Usually, gonadotropin releasing hormone analogues (GnRHa) would be used to block puberty. Recently, prescriptions for GnRHa for gender incongruence has been restricted, including in the United Kingdom.
We're going to look at cyproterone acetate as an alternative for transfeminine adolescents specifically. Cyproterone acetate has antiandrogenic (testosterone blocking) effects in people with testes, and so could be used for transfeminine adolescents.
What is cyproterone acetate and how does it work?
Cyproterone acetate is a medication that suppresses testosterone production. It is commonly used to treat conditions like prostate cancer and hirsutism (unwanted excess hair). It is already used in gender affirming care for trans women because of its testosterone blocking effects.
How is cyproterone acetate used in gender affirming medical treatment?
Studies show that cyproterone acetate is effective at suppressing testosterone levels and enhancing feminising bodily changes (Angus et al., 2019; Burinkul et al., 2021).
Cyproterone acetate has been suggested as an option to block puberty for transfeminine adolescents who have testes because of its known effectiveness in care for adult trans women.
What is the evidence base for cyproterone acetate in transfeminine adolescents?
So far, there has only been one study that specifically investigated cyproterone acetate for transfeminine adolescents (Tack et al., 2017).
This was a retrospective study of 27 transfeminine adolescents who received cyproterone acetate on its own and then in combination with oestrogen.
Cyproterone acetate was shown to be effective at suppressing testosterone and promoting feminising changes. There were some slight and temporary increases in liver enzymes during treatment, but no significant harmful effects were reported.
Other research has investigated cyproterone acetate treatments for precocious (early onset) puberty in cis boys and cis girls (Kauli et al., 1976). No significant harmful effects were reported in this study. This study did not investigate trans adolescents, but it does provide some evidence that cyproterone acetate is reasonably well tolerated in youth.
Is cyproterone acetate safe?
All medicines have side effects. Cyproterone acetate's most significant potential side effects are hepatotoxicity (liver impairment) and increased risk of meningioma (a benign tumour of the lining of the brain).
Liver impairment
Hepatotoxicity occurs in less than 10% of people who take cyproterone acetate (Asscheman et al., 1989; Kumar et al., 2021; Savidou et al., 2006). This ranges from slightly raised liver enzyme levels to acute severe liver failure. Very rarely, deaths have been reported from liver failure started by cyproterone acetate. As such, cyproterone acetate should not be prescribed to people with evidence of liver impairment. People taking cyproterone acetate must have regular blood testing to check their liver enzyme levels.
Liver health is monitored with liver function tests. These measure enzymes that are produced by the liver. Liver enzyme levels are higher in the blood when the liver is damaged. The most easily measured markers of liver injury are the enzymes alanine transaminase (ALT) and aspartate transaminase (AST). However, liver function tests can also include other markers, such as alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), bilirubin, and albumin.
If your ALT or AST levels are higher the usual healthy range, then you may have some degree of liver impairment, and so cyproterone acetate is not recommended for you. If you are taking cyproterone acetate and your ALT or AST levels are elevated, we recommend you stop taking cyproterone and take a different antiandrogen. We also recommend you see your doctor to investigate the liver injury. Your doctor may monitor your liver health with a repeat blood test or arrange an ultrasound of your liver.
Meningioma
There is evidence that cyproterone acetate is associated with increased risk of meningioma.
In a study of 10,876 trans women, the risk of meningioma was 2.07 per 10,000 people per year in trans women who were taking cyproterone acetate (0.027%), compared to 0 in trans women who were not taking cyproterone acetate.
Further data on cis girls and cis women found that people who were taking cyproterone acetate were 5 times more likely to develop meningioma than people who were not taking cyproterone acetate. The risk of meningioma was greater with higher doses of cyproterone acetate (Weill et al., 2021).
The absolute risk of meningioma is still low, but it's important to acknowledge that cyproterone acetate does increase the lifetime risk of developing meningioma.
References
Angus, L., Leemaqz, S., Ooi, O., Cundill, P., Silberstein, N., Locke, P., Zajac, J. D., and Cheung, A. S. (2019). “Cyproterone acetate or spironolactone in lowering testosterone concentrations for transgender individuals receiving oestradiol therapy”. Endocrine Connections, 8: 935–940.
Asscheman, H., Gooren, L. J., and Eklund, P. L. (1989). “Mortality and morbidity in transsexual patients with cross-gender hormone treatment”. Metabolism: Clininical and Experimental, 38: 869–873.
Burinkul, S., Panyakhamlerd , K., Suwan, A., Tuntiviriyapun, P., and Wainipitapong, S. (2021). "Anti-Androgenic Effects Comparison Between Cyproterone Acetate and Spironolactone in Transgender Women: A Randomized Controlled Trial". Journal of Sexual Medicine, 18 (1): 1299-1307.
Kauli, R., Pertzelan, A., Prager-Lewin, R., Grünebaum, M., and Laron, Z. (1976). "Cyproterone acetate in treatment of precocious puberty". Archives of Disease in Childhood, 51 (3): 202-208.
Kumar, P., Reddy, S., Kulkarni, A., Sharma, M., and Rao, P. N. (2021). “Cyproterone Acetate-Induced Acute Liver Failure: A Case Report and Review of the Literature”. Journal of clinical and experimental hepatology, 11: 739–741.
Savidou, I., Deutsch, M., Soultati, A. S., Koudouras, D., Kafiri, G., and Dourakis, S. P. (2006). “Hepatotoxicity induced by cyproterone acetate: a report of three cases”. World Journal of Gastroenterology, 12: 7551–7555.
Tack, L. J. W., Heyse, R., Craen, M., Dhondt, K., Vanden Bossche, H., Laridaen, J., and Cools, M. (2017). "Consecutive Cyproterone Acetate and Estradiol Treatment in Late-Pubertal Transgender Female Adolescents". Journal of Sexual Medicine, 14 (5): 747-757.
Weill, A., Nguyen, P., Labidi, M., Cadier, B., Passeri, T., Duranteau, L., Bernat, A. L., Yoldjian, I., Fontanel, S., Froelich, S., and Coste, J. (2021). “Use of High Dose Cyproterone Acetate and Risk of Intracranial Meningioma in Women: Cohort Study”. British Medical Journal, 372: n37.