High-dose cyproterone acetate: potential risk of (multiple) meningiomas
- Medicines and Healthcare products Regulatory Agency
- 1 October 2009
- Therapeutic area:
- Anaesthesia and intensive care, Cancer, Endocrinology, diabetology and metabolism, and Psychiatry
Patients with existing meningioma or a history of meningioma must not be prescribed high-dose (≥25 mg per day) cyproterone acetate.
Article date: October 2009
Cyproterone acetate-containing products
Cyproterone acetate is a derivative of progesterone, and has progestagenic, antiandrogenic, and antigonadotrophic effects. High-dose preparations available in the UK include Cyprostat-50 and Cyprostat-100, which are indicated for use in the treatment of prostate cancer (dose 50–300 mg per day). Cyproterone acetate is also available as Androcur-50, which is indicated for the control of libido in men with severe hypersexuality or sexual deviation (or both). In some EU countries, Androcur-50 is used for the treatment of androgenisation in women. Although this is not a licensed indication in the UK, there is some evidence that high-dose cyproterone acetate is being used for this purpose here.
Lower-dose cyproterone acetate (ie, 2 mg) is available for use in women as co-cyprindiol (Dianette) in combination with 35 micrograms ethinylestradiol for the treatment of severe acne that is refractory to prolonged antibiotic therapy, and for moderately severe hirsutism.
Meningiomas are the most common intracranial tumours, with an annual incidence of six per 100 000 in the general population. Multiple meningiomas account for approximately 1–10% of all cases. Though histologically benign, they can have serious consequences. The potential role of sex hormones in the development of meningiomas has been postulated: approximately 70% of meningiomas express progesterone receptors and about 30% express oestrogen receptors.1
The occurrence of (multiple) meningiomas has been reported in association withlonger-term use (years) of cyproterone acetate at doses of 25 mg/day or higher.
Summary of evidence
Up to September 2009, 36 cases of meningioma, of which 19 described multiple meningioma, have been reported worldwide in association with high-dose cyproterone acetate. Nine cases were discussed in a published case series,2; and 27 cases are unpublished case reports. Of the 36 cases, 32 occurred in women and four in men. Duration of treatment with cyproterone acetate ranged from 4 years to 27 years, and in all but one case it was prescribed at doses higher than 25 mg per day. 31 of the cases were from France (which compared with other countries has extensive use of high-dose cyproterone acetate). None of the reported cases had a fatal outcome.
A retrospective cohort study with nested case-control analysis is currently being done by the brand-leader marketing authorisation holder using data from The Health Improvement Network database (THIN) in the UK, to further investigate the association between cyproterone acetate and meningioma. The main study objectives will be to estimate the incidence of meningioma in the general population and among users of cyproterone acetate, and to examine whether there is a dose-response relationship and a duration-response relationship between use of cyproterone acetate and meningioma.
Product information for all products in the UK that contain high-dose cyproterone acetate will be updated in line with the advice below.
Advice for healthcare professionals:
- Patients with existing meningioma or a history of meningioma must not be prescribed cyproterone acetate at doses of 25 mg per day or higher (ie, should not receive Cyprostat-50, Cyprostat-100, or Androcur-50)
- This advice does not apply to medicines that contain low-dose cyproterone acetate such as co-cyprindiol (Dianette)
Article citation: Drug Safety Update Oct 2009, vol 3 issue 3: 3.
Published: 1 October 2009