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Risk of meningioma and progestins in oral contraception: the data are reassuring

On December 18, 2024, the EPI-PHARE scientific interest group bringing together the National Health Insurance Fund (CNAM) and the National Medicines Safety Agency (ANSM) presented the results of its latest study “Oral contraception and risk meningioma” on the risk of occurrence of this generally benign tumor of the meninges (membranes enveloping the brain and spinal cord) linked to exposure to a progestin in contraception oral.

The conclusions indicate the absence of an increased risk of meningioma in women using contraception containing levonorgestrel, alone or in combination with ethinyl estradiol (this synthetic derivative of estradiol is the most commonly prescribed estrogen in the world). In addition, the study notes a very small increase in risk for contraception based on desogestrel alone, in the event of prolonged use in women over 45 years of age. In short, reassuring data.

Why was it important to assess the risk of meningioma linked to contraceptive progestins?

The study conducted by EPI-PHARE is a continuation of research that has established a link between certain progestins (non-contraceptive) and the risk of meningioma. This work had already highlighted this risk for molecules such as cyproterone acetate (Androcur), chlormadinone acetate (Lutéran which is no longer marketed), nomegestrol (Lutényl, in fibroids, premenstrual syndrome) , medroxyprogesterone acetate (Depo Provéra), medrogestone (Colprone) and promegestone (Sugestone).

The study “Oral contraception and risk of meningioma” in detail

The study presented analyzes in real conditions the risk of intracranial meningioma requiring surgical intervention between 2020 and 2023, associated with the use of certain contraceptive progestins. The molecules studied include desogestrel (75 µg), levonorgestrel (30 µg) and the levonorgestrel-ethinylestradiol combination (50-150 µg), oral contraceptives widely used in . The study is based on data from the National Health Data System (SNDS). In total, 8,391 women operated on for intracranial meningioma in France between 2020 and 2023 were included in this analysis.

Conclusions: The use of levonorgestrel, alone or in combination with ethinyl estradiol, is not associated with an increased risk of intracranial meningioma, independent of duration of exposure.

67,000 women users for a case of operated meningioma

On the other hand, a very small increase in risk was identified in women over 45 years of age using contraceptives based on desogestrel alone dosed at 75 µg during prolonged use. This risk becomes perceptible after 5 years of use and doubles after 7 years of exposure. Despite this, the risk associated with desogestrel remains significantly lower than that reported with the use of cyproterone acetate (Androcur), chlormadinone acetate (Lutéran) or nomegestrol (Lutényl). To get an idea, the study estimates that one case of operated intracranial meningioma occurs for 67,000 women exposed to desogestrel, all uses combined, and one case for 17,000 women with exposure exceeding 5 years.

What recommendations for women?

For women using contraception containing desogestrel, such as Antigone, Optimizette, Cerazette, Elfasette or Desogestrel 75 mcg, a very small increase in the risk of meningioma is observed with prolonged use in women over 45 years of age.

Pending risk reduction measures to come in early 2025, experts issue preliminary recommendations addressed to the women concerned:

· Do not stop using contraception without medical advice.

· Consult a doctor, gynecologist or midwife if you have symptoms such as:

– frequent headaches;

– weakness or paralysis of the limbs;

– language or hearing disorders;

– smell problems;

– memory problems;

An MRI may be considered depending on your symptoms.

· If a meningioma is discovered, contraception must be stopped in consultation with a healthcare professional, and neurosurgical advice is essential.

· If you have a history of meningioma or if meningioma is diagnosed, avoid any progestin-only contraception or progestin-only treatment.

· Systematically inform your doctor or midwife of your history of progestin treatment.

· For all women, regardless of contraception, an annual reassessment of contraception is necessary until menopause.

Source: Progestin oral contraception and risk of intracranial meningioma A case-control study using data from the national health data system (SNDS) December 19, 2024, CNAM-ANSM: EPI-PHARE.COM; ANSM press release of 12/19/24

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