The different methods

There are different “methods” in feminizing HRT, or medication regimes, whith each their pros and cons. Here are the main ones.

Monotherapy

As we have described in the “Basic science” section, monotherapy consists in using only exogenous estradiol to reduce the levels of testosterone to target levels, thanks to the negative feedback mechanism.

In other words, you take enough estradiol which does the two things you want: reduce your testosterone, increase your estradiol. Simple enough. Where’s the catch? There is not really any.

Pros:

• Very easy to put in place - take enough estradiol until testosterone crashes down.
• Avoid taking androgen blockers with their lot of side effects
• Higher doses of estradiol usually means better mental health and libido.
• If you are paying for your medication - it can be a cheap option. Both gel and injections are usually cheap.

Cons:

• You have to make sure that you keep your estradiol levels high enough. The threshold to activate the negative feedback is different for each person, but is usually situated around 200 pg/ml.
• Not compatible with all routes of administration, especially oral and patches. Injections are ideal but unavailable through the regular market in many countries, including Sweden. Possible with gel depending on skin receptivity, and using higher doses and/or scrotal method.

Estradiol + progesterone

This could be considered a variation of monotherapy, since the main principle remains the same: using estrogens to naturally reduce testosterone through negative feedback. Adding progesterone can act as a minor complement in case estrogens themselves are not high enough to start negative feedback.

The use of progesterone for feminization, however, is still debated, and its role remains unclear. There are a few things to know in case you decide to take it:

• As we said, it has a small anti-androgen power for AMAB (by negative feedback), but you should not count on it as the only way to efficiently bring down your T. It can be interesting in combination with a relatively high dose of estradiol - as a complement to monotherapy.
• Its role on breast growth is still unclear. Some say it helps from the beginning, but much research suggests it can also limit or block breast growth if taken too soon. The main recommendation is to start after reaching stage 3 of Tanner scale (approx. 2 years of HRT).
• Using oral route (swallowing) results in no effects whatsoever, since the liver first pass will convert and eliminate nearly all of the progesterone. The new converted molecule can cause somnolence and other mood effects, which are actually appreciated by some people. So if you want those effects, you can eat the pill, but it will have, for sure, no effects on breast development and/or testosterone blocking. Otherwise, the best way to reach useful levels is rectal administration, if you get those soft pills. Put one (100mg to 200mg) up your butt before going to sleep.
• In any case, always use bioidentical progesterone, and not synthetic progestogens.

Estradiol + blockers

This consists in using an androgen blocker (blocking either production or reception), in complement to estrogens. There are many androgen blockers, each with different effects and risks. We’ll come back in the next section to all of them in detail. Cyproterone acetate (sold under the name Androcur in many countries) is one of them, even though technically, it is a synthetic progestogen, meaning that its action relies on negative feedback, like monotherapy. Unlike bioidentical progesterone, its antiandrogenic power is extremely strong. However, it doesn’t make it a safe blocker since, unlike bioidentical progesterone, it comes with a bunch of frequent and significant health risks that are common to synthetic progestogens.

Pros:

• You can independently adjust your levels of T and E. (Does not apply to receptor blockers)
• It is the only way to block testosterone if monotherapy doesn’t work for you (insensitivity to gel, or you can’t take high dosage of estrogens…).

Cons:

• You have to make sure that your are not underdosed in estrogens, since being deficient in both sex hormones at the same time can be dangerous (physically and mentally - mainly risks of osteoporosis and depression) NOTE THAT ANDROGEN BLOCKER SHOULD NEVER BE TAKEN ALONE.
• Lots of androgen blockers are known to have annoying if not dangerous side effects. It is the case of Androcur, widely used in Europe.

Dr. Will Power’s method

The main difference is that Power’s research and experience seem to show that putting estrone (E1) into the equation is important. His idea is to start with higher estrone levels for around 6 months by using oral estradiol pills. As we’ve said before, if simply swallowed, most of the estradiol of these pills is converted to estrone. Power claims that this is closer to the hormonal balance evolution in ciswomen puberty, and that initial exposure to estrone helps increase the amount of estrogen receptors. The idea is to prepare the ground for estradiol, which comes after the first 6 months, by maximizing the reception capacities. Introduction of estradiol (E2) after the 6 months of dominantly estrone therapy is realized at high, monotherapy-like dosage (usually injections, sometimes gel). As we said, blockers are sometimes used to complement, as well as progesterone after reaching Tanner stage 3 (around 2 years of HRT).

This initial estrone treatment is what differentiates his method, and also what makes it controversial among healthcare practitioners and the trans community. Indeed, estrone exposure is associated with higher and more frequent risks than estradiol, and Power’s claims of its interest for optimizing the reception of estradiol is still to be proven. Scientifically speaking, Dr Will Power’s method is still considered theory.