Prolonged Use of Cyproterone Acetate Links to Brain Tumor

A study of over 250,000 women in France published today in The BMJ found that long-term high-dose usage of the hormone medication cyproterone acetate is related to an elevated risk of getting a brain tumor.

The higher the dose and the longer the medicine is taken, the higher the risk of meningioma, which is a typically non-cancerous brain tumor that develops in the layers of tissue (meninges) that surround and protect the brain and spinal cord. However, the risk decreases significantly after discontinuing medication.

Cyproterone acetate is a synthetic progestogen that reduces testosterone levels. It is used in males to treat inoperable prostate cancer and in women to cure severe acne and excessive hair growth. Birth control pills and hormone replacement therapy both employ very modest dosages.

Since 2007, many incidences of meningioma have been documented in both men and women after taking high-dose cyproterone acetate (25-100 mg daily) for 5-30 years. However, there is a paucity of high-quality published evidence on this link.

To fill this knowledge vacuum, researchers set out to examine the real-world impact of extended usage of high-dose cyproterone acetate (25 or 50 mg/day) on the risk of meningioma in girls and women.

The main analysis was based on data from 253,777 girls and women aged 7 to 70 years (average age 29) living in France who began taking cyproterone acetate between 2007 and 2014.

All subjects had received at least one prescription for high-dose cyproterone acetate and had no prior history of meningioma, benign brain tumor, or long-term illness.

Participants were classified as exposed when they received a cumulative dosage of at least 3 g during the first six months (139,222 participants), and as very barely exposed (control group) when they received a cumulative dose of less than 3 g (114,555 participants).

Gynecologists were mostly responsible for initiating treatment in both groups. Participants were monitored until the end of 2015, and any surgery or radiotherapy for meningioma was documented.

In the main study of women starting cyproterone acetate, the researchers discovered 69 meningiomas in the exposed group and 20 meningiomas in the control group treated with surgery or radiotherapy.

This is equivalent to a rate of 23.8 per 100,000 person years in the exposed group and 4.5 per 100,000 person years in the control group.

The majority of cases (60%) involved women over the age of 45, and nearly all (96%) required invasive surgery. After controlling for other risk factors such as age and medical history, cyproterone acetate was linked to a sevenfold higher incidence of meningioma.

In a follow-up study of 123,997 women who had previously used cyproterone acetate in 2006, the researchers discovered 463 cases of meningioma.

However, the risk of meningioma fell significantly once medication was discontinued.

This is an observational study, and the researchers acknowledge some limitations that may have influenced their findings. Furthermore, they believe this study underestimates the overall rate of meningiomas because most tiny or asymptomatic tumors would not have required surgery.

Nonetheless, this was a big study based on national prescription data, and the substantial dose-dependent connection, together with the reduction in risk after discontinuing therapy, point to a biologically plausible causal relationship.

As a result, they recommend that people who have been taking high doses of cyproterone acetate for at least three to five years be advised of the elevated risk of meningioma.

The reasons for prescription cyproterone acetate should also be carefully established, with the lowest possible daily dose chosen.

When high-dose cyproterone acetate must be used for an extended period of time, meningioma screening should be performed more thoroughly. They further recommend that patients with documented meningioma quit cyproterone acetate.

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