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 transgender or non-binary patents for gender affirmation. Certain hormones and medications can help feminize or masculinize even someone who has gone through an undesirable puberty.

This website is intended to be a resource for AMAB transgender individuals seeking feminization.

What can HRT do for me?

For AMAB transgender individuals who desire female secondary sex characteristics, estradiol hormone therapy is the most common practice: Lowering one's testosterone level and raising one's estradiol (AKA E2, the most biologically active estrogen) levels, targeting that of an average cisgender woman. Transfeminine HRT can also involve many other medications, such as progestogens or antiandrogens. The end result is the feminization of the body. You will see changes such as healthier skin, female fat redistribution throughout your 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 oil	Reversible	1-2 months	1-1.5 years
Skin softening	Reversible	1-2 months	1-2 years
Decreased libido	Reversible	days-weeks	weeks-months
Decreased 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, only laser/electrolysis can stop it entirely.

***: Transfeminine 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 with transfem HRT is to bring your hormone levels, most notably for feminization being estradiol and testosterone, 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, progestogens, antiandrogens and other niche or specific medications such as hair loss treatments or 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 level a premenopausal female would be:

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 try and 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.

Estradiol-only HRT, also known as monotherapy, where estradiol provides both feminization and is dosed high enough to suppress testosterone into female ranges, is both possible and common. Monotherapy removes or reduces certain potential risks and side effects that one might see if they were on an antiandrogen, along with their estradiol dosage, 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 ROI suitable for monotherapy. It's rare for someone to be unable to achieve proper levels through injections. There are several common esters used for injectable estradiol. These include Valerate, Cypionate, Enanthate, and the much less common but still worth mentioning Undecylate.

Dosages may be inconsistent on injections and vary wildly from person to person, though there is a reasonable 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 immediately before a new dosage at the "trough" after a few weeks.

The most significant difference between the esters is their stability or 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 its peak comes later than cypionate, so it's 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. Likely, 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's possible to extend the time between your dosages from every five days with valerate up to every seven and even every other week with cypionate or valerate (though that might be pushing it, ten days is a much safer bet).

This lovely simulator can be helpful if you are trying to extend your dosage. It averages the estradiol level of many people on injections into a graph based on several studies, but remember, it can be highly inaccurate. It shouldn't be used alone to find a dosage. I was on a prescription dosage of 8mg estradiol valerate, with my trough (lowest level, right before the next injection) was over 650 pg/ml; its estimate is just below 200 pg/ml.

No Access to Bloodwork

We cover how to get blood tests even without a doctor or prescription HRT here, but if you cannot get bloodwork, all you can do is take a reasonable dosage and hope it works. Some things to look out for to try and 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 it can be very hard or impossible to get proper levels without an antiandrogen. Common antiandrogens for transfem HRT are cyproterone acetate, spironolactone, or 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 slows or stops the growth of cancerous cells. This is perfect for HRT because it prevents the effects of testosterone. It is commonly dosed in 25-50mg/day. Keep in mind when taking bicalutamide that it doesn't block testosterone production; blood levels may significantly increase. It prevents testosterone from attaching to its receptors, so while you still have it in your blood, on a proper dosage, you will not have any androgenic side 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. Cyproterone acetate reduces testosterone levels very efficiently, even without estrogens. Cypro is most effective in daily doses of 10mg, though most take 12.5mg because they split one 50mg pill five times.

Spironolactone is one of the most common antiandrogens used in transfeminine hormone therapy. It is also a diuretic, so it may make you pee more often. Spiro helps your body retain potassium, so you should be mindful when having foods with a lot of it. Spironolactone is a weaker antiandrogen compared to the two above but is safe and commonly prescribed in the US. Typically dosed at 100-200mg daily.

Oral or Sublingual Estradiol

If you cannot handle or source injections, oral estradiol is another option. Usually taken with an antiandrogen in the section above, there are two most common forms of estradiol in pills: ethinyl estradiol and estradiol valerate. They are both very similar, though there are minor differences in 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. Both get the job done.

You can take oral estradiol two ways: Swallow or sublingually. Sublingual absorption of estradiol is relatively new but very promising. Sublingual dosing achieves much higher levels and avoids passing through the liver, which is safer and reduces the risk of blood clots, though it may require more frequent dosing, leaving your system much faster.

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 ROI for transfem HRT. It's 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 may also be used if testosterone can't 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 be within cis ranges or block testosterone, with a typical dosage being 100-400mcg per day. Patches must be changed weekly or twice weekly.

Progesterone and 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.