Cyproteron knyttet til 7–19 gange højere risiko for meningeom i dansk register; transkvinder nu de fleste nye brugere

Cyproteronacetat og risiko for meningeom: en landsdækkende kohortestudie

Authors
Anders Pretzmann Mikkelsen, Iben Katinka Greiber, Nikolai Madrid Scheller, Malene Hilden, Øjvind Lidegaard
Journal
Journal of Neurology, Neurosurgery & Psychiatry
Year
2022

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

  • Studiet dækkede omkring 5,7 millioner danskere, hvoraf 1.982 havde taget cyproteronacetat (CPA).
  • 16 af 8.957 meningeomer (normalt ikke-kræftagtige hjernetumorer) forekom hos personer, der havde taget CPA.
  • Personer med en samlet dosis på 0,1 til 10 gram havde cirka 7 gange risikoen for ikke-brugere, og dem over 10 gram havde cirka 19 gange risikoen.
  • Tidligere brugere, der var stoppet med CPA, havde stadig cirka 5 gange risikoen for personer, der aldrig tog det.
  • Nye CPA-brugere steg fra 18 til 62 pr. million mennesker mellem 2013 og 2019, og andelen, der var trans, steg fra 18 % til 68 %.
  • Til sammenligning når en typisk dosis for transkvinder på 50 mg om dagen 10 gram på under 7 måneder.
  • Resultaterne stemmer overens med et stort fransk studie (Weill og kolleger, 2021), der også fandt, at risikoen steg kraftigt med dosis.

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.