REPORT

CST Public consultation on treatments Lotényl, Lotéran and their generics and the risk of meningioma

Monday November 2, 2020 by videoconferencing

CST members :

• Sébastien Froelich, president (neurosurgeon),
• Geneviève Plu-Bureau (gynecologist),
• Etienne Richer (gynecologist),
• Jacques Young (endocrinologist),
• Henry Dufour (neurosurgeon),
• Martine Alt-Tebacher (CRPV pharmacologist),
• Thierry Brillac (general practitioner),
• Alain Weill (Epiphare epidemiologist),
• Sabine Trébaol (in charge of institutional relations of the Endofrance association),
• Marianne Niosi (Executive Director of the National Confederation of Family Planning),
• Angèle Mbarga (President of the Fibrome Info France association),
• Axelle Ayad (representative of the Endomind association),
• Emmanuelle Huet-Mignaton (president of the AMAVEA association)

The ANSM document presented in PowerPoint is here

Other documents concerning this meeting: https://www.ansm.sante.fr/l-ansm/comites-scientifiques-specialises-temporaires/comites-scientifiques-temporaines/comites-scientifiques-temporaines/stst-macroprogestifs-et-risque-de-meningioma

Presentation of the problem by the director general of the ANSM , M Dominique Martin :

The assessment of the risk of meningioma under Lutéran/Lotényl follows that of the Androcur, in order to achieve a fair balance in the prescription. The work on the Androcur is positive, since exposure to this drug was divided by 6. Surprises is a French specificity

The general context was recalled by Isabelle Yoldjian : progestins have multiple and varied indications, which must be reviewed, and the balance of profits/risk reassessed for each indication. A mailing was again sent to healthcare professionals in October, in alerting them to the risk of meningiomas with these two treatments (the first mailing dates from February 2019). It is interesting to note that at each communication, the prescriptions fall. France is the first prescribing country of progestins.

Presentation of the epidemiological study Epi-Phare by Alain Weill

Epidemiology is the estimate of a risk. The study runs from 2007 to 2019, with a survey on more than 1 million women, with the aim of measuring the risk of meningiomas. We know that one of the risk factors is ionizing radiation, pregnancy, and more rarely type 2 neurofibromatosis. Meningioma has slow growth, and it is not the biggest meningiomas that can be a problem, but their location: small meningiomas can create big problems. It is a rare disease: 8/100,000, with the same frequency on the whole planet. The prescriptions in France are mainly those of gynecologists.

The longer the exposure, the greater the risk of meningiomas. The higher the dose, the more the risk also grows. When you stop treatment, after a year, the risk of being operated on or undergoing radiotherapy is identical to those untreated. As with Androcur, there is a dose-effee relationship.

Risks of meningiomas with Androcur 4/1000, with Lotényl 2/1000 and with Lutéran 1/1000.

Number of meningiomas operated: 1000 cases between 2007 and 2018. From 2019, there is a notoriety bias because of the ANSM alerts ( note of the association: for us, it is the opposite, there is a non-information bias before 2019).

Alain Weill: "The person to whom it happens is dramatic, even if it's rare".

Surgical approach to the management of meningiomas under progestins by Sébastien Froelich

For Sébastien Froelich , we cannot speak of meningiomas surgery without talking about stopping treatment. Symptoms are mainly due to the compression of the brain. Meningiomas due to drugs have particularities in number and location. As surgery is not trivial, it is always better to avoid it. He confirms that this is not the important size, but location and symptoms. Meningioma can make bone, and sphero-orbital meningiomas are very common when taking progestins.

Unfortunately the literature is not very clear on the hormone-household link.
There are many future projects: national register, studies on all progestins, pregnancy with meningioma, evolution after decor on decades. There, we are just 10-15 years old in hindsight. Urgency to disseminate information and have European and international studies.

Hearings of associations, health professionals and learned companies

Medical approaches, use of progestins in gynecology by Florence Tremollieres (for CNGOF, CNEGM, the PGR national reference center, and the FNCGM): bushy intervention, which can be remembered that the Hors AMM is not a problem and that it is often a question of contraception, while they are not contraceptives. Luteran is authorized for endometriosis, which it was pointed out to be a chronic pathology. These treatments have no indication for fibroids, and the Fibrome Info France association confirmed that these treatments were ineffective for this indication. Etienne Richer said that drug treatments could be replaced by trompeting ligatures, for example, or that it was necessary to do more surgery for endometriosis. Likewise hysterectomy is much less practiced in France than in the USA for example.

Hearing Yann Mazens / Jean Pierre Thierry for France Assos Health

It has been insisted on the problem of significant misuse of these treatments, and over-prescription outside the AMM which promotes trivialization, which is a French particularism. Professionals lack information, and letters to professionals are not sufficient.

Talking about benign tumors harms communication on the sometimes dramatic consequences of meningiomas.

Patients will seek information in the media, but this information is not always reliable.

The recall of patients beyond the 24-month period is quite possible with the help of the Sniiram.

Hearings of 8 patients

Pointed issues:

• Drop in libido
• Not taking into account the particular demand of the woman, the doctor often does not give the choice.
• Long -term women's monitoring problem
• Not taking into account fatigue when meningiomas are there and trivialization of symptoms.
• Weight gain
• Depressive symptoms
• No information on the risk of meningiomas
• Signing an order is a serious act

Isabelle Yoldjiabn concludes saying that

• Letters are planned with the CNAM to inform the risk of Lotéran and Lotényl, but that in view of the current epidemic situation, they cannot be sent quickly. In the meantime, a relay will be on the Ameli site. fr
• The next meeting of December 16 will determine the information to be sent to healthcare professionals and patients, the revision of the benefit/risk balance for each indication (and what indications are to be kept), and the monitoring measures by imagery will be completed.

You will have to be vigilant on the proof levels given by gynecologists for each indication. We cannot decide on opinions, nor on consensus. To know if the studies are there, and the levels of evidence sufficient, even if Geneviève Plu-Bureau underlines that we will never have randomized studies and that we must absolutely keep these progestins!

Thierry Brillac spoke of the primary dialogue between doctors and patients, dialogue underlined by a HAS document in 2013: "Patients and health professionals, decide together". In view of the testimonies collected, we see that we are far from it in many cases!

Reminder: Isabelle Yoldjian, in the preparatory meeting that we had on October 27, associations and ANSM, told us that "natural progesterone", it does not exist ! In general, moreover, natural hormones do not exist. A cachet is not natural, it is chemical and it is a medication .

The video will be available on YouTube, it lasts more than 4 hours.

The second part of the CST meeting to decide on the future of Lotéran and Lotényl will take place on December 16 .

Communication from the ANSM HERE

Emmanuelle Huet-Mignaton

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