Chlormadinone acetate (Luteran and generics) and Nomegestrol acetate (Lutenyl and generics), two progestins indicated in the treatment of various gynecological diseases – fibroids, endometriosis, mastopathies … – but also used as contraceptives, induce a meningioma risk, alarmed on June 17, the Medicines Agency (ANSM).
ANSM is based on an epidemiological study* according to which women with a treatment duration of more than 6 months tripled their risk of meningioma compared to unexposed women. It increases with the dose used and the duration of treatment: risk multiplied by 12.5 after 5 years of lutenyl and by 7 after 3.5 years of lutéran. It would also be three times higher for women aged 35 to 44 than for women aged 25 to 34.
After this study, the ANSM recommends that health care providers reassess the relevance of these treatments on a case-by-case basis and limit the doses and duration of the prescription. For women over 35 years old, on Lutéran or Lutényl for at least 5 years or with abnormal symptoms (frequent headaches, vision, language, hearing, memory, dizziness, etc.)., A brain MRI may be prescribed by the doctor. According to the ANSM, 50 to 100 meningiomas per year can be attributed to very long-term use of these treatments.
While these recommendations for women can be terrifying, currently on Lutéran or Lutényl, sometimes for years, without even being informed of the risks, the CNGOF (National College of Gynecologists and Obstetricians), in partnership with the CNEGM (National College of Teachers of Medical Gynecology), would like to reassure them and reassess the balance between risks and benefits of these medicines.
Dr. Geoffroy Robin, gynecologist and chairman of the CNGOF Medical Gynecology Commission, says at the outset, “women under Lutéran or Lutényl should not panic because of the rarity of meningiomas.” And to continue: “Granted, these numbers may seem high and frightening, but they must be weighted because of the very low annual incidence of meningiomas in the general population: about 8 to 10 cases / 100,000 people / year or 0.008 to 0, 01% of the general population / year! “To understand this clearly, the doctor explains that a very small figure multiplied by a high figure remains very small. “Before we demonize a therapeutic class, we have to put it into perspective, rather it is a new side effect that remains very rare in absolute value.”
Remember that too meningioma is a benign brain tumor in the vast majority of cases. “It is never about chemotherapy treatment or the appearance of metastases, the doctor reassures. When you stop treatment with progestin, the progesterone sensitive meningiomas (2/3 of them) usually empty. Without surgery and require “simple” monitoring “. There can be no causal relationship for the remaining 1/3, Geoffroy Robin assures. “If you stop treatment with progestin and the meningioma does not move, it is because there is no progesterone receptor, so you cannot burden the treatment.”
On the other hand, this link exists, however weak it may be, and according to the CNGOF it is necessary to take it into account and analyze it well to know which patient we can give treatment to, which others it is necessary to offer monitoring, or even stop.
Specific, professionals are no longer allowed to repeat treatments with closed eyes without asking questions. You have to re-evaluate. Sometimes women even started their treatment 20 or 25 years earlier.
For example, to avoid bleeding rules in the case of platelet pathologies, there is no alternative to progestin in women at risk of thrombosis (who cannot use estrogens). And often this treatment is extended for years. It is not appropriate that women still fall under Lutéran after 50 years because they had young bleeds and that we did not check whether we could stop it at menopause. “
These drugs are also sometimes prescribed (excluding marketing authorization) as contraception for women at cardiovascular risk for whom estrogen progestins are contraindicated. Here, too, we must reassess.
Conversely, it is not a matter of demonizing extensive prescriptions, it is always a case by case, the doctor continues. “We shouldn’t forget about the benefits of these drugs for patients and ask what alternatives we can offer?” Very often, he notes, “they have been prescribed progestins because they have estrogen contraindications, we are already at the end of the day …” In addition, you should know that sometimes these treatments make it possible to “escape” heavy and psychologically difficult operations, such as hysterectomy ‘.
For the time being, “patients should not hesitate to speak to their gynecologists as soon as they see them again,” advises Geoffroy Robin. And according to the ANSM’s recommendations, “if they are over 35 years old and have been treated for more than five years, request an MRI.”
Admittedly, the ANSM had already raised the alarm in February 2019, after identifying cases of meningioma. That prevents it some women are not informed and rightly have questions. “It is a message that I have personally been passing on to my patients since the first ANSM alert a year ago, I open up the discussion and explain it. The fact of explaining the numbers is ultimately comforting to patients. helps to put things in perspective. “
ANSM has announced that it will “begin a consultation phase with caregivers and patients in the fall.”
At this time, MRI is indicated from 35 years after 5 years of use. But this position could be refined in the coming months. Now is the time to reassess the benefit-risk balance. To this end, medical and obstetrician gynecologists will go hand in hand to work on all indications of macroprogestestins and propose indications on a case-by-case basis, in particular according to the available alternatives, and to specify the monitoring methods (MRI) according to age, duration of the prescription and risk factors. The conclusions of this reassessment are submitted to the ANSM in September 2020.
The doctor also emphasizes that the increase in risk, after 6 months of treatment, appears to be very rapid and even “surprising”, even though it remains very low in absolute value (we assume 0.01% risk of meningioma for those not on treatment with users of 0.034% use). “In my opinion, a molecule is unable to convert a normal meningeal cell into a benign tumor cell in such a short time. This shows that there is likely to be a treatment promoting effect in patients who already have cells. change a meningioma. ”Geoffroy Robin says it would be interesting to know if there are any markers or risk factors that make some women more vigilant.