Is cyproterone safe to use during gender transition?

Cyproterone acetate is a synthetic hormone used to suppress testosterone. In the context of gender transition, particularly among transfeminine individuals, it has historically been prescribed to reduce the influence of testosterone and facilitate the physical effects of estrogen therapy. However, despite its widespread use in some countries, concerns about its safety have become more prominent. This article summarises what the published evidence and regulators say about cyproterone during gender transition.

Cyproterone functions as an antiandrogen, meaning it blocks the effects of androgens such as testosterone.

It also has progestogenic properties, mimicking the effects of the hormone progesterone. This dual action has made it appealing in hormone therapy regimens for transfeminine individuals seeking to suppress secondary male characteristics. However, safety concerns—particularly involving brain tumours, liver enzyme changes, and mood disorders—have led to reevaluation of its role in gender-affirming care.

One of the most serious risks associated with cyproterone is the development of meningiomas, which are usually benign tumors that form in the membranes surrounding the brain and spinal cord.

The European Medicines Agency (EMA) began reviewing cyproterone's safety in 2019 following reports of meningioma cases among long-term users of the drug. A large study by Weill and colleagues, published in 2021 in the BMJ, examined French national health-insurance data covering 253,777 people exposed to cyproterone and a comparison group of over 10,000 people with low-dose exposure. The researchers reported that people taking 25 mg a day or more over several years had a markedly increased risk of developing a meningioma, and that the risk rose with cumulative dose. The study used a retrospective cohort method based on national health insurance records and counted meningioma diagnoses against prescription exposure. It is observational rather than a randomised clinical trial, so it cannot prove cause on its own, but its size and the strength of the dose relationship are why regulators treated it as a serious safety signal.

Following these findings, the EMA restricted cyproterone in February 2020. The restriction is not a 10 mg daily ceiling, which is a common misreading. The agency said that medicines containing 10 mg a day or more should be used for hirsutism, androgenic alopecia, acne and seborrhoea only after other treatment options — including lower-dose cyproterone products — have failed, that the dose should be reduced to the lowest effective one, and that cyproterone must be stopped permanently in anyone diagnosed with a meningioma. The agency did not ban the drug, but it emphasised medical monitoring. Prescribing practice for gender-affirming care varies between countries and services, and doses used there are set by the prescriber, not by this article.

Liver effects are another area of concern. Cyproterone product information lists changes in liver enzymes, and, rarely, drug-induced hepatitis and liver failure, which is why clinicians who prescribe it commonly check liver function periodically. What is not available is a reliable head-to-head trial comparing cyproterone with spironolactone on liver outcomes in transfeminine patients — so any claim that one is measurably harder on the liver than the other in this population should be treated as unproven.

Cyproterone's impact on mental health has also been raised.

Depression and mood changes are listed as adverse effects in cyproterone product information, and both clinicians and community members describe them. There is, however, no published controlled trial that establishes how common these effects are during gender-affirming therapy, or that ties them to a particular dose. Anyone who notices a change in mood on cyproterone should raise it with their prescriber rather than adjust the dose themselves.

It is important to note that cyproterone is not approved by the U.S. Food and Drug Administration (FDA), and therefore it is not commonly used in the United States for gender-affirming care. Instead, medications such as spironolactone and bicalutamide are more prevalent. Spironolactone works mainly by blocking the androgen receptor, has a weaker effect on androgen production, and is also a potassium-sparing diuretic; it can raise potassium levels and affect blood pressure. Bicalutamide directly blocks testosterone receptors and has been associated with liver toxicity in rare cases. Neither of these drugs is risk-free, and both require regular clinical monitoring.

In summary, cyproterone has been an integral part of hormone therapy for many transfeminine individuals, especially in countries where alternatives are less accessible, and published evidence points to real health risks, particularly with long-term use and higher doses.

The association with meningiomas has prompted major regulatory bodies to limit its use.

Liver monitoring and mental health support are part of care when this drug is prescribed. No treatment described here can be called safe in the abstract; the evidence supports individualised treatment plans, monitoring, and informed decision-making with a clinician who knows the person's history.

Talk to a doctor or pharmacist before starting, stopping, changing the dose of, or combining cyproterone acetate. Cyproterone is a teratogen: product information contraindicates it in pregnancy, advises effective contraception for anyone who could become pregnant, and advises against handling broken or crushed tablets.

References

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: a population-based cohort study. BMJ, 372, n37. https://www.bmj.com/content/372/bmj.n37

European Medicines Agency. (2020). Restrictions in use of cyproterone due to meningioma risk. https://www.ema.europa.eu/en/news/restrictions-use-cyproterone-due-meningioma-risk