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

• 该研究涵盖约570万丹麦人，其中1,982人曾服用醋酸环丙孕酮（CPA）。
• 8,957例脑膜瘤（通常为非癌性脑肿瘤）中有16例发生在服用过CPA的人身上。
• 总剂量为0.1至10克的人风险约为未使用者的7倍，超过10克的人风险约为19倍。
• 已停用CPA的过往使用者，风险仍约为从未服用者的5倍。
• 2013年至2019年间，新增CPA使用者从每百万人18人升至62人，其中跨性别者的比例从18%升至68%。
• 作为参照，跨性别女性每天50毫克的典型剂量在不到7个月内就达到10克。
• 这些结果与一项大型法国研究（Weill及同事，2021年）相符，该研究也发现风险随剂量急剧上升。

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.