High doses of drug cyproterone acetate (CPA), a drug widely-used in the hormonal treatment of conditions like hirsutism, early puberty, and prostate cancer, have been linked to an increased risk of meningioma, the most common type of benign brain tumour, finds a meta-analysis of more than 8m patients.
Typically slow-growing, meningiomas are benign tumours, which are often revealed incidentally by imaging but can cause significant disability due to compressing or squeezing the adjacent brain, nerves and vessels and pressure effects within a fixed cranial vault.
Recent studies have reported an association between the growth of meningiomas and hormonal treatments, particularly prolonged and high dose use of the drug cyproterone acetate (CPA).
High doses of cyproterone acetate (> 50 mg/day) are usually prescribed to male patients with inoperable prostate cancer, which leads to excessive hair growth, and male-to-female transsexual hormonal therapy. Lower doses (2-10 mg/day) of the drug are typically used in combination with oestradiol to treat androgen-associated alopecia or female seborrhoea.
Given the drug’s widespread use, researchers at the Universities of Bristol, Cambridge and the National University of Singapore, conducted a systematic review and meta-analysis study using four studies comprising a sample of 8,132,348 patients, to assess the evidence of the association between cyproterone acetate and incidence of meningiomas.
The sample included 165,988 patients who were identified as taking cyproterone acetate at varying dose amounts. Using these data, the team analysed the occurrence of meningioma in patients using high versus low dose cyproterone acetate and found a significant association between high dose usage and increased risk of meningioma. However, this association was not found with low doses.
Keng Siang Lee, a medical student and the study’s lead author from Bristol Medical School at the University of Bristol, said: “The cause of meningiomas is controversial but there is strong evidence to suggest a plausible role for sex hormones in the onset of meningioma. We know it has a predilection for females especially after puberty. Furthermore, fluctuations in meningioma growth during the menstrual cycle, pregnancy, and breastfeeding have also been well-documented. We are also aware of the well-characterised distribution of progesterone, oestrogen, and androgen receptors in certain meningiomas located at the base of the skull.
“In light of these results, prescription of high-dose cyproterone acetate, especially for off-label indications, should be considered carefully. Additionally, we suggest that routine screening and meningioma surveillance by brain MRI for patients prescribed with cyproterone acetate should be a reasonable clinical consideration if given at high doses for long periods of time.
“However, our study underscores the current limited evidence about the risk of intracranial meningioma associated with low dose cyproterone acetate. It is still unknown whether or not cyproterone acetate below a certain threshold may be completely safe in terms of the risk of meningioma. The results obtained herein suggest the necessity for further clinical research on intracranial meningioma associated with cyproterone acetate.”
The research was published in Nature’s Scientific Reports.
Study details
A systematic review and meta-analysis of the association between cyproterone acetate and intracranial meningiomas
Keng Siang Lee, John J. Y. Zhang, Ramez Kirollos, Thomas Santarius, Vincent Diong Weng Nga, Tseng Tsai Yeo.
Published in Scientific Reports on 4 February 2022.
Abstract
The influence of exposure to hormonal treatments, particularly cyproterone acetate (CPA), has been posited to contribute to the growth of meningiomas. Given the widespread use of CPA, this systematic review and meta-analysis attempted to assess real-world evidence of the association between CPA and the occurrence of intracranial meningiomas. Systematic searches of Ovid MEDLINE, Embase and Cochrane Controlled Register of Controlled Trials, were performed from database inception to 18 December 2021. Four retrospective observational studies reporting 8,132,348 patients were included in the meta-analysis. There was a total of 165,988 subjects with usage of CPA. The age of patients at meningioma diagnosis was generally above 45 years in all studies.
The dosage of CPA taken by the exposed group (n = 165,988) was specified in three of the four included studies. All studies that analysed high versus low dose CPA found a significant association between high dose CPA usage and increased risk of meningioma. When high and low dose patients were grouped together, there was no statistically significant increase in risk of meningioma associated with use of CPA (RR = 3.78 [95% CI 0.31–46.39], p = 0.190).
Usage of CPA is associated with increased risk of meningioma at high doses but not when low doses are also included. Routine screening and meningioma surveillance by brain MRI offered to patients prescribed with CPA is likely a reasonable clinical consideration if given at high doses for long periods of time. Our findings highlight the need for further research on this topic.
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