Meningioma Risk Increased With Depot Medroxyprogesterone Acetate Use

Depot medroxyprogesterone acetate (dMPA) use is associated with an increased risk for meningioma incidence, according to results of a large, real-world cohort analysis published in JAMA Neurology.

Researchers utilized the TriNetX US Collaborative Network to determine whether exogenous hormone exposure from progestins increased meningioma risk.

In a retrospective, population-based, propensity-matched cohort study (N=10,425,438; mean age, 33.4 years), the researchers compared meningioma incidence in women exposed to dMPA (n=88,668), oral medroxyprogesterone acetate (oMPA; n=736,443), a combined oral contraceptive (COC; n=388,192), an intrauterine device (IUD; 614,666), a progestin-only pill (POP; 39,406), or a subdermal implant (SDI; n=172,188), vs women with no hormonal exposure (n=8,186,531).

Analyses covered the period between December 2004 and December 2024. The primary outcome was any subsequent meningioma diagnosis.

The dMPA group had a mean (SD) age of 26.2 (9.4) years, 51.1% were White, and the mean (SD) body mass index (BMI) was 28.4 (8.2) kg/m². Compared with matched control individuals, dMPA use was associated with a higher risk for meningioma (relative risk [RR], 2.43; 95% CI, 1.77-3.33). Incidence rates were 7.39 vs 3.05 per 100,000 patient-years in the dMPA and control groups, respectively. The number needed to harm (NNH) between the dMPA and control cohorts was 1152 patients, with an attributable risk percentage of 59%.

Compared with matched controls, RRs rose to 3.00 (95% CI, 1.47-6.13) with 4 to 6 years of dMPA exposure and 3.90 (95% CI, 1.95-7.81) with more than 6 years of exposure. Additionally, starting dMPA after age 31 was associated with significantly higher risk, with risk peaking at ages 31 to 40 years (RR, 3.77; 95% CI, 2.05-6.95).

Comparatively, oMPA was associated with a smaller but statistically significant increase in meningioma risk (RR, 1.18; 95% CI, 1.10-1.27; NNH, 3020). No increased risk was observed for COCs, IUDs, POPs, or SDIs vs control individuals.

In contrast with dMPA and oMPA, COCs (RR, 0.74; 95% CI, 0.60–0.90), IUDs overall (RR, 0.87; 95% CI, 0.77–0.97), and specifically 52-mg levonorgestrel IUDs (RR, 0.79; 95% CI, 0.63–0.98) were associated with modestly lower risk for meningioma. When directly compared with other contraceptive categories, dMPA consistently showed higher relative risks.

The findings are limited by the use of insurance coding, variability in live database updates, and limited information on time to meningioma diagnosis.

“In this US population cohort study, we demonstrated that patients using injection dMPA had a greater RR of developing a meningioma diagnosis compared with matched patients using oMPA, other contraceptives, or controls,” the study authors concluded.