Lutéran / Lutényl and the risk of meningioma: ANSM recommendations

ANSM alerted women to the increased risk of meningioma associated with drugs containing nomegestrol (Lutenyl and its generics) and chlormadinone acetate (Lutéran and generics).

These drugs, sold by nine laboratories, are derivatives of a hormone, progesterone. They are used in particular against menstrual disorders, premenstrual syndrome, menopause and endometriosis. Lutényl and Lutéran may also have been prescribed as birth control pills or as acne treatment, uses outside the approved indications.

Preliminary recommendations about taking these treatments were published in June 2020. The definitive ones were published on January 12, 2021 after discussions led by the expert committee made up of doctors and associative actors. The objective: to define the conditions of treatment with these drugs by considering the risk of meningioma.

What are the risks ? What patients should do and what follow-up should they have Here is what you need to know about medicines containing nomegestrol and chlormadinone acetate.

An increased risk of meningioma

Meningioma is a brain tumor, most often benign, which develops from the membranes that surround the brain. Its treatment is based on surgery, the consequences of which can be significant.

The increased risk of meningioma was confirmed by a epidemiological study. The latter, led by experts from Epi-Phare, a public expertise structure bringing together the Medicines Agency and Health Insurance, was announced a few months ago following cases of meningiomas associated with their use.

A risk multiplied by 3 after 6 months of treatment

The study, the results of which were announced on June 8, 2020, at a meeting of the scientific committee dedicated to this monitoring of macroprogestogens confirms a significant increase in risk depending on the dose, the duration of treatment and the patient’s age.

Women treated more than 6 months with the drugs in question would have a risk multiplied by 3.3 for nomegestrol acetate and 3.4 for chlormadinone. “Then by 12.5 from a cumulative dose corresponding to 5 years of treatment for nomegestrol acetate and by 7 from a cumulative dose corresponding to 3.5 years of use of chlormadinone acetate . “

The risk of a meningioma requiring intracranial surgery also increases with age. It is 3 times higher in women aged 35 to 44 than in those aged 25 to 34.

This study was set up following the drastic supervision measures taken for the same reasons with regard to a first drug, Androcur (Bayer laboratory) and its generics (active ingredient: cyproterone acetate). In the case of Androcur and its generics, the ANSM had pointed out that these drugs, taken in high doses for more than six months, are at the origin of a well-established increased risk of developing these brain tumors (meningiomas ) most often benign.

ANSM recommendations

The drug agency points out two important points January 12, 2021 : situations in which the benefit-risk balance of these treatments is favorable and monitoring of patients by brain imaging.

Here are the indications for which the benefit-risk ratio is considered favorable. Note that the patient concerned is a woman of childbearing age and whose therapeutic alternatives have failed or are contraindicated:

• Nodesgestrol acetate 5mg (Lutenyl and generics): functional hemorrhages, menorrhagia linked to fibroids preoperatively and severe mastopathy;
• Chlormadinone acetate 5 and 10 mg (Lutéran and generics): endometriosis, functional hemorrhages, menorrhagia linked to fibroids preoperatively and severe mastopahia.

For these two drugs, the treatment should be as short as possible and the benefit-risk ratio re-evaluated once a year at least.

The following are the situations in which the risk-benefit ratio of these drugs is considered unfavorable:

• Menopause, artificial cycle in association with estrogen;
• Cycle irregularities;
• Premenstrual syndrome (essential dysmenorrhoea);
• Non-severe mastodynia;
• Contraception (without associated cardiovascular risk factor).

MRI monitoring

Brain imaging examination should be performed:

• “at any time during or after treatment in the event of signs suggestive of meningiomas;
• after 1 year of treatment when the treatment needs to be continued, then 5 years after the first MRI, then every 2 years as long as the treatment is continued;
• at the initiation of treatment in the event of identified risk factors for meningioma (history of encephalic radiotherapy in childhood or type 2 neurofibromatosis). “

Furthermore, “if the establishment of hormonal treatment is planned or when pregnancy is desired by the patient, and in the event of a history of meningioma (operated or not) in connection with the intake of nomegestrol acetate, chlormadinone or cyproterone, multidisciplinary management must be put in place “.

ANSM invites healthcare professionals to put these recommendations into practice “and patients to approach their doctor to discuss it”. She specifies in her press release that the committee of experts will meet again on January 22 to discuss information documents intended to accompany these recommendations.

What if I take Lutényl or Lutéran?

The ANSM advises patients to discuss with the doctor during an upcoming gynecology consultation, to be attentive to symptoms suggestive of a meningioma and to consult in the event of:

• Frequent headaches;
• Vision, language or hearing disturbances;
• Dizziness;
• Memory impairment.