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Cyproterone acetate and risk of meningioma: a nationwide cohort study
  1. Anders Pretzmann Mikkelsen1,2,
  2. Iben Katinka Greiber2,3,
  3. Nikolai Madrid Scheller1,4,
  4. Malene Hilden1,5,
  5. Øjvind Lidegaard1,2
  1. 1 Department of Gynaecology, Rigshospitalet, Copenhagen, Denmark
  2. 2 Deptartment of Clinical Medicine, University of Copenhagen, Cobenhavn, Denmark
  3. 3 Department of Obstetrics, Rigshospitalet, Copenhagen, Denmark
  4. 4 Department of Surgery, Queen Ingrid's Hospital, Nuuk, Greenland
  5. 5 Centre for Gender Identity, Rigshospitalet, Copenhagen, Denmark
  1. Correspondence to Dr Anders Pretzmann Mikkelsen, Department of Gynaecology, Rigshospitalet, Copenhagen, Denmark; anders.mikkelsen{at}regionh.dk

https://doi.org/10.1136/jnnp-2021-326138

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    Introduction

    Cyproterone acetate (CPA) has in preliminary studies been linked to the development of meningiomas. Possibly, CPA may induce or increase meningioma growth due to antiandrogen and proprogestin properties, as two-thirds of meningiomas express progesterone and androgen receptors.1 Among individuals assigned male sex at birth, CPA is used to treat prostate cancer, hypersexuality disorder, and as feminising hormone therapy. In individuals assigned female sex at birth, it is used in the treatment of acne, hirsutism, seborrhoea, hair loss and in a low-dose variant in combination with ethinylestradiol in birth control pills.2

    A recent cohort study comparing females exposed to high cumulative doses versus low cumulative doses of CPA, found a 6–20 fold increased risk of meningioma.3 Subsequently, the European Medicines Agency’s (EMA) issued a recommendation to restrict CPA to less than 10 milligrams per day.4

    In this nationwide study, we assessed national trends in use of CPA and the risk of meningioma according to cumulative exposure to CPA, as compared with non-users.

    Methods

    Study population

    In this prospective register-based cohort study, we used nationwide Danish registers to identify all individuals born between 1930 and 2000. Individuals were included in the study at age 15, date of immigration to Denmark or 1 January 1995, whichever came last. Study participants were then followed until a diagnosis of meningioma, neurofibromatosis type 2, death, emigration or 31 December 2017, whichever came first. We excluded individuals with prior meningioma, intracranial surgery, neurofibromatosis type 2 or who died before inclusion. Spinal or cerebral meningioma was the event of interest, defined using diagnosis codes in the National Patient Register or the Cancer Register (details in online supplemental file, …

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    Footnotes

    • Twitter @apmikkelsen

    • Contributors APM, NMS and ØL conceptualised the study. APM conducted statistical analyses and wrote the initial draft. All authors critically revised the manuscript.

    • Funding The current investigation was funded by a grant from The Research Fund of Rigshospitalet, Copenhagen University Hospital grant number E-22 515–01.

    • Disclaimer The funders had no role in the design of the study, in the collection, analysis, and interpretation of the data, in the writing of the report; or in any decision related to publication.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Author note Software used for data management and statistical analyses was R version 4.0.2, and packages data.table version 1.13.0, and survival version 3.2–3.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.