Risk of meningioma among users of high doses of cyproterone acetate as compared with the general population: evidence from a population‐based cohort study

Abstract

WHAT IS ALREADY KNOWN ON THIS SUBJECT• Information from the spontaneous reporting system raised the hypothesis of an increased risk of meningioma in patients treated with high doses of cyproterone acetate (CPA).• Meningiomas are known to be hormone-sensitive tumours and express progesterone receptors and CPA has an anti-androgenic, progestagenic and antigonadotropic effect. • More formal evidence from epidemiological studies is lacking. WHAT THIS STUDY ADDS• This population-based cohort study supports the hypothesis that the exposure to high dose CPA increases the risk of meningioma • The increased risk was observed both in men and women and was only relevant for exposures longer than 1 year. AIMInformation from the spontaneous reporting system raised the hypothesis of an increased risk of meningioma in patients treated with high doses of cyproterone acetate (CPA). The objective of this study was to test the hypothesis of an increased risk of meningioma among users of high dose CPA as compared with non-users in a medical records computerized database. METHODSA retrospective cohort study was performed in a Spanish primary care database (BIFAP). Meningioma incidence rates were compared in patients exposed to high dose CPA (users) with those non-exposed and with those exposed to low dose CPA. Poisson regression analysis was used to estimate the incidence rate ratios after adjusting for age and gender. RESULTSAmong 2474 users of high dose cyproterone (6663 person-years) four meningioma cases were identified, resulting in an incidence rate (IR) of 60.0 (95% CI 16.4, 153.7) per 100 000 person-years, which was significantly higher than that observed among the non-users (IR 6.6; 95% CI 6.0, 7.3) and among women users of low dose cyproterone (IR 0.0, 95% CI upper limit 5.5). After adjusting for age and gender, patients exposed to high dose CPA showed an increased risk of meningioma of 11.4 (95% CI 4.3, 30.8) as compared with non-users. CONCLUSIONSThe results of this study support the hypothesis that the exposure to high dose CPA increases the risk of meningioma.

A review of the physical and metabolic effects of cross-sex hormonal therapy in the treatment of gender dysphoria

“…27 There have also been reports of the development of meningioma associated with the use of high-dose cyproterone acetate, 58 with an adjusted relative risk of 11.4 (95% CI ¼ 4.3 to 30.8) as compared with non-users. 58 Spironolactone is a mineralocorticoid receptor antagonist that acts as an androgen receptor partial antagonist as well as an oestrogen receptor agonist. As such, in addition to blocking the androgen receptor (which is its primary purpose in this situation), it also has a significant oestrogenic action at the doses used in transwomen.…”

“…6,8 Testosterone therapy has important effects on cognition. Aggression and general drive are increased when testosterone is given to men, 58 testosterone having a general activating role in cognition. 68 Transmen report that they have more energy, aggression and there is an increase in libido.…”

“…68 Transmen report that they have more energy, aggression and there is an increase in libido. 58 Psychologically, patients feel more masculine and generally more settled in their new gender role once testosterone therapy has commenced. There is also an improvement in visio-spatial ability in these individuals.…”

“…58 The physical changes that occur mimic male puberty and therefore take two to five years to complete. 4,7,8 Traditionally, testosterone has been administered in the form of mixed testosterone esters given as Sustanon injections 250 mg two to four weekly.…”

“…5,7 Ovarian cancer risk appears to be very low; there have been only three cases reported following testosterone therapy for a prolonged period. 58 Exogenous testosterone treatment is also associated with the development of a polycystic morphology, [63][64][65] the implications of this in the longer term are unknown and so oophorectomy is usually performed at the time of hysterectomy.…”