Prolonged use of injectable contraceptive tied to brain tumor diagnoses

From Case Western Reserve University School of Medicine and Cleveland Clinic, investigators report that depot medroxyprogesterone acetate use was associated with a higher relative risk of meningioma brain tumor diagnosis in US women, with risk concentrated after more than four years of exposure or initiation at older than 31 years.

Meningiomas are non-cancerous brain tumors that account for about 40% of primary brain tumors in the US and occur more often in women. Depot medroxyprogesterone acetate is a progestin used by women for contraception and the treatment of abnormal uterine bleeding or endometriosis.

Likely due to the increased rates noted in women, previous studies have examined hormone exposure, with reported progesterone receptor expression in many tumors and estrogen receptor expression in a smaller share. Publications from France and a US insurance database have linked depot medroxyprogesterone acetate exposure with meningioma surgery or diagnosis.

In the study, “Depot Medroxyprogesterone Acetate and Risk of Meningioma in the US,” published in JAMA Neurology, researchers designed a retrospective population-based cohort analysis to examine the relative risk of meningioma diagnosis among users of dMPA and other contraceptives (including oMPA, combined oral contraceptives, IUDs, progestin-only pills, and subdermal implants).

Data came from TriNetX, a US network of 68 health care organizations, covering December 2004 to December 2024. Eligible females totaled 61,588,239, with 10,425,438 patients meeting inclusion eligibility across exposure and control groups.

Group sizes included control (n=8,186,531), depot medroxyprogesterone acetate (n=88,668), oral medroxyprogesterone acetate (n=736,443), combined oral contraceptives (n=388,192), intrauterine devices (n=614,666), copper IUD (n=29,666), 52 mg levonorgestrel IUD (n=180,035), 13.5/19.5 mg levonorgestrel IUD (n=22,643), progestin-only pills (n=39,406), and subdermal implants (n=172,188).

Analyses showed that depot medroxyprogesterone acetate users had a 143% higher risk of meningioma diagnosis than matched controls, with incidence 7.39 per 100,000 patient-years in the injection cohort and 3.05 in controls.

Exposure duration indicated a 200% higher risk at four to six years of use and a 290% higher risk at more than six years.

Age-at-initiation strata indicated a 277% higher risk when starting at 31–40 years, 175% higher at 41–50 years, and 220% higher when starting after 50.

Oral medroxyprogesterone acetate showed an 18% higher risk versus controls.

No increased risk appeared for combined oral contraceptives, IUDs overall, progestin-only pills, subdermal implants, copper IUD, or low-dose levonorgestrel IUD.

Decreased risk estimates were 26% lower for combined oral contraceptives, 13% lower for intrauterine devices overall, and 21% lower for the 52 mg levonorgestrel IUD.

Investigators conclude that depot medroxyprogesterone acetate use correlated with a higher likelihood of meningioma diagnosis, most evident with more than four years of exposure or when started after age 31.

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Prolonged use of certain hormone drugs linked to increased brain tumor risk