Intro to HRT

Hormone replacement therapy, or HRT, is a relatively common medical treatment used in many contexts. Despite what many may think, this is not a new or experimental practice, nor is it exclusive to transgender individuals. Hormone replacement therapy has been used for over half a century, starting its use in the 1960s and is widely popular in treating menopause in AFAB (assigned female at birth) patients.

In this page, we will cover how HRT can be used in AMAB (assigned male at birth) patients for gender affirmation, a type of HRT known as feminizing HRT. Feminizing HRT can have profound effects even on patients who are post-puberty, and has the potential to significantly improve quality of life for transfeminine individuals.

What can HRT do for me?

Feminizing HRT seeks to lower a patient's testosterone level and raise their estradiol (AKA E2, the most biologically active estrogen) level, targeting levels similar to those of an average cisgender woman. Feminizing HRT can also involve many other medications, such as antiandrogens or progestogens. The end result is overall feminization of the body and its secondary sex characteristics. Changes may include healthier skin, female fat redistribution throughout the body, and breast growth.

Below is a chart outlining most of the common changes from HRT:

Effect	Permanence	Expected Onset	Maximum effect
Body fat redistribution	Reversible	1-2 months	2-5 years
Decreased muscle mass	Reversible	1-2 months	1-1.5 years
Decreased skin oiliness	Reversible	1-2 months	1-1.5 years
Skin softening	Reversible	1-2 months	1-2 years
Decreased libido	Reversible	days-weeks	weeks-months
Less or no random erections	Reversible	days-weeks	weeks-months
Erectile dysfunction*	Reversible	days-weeks	weeks-months
Breast development	Irreversible	2-6 weeks	2-6 years
Decreased testicular volume	Variable	1-3 months	2-3 years
Decreased sperm production	Variable	2-6 weeks	1-3 years
Decreased semen volume	Veriable	2-6 weeks	1-3 years
Slowing of body & facial hair growth**	Reversible	1-3 months	6 months-1 year
Voice changes***	N/A	none	none
Reversal of male pattern hair loss****	Reversible	1-3 months	1-2 years

*: Most individuals do not experience erectile dysfunction.

**: HRT will slow down body and facial hair growth, but only laser or electrolysis can stop it entirely.

***: Feminizing HRT does not cause an effect on an individual's vocal folds.

****: Male pattern hair loss can be prevented with HRT, but reversal of hair loss is rare.

So, what should I take, and how much?

Again, the goal of feminizing HRT is to bring your hormone levels (estradiol and testosterone in particular) from your current male range to that of a healthy cisgender woman. On top of this, there are some medications and other hormones we will cover, such as antiandrogens, progestogens, and other niche or specific medications, including hair loss treatments and more experimental methods for feminization.

Before we talk about specific medications, you need to have a basic understanding of the target hormone levels. For feminization to be effective, you should be within the levels of a premenopausal female:

100-200 pg/ml estradiol & <50 ng/dl testosterone.

Blood tests are the only effective way to measure these levels and are extremely important in minimizing the risks of HRT and maximizing its effectiveness. We will talk about how to manage being in a situation where you cannot access bloodwork. This is not impossible, but we highly recommend against it.

Now, onto the fun stuff: what to take, and how to dose it.

Injection monotherapy

The big one. Estradiol is the most biologically active estrogen and heavily contributes to feminization. On top of this, it contributes to the suppression of testosterone.

In estradiol-only HRT, also known as monotherapy, estradiol alone provides both feminization and suppression of testosterone into female ranges. This is possible because of estradiol's suppressing effect on testosterone by itself at high enough levels. Monotherapy removes or reduces certain potential risks and side effects that may be caused by antiandrogens used to help with testosterone suppression, but usually requires more estradiol and is much harder to achieve with specific routes of administration such as oral or transdermal.

Injections are an excellent example of an ROA suitable for monotherapy. It is rare for someone to be unable to achieve proper levels through injections. There are several common esters (chemical variations) used for injectable estradiol. These include valerate, cypionate, enanthate, and less commonly, undecylate.

Effective dosages vary wildly from person to person, though there is a reasonable range of starting dosage. If you have access to bloodwork, finding your dosage should be simple. Start with a sane dosage that works for most people, which we are about to cover now, and get a blood test just before the next injection at the "trough", or lowest level in your cycle, after a few weeks.

The most significant difference between the esters is their stability, or biological half-life. Estradiol valerate has a half-life of 4-5 days, cypionate 8-10 days, and enanthate 5-7 days. However, research suggests that enanthate's peak comes later than cypionate, so it is generally best to treat them the same. Valerate is the most common pharma-grade ester in the US due to the cypionate shortage. Enanthate is the most common ester found in homebrew due to its incredible stability, and is prescribed in some countries.

This graph shows reasonable starting monotherapy injection dosages. It is possible that you may not need to adjust your regimen past this.

Ester	Elimination Half life	Starting dosage	Maximum time in between injections
Valerate	4-5 days	3.5mg/5 days	7 days
Cypionate	8-10 days	4mg/7 days	14 days
Enanthate	5-7 days*	4mg/7 days	14 days

These dosages must be adjusted based on bloodwork. It is possible to extend the time between your dosages from every 5 days with valerate up to every 7 or even every 2 weeks with cypionate or enanthate (however 10 days is a much safer bet).

This lovely simulator can be helpful if you are trying to approximate your dosage. It averages the estradiol level of many people on injections into a graph based on several studies, but it is important to remember that it can be highly inaccurate on an individual basis and should not be used as a replacement for bloodwork. I was on a prescription dosage of 8mg estradiol valerate, with my trough (right before the next injection) over 650 pg/ml; the simulator's estimate is just below 200 pg/ml.

No access to bloodwork

Dosing your HRT without bloodwork may be unsafe and could lead to complications; it is highly recommended that you get bloodwork if at all possible. We cover how to get blood tests even without a doctor or prescription HRT here, but if you absolutely cannot get bloodwork, all you can do is take a reasonable dosage and hope it works. Some things to look out for to guess if your dosage is working are breast growth, nipple sensitivity (sensitivity is rarely constant and can go away for long periods), and general changes HRT is supposed to have on a person.

How to do an injection

Injecting medication is a relatively straightforward process but easy to screw up. Learn how to do a proper injection here.

Antiandrogens AKA testosterone blockers

Antiandrogens are medications that counteract the effects of androgens—male sex hormones such as testosterone or DHT. High-dose estradiol is an effective antiandrogen, but for some patients it may be very hard or impossible to get proper levels without an antiandrogen. Common antiandrogens for feminizing HRT are cyproterone acetate, spironolactone, and bicalutamide. These medications all work in different ways to suppress androgens.

Bicalutamide is an antiandrogen also used to treat prostate cancer by blocking the effects of testosterone, which in turn slows or stops the growth of cancerous cells. This testosterone blocking effect is desirable in feminizing HRT, and as such, bicalutamide is a common choice of antiandrogen. It is commonly dosed at 25-50mg/day. Keep in mind when taking bicalutamide that it does not block testosterone production; testosterone blood levels may significantly increase. Instead, it prevents testosterone from attaching to its receptors. Although you still have it in your blood, on a proper dosage you will not experience any androgenic effects.

Cyproterone acetate is a progestin with androgenic and progestogenic effects. Like bicalutamide, it is used in treating prostate cancer. It is not approved for use in the US but is a standard option in many other countries. Even without estrogens, cyproterone acetate reduces testosterone levels very efficiently. Cyproterone acetate is most effective in daily doses of 10mg, though most patients take 12.5mg because they split one 50mg pill into 4 pieces.

Spironolactone is one of the most common antiandrogens used in feminizing HRT. It is also a diuretic, and as a result may cause you to urinate more often. Spironolactone helps your body retain potassium, so you should be mindful when consuming potassium-rich foods while taking it. Spironolactone is a weaker antiandrogen compared to the two above, but is relatively safe and commonly prescribed in the US. It is typically dosed at 100-200mg daily.

Finasteride is an antiandrogen used in treating prostate inflammation and male pattern hair loss. It inhibits the conversion of testosterone into its more potent form, DHT (dihydrotestosterone). Finasteride does not lower testosterone significantly and should not be used as a replacement for the antiandrogens above, although it is an effective treatment for hair loss.

Before taking any antiandrogen, it is important to understand the safety profile and possible side effects. Be sure to monitor yourself for side effects when starting a new medication, and consult your doctor if you experience any serious issues.

Oral or sublingual estradiol

If you cannot handle performing injections, or are unable to source injectable estradiol, oral or sublingual estradiol tablets are another option. Usually taken with an antiandrogen, estradiol tablets are commonly composed of one of two common forms of estradiol: ethinyl estradiol or estradiol valerate. They are both very similar, with only minor differences in their half-lives. Ethinyl estradiol has a slightly longer half-life, and 1mg of estradiol valerate orally equals 0.76mg of ethinyl estradiol. Overall, you don't have to be super picky, and either one is likely to be just as effective.

While oral estradiol is administered simply by swallowing the tablet, sublingual ROA for estradiol is administered by placing the tablet under the tongue, where it is absorbed through the dense blood vessels found in the connective tissue. Relatively new but very promising, sublingual dosing achieves much higher levels when compared to oral dosing, and avoids passing through the liver, which is safer and reduces the risk of blood clots. However, it generally requires more frequent dosing, as it has a much shorter half-life.

This graph shows the dosage and frequency of oral estradiol.

Route of Administration	Low/Initial Dosage	Maximum Dosage	Frequency
Oral	2-4mg/day	6-8mg/day	1-2x daily
Sublingual	1-2mg/day	4-6mg/day	2-3x daily

The dosages above should be divided throughout the day according to the frequency, not multiplied.

Transdermal estradiol

Transdermal estradiol is another ROA for feminizing HRT. It is one of the safest methods, prescribed especially in older patients or those with risk factors such as tobacco use. Typically, a patch or gel is applied to the skin, but less commonly, a spray form of estradiol can be used. A common downside of transdermal estradiol is that many find it hard or infeasible to achieve cisgender hormone levels; antiandrogens are often used in conjunction if testosterone cannot be suppressed by the estradiol alone.

Patches can come in dosages up to 100mcg released per day; often, it takes wearing multiple 100mcg patches at a time to remain within target ranges or effectively block testosterone, with a typical dosage being 100-400mcg per day. Patches must be changed weekly or twice weekly.

Progesterone

The effects of progesterone in transgender women is very controversial. Some say, that there are no effects at all, while others believe that there are improvements in permanent fat distribution. There are many articles & studies about this topic, and we will not teach one specifically. You can go check the progesterone page for more information on individual theories.

The TLDR is: it is known that progesterone has anti-depressant effects, and allows water weight to move to more feminine areas. Due to a lack of studies, we cannot definitively say any more information.

Experimental HRT

There are a few somewhat common medications—pioglitazone or estrone, for example—that some people claim help with feminization. This section will probably take a while to write and research. For now, it is empty.