Paris—Women who receive the hormone drug cyproterone acetate over an extended period of time increase their risk of developing a brain tumor, according to a large French study.

The report in the BMJ involved a trial of more than 250,000 women. Researchers from the French government, the University of Paris, and colleagues determined that that higher the dose and the longer the drug is taken for, the greater the risk of meningioma, a mostly noncancerous brain tumor arising in the meninges that surround and protect the brain and spinal cord.

The study advises that risk declines significantly when treatment is ended. Background information in the article notes that, since 2007, several reported cases of meningioma have been associated with prolonged use (5 to 30 years) of high-dose cyproterone acetate (25 mg to100 mg daily) in both men and women, but this is the first study with good-quality published evidence on the link.

Cyproterone acetate, a synthetic progestogen that lowers testosterone levels, is used in men to treat inoperable prostate cancer and in women for severe acne and excessive hair growth. In addition, very small doses are also used in birth control pills and hormone replacement therapy, the authors add.

The observational cohort study used data from SNDS, the French administrative healthcare database, between 2007 and 2015. Included were 253,777 girls and women aged 7 to 70 years living in France who started cyproterone acetate between 2007 and 2014. Participants had at least one reimbursement for high-dose cyproterone acetate and no history of meningioma or benign brain tumor, or long-term disease status.

Exposure was defined as a dose of at least 3 g during the first 6 months, which was the case for 139, 222 participants; the control group was very slightly exposed, defined as receiving a cumulative dose of less than 3 g.

An additional analysis looked at 10,876 male-to-female transgender participants.
The focus was on surgery (resection or decompression) or radiotherapy for one or more intracranial meningiomas.

The authors report that 69 meningiomas in the exposed group (during 289,544 person-years of follow-up) and 20 meningiomas in the control group (during 439,949 person years of follow-up) were treated by surgery or radiotherapy. That translates to an incidence of meningioma in the two groups of 23.8 and 4.5 per 100,000 person years, respectively (crude relative risk 5.2, 95% CI, 3.2 to 8.6; adjusted hazard ratio 6.6, 95% CI, 4.0 to 11.1).

The study team explains that the adjusted hazard ratio for a cumulative dose of cyproterone acetate of more than 60 g was 21.7 (10.8 to 43.5). After discontinuation of cyproterone acetate for 1 year, however, the risk of meningioma in the exposed group was 1.8-fold higher (1.0 to 3.2) than in the control group.

In a complementary analysis, 463 women with meningioma were observed among 123,997 already using cyproterone acetate in 2006 (risk of 383 per 100,000 person-years in the group with the highest exposure in terms of cumulative dose). The additional analysis of transgender participants also revealed a higher risk of meningioma—three per 14,460 person-years; 20.7 per 100,000 person years.

The researchers suggest that meningiomas located in the anterior skull base and middle skull base, particularly the medial third of the middle skull base, involving the spheno-orbital region, appeared to be specific to cyproterone acetate.

“A strong dose-effect relation was observed between use of cyproterone acetate and risk of intracranial meningiomas. A noticeable reduction in risk was observed after discontinuation of treatment,” the authors conclude.

They advise that patients who use high-dose cyproterone acetate for at least 3 to 5 years should be informed about the increased risk of meningioma and that reasons for prescribing the product should also be clearly defined and the lowest possible daily dose used.

If prolonged use of high-dose cyproterone acetate is necessary, more thorough screening for meningioma should be considered and it should be discontinued in patients with a documented meningioma, the researchers add.

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