DENMARK — Danish researchers led by Charlotte Wessel Skovlund of the Danish Medicines Agency published a study in JAMA Network Open reporting an association between progestogen contraceptive use and an increased risk of meningioma. The nationwide case-control study, covering the years 2000 to 2024, identified 1,473 women with meningioma diagnoses and matched them with 14,717 control patients without the condition using data from Danish national registries.

Women who used progestogen contraceptives had an increased risk of meningioma. This association extended to oral contraceptives and intrauterine devices (IUDs). Eight of the 12 progestogen formulations included in the analysis had associations with meningioma. Odds ratios for meningioma versus non-users ranged from 40% higher for levonorgestrel to more than four times higher for injectable medroxyprogesterone. Use within the past year was associated with the highest risk, which disappeared five years after discontinuation.

Injectable medroxyprogesterone was associated with the highest risk, with an odds ratio of 4.55 (95% CI 2.19-9.45). Other associations included oral desogestrel (OR 1.73, 95% CI 1.17-2.56), desogestrel-ethinyl estradiol (OR 1.66, 95% CI 1.31-2.10), cyproterone (OR 1.61, 95% CI 1.00-2.59), drospirenone (OR 1.58, 95% CI 1.05-2.37), high-dose levonorgestrel IUD (OR 1.58, 95% CI 1.28-1.94), gestodene (OR 1.44, 95% CI 1.17-1.77), and levonorgestrel (OR 1.40, 95% CI 1.12-1.76). Nonsignificant associations were found for norethisterone combination, low-dose levonorgestrel IUD, norgestimate, and norethisterone.

Skovlund said, "The numbers needed to harm differed greatly depending on the specific progestogen used and the age group, with the highest risk observed for the oldest women." She added, "Medroxyprogesterone showed the highest risk with relatively low numbers needed to harm, whereas all combined oral contraceptives, oral progestogen-only contraceptives, and IUDs had relatively high numbers needed to harm, especially among the youngest women." Skovlund also stated, "The present study suggests an increased risk of meningioma for several progestogens not previously associated with meningioma."

Prior research supports a link between progestogen and meningioma. A French study involving 18,000 women who underwent intracranial surgery showed a 19-fold greater risk among users of cyproterone acetate, which is not available in the U.S. An earlier French study of 250,000 women indicated a sixfold greater risk with cyproterone acetate. A U.S.-based study of almost 90,000 women reported a relative risk of 2.43 with depot medroxyprogesterone compared to non-users, while the risk increased to 1.18 among users of oral medroxyprogesterone acetate. Swedish investigators observed a 76% higher odds among users of hormonal contraceptives generally, noting a fivefold increase with depot medroxyprogesterone, which declined to 1.34 for other progesterone contraceptives.

Why It Matters

The FDA approved a label change for depot medroxyprogesterone late last year to include a warning about meningioma risk. The American College of Obstetricians and Gynecologists has published patient education and counseling information regarding the link, advising members to engage in shared decision-making discussions. The European Medicines Agency has assessed meningioma risk for various progestogen contraceptives and approved updated product information for cyproterone, nomegestrol, chlormadinone, and medroxyprogesterone.