The Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) has agreed on a direct healthcare professional communication to alert practitioners to a small increased risk for meningioma associated with desogestrel- or etonogestrel-containing contraceptives. Safety information for the products will be amended accordingly.

Desogestrel and etonogestrel are third-generation progestogenic steroids with contraceptive effects. Desogestrel is available as oral tablets, while its active metabolite etonogestrel may be incorporated into implants or, in combination with ethinylestradiol, vaginal rings. 

The recommendations follow publication of a large case-control study based on the French national health data system (Système National des Données de Santé) published in last month’s BMJ. The study included 8391 women needing surgery for intracranial meningioma between 2020 and 2023, each matched for year of birth and area of residence with 10 control women without intracranial meningioma. 

Women’s use of oral contraceptives containing desogestrel 75 µg, levonorgestrel 30 µg, or levonorgestrel 50-150 µg combined with estrogen was used to calculate odds ratios (ORs). There was no excess risk for intracranial meningioma associated with levonorgestrel, either alone or combined with estrogen, regardless of duration of use.

For desogestrel, the OR for risk for intracranial meningioma was 1.02 (95% CI, 0.77-1.34) with short-term use but rose to 1.32 (95% CI, 1.14-1.53) after prolonged use. The OR was 1.51 (95% CI, 1.17-1.94) for 5-7 years’ use, and 2.09 (95% CI, 1.51-2.90) with use for 7 or more years.

Excess risk was greater in women with meningiomas located in the middle or anterior part of the skull base (OR, 1.90; 95% CI, 1.47-2.46; and OR, 1.50; 95% CI, 1.17-1.93, respectively) and in those who had previously used a progestogen already known to be associated with increased risk, such as cyproterone, nomegestrol, medroxyprogesterone, or chlormadinone (OR, 3.30; 95% CI, 2.64-4.11).

PRAC said the risk for meningioma was low but increased with longer use of desogestrel. The French researchers estimated that, for every 67,300 women who used the drug, there would be one additional case of intracranial meningioma requiring surgery. The increased risk was no longer evident 1 year after women stopped taking desogestrel.

New Contraindication 

Professionals should consider previous progestogen use before starting a woman on desogestrel or etonogestrel, the EMA recommended. Use of these drugs is now contraindicated in women who have a meningioma or have had one in the past. Prescription should be discontinued if meningioma is diagnosed while a woman is using one of these agents.

Meningiomas are usually benign and slow growing but may cause serious problems depending on their size and location. Women using desogestrel or etonogestrel should be monitored for suspicious signs and symptoms such as changes in vision, hearing loss or tinnitus, anosmia, worsening headaches, memory loss, seizures, or limb weakness.

PRAC said that the product information for the two drugs will now be updated to include meningioma as a side effect, with a frequency “not known,” together with new contraindications and warnings.

The healthcare professional communication will be disseminated to healthcare professionals by the marketing authorization holders and published on the EMA’s Direct Healthcare Professional Communications page and in national registers in EU Member States.