The risk was known, but not its magnitude. A vast study carried out by the National Health Insurance Fund (CNAM) shows that the risk of meningioma, a tumor in the most often benign brain, increases sharply with the taking of a progesterone derivative.

It is "multiplied by 7 for women treated with high doses of cyproterone acetate, marketed under the name of" Androcur "(Bayer) and generics, over a long period (more than six months) and by 20 after five years of treatment at one dose of a 50 mg tablet per day" .

Androcur is prescribed, according to the official indication, to fight excessive hair (hirsutism) in women and certain forms of prostate cancer in humans. But it is widely used outside its marketing authorization (MA), in the treatment of endometriosis, certain forms of acne, etc. It can also be prescribed for transgender people for its antiandrogenic properties. In France in 2017, 90,000 women took cyproterone acetate (25 % of Androcur), which represents 60 % of the European market.

Made public on August 27 by the National Medicines Safety Agency (ANSM) - It will be published in the coming months -, "this study, conducted with the neurosurgery service of the Lariboisière hospital in Paris was carried out on 400,000 women who consumed cyproterone acetate (tablets dosed at 50 mg) between 2006 and 2015, a very important population," said Doctor Alain Weill Deputy of the CNAM Public Health Studies Department, which piloted this work.

"A relatively low risk"

In total, more than 500 cases of operated meningiomas have been identified. Most often, these benign tumors were operated because the patient had symptoms (aphasia, speech disturbances, etc.). The most frequent tumor of the central nervous system after 35 years (around 30 %), meningioma is benign in two thirds of the cases. It develops from the membranes that wrap the brain and spinal cord (the meninges), with an incidence of 9 to 10 cases per 100,000 inhabitants. He touches two to three women for a man. Reference treatment is surgery.

Let's go back to the study: " the greater the cumulative dose, the greater the risk of meningioma " explains Alain Weill. Most of the time, meningiomas stabilize or regress the cessation of treatment, which strengthens the causal link. “The absolute risk of meningioma for women with large doses was 0.4 % per year. A risk that remains relatively low, even for women taking large doses , ”he tempers. The Minister of Health, Agnès Buzyn, has also reassured. Thursday, September 13, she said on the daily CNews : “It is not cancer. It is not a health scandal. »»

However, this announcement has aroused concern in patients. Five women treated by this medication and operated with a meningioma, with some important consequences for some, have also decided to initiate a complaint against the Bayer laboratory and the ANSM, their lawyer told AFP, Charles-Joseph Oudin, Friday, September 14.

The link between estro -rogestative and meningiomas is not new. A first case mentioning the Androcur was described in 2007 in the NEJM by an Italian team, that of a transsexual young man who took Androcur in very high doses (100 mg/day) with other treatments. He presented behavioral disorders, which was put on the account of his new condition, then had very headache and had visual field disorders. MRI revealed huge meningioma. The authors then attributed the rapid growth of the tumor to high -dose hormonal treatments, without specifically citing the Androcur.

In France, it is Sébastien Froelich, then young neurosurgeon in Strasbourg, who is first intrigued by one of his patients, whom he must operate because of many meningiomas and who risked losing their sight. She was taking Androcur . Like two other patients who came in consultation in 2007. "One could not be operated on but saw his tumor regress when you stop treatment ," recalls Professor Froelich. His team continued his investigations. It has become his workhorse. The French health authorities alerted to this risk in 2009, then European bodies made the medication notice modified in 2011, adding meningioma in side effects.

Strong point, a study, published in 2011 and funded by Bayer, had not shown an association. She focused on English women, exposed to low doses. A conclusion that had sown confusion. In 2016, Professor Sébastien Froelich, who became head of the neurosurgery service at Lariboisière Hospital (AP-HP), contacted the CNAM with one of his patients who became a doctor. "I did not expect such high figures ," he said, while deeming them "most likely underestimated", because this study only takes into account the operated meningiomas. " By its importance, the CNAM cohort study is now undeniably established this strong link between exposure to this medication and the appearance of meningiomas ," comments Professor Jacques Young, endocrinologist at Bicêtre Hospital (AP-HP).

However, "it is not necessary to withdraw the product ," it is said at the ANSM, which will bring together on October 1 ^a group of experts to review the recommendations. Many prescribers believe that his indications must be limited. However, "cyproterone acetate has a certain interest. There is no equivalent to deal with acnes that can be very disabling, cases of lupus ..., warns Professor Anne Gommpel, gynecologist. Besides its indications, it has the interest of not having vascular risk. A risk that occurs when taking certain contraceptives . As for Diane 35 , this anti-acne drug prescribed as contraception, suspected of being behind thrombosis, it contains cyproterone acetate but in doses much lower than androcur. Suspended for a while, this medication was returned to the market .

Genetic profile of tumors

The relationship between meningiomas and sex hormones is in any case obvious. There are progesterone receptors in most meningiomas. "A central question is whether cyproterone acetate is responsible for the progression of already existing meningiomas, or responsible for the appearance of these tumors" , points out Michel Kalamarides, neurosurgeon in Pitié-Salpêtrière. The genetic profile on the one hand tumors linked to the drug is different. "There is an over-representation of certain genes, and in particular PIK-3CA, transferred in 2 % of the“ all coming ”meningiomas, but in 35 % of tumors under Androcur" , according to a study published in Annals of Oncology, which relates to 40 cases, notes Michel Kalamarides. “We have analyzed 40 others which also show this trend; The study is underway , ”he continues. However, this gene is most frequently transferred to breast cancers, endometrium, and cervix. In addition, the meningiomas appearing on Androcur have different locations and are more numerous.

Another concern for health authorities: other hormonal menopause treatments, already suspected of increasing the risk of thromboembolic diseases, breast cancer, could also promote meningiomas ... cases have been detected with these molecules, including lutenyl and luteran . A study will be launched on this subject by the ANSM and the CNAM. "These progestins most likely increase the risk of meningioma, we will study them in the same way as Androcur ," said Alain Weill. "Especially since some women could stop cyproterone acetate and take another progestogen with similar effects ," he continues. It remains to quantify the risk linked to molecules which are prescribed to a high number of women (15 % to 20 % of women between 50 and 52 years) - even if these figures of 2011 must be updated.

Note from the association on September 19, 2020:
Patient representatives invited by the ANSM at the CST Androcur from October 2018 to June 2019, only made decisions that were already made in September 2018. There was already talk of Lutéran and Lotényl and studies that will follow. Do associations serve only as a deposit for the ANSM decisions, which can communicate that it works with patients? And do patients think they have power, which is in fact zero? We can legitimize the question.

It should also be noted that what the CST decided has so little impact that the newspaper Le Monde did not mention it in 2019 ... See here