Depot Medroxyprogesterone Acetate and Risk of Meningioma in the US

Importance There lacks data clarifying the meningioma risk conferred by depot medroxyprogesterone acetate in the US. Objective To examine the relative risk of meningioma diagnosis in women using depot medroxyprogesterone acetate and other related progestins. Design, Setting, and Participants This retrospective population-based cohort study used data from TriNetX, a US national database of 68 health care organizations. Data were analyzed from December 2004 to December 2024. The incidence of meningioma diagnosis was compared between treatment groups through propensity-score matched analyses. Participants included a sample of females with use of only 1 of the following progestins/contraceptives: depot medroxyprogesterone acetate, oral medroxyprogesterone acetate, combined oral contraceptives, intrauterine devices, progestin only pills, or subdermal implantable contraceptive. The control group included females without use of these hormonal treatments. Of the 118 289 082 total patients in TriNetX at the time of analysis, 61 588 239 patients were female and eligible. Exposures Patients were defined using diagnostic codes from the International Classification of Diseases, Current Procedural Terminology , and RxNorm codes within TriNetX. Main Outcome and Measure The main outcome was meningioma diagnosis. Relative risks and number needed to harm were calculated. Results There were 10 425 438 patients that met inclusion criteria with a mean age of 33.4 years at inclusion. After propensity score matching, 88 667 patients with mean age of 26.2 years at inclusion were in the depot medroxyprogesterone acetate group. Use of depot medroxyprogesterone acetate had a relative risk of 2.43 (95% CI, 1.77-3.33) for meningioma diagnosis compared with controls. Notably, this risk was confined for patients with longer than 4 years of exposure or starting the prescription at ages older than 31 years. Oral medroxyprogesterone acetate had increased relative risk of 1.18 (95% CI, 1.10-1.27) compared with controls. No increased risk of meningioma diagnosis was found with any other contraceptive. The number needed to harm for the depot medroxyprogesterone acetate was 1152 patients and 3020 patients for oral medroxyprogesterone acetate. Conclusions and Relevance In this study, women receiving depot medroxyprogesterone acetate had a greater relative risk of subsequent meningioma diagnosis, especially with prolonged exposures and starting the medication at older ages. The high number needed to harm suggests low clinical risk overall.