Female sex, aging, intracranial irradiation, and, to a lesser extent, obesity and Black race are known risk factors for intracranial meningioma. Prolonged use of certain progesterones, such as cyproterone acetate and medroxyprogesterone acetate, has been linked to an increased risk of intracranial meningioma. These typically benign tumors can cause significant neurological symptoms requiring surgery, but often shrink after the drug is discontinued. Desogestrel and levonorgestrel are widely used as oral contraceptives in Europe. Despite their widespread and growing use, data on their association with meningioma risk remain limited. Prior studies lack data on long-term use and specific types of progesterone.
A recent study published in BMJ aimed to evaluate the risk of intracranial meningiomas associated with oral contraceptives containing desogestrel 75 µg, levonorgestrel 30 µg, or levonorgestrel 50-150 µg, combined with estrogen, and the duration of use (long-term [≥1 year] and short-term [<1 year]). This study also describes surgical cases by age, location, and tumor severity.
In this case-control study, data were collected from the French national health data system (Système National des Données de Santé [SNDS]). All females of any age residing in France who underwent intracranial meningioma surgery from January 1, 2020, to December 31, 2023, were included. This study excluded women with pregnancy within 3 years, prior meningioma hospitalization (2018-2019), desogestrel-based combined pills due to limited data (2009-2013), and levonorgestrel emergency pills due to their occasional use. Statistical analysis was performed using the logistic regression method through SAS software version 9.4.
A total of 92,301 females (mean age = 59.7±12.9 years) were included in this study.  Of these, 8392 women underwent intracranial meningioma surgery. Each patient was matched to 10 control females who did not have intracranial meningioma. Among 8392 patients, 3.4% of women used desogestrel (3.3% controls), 0.2% used levonorgestrel (0.2% controls), and 1.9% used levonorgestrel combined with estrogen (2.3% controls).
The use of desogestrel was linked to an increased risk of intracranial meningioma with an odds ratio of 1.25 (95% confidence interval [CI]: 1.10 to 1.42). This risk was found to be 1.02 (0.77 to 1.34) for short-term and 1.32 (1.14 to 1.53) for prolonged use of desogestrel. The risk became significant after five years of desogestrel use and increased with longer duration, including 1.70 (1.39 to 2.08) for >5 years, 1.51 (1.17 to 1.94) for 5-7 years, and 2.09 (1.51 to 2.90) for ≥7 years. In contrast, there was a non-significant association observed between the increased risk of intracranial meningioma and use of levonorgestrel, whether alone (odds ratio = 1.44 [0.87 to 2.40]) or in combination with estrogen (0.92 [0.77 to 1.09]). Â
The increased risk was observed more in women with meningiomas located in the middle (1.90 [1.47 to 2.46]) and anterior (1.50 [1.17 to 1.93]) parts of the skull. Additionally, women who had previously used progestogen, known to increase the risk, showed a significantly higher odds ratio of 3.30 with a CI of 2.64 to 4.11.
Limitations of this study include a lack of data on non-reimbursed medications, clinical indications, prior radiation exposure, and ethnicity. SNDS did not confirm actual drug intake. Some associations may be due to chance or limited power.
In conclusion, this study found that levonorgestrel, whether used alone or in combination with estrogen, did not increase the risk of intracranial meningioma, regardless of the duration of use (short-term or long-term). For desogestrel, one case of this tumor requiring surgery was estimated to occur for every 67,300 women using it. The increased risk was no longer reported within a year after discontinuing desogestrel.
Reference: Roland N, Kolla E, Baricault B, et al. 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
