Transfeminine Guide: Risks

Side Effects/risks:

All recommended tests mentioned in this section can be tested from blood samples taken during a regular blood test. You don’t have to get fancy expensive tests.

Hormone therapy in general is very safe and effective as long as you take a reasonable dose.

Estradiol

All forms of estrogen will increase your risk of blood clots forming in blood vessels (thrombosis), including serious conditions relating to thrombosis (e.g. deep vein thrombosis, pulmonary embolism). The likelihood of this is still very low in absolute risk but it is present. The risk of getting blood clots on HRT is essentially comparable to that of cis women if you take a modest HRT regimen.

Higher levels of estradiol means higher blood clot risk.

Assuming identical blood estradiol levels, oral estradiol carries a higher risk of blood clots compared to other administration methods. This is because oral estradiol is processed by the liver, which increases the production of clotting factors and, consequently, the risk of thrombosis.

However, since other methods such as transdermal or injectable estradiol typically produce higher blood estradiol levels, the specific risks associated with oral estradiol are generally not relevant in practice.

To clarify, this means that the higher blood estradiol levels produced by, for example, injectable estradiol, will generally lead to a blood clot risk comparable what would be seen with standard oral estradiol regimens.

Spironolactone:

The main reason spironolactone is not recommended is because spiro is a very weak antiandrogen. There are just better options out there.

It’s very safe, but common side effects include increased thirst, salt cravings and frequent urination due to it being a diuretic (makes your body get rid of water faster).

Spiro is also known to reduce blood pressure, which can make it hard for some people to attain erections.

Ideally you should get U&E (urea and electrolytes) tested for (basically see if you’re dehydrated) if you are on spiro.

If you are predisposed to developing hyperkalemia (elevated potassium levels), you should also get your potassium levels tested regularly if you take spironolactone, as spiro can cause your body to retain more potassium. For the vast majority of people though, hyperkalemia is not a relevant concern.

Cyproterone acetate:

Extremely high doses of cyproterone, mostly found above 50mg/day and 100mg/day can increase risks of a myriad of different harsh side effects, mainly increased risk of prolactinomas and meningiomas (small benign brain tumors).

At dosages relevant to transfeminine people (6.25-12.5mg/day) the risk profile is much different. The same risks are still present but much lower at smaller doses.

Cyproterone is also known to slightly increase blood clot risk, although the increase in risk is quite low at dosages used in trans people.

Cypro may increase the risk of B12 deficiency and slightly increase depression risk. Despite the relative safety at these doses, ideally you should still get prolactin (PRL) and B12 tested to make sure it’s within a healthy range. These risks are cumulative (risks gradually get higher the longer you stay on cyproterone).

Bicalutamide:

Bicalutamide tends to preserve libido and sexual function better than other anti androgens. Some people may see this as an unwanted effect.

The main risk of bicalutamide is severe liver toxicity and lung toxicity. The chances of either happening are about 1/4000 in cis male prostate cancer patients. All published case reports of either severe liver or lung toxicity have been in cis men over 59 years of age. Risk of liver toxicity can be monitored if you get regular liver function tests (done by analyzing blood from a regular blood test sample).

It’s strongly recommended to get liver function tests within the first week of starting bicalutamide, 1 month after starting bicalutamide, and then every 3 months until the 1 year mark.

After a year of normal liver function tests, you can stop taking them. The risks of bicalutamide after a period of time with no side effects are known to not be cumulative (you can confidently assume that your risk of lung/liver toxicity will not increase over time if it’s already been a period of time without symptoms). The risk of both lung and liver toxicity is essentially zero after a year without issues.

Out of the millions of men who have taken bicalutamide for prostate cancer treatment, there have been a few reported cases where bicalutamide induced a severe light sensitivity condition. Again, the risk for this does not seem to be cumulative after a period of time with no symptoms.

Despite these possible side effects, the absolute risk of any severe outcomes occurring on bicalutamide is extremely low. With the added benefit that bica has essentially no common side effects like spiro or cypro.

GNRH Agonists/Antagonists:

If you have already gone through an AMAB/testosterone puberty, you will experience a temporary flareup of testosterone when you start taking a GNRH agonist for the first time. If you want to avoid this temporary T flare up, you can take cyproterone or bicalutamide for the first 3 weeks of use. You can also double the recommended dose of buserelin during the first week (see the buserelin section under Dosing).

GNRH antagoninsts (a medication class that is very similar to GNRH agonists) like Relugolix do not have a testosterone flareup effect like GNRH agonists have. This class of medication has no unique side effects.

More information on blood testing will be found later in this guide in the Blood Testing section.