The post only covers treatment with medication, which might receive as part of a gender affirming medical care (GAMC) package, alongside therapy and potentially surgery.
I have only dealt with people who have testes, because medication regimes for people with ovaries are simpler. Yes, I know, the title of this 'how to' is awkward, but it is accurate.
DO NOT use this guide to self medicate – it is only here to allow you to understand medication you receive as part of a GAMC package. I have deliberately left out dosing guidelines so nobody is tempted to start.
I have not dealt with herbal remedies because they are not evidenced.
Once you have read this, you should be better informed about what medication you are likely to find yourself on, and if you are already on medication, why you are on it.
Be aware that some specialists can become very attached to specific medications because they're familiar with them, have had good results with them, or have been inspired by presentations, or whatever. However, the medication isn't going inside them, it's going inside you! So if you are offered a medication which strikes you as unusual, explore why your specialist is offering it. Or ask around here.
Most people will be started on two different classes of medication which work together to achieve the same goal.
First group
This medication will be chosen from one of two classes, both of which act to drop levels of testosterone. If your GAMC includes an orchiectomy (orchidectomy in the UK) then after the surgery your need for drugs from this group will change.
The aim here is to get your testosterone (T) down, a secondary benefit being to reduce the amount of estrogen - oestrogen in the UK - needed. The medication you take from this class will be one from either:
1. Cyproterone acetate – an antiandrogen commonly used in Europe excluding UK, not available in US.
Or...Spironolactone, or perhaps bicalutamide – two antiandrogens commonly used in the US.
2. A gonadotropin releasing hormone agonist (GnRHA) – the use of these is most common in UK.
Second group
You will be given a female sex hormone:
1. Estrogen for sure.
2. It is possible you might also be given a progestogen, sometimes called P4, but evidence is lacking for the efficacy of these hormones in transgender women and use is mainly in the US. Clinical trials are very much needed.
About Antiandrogens
Cyproterone is an anti-androgen and - as with all drugs in this class - is used to suppress testosterone production. In the UK its only indications are for hypersexuality and sexual deviation in men, and it is not prescribable in the US as far as I am aware. Cyproterone's side effects include raised prolactin levels and a form of brain tumour known as meningioma. It is not clear what the long term significance of raised prolactin levels is if they happen with this medication, but the increase is greater than with spironolactone.
If you develop symptoms like production of breast milk or visual field changes, your prolactin levels need to be measured and your pituitary gland scanned. In fact, if you have ever been on an antiandrogen, a prolactin check and scan are worth querying if you experience visual field loss.
Bicalutamide is another antiandrogen, originally developed as a treatment for hormonally dependent prostate cancers. In common with other antiandrogens, breast growth is a useful side-effect but it can cause serious issues in people who have blood clotting disorders, liver disease or diabetes.
Spironolactone was developed as a potassium-sparing diuretic but subsequently found to have antiandrogen effects. No surprises, its side-effects include raised potassium (so you'll need regular blood tests for that, but you're getting those anyway), more frequent trips to the bathroom and slightly lowered blood pressure (maybe faints and dizzy spells).
Spironolactone also raises prolactin, though not as much as cyproterone. The long term implications of this aren't clear and may not be important, but if you develop visual changes or start producing milk, a prolactin level test and a pituitary scan are next up for you.
If you are worrying about potential risks of spironolactone being stopped suddenly, it is a relatively frequent event in other areas of medicine, because when spiro causes high potassium levels, there is no choice but to stop or cut the dose.
About GnRHAs
GnRHAs work by desensitising the sensors for gonadotropin releasing hormone and were originally developed for the treatment of hormone dependent prostate cancers. They mess up the body's ability to make testosterone, acting at the pituitary level.
GnRHAs are very efficient at dropping testosterone, but a potential side-effect is thinning of your bones, unless the dose of estrogen is sufficient to balance this out. Fortunately a sufficient estrogen level can normally be achieved using doses of hormone replacement therapy licensed – and hence researched – in post-menopausal cis women.
In common with other medications listed in this short guide, the use of GnRHAs for transgender care is off-label, because they were not originally tested and licensed for this use, but research is on-going (this is the one thing we can thank the Cass report for.)
The advantage of using GnRHAs in parallel with estrogen is that without them, the dose of estrogen would need to be much higher, increasing the risk of side-effects such as deep venous thrombosis.
About estrogen
As I hope everyone reading this knows, this is the female equivalent of testosterone and it is usually given in formulations which were developed for estrogen only hormone replacement therapy in cis women. Estrogens may be prescribed in oral form, as patches, or implanted pellets and the one serious adverse effect to watch for is deep venous thrombosis (DVT). A DVT is bad enough, but if they embolise, you can stroke out.
Other than that, side effects are relatively few compared to the benefits, although patches can cause skin irritation. An advantage of patches is most are left on for several days, while pellets usually last six months. On the other hand, a snag with patches is absorption can vary from one individual to the next and it can be much better when they are on some areas of skin than others.
Working to find a prep that works for you and which you tolerate well is worth the effort, because you will be on estrogen for a long time.
About progestogens
See above. In the situation this 'how to' applies to, most of the benefits of using progestogens remain theoretical because there isn't much data available about how well, or even if they work, or what their adverse effects might be.
What will happen to me on treatment?
Changes in your body can take months to begin and years to complete. This is no different to the response of a girl's body to the onset of puberty. Most find a noticeable reduction in body hair, redistribution of fat to the pelvic area, skin changes – it gets softer – and of course, breast growth. Your areolas will become larger, basically through stretching, as your breasts enlarge, but the cup size you will end up with is more influenced by your genes than the treatment regime.
You will be unlikely to experience much reduction in facial hair or changes to the carrying angle of your hips or widening of your bony pelvis. Voice changes are unlikely either, but can be addressed with voice training. Your testes will shrink some but that may not be noticeable.
What is 'off-label' prescribing?
All of these drugs were developed for uses other than GAMC, which means the treatment benefits for you are not ones the drugs were licensed for – this is known as 'off label' prescribing. In some cases, the benefits for people going through GAMC are caused by what were once regarded as annoying side-effects of the drugs.
In other cases, notably antiandrogens, continued use of the class has more to do with historic patterns of care than modern therapeutics, but you can make a strong argument in favour too - there is more data available about drugs in this class than there is about the newer GnRHAs, for example. Ultimately, if antiandrogens don't work or you experience side-effects, GnRHAs are an alternative.
Is off label use of drugs bad?
Most often the answer is no. Off-label means, 'prescribed for a purpose not within the licensed uses for the medication listed on the data sheet.'
This sounds scary, but if doctors were not allowed to prescribe off label, many commonly used and beneficial medicines would have to be withdrawn with potentially disastrous results. If you want an example, until comparatively recent times, many medicines routinely used in paediatric care had never been licensed for use in children.
Such medication was and is used because the dosing regimes are thought to be safe thanks to trial and error. That does not rule out retrospective research picking up on adverse effects nobody spotted. It has happened and will continue to happen.
If you look at a medication like spironolactone, it was released in 1959 and has been used in millions of people worldwide for its 'on label' indications. It was through on label use that its 'feminising' effects on men became known. After the mechanism for that was worked out, spironolactone has been found useful for everything from treating unwanted hair growth in women to polycystic ovary syndrome. In a different galaxy, spironolactone might have been licensed as an antiandrogen, in which case it would probably carry a warning, 'Just watch out for their potassium, okay?'
GnRHAs are newer, so we know less about their long term side effects, but they've been around long enough to be reasonably sure of their efficacy in adults.
Can off-label use of drugs be harmful?
Yes. In some cases, it can be.
As happens in any pioneering area of medicine – and GAMC is one – every new treatment comes complete with champions who emphasise its advantages, and foes who point to the disadvantages and make the sign of the evil eye whenever the indication is mentioned.
Do not ever forget you are the one taking the treatment and so it pays to ask lots of questions and read the research before you take the risk.
With most of the medications listed here, the risk is small compared to the potential benefits, but sometimes, as in the case of progestogens, we can't quantify either the benefits or the risks without research in people who are transitioning. So it could be in a decade or two we'll be wondering why we were so cautious of progestogens, or we could be wondering why we were mad enough to try them. We do not know.
It goes without saying all these medications have powerful effects, so need to be taken under the care of properly accredited physicians. There aren't many transgender people and these are still pioneering days, so any feedback you can give about possible side-effects and benefits will help research projects and improve the experience of future generations.
