https://www.vidal.fr/actualites/30117-progestififies-et-risque-de-meningiome-un-effet-de-classe.html
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.
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.
A month after its implementation by the National Agency for the Safety of Medicines and Health Products (ANSM) [ 1 ], the Temporary Scientific Committee (CST) of experts issued the first recommendations [ 2 ] to secure the use of four progestins ( see box ) . The risk of meningioma cannot be excluded with progestins other than those based on cyproterone, nomestrol and chlormadinone acetate. Studies are currently underway to assess this risk.
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).
| Progestogen and dosage | Marketed specialties (March 2023) |
| Diénogest 2 mg | Generics of Visanne (which is no longer marketed): Dimetrum, Endovela, Sawis
NB : In France, there are also two contraceptives associating Diénogest 2 mg and Ethinylestradiol (Ombien, Misolfa) or Diénogest (2 and 3 mg) and Estradiol (Qlaira). |
| Dydrogesterone 10 mg | Duphaston
NB . Dydrogesterone also comes into the composition of Climaston, in association with Estradiol. |
| Medrogesterone 10 mg | Colprone |
| Progesterone 100 mg and 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
Since 2019, epidemiological studies, notably French, have made it possible to specify the relationship between progestins based on Nomestrol (Lentenyl), Chlormadinone (Luteran) and Cyproterone (Androcur) and the risk of meningioma. This risk increases with the dose received, and the duration of treatment. France, then the European Union, set up a set of measures to supervise the use of these drugs ( cf. our article of November 17, 2022 ).
In France, reinforced monitoring conducted on all progestins highlighted cases of meningioma occurring during treatments by other progestins, suggesting a class effect.
"Among the cases of meningiomas declared under progestin treatment, those reported with Medrogestone (Colprone) and progesterone at 100 mg and 200 mg (utrogestan and generics) are particularly suggestive of a role of these drugs given stabilization or tumor regression when you stop treatment ," comments ANSM.
These first observations led to mention the risk of meningioma in the summary of product characteristics (RCP) and Colprone notice.
The ANSM has seized the European Pharmacovigilance Committee (PRAC) in order to initiate a European evaluation.
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
These recommendations are likely to evolve in order to take into account the results of new epidemiological studies.
Studies carried out by the Scientific Interest Group (GIS) Epiphare are currently underway, and aim to confirm or deny the relationship between progestins and meningioma, based on health data from the basics of health insurance.
