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Toward a lowest effective dose of cyproterone acetate in trans women : results from the ENIGI study

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Abstract
Context: Cyproterone acetate (CPA) is a competitive inhibitor of the androgen receptor and exerts negative hypothalamic feedback. It is often used in combination with estrogens in trans women to achieve feminization. However, CPA has been associated with side effects such as changes in liver enzyme concentrations and increases in prolactin concentrations. The question is whether the testosterone-lowering effect, as well as these side effects, are dose dependent. Objective: To assess the lowest effective dose of CPA in trans women to prevent side effects. Methods: This longitudinal study, conducted at gender identity centers in Amsterdam, Ghent, and Florence, is part of the European Network for the Investigation of Gender Incongruence (ENIGI), a multicenter prospective cohort study. Participants were trans women (n=882) using estrogens only or in combination with 10, 25, 50, or 100 mg CPA daily. The primary outcome measure was the concentration of testosterone at 3 and/or 12 months of hormone therapy. Results: Using estrogens only (without CPA) led to testosterone concentrations of 5.5 nmol/L (standard error of the mean [SEM] 0.3). All doses of CPA resulted in testosterone concentrations below the pre-defined threshold of suppression of 2 nmol/L (10 mg, 0.9 nmol/L, SEM 0.7; 25 mg, 0.9 nmol/L, SEM 0.1; 50mg, 1.1 nmol/L, SEM 0.1; 100 mg, 0.9 nmol/L, SEM 0.7). Higher prolactin and lower high-density lipoprotein concentrations were observed with increasing doses of CPA. No differences in liver enzyme concentrations were found between the doses. Conclusion: Compared with higher doses of CPA, a daily dose of 10 mg is equally effective in lowering testosterone concentrations in trans women, while showing fewer side effects.
Keywords
trans people, hormone therapy, anti-androgen, cyproterone acetate, testosterone, SEX HORMONE-TREATMENT, VENOUS THROMBOEMBOLISM, THERAPY, ENDOCRINE, SUPPRESSION

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MLA
Kuijpers, Suzanne M. E., et al. “Toward a Lowest Effective Dose of Cyproterone Acetate in Trans Women : Results from the ENIGI Study.” JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, vol. 106, no. 10, 2021, pp. E3936–45, doi:10.1210/clinem/dgab427.
APA
Kuijpers, S. M. E., Wiepjes, C. M., Conemans, E. B., Fisher, A. D., T’Sjoen, G., & den Heijer, M. (2021). Toward a lowest effective dose of cyproterone acetate in trans women : results from the ENIGI study. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 106(10), E3936–E3945. https://doi.org/10.1210/clinem/dgab427
Chicago author-date
Kuijpers, Suzanne M. E., Chantal M. Wiepjes, Elfi B. Conemans, Alessandra D. Fisher, Guy T’Sjoen, and Martin den Heijer. 2021. “Toward a Lowest Effective Dose of Cyproterone Acetate in Trans Women : Results from the ENIGI Study.” JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM 106 (10): E3936–45. https://doi.org/10.1210/clinem/dgab427.
Chicago author-date (all authors)
Kuijpers, Suzanne M. E., Chantal M. Wiepjes, Elfi B. Conemans, Alessandra D. Fisher, Guy T’Sjoen, and Martin den Heijer. 2021. “Toward a Lowest Effective Dose of Cyproterone Acetate in Trans Women : Results from the ENIGI Study.” JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM 106 (10): E3936–E3945. doi:10.1210/clinem/dgab427.
Vancouver
1.
Kuijpers SME, Wiepjes CM, Conemans EB, Fisher AD, T’Sjoen G, den Heijer M. Toward a lowest effective dose of cyproterone acetate in trans women : results from the ENIGI study. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM. 2021;106(10):E3936–45.
IEEE
[1]
S. M. E. Kuijpers, C. M. Wiepjes, E. B. Conemans, A. D. Fisher, G. T’Sjoen, and M. den Heijer, “Toward a lowest effective dose of cyproterone acetate in trans women : results from the ENIGI study,” JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, vol. 106, no. 10, pp. E3936–E3945, 2021.
@article{8745367,
  abstract     = {{Context: Cyproterone acetate (CPA) is a competitive inhibitor of the androgen receptor and exerts negative hypothalamic feedback. It is often used in combination with estrogens in trans women to achieve feminization. However, CPA has been associated with side effects such as changes in liver enzyme concentrations and increases in prolactin concentrations. The question is whether the testosterone-lowering effect, as well as these side effects, are dose dependent. 

Objective: To assess the lowest effective dose of CPA in trans women to prevent side effects. 

Methods: This longitudinal study, conducted at gender identity centers in Amsterdam, Ghent, and Florence, is part of the European Network for the Investigation of Gender Incongruence (ENIGI), a multicenter prospective cohort study. Participants were trans women (n=882) using estrogens only or in combination with 10, 25, 50, or 100 mg CPA daily. The primary outcome measure was the concentration of testosterone at 3 and/or 12 months of hormone therapy. 

Results: Using estrogens only (without CPA) led to testosterone concentrations of 5.5 nmol/L (standard error of the mean [SEM] 0.3). All doses of CPA resulted in testosterone concentrations below the pre-defined threshold of suppression of 2 nmol/L (10 mg, 0.9 nmol/L, SEM 0.7; 25 mg, 0.9 nmol/L, SEM 0.1; 50mg, 1.1 nmol/L, SEM 0.1; 100 mg, 0.9 nmol/L, SEM 0.7). Higher prolactin and lower high-density lipoprotein concentrations were observed with increasing doses of CPA. No differences in liver enzyme concentrations were found between the doses. 

Conclusion: Compared with higher doses of CPA, a daily dose of 10 mg is equally effective in lowering testosterone concentrations in trans women, while showing fewer side effects.}},
  author       = {{Kuijpers, Suzanne M. E. and Wiepjes, Chantal M. and Conemans, Elfi B. and Fisher, Alessandra D. and T'Sjoen, Guy and den Heijer, Martin}},
  issn         = {{0021-972X}},
  journal      = {{JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM}},
  keywords     = {{trans people,hormone therapy,anti-androgen,cyproterone acetate,testosterone,SEX HORMONE-TREATMENT,VENOUS THROMBOEMBOLISM,THERAPY,ENDOCRINE,SUPPRESSION}},
  language     = {{eng}},
  number       = {{10}},
  pages        = {{E3936--E3945}},
  title        = {{Toward a lowest effective dose of cyproterone acetate in trans women : results from the ENIGI study}},
  url          = {{http://doi.org/10.1210/clinem/dgab427}},
  volume       = {{106}},
  year         = {{2021}},
}

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