives.

Sixth, the p value for the odd ratio of solo use of progestin-only methods was 1.0, so it did not achieve 0.05 value expected for 95 percent confidence. The p values for other findings also did not meet the standard for 95 percent level of confidence.

Bottom-line? This study does not provide compelling evidence of risk.


—Deborah Kowal, MA, PA, President, Contraceptive Communications, Inc.


[1] Anderson L, Friis S, Hallas J, et al. Hormonal contraceptive use and risk of glioma among younger women: a nationwide case-control study.  Br J Clin Pharmacol 2014 Oct 26. doi: 10.1111/bcp.12535. [Epub ahead of print]

[2] Park A. Birth control pill risks may now include brain cancer. Time 2015, Jan. 22.

[3] Mozes A. birth control pill may be linked to rare brain tumors. CBS News 2015; Jan 22, 2:25 pm.

[4] Qi Z, Shao C, Zhang X, et al. Exogenous and endogenous hormones in relation to glioma in women: a meta-analysis of 11 case-control studies. PLOS One 2013;8:1-11. doi:10.1371/journal.pone.0068695

[5] Wigertz A, Lonn S, Mathiesen T, et al. Risk of brain tumors associated with exposure to exogenous female sex hormones. Am J Epidem 2006;164:629-36.

[6] Grimes D, Schulz K. False alarms and pseudo-epidemics: the limitations of observational epidemiology. Obstet Gynecol 2012;120:920-7.