Androcur - Interview with Professor Froelich in Libération on September 10, 2018.
This interview follows the information given by the ANSM in the summer of 2018, regarding the increased risk of developing meningiomas under cyproterone acetate (Androcur).
Sébastien Froelich: "Little risk with less than five years of treatment"
By Sabrina Champenois — September 10, 2018 at 7:36 PM
Androcur can cause meningiomas, but these are benign, emphasizes neurosurgeon Sébastien Froelich, who participated in the study.
- Sébastien Froelich: "Little risk with less than five years of treatment"
Head of the neurosurgery department at Lariboisière Hospital in Paris, Sébastien Froelich is the originator and participant in the study on Androcur conducted by the Health Insurance Fund, the results of which have just been made public by the National Agency for the Safety of Medicines and Health Products (ANSM).
A slight wave of panic has begun to circulate around Androcur. Is it justified?
The concern is legitimate. I understand that, for a patient taking Androcur, these results are a source of anxiety. Because the risk is not negligible, and it is probably underestimated since we only considered surgically removed meningiomas (1). And there are approximately 80,000 women taking Androcur in France.
Now, what you need to know is that the risk of meningioma increases with the duration of treatment and depending on the dosage. For example, the Diane 35 pill, which is no longer used, contained cyproterone acetate, like Androcur, but only 2 mg, and in my practice, I haven't observed any link between taking this pill and meningioma. The risk of meningioma with Androcur occurs at higher doses and, especially, when it is taken for a long period. Simply put: the longer you take Androcur at high doses, the greater the risk of developing one or more meningiomas. The patients I've seen in consultation after a meningioma diagnosis rarely had been using it for less than five or six years. So, I have little concern for patients who have been taking cyproterone acetate for two, three, or four years. For durations exceeding five years, a follow-up MRI would probably be necessary. Specific recommendations will be discussed soon during the meeting organized in early October by the ANSM, which will bring together endocrinologists, gynecologists, neurosurgeons, experts from the National Health Insurance Fund (Cnam)..
“Meningioma,” “tumor,” these terms are anxiety-inducing…
Yes, and having read and heard some misinformation lately, I want to clarify the following: a meningioma is not cancer. It is a benign tumor in 70% to 80% of cases, and in my experience, meningiomas associated with cyproterone acetate are always benign. I have never seen an aggressive one. In the majority of cases, simply stopping the medication is enough for the meningioma to stabilize or regress. However, surgery is sometimes necessary when the symptoms are severe and significant.
Testimonies from patients describe significant after-effects, particularly visual ones…
A meningioma is a tumor that develops in the membranes surrounding the brain. It causes symptoms because it compresses the brain. Meningiomas associated with Androcur occur primarily in the anterior parts of the skull (mostly in the frontal regions) and in the anterior and middle parts of the skull base, the structure on which the brain rests. The optic nerves are located in the anterior part of the skull base. Therefore, one of the common symptoms of this type of meningioma is vision problems related to compression of the optic nerve or the optic chiasm (the point where the two nerves cross). However, other symptoms are possible, depending on the exact location of the meningioma(s), which varies.
Why are men not included?
Because this treatment is only used in men for prostate cancer. Its use is, I believe, quite rare and for shorter periods. I have only once seen a patient with a meningioma linked to Androcur.
What is the link between meningiomas and hormones?
Meningiomas are slightly more than twice as common in women. These tumors contain receptors for progesterone and, to a lesser extent, estrogen. Progesterone levels rise in women during the second phase of their menstrual cycle, after ovulation, and during pregnancy. Therefore, as neurosurgeons, we have long known that progestins (steroid hormones with an action similar to progesterone, found in hormone replacement therapy for menopause) can influence the growth rate of meningiomas.
I first became aware of a possible link between meningiomas and cyproterone acetate in 2004 when I was a young neurosurgeon at the Strasbourg University Hospital. I had to perform emergency surgery on a patient with multiple meningiomas who was losing her sight. She was taking cyproterone acetate, and I had her stop this treatment simply because it is also a progestin. But at that time, I hadn't yet grasped the strong link between this drug and this patient's meningiomas. Three years later, I saw two patients in consultation with similar multiple meningiomas, who were also taking Androcur. That raised my suspicions. A third patient, admitted shortly afterward and deemed inoperable, saw her meningioma shrink after stopping the treatment. It was from that point on that I became more particularly interested in Androcur.
France alerted Europe as early as 2009 to the risk of meningioma linked to cyproterone acetate…
Starting in 2008, I presented our observations at neurosurgery, internal medicine, and endocrinology conferences. The French health authorities then became aware of the problem and alerted the European authorities in 2009, who prompted Bayer—the manufacturer and marketer—to amend the drug's information leaflet. France reacted quickly, and by 2011-2012, the risk of meningioma had been added to the Androcur leaflet as a side effect, and Androcur was contraindicated in cases of meningiomas or a history of meningiomas. It's worth noting that France wasn't going to ban the drug, given that my observations were based on only eight patients.
A study was indeed published in 2011, with support from Bayer, but it did not confirm an increased risk of meningioma in women taking cyproterone acetate. This was because the patients studied, who were British, were only exposed to low doses. This did not help in identifying or acknowledging this risk.
Nine years separate the French warning from the study whose results have just been published. That's a long time…
Starting in 2013, with my new team at Lariboisière Hospital, we organized a discussion group about Androcur, with gynecologists and endocrinologists. In 2015, with the help of a patient who is also a doctor and who was very helpful, we convinced the French National Health Insurance Fund (Cnam) of the importance of a national study to assess the extent of the problem.
The French National Health Insurance Fund (Cnam) only has a database dating back to 2006, yet meningiomas linked to cyproterone acetate only appear after several years of treatment. A longer follow-up period was necessary to establish a link. If the study had been conducted earlier, we most likely would not have identified any risk, or only a low risk, because we would not have been able to take into account the duration of exposure to the treatment, which is crucial.
(1) The study included 250,000 women taking Androcur, who were followed for eight years. Only the cases of those who underwent surgery for meningioma were subject to comparative evaluation, which made it possible to define the risk.
Androcur- interview with Profession of Liberation on September 10, 2018
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