Anti-Androgens
Estrogen does the feminizing, but testosterone works against it, so most feminizing regimens include a second medicine to bring it down. These are the anti-androgens. They work in quite different ways: some reduce how much testosterone you make, some block it from acting, and some switch production off at the source.
Which one you're offered depends heavily on where you live. US prescribers mostly use spironolactone. UK and European prescribers have long used cyproterone acetate, and UK gender services now often use GnRH agonist injections. Some people need no anti-androgen at all. Coordinating patients from many countries through Bangkok hospitals, I've seen how much the "standard" regimen depends on the passport. None of the options is simply right or wrong, and the choice belongs with your prescriber. The side effects of each are covered in more detail in risks and side effects; this page is about how they differ and why you might be offered one over another.
On this page
What an anti-androgen is for
Androgens are the hormones, mainly testosterone, that drove your first puberty. While testosterone stays high it keeps body hair coarse, keeps skin oily, maintains erections and libido, and blunts what estrogen can do. Lowering it lets estrogen work and stops or slows scalp hair loss.
Estrogen itself lowers testosterone, because the brain reads high estrogen as a signal to stop asking the testes for more. At a high enough level that's enough on its own. For many people on tablets, patches or gel, though, estrogen alone doesn't bring testosterone down far enough, and an anti-androgen fills the gap. The level most often cited as the aim is under about 50 ng/dL (under about 1.7 nmol/L); estrogen covers the targets and testing.
Spironolactone
Spironolactone is a blood pressure and heart medicine that also blocks testosterone and reduces how much is made. It's cheap and widely available, and it's the default in the US.
It's a diuretic that also makes the body hold on to potassium, which is why potassium and kidney function are in your routine bloods. It may be a poorer fit if you have kidney problems, already-low blood pressure, or take other medicines that raise potassium.
It's a milder anti-androgen than the alternatives. Some people on it still have testosterone above the target range, and some researchers have questioned whether it helps breast development or holds it back. The evidence on that is thin, and prescribers disagree.
Cyproterone acetate
Cyproterone acetate is a strong anti-androgen that has been widely used in the UK and Europe. It isn't approved in the US. It suppresses testosterone effectively, often at doses much lower than were common a decade or two ago.
Its main concern is meningioma, a usually benign tumour of the lining of the brain, with risk that rises with dose and years of use. In 2020 the European Medicines Agency restricted its use and advised the lowest effective dose, and many prescribers have since moved to lower doses, shorter courses or different medicines. It also raises prolactin and can lower mood; risks covers what to watch for.
If you've been on cyproterone for years, especially at an older, higher dose, it's reasonable to ask your prescriber whether your regimen still reflects current guidance. Don't stop it abruptly on your own; testosterone will come back.
Bicalutamide
Bicalutamide blocks testosterone from acting rather than lowering how much there is, so blood tests may show high testosterone while its effects are blocked. It's a prostate cancer medicine used off label for feminization by some prescribers, more often in the US.
It's debated. Supporters like that it's effective and generally well tolerated. The concern is a rare but serious liver injury, which is why people taking it need liver function tests. It's not part of the main published guidelines. Some clinicians have also raised questions about its effects on breast development, and there are few studies in trans women either way. If it's offered, ask how your liver will be monitored and how the prescriber will judge whether it's working, since the usual testosterone number won't tell them.
GnRH agonists
GnRH agonists, such as triptorelin, leuprorelin and goserelin, switch off the brain's signal to the testes, so testosterone production stops almost completely. They're given as injections or implants every one to three months, depending on the product.
In the UK they're commonly used by NHS gender services for adults, partly because of the concerns over cyproterone. They're effective and don't carry spironolactone's potassium issues or cyproterone's meningioma concern. In the US they're rarely used for adults because they're expensive and insurers resist them.
With testosterone switched off, estrogen is doing all of the work of protecting your bones, so an adequate estrogen level really matters. A GnRH agonist without enough estrogen leaves you with low hormones overall, which can mean fatigue, hot flushes and bone loss.
If you're on injections that need to be given on time
Put the next due date in your calendar the day you have each one, and ask your clinic what happens if it's late. Supply problems and missed appointments are the most common reason people end up with a gap.
Estrogen alone
Some people take estrogen with no anti-androgen at all. This is called monotherapy. It works when estrogen levels are high enough to shut down testosterone production on their own, which is easier to reach with injections than with tablets or gel. Some prescribers prefer it because it avoids the side effects of a second medicine. Others are more cautious, because reaching that level means running estrogen higher than they'd otherwise aim for.
After an orchiectomy, or a vaginoplasty that removes the testes, there's no testosterone left to suppress, and the anti-androgen usually goes. Hormones and surgery covers how regimens change after that.
Whether monotherapy suits you depends on your levels, your route and your prescriber's view. If you're interested, ask what estradiol level they'd need to see, and whether they'd consider changing your route to get there.
When your bloods come back
Ask for both numbers, estradiol and testosterone, not just "fine". Whether you need an anti-androgen, and how much, depends on the second number, and it's the one people most often don't know.
Frequently asked questions
Do I need an anti-androgen?
Many people do, but not everyone. Estrogen alone suppresses testosterone if levels are high enough, which is more common with injections, and after an orchiectomy there's nothing left to suppress. See estrogen alone.
Is spironolactone or cyproterone better?
Neither is simply better. Spironolactone is milder and needs potassium checks; cyproterone is stronger but carries a dose-related meningioma concern, so lower doses are now used. The choice is partly about where you live. See spironolactone and cyproterone acetate.
Is cyproterone safe?
It's still prescribed, at lower doses than it used to be, after European regulators linked long-term high-dose use to meningioma. Ask your prescriber whether your dose reflects current guidance. See cyproterone acetate.
Why is my testosterone high on bicalutamide?
Bicalutamide blocks testosterone from acting rather than lowering it, so the blood level can stay high. That's expected, and it's why monitoring on it looks different. See bicalutamide.