Meningioma in users of progestogen contraceptives: a disproportionality analysis of the FDA Adverse Event Reporting System (FAERS).

PURPOSE: Recent observational studies have suggested certain progestogens used for contraception may increase the risk of intracranial meningioma. This study analyzed meningioma reporting among females to the US Food and Drug Administration Adverse Event Reporting System (FAERS) across all progestogen-based contraceptives currently approved in the USA.

METHODS

Disproportionality analysis was performed using individual case safety reports (ICSRs) submitted to FAERS (second quarter of 2016-first quarter of 2024) involving nine progestogens approved for contraception in the US. Eleven Medical Dictionary for Regulatory Activities (MedDRA) preferred terms classified meningioma cases. Crude and adjusted reporting odds ratios (RORs) and 95% confidence intervals (CIs) were estimated using logistic regression. A lower 95% CI > 1.0 and ≥ 3 meningioma cases constituted a disproportionality signal.

RESULTS

During the study period, progestogen contraceptives were reported in 136,654 ICSRs and 283 meningioma cases involving females. Seven progestogens exhibited positive meningioma disproportionality signals in univariable analyses. In multivariable models adjusting for age, weight, use of any medication for contraception, number of associated drug-event pairs, reporter country, and reporter occupation, potential meningioma signals were detected for desogestrel (ROR 2.22; 95% CI 1.29-3.83), levonorgestrel (ROR 3.21; 95% CI 2.11-4.86), and medroxyprogesterone acetate (ROR 4.01; 95% CI 2.10-7.66). Meningioma disproportionality signals for levonorgestrel and medroxyprogesterone acetate persisted through several sensitivity analyses.

CONCLUSION

Notwithstanding the important limitations of disproportionality analyses, these findings add to a growing body of literature describing a potential association between progestogen-based contraceptives and meningioma. Screening should be recommended for progestogen-treated females experiencing symptoms consistent with meningioma.