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

• Die Studie umfasste etwa 5,7 Millionen Dänen, von denen 1.982 Cyproteronacetat (CPA) genommen hatten.
• 16 von 8.957 Meningeomen (meist nicht bösartige Hirntumoren) traten bei Personen auf, die CPA genommen hatten.
• Personen mit einer Gesamtdosis von 0,1 bis 10 Gramm hatten etwa das 7-Fache des Risikos von Nichtanwendern, und solche über 10 Gramm etwa das 19-Fache.
• Frühere Anwender, die CPA abgesetzt hatten, hatten weiterhin etwa das 5-Fache des Risikos von Personen, die es nie genommen hatten.
• Neue CPA-Anwender stiegen zwischen 2013 und 2019 von 18 auf 62 pro Million Menschen, und der Anteil der trans Personen stieg von 18 % auf 68 %.
• Zum Vergleich: Eine typische Dosis für trans Frauen von 50 mg pro Tag erreicht in unter 7 Monaten 10 Gramm.
• Die Ergebnisse stimmen mit einer großen französischen Studie (Weill und Kollegen, 2021) überein, die ebenfalls fand, dass das Risiko mit der Dosis steil anstieg.

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.