Depot Medroxyprogesterone Acetate Linked to Higher Risk of Meningioma in Women

A population-based study published in JAMA Neurology reveals that women using depot medroxyprogesterone acetate (DMPA, Depo-Provera; Pfizer)—a long-acting injectable contraceptive—face a notably higher risk of being diagnosed with meningioma compared with women who use other contraceptives or none at all.¹

Box of depot medroxyprogesterone acetate | Image Credit: © Semi - stock.adobe.com

Meningiomas represent the most common form of primary brain tumor, and although most are noncancerous, they remain clinically significant. The tumors occur relatively infrequently, with an annual incidence of about 6 to 8 cases per 100,000 people, and are most often diagnosed in middle age. Meningiomas are far more common in women than in men, with incidence increasing after puberty and a female-to-male ratio ranging from 2 to 3.5 to 1. Research suggests that female sex hormones play a role in both the development and growth of these tumors.²

“Meningioma is the only intracranial tumor with a clear predominance in women, with increasing incidence after puberty (from 2 to 3.5:1),” wrote Gilles Reuter, MD, PhD, and Britta Wandschneider, MD, PhD, wrote in an accompanying statement. “Over 60% of meningiomas express progesterone receptors.”²

The Study

A research team, led by investigators from the Cleveland Clinic and Case Western Reserve University, analyzed data from the TriNetX database, which includes records from 68 health care organizations across the United States. The study spanned a 20-year period, from December 2004 to December 2024, and examined over 118 million total patients, including approximately 61.6 million women.¹

The retrospective cohort study focused on women who used only 1 type of hormonal contraceptive: DMPA injections, oral medroxyprogesterone acetate, combined oral contraceptives, intrauterine devices, progestin-only pills, or subdermal implants. These groups were compared with women who did not use any hormonal contraceptives. Researchers used propensity score matching to balance the groups and minimize potential biases.¹

Key Findings

The research team found that women using DMPA had a 2.43-fold higher risk of being diagnosed with meningioma compared with women who did not use hormonal contraceptives. The risk was greatest in women who used DMPA for more than four years or who began using it after the age of 31.¹

Women using the oral form had a smaller but still significant increase in risk, about 1.18 times higher than nonusers. No elevated risk of meningioma was seen with combined oral contraceptives, intrauterine devices, progestin-only pills, or subdermal implants. According to the researchers, for every 1152 women using DMPA, one additional case of meningioma would occur. For oral medroxyprogesterone acetate, the number needed to harm (NNH) was 3020.¹

Clinical Recommendations

The authors suggest that clinicians consider these findings when counseling patients, particularly those who are considering or currently using DMPA for contraception. Discussions should weigh the benefits of a reliable, long-acting birth control method against the potential increased risk of meningioma, especially for women planning to use it for many years or those beginning treatment after age 31.¹

Interpretation and Significance

Although the relative risk of meningioma with DMPA is significantly higher than in nonusers, the absolute risk remains low. The high number needed to harm indicates that most women using DMPA will not experience this outcome. However, the findings are important because they highlight a potential safety concern for certain populations, particularly long-term users and those who initiate therapy later in life.¹

The decision should be individualized, taking into account patient health history, contraceptive preferences, and overall risk factors. This study adds to growing evidence that sex hormones can influence the development of certain brain tumors and underscores the need for ongoing monitoring.

REFERENCES

1. Xiao T, Kumar P, Lobbous M, et al. Depot medroxyprogesterone acetate and risk of meningioma in the US. JAMA Neurol. September 2, 2025. doi: 10.1001/jamaneurol.2025.3011

2. Reuter G, Wandschneider B. Depot medroxyprogesterone and meningioma risk. JAMA Neurol. September 2, 2025. doi: 10.1001/jamaneurol.2025.2973