Summary

Cyproterone acetate (CPA) is a drug that blocks testosterone. Outside the US it is widely used in hormone treatment for trans women. Danish researchers used national health records covering nearly everyone in the country to compare rates of meningioma, a usually non-cancerous brain tumour, in CPA users and non-users. Users had about 7 times the risk at lower total doses and 19 times at higher doses, and risk stayed raised after stopping. Most users over the whole period were not trans, but by 2019 two-thirds of new users were, so the finding matters directly for trans women. The fact that risk rose with dose, and that a large French study found the same, makes the link believable. But it rests on only 16 cases and cannot give a risk figure for trans people specifically.

Key findings

• この研究は約570万人のデンマーク人を対象とし、そのうち1,982人が酢酸シプロテロン（CPA）を使っていました。
• 髄膜腫（通常は良性の脳腫瘍）8,957件のうち16件が、CPAを使っていた人に起きました。
• 総用量が0.1～10グラムの人は、使用していない人の約7倍のリスクがあり、10グラムを超える人は約19倍のリスクがありました。
• CPAをやめた過去の使用者も、使ったことのない人の約5倍のリスクがありました。
• CPAの新規使用者は、2013年から2019年に100万人あたり18人から62人に増え、トランスの人の割合は18%から68%に上がりました。
• 参考までに、トランス女性の典型的な用量である1日50 mgは、7か月足らずで10グラムに達します。
• この結果は、用量とともにリスクが急に上がることを同様に見つけたフランスの大規模な研究（Weillら、2021年）と一致しています。

Abstract

[No abstract in the published research letter; this is the abstract of the medRxiv preprint, doi 10.1101/2020.12.29.20248395] Cyproterone acetate (CPA) is a synthetic steroid hormone. We assessed the association between the use of CPA and the risk of developing meningioma. In a historical prospective cohort study, using Danish national healthcare registers we included a cohort of 5,730,654 individuals, among whom 1,982 were exposed to CPA. During follow-up, we identified 8,957 cases of meningioma, of which 16 were exposed to CPA. From 2013 to 2019 the number of new users increased from 18.1 to 62.3 new users per million, while the proportion of new users who were transgender increased from 18.4 to 68.3%. Analyses showed a significantly increased risk of meningioma according to cumulative dose of CPA; 0.1-10 grams of CPA, incidence rate 78.8 (95% CI 15.7-141.9) per 100.000 person years and adjusted hazard ratio 7.0 (3.1-15.6); >10 grams of CPA, incidence 187.5 (71.3-303.7) and adjusted hazard ratio 19.2 (10.3-35.8), as compared to the background population. In conclusion, the cumulative dose of CPA was associated with an increased incidence and hazard ratio of meningioma, showing a dose-response relationship. The number of new CPA users increased more than 3-fold from 2013 to 2019, primarily driven by new transgender users.

Conclusion

The cumulative dose of CPA was associated with an increased incidence and hazard ratio of meningioma, showing a dose-response relationship. The number of new CPA users increased more than threefold from 2013 to 2019, primarily driven by new transgender users. The authors note that the association has now been reproduced in two large cohort studies (with the French Weill et al. BMJ 2021 study), with a clear dose-response effect and large measures of association.