AW and you will JC developed and you can planned the study. AW written the manuscript. BC did analysis administration. BC and you will PN performed mathematical analyses. AW and you will JC made sure opportunity and study administration. All the writers (AW, PN, ML, BC, TP, LD, ALB, IY, SFo, SFr, and you can JC) resulted in interpretation of the investigation and you will revised the new manuscript. Every authors approved the very last manuscript. Brand new relevant publisher (AW) attests that indexed article authors see writing criteria which no anyone else fulfilling the latest conditions have been excluded. AW and you can JC may be the guarantors.
Funding: This study is actually funded from the French Federal Medical insurance Money (CNAM) while the Fitness Product Epidemiology Medical Desire Class (ANSM-CNAM EPI-PHARE SIG). AW, JC, and you will BC are employees off French National Medical insurance Finance, PN was an employee of French Federal Institution to have Medicines and you may Fitness Facts Safety. The current papers is short for the fresh new views of your authors and you may really does not always echo the position of its employers.
Fighting passion: All authors have completed the newest ICMJE consistent disclosure mode at the and you can declare: help off French National Health insurance Fund (CNAM) and the Fitness Device Epidemiology Scientific Attention Classification (ANSM-CNAM EPI-PHARE SIG) towards the filed works; zero economic dating that have one enterprises which may want about recorded work in the earlier 3 years; no other relationship otherwise things which will seem to have swayed the brand new submitted functions.
The lead blogger (AW) affirms that this manuscript try an honest, real and you can transparent account of the investigation are advertised; that no important aspects of the research have been omitted; and therefore one inaccuracies on studies just like the planned (and you can, in the event that relevant, registered) was basically informed me.
Dissemination to users and you may relevant diligent and you can personal groups: The outcome have been presented to patient association agents. Clients who’d made use of cyproterone acetate milligrams over the previous a couple of ages (as well as their general therapists) gotten a reports letter yourself providing more information on what to-do (secondary question S18).
Selection of accepted indicators in the girls and you will girls and product sales off highest serving cyproterone acetate (10 mg and you can fifty mg) by the country during the European countries
Research populations
One or two other sensitiveness analyses have been held: data of 2007-14 exposed otherwise handle classification head cohort have been coordinated to have years at the initiation and you may duration of go after-up, and a good nested circumstances-handle study from the fresh new 2007-fourteen head cohort.
Abilities
Chance, relative chance, and you may adjusted hazard proportion from meningioma based on connection with cyproterone acetate (chief cohort, 2007-14; n=253 777)
The fresh new estimated amount of people with meningioma due to cyproterone acetate is over 500 when you look at the France to your months 2007-15 (62 per year; second question S16). This guess will be based upon a traditional calculation that doesn’t be the cause of people who have a diagnosis one or more year after discontinuation of cyproterone acetate, those with an analysis immediately after a primary classification out of really some open (manage class) and you will then resumption out of cyproterone acetate, and meningiomas treated from the medical realize-right up instead of functions otherwise radiation therapy.
Likewise, the current presence of progesterone receptors from inside the arachnoid structure, of which meningiomas happen, has been noted for five decades.5556575859 Multiple article authors has stated good heterogeneous distribution from progesterone receptors according to the website out of meningiomas. A great rostrocaudal gradient out-of progesterone receptors, with a higher thickness off receptors throughout the skull feet, has usually started claimed, and you can 
was affirmed by several e-books.6061 Our shopping for away from an effective predominance out of anterior head feet meningiomas associated with accessibility cyproterone acetate, a beneficial progestogen, is actually in line with these biological conclusions.
Characteristics with the research
Several limitations also concern the latest clinical and you can histological functions away from meningioma. SNDS cannot consist of analysis towards the consequence of magnetized resonance imaging otherwise histology, otherwise if meningiomas try solitary otherwise several, except for functions that cover distinctive line of anatomical countries.