lutenyl acetate ) and chlormadinone ( luteran and generic) acetate are progestins , derived from a hormone, progesterone. Until now, there have been many indications in particular to deal with gynecological disorders linked to insufficiency in progesterone, especially during the premenopause ( menstrual irregularities , premenstrual syndrome, etc.) but also to reduce abundant rules in the event of fibroids. They were also used to treat endometriosis . These progestins were also sometimes prescribed (excluding MA) as contraceptives for women at cardiovascular risks for which estrogen-progestins were contraindicated.

Problem, alerted this June 17, the Medicines Agency (ANSM) , they increase the risk of meningiomas , tumors that are most often benign located in the meninges, these layers of fabric that cover and protect the brain as well as the spinal cord. The agency had already sounded the alarm in February 2019 , in view of the many cases identified. The notices of use of the two drugs had then been reviewed. According to the ANSM, 50 to 100 meningiomas per year could be attributed to prolonged use of these treatments.

Lotéran, Lotényl… What are the risks?

The ANSM is based on a vast epidemiological study conducted on more than 3 million patients between January 1, 2007 and December 31, 2018 by the Scientific Interest Group Epi-Phare, which brings together the Medicines and Health Insurance Agency. The study confirms an over-risk of meningioma in women exposed to these drugs, with an increase in “significant” risk according to the dose used, the duration of the treatment and the age of the patient. Thus, women whose treatment exceeds 6 months see their risk triple , and the more the duration increases, the more it increases: it is multiplied by 12.5 after 5 years of Lotényl and by 7 after 3.5 years of Lotéran . The study also shows that the risk of intracranial surgery increases with age: it is indeed 3 times higher for women aged 35 to 44, than those between 25 and 34 years old.

What are the recommendations of the drug agency?

Following this study, the ANSM conducted consultation between experts, associations and patients this fall, wishing to express their opinion on the use of these drugs. These filmed hearings are available on the ANSM Youtube channel .

New recommendations based on the reflections carried out by this committee of experts were published by the ANSM on January 12, 2021. Here is what to remember:

• The marketing of Lotéran, Lotényl and Generics is maintained with regard to their therapeutic interest in certain indications.
• Women who take or have taken these treatments are invited to consult their doctor in order to take stock of care , who may be required to evolve depending on the case and/or to set up monitoring by brain imaging according to your situation.
• An examination by brain imaging (MRI) is recommended for any woman who would take lutenyl or luteran for more than a year, whatever the age, then every two years as long as the treatment is continued, and in the event of a symptom evocative of tumor.
• Women should finally be attentive to symptoms evocative of meningioma (frequent headaches, vision, language or hearing disorders, dizziness, memory disorders, etc.) and consult your doctor as soon as possible.

How will patients be informed?

To support the implementation of these recommendations, an information system, drawn up by doctors and associations, is in preparation. This information system will initially be articulated on 2 tools :

• An information document to be given to each patient to start processing or pursuing it. This will specify what a meningioma is and report the level of risk according to the treatment taken. It will alert clinical signs likely to be associated with the presence of meningioma and will specify the conduct to be taken for each situation (re -evaluations at least once a year of the relevance of the processing, conditions for carrying out brain imaging, etc.).

• An annual information certificate to be completed by the patient and her doctor in order to promote exchange during consultation and guarantee the information of women both on the benefit / risk ratio of these drugs and on the methods of imaging by imagery in the event of processing. This certificate of information will be to be presented in pharmacies to obtain the processing, according to conditions which remain to be specified.

These documents, the development of which is the fruit of the consultations carried out with patient associations will be available during the spring, the ANSM said on February 9 .

"We insisted on the importance of informed consent , comments Top Health, Axelle Ayad N'Ciri, who represented the Endomind , as part of the public consultation on Lotényl and Lutéran treatments , organized by the ANSM. But, she continues, "for there to be consent, patients must be fully informed. They must immediately understand that this treatment is not trivial."

She also underlines that the objective of this consultation is neither to have this treatment withdraw from the market, nor to overwhelm the doctors who prescribe it, or to panic women. "You must set up a patient doctor's partnership for a joint decision".

In connection with the CNAM, the ANSM also studies the possibility of sending an individual letter to the doctors who prescribed Lotényl or Lotéran and their generics to invite them to regain contact with the patients concerned in order to reassess the merits of their treatment. In parallel, patients would also receive a personal letter inviting them to consult their doctor.

In what cases can the treatment be maintained or stopped?

ANSM is favorable to maintaining treatment:

When luteran and lutenyl are used in women with gynecological pathologies (functional hemorrhages, fibroid-related hemorrhages, severe mastopathy, endometriosis, menorrhagia) and that therapeutic alternatives have failed or that they are contraindicated. The ANSM, however, recommends a “shortest possible” treatment and a revaluation of the benefit/risk ratio at least once a year.

The ANSM is unfavorable to maintaining treatment in the following indications:

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

An examination by brain imaging (MRI) should be carried out regardless of the age of the patient:

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

Dr. Geoffroy Robin, gynecologist and president of the CNGOF medical gynecology commission had explained to Top Health that " women under Luteran or Lotényl should not panic in view of the rarity of meningiomas". And to continue: "Certainly, these figures may seem high and anxiety -provoking, but they must be weighted due to the very low annual incidence of meningiomas in the general population: around 8 to 10 cases/100,000 people/year or 0.008 to 0.01% of the general/year population."

In addition, remember that meningioma is in the vast majority of cases a benign brain tumor . "He never implies treatment with chemotherapy, nor the appearance of metastases", still reassures the doctor.

However, professionals should no longer prescribe this treatment when there are alternatives (especially in contraception, menopause or for disorders of the menstrual cycle). And when women have no other therapeutic solution, the prescription must be short -lived and reassembled regularly. In any case, women must get closer to their doctor to take stock.

Find out more: Questions / answers on the risk of meningioma under Lotényl / Lotéran and Generics, ANSM, January 2021

Sources: Medicines agency, complete file Lotéran/Lotényl