Endocrine Abstracts

Introduction: Meningiomas are the most common brain tumours and they express progesterone receptors. Cyproterone acetate (CPA) is a synthetic progestogen approved for use as an anti-androgen in Polycystic Ovarian Syndrome (PCOS). We report a case of meningioma probably resulting from long-term CPA treatment and a review of our PCOS cohort for further cases.

Case report: A 47-year-old lady with PCOS was treated with CPA 100 mg once daily for hirsutism and androgenic alopecia for 15 years (cumulative dose-exposure=193g). She developed reduced vision in left eye; an MRI brain revealed a 6-cm left supra-orbital meningioma alongside 2 small separate lesions (0.8 cm & 0.3 cm). CPA was stopped and large mass was resected; histology confirmed Grade 2 meningioma. Smaller lesions were conservatively managed.

Quality Improvement project: To identify further cases of meningioma, a retrospective electronic records’ review of consecutive PCOS patients who were on either CPA or Dianette (CPA 2 mg + Ethinyl Estradiol 35 mg) in University Hospitals of Leicester from 1980 to 2021 was undertaken. n=1302 patients received either CPA or Dianette as current or past treatment (CPA=508; Dianette=794) with a cumulative dose-exposure of 56g/patient. 78/508 CPA patients are currently under active follow-up; 20 are currently on CPA (100 mg=14; 50 mg=6). CPA was stopped in rest due to lack of efficacy, tolerability, compliance, and/or lost to follow-up. Up-to-date imaging & records review of 508 CPA-cohort detected one meningioma occurrence which is described above. No meningioma cases were noted in the Dianette cohort.

Discussion: First described in 2008 and confirmed in a recent French study, there is a 11-fold higher dose-dependent risk of meningioma with 36g to 60g cumulative CPA dose-exposure compared to <3g. In June 2020, Medicines and Healthcare products Regulatory Agency (MHRA) issued guidance to minimise risk of meningioma, limiting high dose (50-100 mg) license for only prostate cancer and male hypersexuality. It is plausible that meningioma is co-incidental in our patient as incidence is 6-10 in 100.000 background population. However, recognised association, potent progestogenic effect and high-dose exposure may potentially incriminate CPA. Given solitary incidence in our cohort, remaining 19 CPA patients are closely monitored, MHRA guidance explained with an option offered to swap to alternate treatment.

Learning points

1) To be aware of meningioma side effect risk in high dose CPA (>50 mg/day) treated patients and consider cessation/swapping to alternate treatment.

2) CPA should be stopped in high risk patients such as PMH of meningioma, radiotherapy or Neurofibromatosis-2 genetic mutation.