Vidal: progestins and risk of meningioma: a class effect?

https://www.vidal.fr/actualites/30117-progestififies-et-risque-de-meningiome-un-effet-de-classe.html

Par David Paitraud – Date de publication : 14 mars 2023 – Image of a watch

Lecture : 6 minutes

Progestins and risk of meningioma: a class effect?

The Committee of Experts responsible for assessing the risk of meningioma associated with 4 progestins (Dienogest, Dydrogesterone, Medrogestone, Progesterone) issued the first recommendations to secure the use of these drugs, awaiting additional data.

Summary

One month after its creation, the Committee of Experts gathered by the National Agency for the Safety of Medicines and Health Products (ANSM) offers preliminary recommendations to reduce the potential risk of meningiom in the event of the use of four progestins (Diénogest, Dydrogesterone, Médrogestone, Progesterone) used in gynecology (gynecological disorders):

These drugs are now contraindicated in the event of a history of meningioma or existing meningioma, with some exceptions to assess in a multidisciplinary consultation meeting;
Before any new prescription of progestins or prescription of a progestogen in relay of cyproterone, chlormadinone or nomestrol, it is recommended to check all the progestins already used and their duration of use;
The treatment must be prescribed at the minimum effective dose with the shortest possible duration of use;
An annual re -evaluation of treatment is necessary;
Magnetic resonance imaging (MRI) is required in the event of neurological clinical signs evocative of meningioma.

These recommendations are added to those already applicable for drugs based on cyproterone, nomestrol and chlormaudinone. They are likely to evolve according to the results of the epidemiological studies in progress, a class effect cannot be excluded currently.

Un mois après sa mise en place par l’Agence nationale de sécurité du médicament et des produits de santé (ANSM) [1], le comité scientifique temporaire (CST) d’experts a émis les premières recommandations [2] visant à sécuriser l’utilisation de quatre progestatifs (cf. Encadré). Le risque de méningiome ne peut pas être exclu avec les progestatifs autres que ceux à base d’acétate de cyprotérone, nomégestrol et chlormadinone. Des études sont actuellement en cours pour évaluer ce risque.

These progestins are used:

In the treatment of gynecological pathologies (endometriosis, fibroids, particularly long and/or abundant rules, cycle disorders),
in hormonal substitutive treatment (including menopause);
In obstetrics (sterility by luteal insufficiency, repeated abortions).

**Box - Progestatives to which the preliminary recommendations of the Expert Committee apply**
Progestogen and dosage	Marketed specialties (March 2023)
diénogest 2 mg	Generics of Visanne (which is no longer marketed): Dimetrum, Endovela, Sawis NB : en France, il existe également deux contraceptifs associant diénogest 2 mg et éthinylestradiol (OEDIEN, MISOLFA) ou diénogest (2 et 3 mg) et estradiol (QLAIRA).
dydrogestérone 10 mg	Duphaston NB. La dydrogestérone entre également dans la composition de CLIMASTON, en association avec l’estradiol.
médrogestérone 10 mg	Colprone
progestérone 100 mg et 200 mg	Utrogestan (100 mg and 200 mg), estima (100 and 200 mg), progestan (100 and 200 mg), Progesterone Biogaran (100 and 200 mg), Progesterone Mylan 100 mg

Risk of meningiom: a class effect cannot be excluded with progestins

Depuis 2019, des études épidémiologiques, notamment françaises, ont permis de préciser la relation entre les progestatifs à base de nomégestrol (LUTENYL), de chlormadinone (LUTERAN) et de cyprotérone (ANDROCUR) et le risque de méningiome. Ce risque augmente avec la dose reçue, et la durée de traitement. La France, puis l’Union européenne, ont mis en place un ensemble de mesures pour encadrer l’utilisation de ces médicaments (cf. notre article du 17 novembre 2022).

En France, une surveillance renforcée menée sur l’ensemble des progestatifs a mis en évidence des cas de méningiome survenus lors de traitements par d’autres progestatifs, suggérant un effet de classe.
« Parmi les cas de méningiomes déclarés sous traitement progestatif, ceux rapportés avec la médrogestone (COLPRONE) et la progestérone à 100 mg et 200 mg (UTROGESTAN et génériques) sont particulièrement suggestifs d’un rôle de ces médicaments compte tenu de la stabilisation ou la régression tumorale à l’arrêt du traitement », commente l’ANSM.

Ces premières constatations ont conduit à mentionner le risque de méningiome dans le résumé des caractéristiques du produit (RCP) et la notice de COLPRONE.
L’ANSM a saisi le comité européen de pharmacovigilance (PRAC) afin d’initier une évaluation européenne.

Recommendations to secure the use of progestins

The first CST recommendations aim to secure the use of progestins in women who need them:

Contraindication situation: In the event of an history of meningioma or existing meningioma, the introduction of a progestin treatment is contraindicated, with some exceptions to assess in a multidisciplinary concertation meeting (made up of gynecologist and/or endocrinologist and neurosurgeon) on the basis of the benefit/individual risk ratio for the people treated and the presence or not of the therapeutic alternatives ;
Take into account the previous treatments by progestogen: before any new prescription or switch between progestins (in particular relays after treatment with cyproterone, nomestrol or chlormadinone), check all the progestins already used and their duration of use during the life of the patient;
Duration and dose: The treatment must be prescribed at the minimum effective dose with the shortest possible duration;
Revaluation of the interest of treatment: the interest in pursuing treatment must be reassessed regularly (every year), especially around menopause, the risk of meningioma increasingly increasing with age.

No systematic MRI, only in case of symptoms

For the moment, the CST recommends brain MRI only in the event of neurological clinical signs evocative of a meningioma:

headache;
vision, language, memory and hearing disorders;
nausea;
dizziness;
convulsions;
loss of smell;
weakness or paralysis.

As a reminder, brain MRI in patients treated by Chlormadinone and Nomestrol must be carried out regardless of age:

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).

Periodic monitoring by brain MRI is set up for patients treated by Cyproterone.

An Epiphare study in progress

Ces recommandations sont susceptibles d’évoluer afin de tenir compte des résultats de nouvelles études épidémiologiques.
Des études menées par le groupement d’intérêt scientifique (GIS) EPIPHARE sont actuellement en cours, et ont pour objectif de confirmer ou d’infirmer la relation entre progestatifs et méningiome, à partir des données de santé issues des bases de l’Assurance maladie.