Cyproterone acetate and risk of meningioma: a nationwide cohort study
Anders Pretzmann Mikkelsen, Iben Katinka Greiber, Nikolai Madrid Scheller, Malene Hilden, Øjvind Lidegaard
Abstract
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. ### 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, …