Depo-Provera injection

A New Look at Depo-Provera and Brain Tumour Risk

Depo-Provera (depot medroxyprogesterone acetate; DMPA) is a widely used and effective medication. For many, it’s a convenient, long-acting contraceptive. For others, it’s a vital tool for managing the debilitating pain of conditions like endometriosis.

As with any medication, understanding its full safety profile is essential. Recent large-scale studies have shed new light on a potential link between DMPA and a specific type of brain tumour called a meningioma. 🧠

What Did the New Research Find?

Following earlier signals and progestin-meningioma associations, two recent high-impact studies provide important data:

  • A French national case-control study published in The BMJ examined use of oral contraceptives containing desogestrel or levonorgestrel and risk of intracranial meningioma.
  • A US retrospective cohort study published in JAMA Neurology assessed the association between DMPA use (and other progestins) and meningioma risk in a cohort of over 10 million women.

Key details from the JAMA Neurology paper:

  • Study design: Retrospective, population-based cohort using the TriNetX US database (2004–2024).
  • Participants: 10,425,438 women meeting inclusion criteria; after propensity-score matching, 88,667 women in the DMPA group were compared with matched controls.
  • Main outcome & exposure groups: Women who used exactly one type of progestin or contraceptive (e.g. DMPA, oral medroxyprogesterone acetate, combined oral contraceptives, IUDs, progestin-only pills, or implant). The control group comprised women without exposure to those hormonal treatments.
  • Findings:
    • Relative risk for meningioma diagnosis in the DMPA (injectable) group: 2.43 (95% CI 1.77 – 3.33) compared with controls.
    • The elevated risk was concentrated among women with >4 years of DMPA use or who initiated DMPA after age 31.
    • Oral medroxyprogesterone acetate (pill form) had a smaller relative risk: 1.18 (95% CI 1.10 – 1.27).
    • No increased meningioma risk was observed with other contraceptive modalities.
    • Number needed to harm (NNH): ~1,152 for DMPA; ~3,020 for oral medroxyprogesterone acetate.

These detailed results ground the risk estimates in rigorous data, showing that while there is a measurable association, the absolute risk remains low.

Putting the Risk Into Perspective

That “2.4 times higher risk” figure can sound striking. But it’s helpful to frame it correctly:

  • This is a relative risk increase; the absolute risk remains very low. An NNH of ~1,152 means roughly one additional case of meningioma per 1,152 women using Depo-Provera (versus nonusers).
  • This is not the first time a progestin has been implicated in meningioma risk. For instance, cyproterone acetate has been associated with markedly greater risk (often >20×, depending on cumulative dose).
  • In the BMJ study, prolonged continuous use of desogestrel 75 µg (≥5 years) was linked to a modest elevation in intracranial meningioma risk (OR up to ~2.09 for ≥7 years). No excess risk was observed for levonorgestrel, alone or combined with oestrogen. Roland et al. estimated an NNH of ~67,300 for desogestrel overall.

Together, these data suggest a plausible but modest risk increase with Depo-Provera dramatic than with some higher-potency progestins—but one worth acknowledging.

The Critical Role of Depo-Provera in Managing Endometriosis

For individuals with endometriosis or chronic pelvic pain, Depo-Provera often exceeds its contraceptive role. By suppressing the menstrual cycle, it helps reduce inflammation, pain, and heavy bleeding.

When one’s daily life is severely disrupted by endometriosis, the benefits of symptom control are profound. The decision to use Depo-Provera in this scenario demands a different calculus: does the quality-of-life gain outweigh the very small absolute risk of meningioma? For many, it likely does.

What Should You Do With This Information?

This new research is a prompt for conversation, not alarm.

  1. Understand your “why”. Are you using Depo-Provera for contraception or to manage a condition like endometriosis (or heavy bleeding)?
  2. Keep risk in context. The absolute risk is low, and is considerably smaller than risks seen with other progestins.
  3. Have a shared decision-making discussion with your doctor. Use this data to guide a conversation about your personal medical history, duration of use, therapeutic goals, and potential alternatives.

References

  1. Roland N, Kolla E, Baricault B, Dayani P, Duranteau L, Froelich S, Zureik M, Weill A. Oral contraceptives with progestogens desogestrel or levonorgestrel and risk of intracranial meningioma: national case–control study. BMJ 2025;389:e083981. doi:10.1136/bmj-2024-083981.
  2. Xiao T, Kumar P, Lobbous M, Yogi-Morren D, Soni P, Recinos PF, Kshettry V. Depot Medroxyprogesterone Acetate and Risk of Meningioma in the US. JAMA Neurol. Published online September 2, 2025. doi:10.1001/jamaneurol.2025.3011.
Published: 2025-10-11