Depo-Provera and Increased Risk of Meningioma: FDA-Label Update.
Written by: Anna Ryabets-Lienhard, DO as part of Drugs and Therapeutics Committee
In December 2025, the U.S. Food and Drug Administration (FDA) approved an update to the U.S. Prescribing Information for Depo‑Provera, adding a warning about a potential increased risk of meningioma, a typically benign intracranial tumor. The warning applies to both FDA‑approved injectable formulations of medroxyprogesterone acetate (MPA): Depo‑Provera CI (150 mg intramuscular) and Depo‑SubQ Provera 104 (104 mg subcutaneous)1,2.
This labeling change was influenced by emerging observational data, including a large population‑based case–control study published in The BMJ, which identified an increased risk of intracranial meningioma associated with prolonged use (≥ 1 year) of injectable MPA, particularly the 150 mg formulation3. In that study, prolonged exposure was associated with an approximately 5.6‑fold increase in odds of surgically treated intracranial meningioma (adjusted OR 5.55; 95% CI 2.27–13.56).
The updated FDA labeling states that cases of meningioma have been reported following repeated administration of MPA, primarily with long‑term use. While the absolute risk of meningioma remains low, physicians and clinicians are advised to counsel patients regarding this risk, monitor for signs or symptoms suggestive of meningioma (which include hearing loss or ringing in the ears, headaches, changes in vision, and seizures), and discontinue Depo‑Provera if a meningioma is diagnosed1. Although the strongest epidemiologic evidence relates to the 150 mg intramuscular formulation, the FDA applied the warning to both injectable products based on shared active ingredient, pharmacologic plausibility, and regulatory safety principles.
References:
- U.S. Food and Drug Administration. Depo‑Provera CI (medroxyprogesterone acetate injectable suspension) Prescribing Information. Revised December 2025. Drugs@FDA. DEPO-PROVERA CI
- U.S. Food and Drug Administration. Depo‑SubQ Provera 104 (medroxyprogesterone acetate) Prescribing Information. Revised December 2025. Drugs@FDA.
- Roland N, Neumann A, Hoisnard L, et al. Use of progestogens and the risk of intracranial meningioma: national case–control study. BMJ. 2024;384:e078078.
Written by: Anna Ryabets-Lienhard, DO as part of Drugs and Therapeutics Committee