Studies
12 birth control formulations, ranked by meningioma risk
A Danish government study tested 12 contraceptive formulations against meningioma risk. Four showed no signal at all. Here's the full table.
Which birth control formulations carry a meningioma risk signal?
Of 12 progestogen-based formulations tested, one stood far apart from every other result: the injectable shot behind Depo-Provera.
A 2026 study run by the Danish Medicines Agency looked at 12 different progestogen-based birth control formulations, pills, an injectable, and IUDs, and compared each one’s meningioma risk against women who used no hormonal contraception at all. Meningioma is a usually non-cancerous brain tumor.
The agency matched 1,473 women diagnosed with meningioma to 14,717 women who weren’t, all drawn from Denmark’s national health registers. That design is a population-based case-control study, not a randomized trial and not a cohort study. It’s built to measure association across a population, not to establish that any one woman’s diagnosis was caused by any one contraceptive.
Eight of the 12 formulations tested showed a statistically significant association with meningioma. Four didn’t. And one formulation stood far apart from every other result in the table.
Injectable medroxyprogesterone, the drug in Depo-Provera, showed the strongest signal by a wide margin: an odds ratio of 4.55, with a 95% confidence interval of 2.19 to 9.45. The next-highest formulation, the desogestrel progestogen-only pill, came in far lower, at an odds ratio of 1.73. DMPA’s number isn’t a small step above the rest of the table. It runs roughly two and a half times the next-closest figure, and it’s the only formulation in the study with a confidence interval that stays above 2.0 at its lower bound.
Of 12 contraceptive formulations tested, the injectable shot carried the strongest meningioma signal by a wide margin.
Odds ratio and 95% confidence interval for each formulation, versus non-users. Sorted highest to lowest.
| Formulation | Odds ratio (95% CI) | Statistically significant? |
|---|---|---|
| Injectable medroxyprogesterone (DMPA, the depo shot) | 4.55 (2.19–9.45) | Yes |
| Desogestrel, progestogen-only pill | 1.73 (1.17–2.56) | Yes |
| Desogestrel, combined pill | 1.66 (1.31–2.10) | Yes |
| Cyproterone, combined pill | 1.61 (1.00–2.59) | Borderline |
| Drospirenone, combined pill | 1.58 (1.05–2.37) | Yes |
| Levonorgestrel IUD, high-dose (52mg) | 1.58 (1.28–1.94) | Yes |
| Gestodene, combined pill | 1.44 (1.17–1.77) | Yes |
| Levonorgestrel, combined pill | 1.40 (1.12–1.76) | Yes |
| Norethisterone, combined pill | 1.38 (0.77–2.47) | No |
| Levonorgestrel IUD, low-dose (13.5/19.5mg) | 1.14 (0.59–2.22) | No |
| Norgestimate, combined pill | 1.04 (0.70–1.54) | No |
| Norethisterone, progestogen-only pill | 0.95 (0.57–1.57) | No |
Source: JAMA Network Open 2026;9(7):e2622603, Danish Medicines Agency registry study
Whatever number sits next to your method, the absolute risk stays small. For the great majority of women who’ve used any of these formulations, this diagnosis never happens.
The full table, plain English
An odds ratio above 1.0 means the study found more meningioma diagnoses among women who used that formulation than expected. An odds ratio of 1.0 or below means it didn’t. But the number alone isn’t enough. The 95% confidence interval next to it tells you how much to trust that number.
When a confidence interval’s lower bound sits below 1.0, like the four formulations marked “No” in the table, the study can’t rule out that the real effect is zero. That’s why the Danish Medicines Agency calls those four “not significant,” not “safe” and not “risk-free.” It means this particular study didn’t find strong enough evidence either way for those four.
Cyproterone’s combined pill sits right on that line. Its confidence interval runs from 1.00 to 2.59, so the study is marked “borderline.” One more diagnosis in the data either direction could move it across the threshold.
The seven formulations marked “Yes” all have confidence intervals that stay entirely above 1.0. Add cyproterone’s borderline result, which sits right on the 1.0 line, and that’s eight of twelve with a statistically significant association. Among those eight, DMPA’s signal is the strongest by a wide margin.
Why the injectable shot’s number is different from the pills and IUDs
DMPA works differently from the pills and IUDs on this table. It’s a progestin delivered by injection, at a higher and steadier dose than a daily pill or a hormonal IUD releases locally. The pills on this table mostly deliver a lower, combined dose that includes estrogen alongside a progestin. The IUDs release their hormone directly in the uterus, with far less reaching the rest of the body.
The Danish study didn’t test why DMPA’s number came out highest. It reported what the data showed: among the 12 formulations it could measure with enough data to report, DMPA’s association with meningioma was the strongest one found.
What this study is, and what it isn’t
This is a population-based case-control study, not a randomized trial. Researchers started with women who already had a meningioma diagnosis, then looked backward at what contraceptives they’d used. That design measures association, not individual cause. It can’t tell you whether Depo-Provera caused any one woman’s meningioma diagnosis. No court has ruled on that question, and the litigation’s own hearing on this science hasn’t happened yet.
The risk this study found isn’t a flat, lifetime multiplier either. The study reports that the excess risk concentrates in current or recent use, and for most of the formulations tested, it faded within about five years of stopping. A number like 4.55 describes the study’s finding for women using DMPA now or recently, not a permanent multiplier that follows a woman for the rest of her life.
One more precision point: this study’s meningioma count includes spinal meningioma, not only meningioma in the skull. That’s a slightly broader outcome definition than some other studies use.
This is also a new finding, not a finalized regulatory decision. The Danish Medicines Agency has referred it to the European Medicines Agency’s safety committee, the PRAC, for review. That’s the same committee that concluded a related meningioma risk back in 2024, more than a year before the FDA acted. This newer Danish referral hasn’t been ruled on. Per the agency’s own statement: if the committee finds sufficient evidence, that could eventually lead to a label update, but the committee has to assess the study first.
The absolute risk stays small
A relative number like an odds ratio only means something next to how common meningioma is in the first place. In Denmark, where this study was run, the agency’s own reported baseline is 12.6 diagnoses per 100,000 people a year, and 17.9 per 100,000 among women specifically. In the agency’s own words: “at the individual level it is a very small risk and an extremely rare side effect.”
Meningioma is a usually non-cancerous brain tumor, and none of this changes that. Non-cancerous doesn’t mean minor. A meningioma diagnosis can still mean monitoring, surgery, and lasting neurological change for the women who get one. It also means, for the great majority of women who’ve used any of these formulations, including DMPA, this diagnosis never happens.
This Danish figure is one of three primary studies that have reported a meningioma signal for the depo shot, each measuring a slightly different question. If you want to see how this 4.55 figure compares to the other two, we’ve laid all three out side by side.
Find out where you stand
You don’t need to read a study table to know if this applies to you. Two questions tell you where you stand, no name, phone, or email required yet.