Most often prescribed off-label, as a contraceptive or treatment against acne and endometriosis, Androcur® multiplies the risk of brain tumor by 20. It is the same active principle as the Diane® pill, 25 times more dosed, but without necessarily the same thromboembolic risks. Explanations.
After 3 pillse and 4e generation, it is the turn of Androcur® to be the subject of a new drug crisis, or even a future health scandal.
Thanks to the relentlessness of neurosurgeons who made the link between this drug and the increased risk of meningioma early on (10 years ago anyway), an investigation was carried out by the ANSM and it reveals that this anti-androgen quite commonly prescribed as contraceptive or treatment for acne and endometriosis, multiplies by 7 the risk of meningioma after 6 months and by 20 after 5 years of treatment.
A tumor more common in women
The meningioma is a so-called “benign” tumor, which develops in the meninges, and compresses the part of the brain opposite, since the cranial box is made of bone and is therefore inextensible. Meningiomas represent a third of intracranial tumors and are more common in women because of their hormone dependence on progesterone: there are progesterone receptors on meningiomas and these would be stimulated with cyproterone acetate.
The development of meningiomas, usually slow, would be abnormal under this treatment, with a faster development and multiple meningiomas. It is possible to see the meningioma regress when the Androcur is stopped. The severity of this tumor is due to its size and location, with for example a risk of blindness if a meningioma is located near the optic tract.
A risk of meningioma multiplied by 20
On his website, the National Medicines Safety Agency (ANSM) recognizes that since 2009, “cyproterone acetate has been the subject of special monitoring following the signal issued by France at European level on the risk of the appearance of meningioma . The evaluation of this signal by the European Medicines Agency (EMA) led to this risk being included in the leaflet of the medicinal product in 2011 “.
According to one pharmaco-epidemiological study conducted by the Health Insurance in collaboration with the neurosurgery department of Lariboisière, the risk of meningioma is multiplied by 7 for women treated with high doses over a long period (more than 6 months) and by 20 after 5 years of treatment . There is, in fact, a strong relationship between dose and effect, the risk being multiplied by more than 20 beyond a cumulative dose of 60 g, i.e. approximately 5 years of treatment at 50 mg / d or 10 years of treatment at 25 mg / d (when the treatment is taken for 20 days per month).
Figures that could be underestimated, explains to The Express Dr Isabelle Yoldjian, head of the endocrinology drugs pole at the ANSM. “These figures are based on the analysis of the only cases operated. However, doctors do not always remove tumors, because they can regress after stopping treatment. And some can also go unnoticed for a long time.” According to the French Health Insurance study, more than 500 women taking Androcur or one of its generics underwent an operation for a meningioma between 2007 and 2015.
An anti-androgen especially prescribed “off-Marketing”
Marketed since the 1980s by Bayer laboratories, Androcur (and its generics) is an anti-androgen prescribed for years to thousands of women (57,000 in 2017, according to Health Insurance). Belonging to the class of steroidal anti-androgens, cyproterone acetate, the active substance in Androcur, is normally used to treat prostate cancer or hirsutism, an extreme development of hair growth, at a dose of 50 mg per day. In addition, cyproterone acetate is indicated at a dose of 100 mg per day in the treatment of paraphilias. But that’s not its only use.
Since cyproterone acetate blocks the effects of testosterone, Androcur and its generics are regularly prescribed for women with severe acne, endometriosis or as contraception (especially in hyperandrogenism). However, Androcur has never received validation of these last three indications from the health authorities (marketing authorization or “Marketing Authorization”): these are “non-Marketing Authorization” prescriptions, that is. that is to say not validated, even if some scientific publications allow doctors to believe that cyproterone acetate is effective there.
A rising scandal
The risks concerning the drug have been known for a long time (2008), doctors are already informing patients but they could always be criticized for not doing enough, and especially since the majority of prescriptions seem to be off-label. Already, many voices are raised to ask why Androcur® and its generics continued to be prescribed to long-term patients for acne “with more or less hair”.
Androcur has been the subject of special monitoring since 2009 by the EMA and the notification of the risk of meningioma is on the drug leaflet, with a contraindication in the event of a history or presence of a meningioma. In terms of patient information, this is considered the minimum! In a survey cited by the HAS in 2012 (IMS survey), when the reimbursement was renewed, hirsutism and prostate cancer only represented 30% of prescriptions! The numbers may have changed, but it would be good if they were provided to us. Insofar as Androcur® is widely generic, the Bayer laboratory can hardly be considered responsible for current non-MA prescriptions. Who will be?
A scandal that follows that of the Diane 35® pill
Finally, cyproterone acetate is the principle that is also contained in the Diane 35® pill, a pill that hit the headlines due to an increased risk of phlebitis and pulmonary embolism, or even stroke.
Studies have shown that the risk of venous thromboembolism is 1.5 to 2 times greater in users of Diane and 3rd and 4th generation pills than in users of combined oral contraceptives (COCs) containing levonorgestrel. From this point of view, the risk of thromboembolism with Androcur® is clearly indicated in the package leaflet, but some studies and literature reviews state that the thromboembolic risk would be lower.
The ANSM created in June “a temporary specialized scientific committee (CSST) which aims to discuss the conditions of use and prescription of these drugs in order to limit this risk”. New recommendations drawn up with the learned societies concerned should be issued “by the end of the year” specifying the indications which justify a possible excess risk, the maximum doses and durations, as well as monitoring. In the meantime, “patients and health professionals can report any adverse reaction suspected of being linked to a drug, directly on the declaration portal of the ministry in charge of health”: signaling-sante.gouv.fr
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