Progestogen Contraceptives Associated With Increased Risk of Meningioma: JAMA
Denmark: A large Danish study published in JAMA Network Open has found that women using progestogen-containing contraceptives had a significantly increased risk of developing meningioma, the most common benign brain tumor. Consistent with previous research, injectable medroxyprogesterone was associated with the highest risk, while the study also identified elevated risks with oral progestogen formulations and progestogen-releasing intrauterine devices (IUDs). These findings highlight the importance of considering potential long-term neurological risks when prescribing progestogen-based contraceptives.
Although high-dose progestogens are already recognized as a risk factor for meningioma, evidence regarding contraceptive-dose progestogens has remained limited. To investigate whether commonly used hormonal contraceptives also increase this risk, the researchers evaluated the association between different contraceptive progestogens and incident meningioma in a nationwide Danish population.
For this purpose, Nicklas Hasselblad Lundstrøm from the Danish Medicines Agency and colleagues conducted a nationwide nested case-control study using Danish health registers covering 25 years from 2000 to 2024. The study included approximately 3 million women aged 15 to 59 years. Researchers identified 1,473 women diagnosed with meningioma and matched each case with 10 controls based on age, birthplace, and marital status. Contraceptive exposure was determined using prescription dispensing records and procedural data, with women categorized according to their most recent progestogen use before diagnosis. The primary outcome was a newly diagnosed meningioma identified through the Danish National Cancer Register.
The analysis showed that several contraceptive progestogens were associated with an increased risk of meningioma, with the highest risks generally observed among current or recent users.
Key findings
- Recent use of combined oral contraceptives containing cyproterone, desogestrel, drospirenone, gestodene, or levonorgestrel was associated with a modestly increased risk of meningioma.
- Oral progestogen-only contraceptives containing desogestrel were also associated with a higher risk, whereas norethisterone showed no significant association.
- Injectable medroxyprogesterone was associated with the highest risk of meningioma, with more than a fourfold increase compared with non-users.
- High-dose levonorgestrel-releasing intrauterine devices (IUDs) were associated with an increased risk, while low-dose levonorgestrel IUDs were not.
- The highest risk was observed among women with current or recent contraceptive use within the previous year.
The researchers acknowledged several limitations, including possible exposure misclassification, insufficient cases for some progestogens, limited recent use of norethisterone and norgestimate, and the short follow-up period for low-dose levonorgestrel IUDs.
They concluded that several contraceptive progestogens, including combined oral contraceptives, oral desogestrel-only pills, high-dose levonorgestrel IUDs, and injectable medroxyprogesterone, were associated with an increased risk of meningioma. They noted that these findings may help guide contraceptive prescribing and informed treatment decisions.
Reference:
Hasselblad Lundstrøm N, Hjorslev Knudgaard M, Skaarup Pedersen M, Schougaard Christiansen ML, Wessel Skovlund C. Contraceptive Progestogens and Incident Meningioma. JAMA Netw Open. 2026;9(7):e2622603. doi:10.1001/jamanetworkopen.2026.22603
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