Contraceptive Tied to Higher Brain Tumor Risk in Women

 The birth control method depot medroxyprogesterone acetate (dMPA) has been linked to a twofold increased risk for a common brain tumor type.

The risk for meningioma associated with dMPA, commonly known as Depo-Provera, was greatest in women who began using the injection after age 31 years or who used it for 4 years or more.

The findings of this study come amid ongoing lawsuits, which allege that Pfizer, the manufacturer of Depo-Provera, failed to inform users about this risk.

However, the investigators noted that the number needed to harm (NNH) is high, suggesting a relatively low overall clinical risk.

“The main point of our study is that we need to spread awareness of this potential risk of meningioma development with dMPA exposure, especially for those at increased risk of meningioma due to other risk factors such as prior brain radiation, history of breast cancer, and certain genetic conditions such as neurofibromatosis,” principal investigator Varun Kshettry, MD, and a neurosurgeon at Cleveland Clinic in Cleveland, told Medscape Medical News.

The study was published online on September 2 in JAMA Neurology.

A Common Tumor Type

Meningioma is the most common primary brain tumor, and women are twice as likely as men to develop this tumor type. This risk increases as women age, likely due to interactions between tumor receptors and female hormones.

A previous matched case-control study based on French data showed that long-term use of dMPA was associated with a 5.5-fold increased risk for meningioma.

The current study corroborates the findings of the French study, Kshettry said, but he noted that it only included patients who had undergone surgery for meningiomas, and that of these individuals, only a small number reported dMPA use.

For their research, Kshettry and colleagues evaluated over 80,000 women with dMPA exposure in the US over a 20-year period using a cohort study design. They also included individuals who used dMPA and did not develop meningioma, allowing them to calculate clinical risk.

Data from 10,425,438 female patients (mean age, 33 years) from TriNetX, a national health database, were included in the study. Patients with previous meningiomas were excluded from the analysis.

Patients were grouped on the basis of use of a single type of birth control: oral or injectable medroxyprogesterone acetate, combined oral contraceptives, intrauterine devices, progestin-only pills, or subdermal implants. Women who did not use any of the evaluated contraceptives served as controls (n = 8,186,531).

The researchers used propensity score matching to gauge the rate of meningioma diagnosis (based on International Classification of Diseases, 10th Revision codes) in these groups and controlled for several confounders including race, age, BMI, and neurofibromatosis.

Compared with control individuals, dMPA use was associated with an increased risk for meningioma (relative risk, 2.43; 95% CI, 1.77-3.33), and the investigators determined that 59% of meningioma cases could be attributed to dMPA.

The NNH was 1152 patients, meaning that 1152 women would have to use dMPA before one developed a meningioma.

Oral medroxyprogesterone acetate was associated with a 1.18 relative risk for a meningioma diagnosis compared with control individuals (95% CI; 1.10-1.27). The NNH was 3020 patients. The researchers found no increased risk for meningioma diagnosis with any of the other contraceptives.

“Our data suggest as well that prolonged exposure and older age with dMPA use both appear to increase the risk of meningioma,” Kshettry said.

Limitations of the study include potential variations among patient data from the live database and that the timeline of meningioma diagnosis could not be assessed.

‘Overall Low Clinical Significance’

In an accompanying editorial, Gilles Reuter, MD, PhD, and Britta Wandschneider, MD, PhD, at the Department of Neurosurgery, Centre Hospitalier Universitaire de Liège in Liège, Belgium, said the findings indicated “overall low clinical significance that does not justify modification of the MPA treatment indication.”

They recommend that every woman presenting with a meningioma undergo a thorough review of her overall medical history, with special attention to gynecologic and hormonal factors.

“Overall, this large study demonstrates that the dMPA-associated meningioma risk remains very low but provides healthcare professionals with data to counsel women taking these medications that meningioma may be a risk to consider,” Reuter and Wandschneider wrote.

https://www.medscape.com/viewarticle/contraceptive-tied-higher-brain-tumor-risk-women-2025a1000o2s