Cyproterone acetate

Cyproterone acetate is a very potent antiandrogen (testosterone blocker), and a very potent, artificial form of progesterone (Neumann, 1994). It dramatically lowers the production of testosterone, but carries more long-term health risks than most other antiandrogens available.

Key points

Dramatically lowers testosterone levels
Exerts the same effect as progesterone, only more powerfully
Increases risk of blood clots and certain types of brain tumors
Liver function monitoring advisable
Prolactin monitoring advisable
Vitamin B12 monitoring or supplementation advisable
Maximally effective at a dose of up to 10 mg
Important to take as little as possible, for as short a time as possible

Dosing

In the past, cyproterone acetate was often used at extremely high dosages of 50 - 300 mg daily. We now know that when combined with estrogen, dosages above 10 mg are not any more effective, but do significantly increase the risk of cancer, blood clots, and other serious complications (Aly, 2019; Kuijpers et al., 2021; Zohar et al., 2021).

Cyproterone acetate is a pill that is swallowed. It is ideally taken at dosages of approximately 5 - 10 mg daily. For some people, even lower dosages may be enough (Aly, 2019).

Because many available formulations of pills contain extremely high dosages, trans people often split their cyproterone acetate pills using a knife or pill cutter. As a result, in practice, many trans people take dosages such as 12.5 mg daily, 12.5 mg every other day, or even 12.5 mg every third day. This type of dosing is possible because cyproterone acetate stays in the body for several days.

Risks & management

Taking cyproterone acetate increases the risk of brain tumour (meningioma), with a higher lifetime exposure causing higher risk. In Weill et al. (2021), a lifetime dose below 6 grams of cyproterone acetate does not cause a meaningful increase in risk, but at 6 - 12 grams, the risk of developing meningioma doubles, and rises dramatically further at even higher doses.

This means that to avoid any increase in meningioma risk, it's best to take cyproterone acetate for no longer than:

1.25 years (15 months) when taking 12.5 mg daily
2.5 years (31 months) when taking 12.5 mg every other day

If this is not possible, the risk can be limited to a two-times increase by taking it no longer than:

2.5 years (31 months) when taking 12.5 mg daily
5.2 years (63 months) when taking 12.5 mg every other day

Lifetime exposure beyond 12 grams can sharply increases the risk of developing a meningioma by as much as 6-20 times depending on dosage.

High dosages of cyproterone acetate have a very small risk of causing life-threatening injury to the liver. It's unclear how significant this risk is at low dosages, but nonetheless, it it's likely advisable to monitor liver function through blood testing when using cyproterone acetate (Heinemann et al., 1997).

Cyproterone acetate can cause high prolactin levels, and can cause a type of non-cancerous brain tumour called a "prolactinoma" to develop. It is advisable to regularly check prolactin levels through blood tests when using cyproterone acetate (Wilson et al., 2020).

Cyproterone acetate can cause vitamin B12 deficiency, even at low dosages. It is therefore advisable to take a vitamin B12 supplement, or to regularly check vitamin B12 levels through blood testing while taking cyproterone acetate (Diamanti-Kandarakis, 1999).

Interactions

Most people do not need to take multiple antiandrogens at once.

Cyproterone acetate may interact with various antibiotics, antifungal medications and epilepsy medications, as well as grapefruit, green tea extract, and St. John’s Wort (Wiki).

While not dangerous, there is unlikely to be much benefit to combining cyproterone acetate and progesterone, as cyproterone acetate itself is already an extremely powerful form of progesterone.

Other information

Cyproterone acetate is also called "Androcur", "Procur", "Siterone", "CPA", and "Cypro." The term "cipro", which is ordinarily used to refer to the antibiotic ciprofloxacin, is also sometimes used to refer to cyproterone acetate.

References

Aly. (2020). Low Doses of Cyproterone Acetate Are Maximally Effective for Testosterone Suppression in Transfeminine People. Transfeminine Science. [URL]
Diamanti-Kandarakis E. (1999). Current aspects of antiandrogen therapy in women. Current pharmaceutical design, 5(9), 707–723. [DOI:10.2174/1381612805666230111201150]
Even Zohar, N., Sofer, Y., Yaish, I., Serebro, M., Tordjman, K., & Greenman, Y. (2021). Low-Dose Cyproterone Acetate Treatment for Transgender Women. The journal of sexual medicine, 18(7), 1292–1298. [DOI:10.1016/j.jsxm.2021.04.008]
Heinemann, L. A., Will-Shahab, L., van Kesteren, P., Gooren, L. J., & Collaborating Centers (1997). Safety of cyproterone acetate: report of active surveillance. Pharmacoepidemiology and drug safety, 6(3), 169–178. [DOI:10.1002/(SICI)1099-1557(199705)6:3<169::AID-PDS263>3.0.CO;2-3]
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. The Journal of clinical endocrinology and metabolism, 106(10), e3936–e3945. [DOI:10.1210/clinem/dgab427]
Neumann F. (1994). The antiandrogen cyproterone acetate: discovery, chemistry, basic pharmacology, clinical use and tool in basic research. Experimental and clinical endocrinology, 102(1), 1–32. [DOI:10.1055/s-0029-1211261]
Weill, A., Nguyen, P., Labidi, M., Cadier, B., Passeri, T., Duranteau, L., Bernat, A. L., Yoldjian, I., Fontanel, S., Froelich, S., & Coste, J. (2021). Use of high dose cyproterone acetate and risk of intracranial meningioma in women: cohort study. BMJ (Clinical research ed.), 372, n37. [DOI:10.1136/bmj.n37]
Wilson, L. M., Baker, K. E., Sharma, R., Dukhanin, V., McArthur, K., & Robinson, K. A. (2020). Effects of antiandrogens on prolactin levels among transgender women on estrogen therapy: A systematic review. International journal of transgender health, 21(4), 391–402. [DOI:10.1080/15532739.2020.1819505]