HRT: A Transfem's Guide
I should preface this essay by saying: I am not a doctor. I am not a licensed medical professional of any kind. I initially sat down to write this because (1) other trans people ask me a lot of questions about hormones, and I felt I ought to put them all in one place, (2) I want to contribute to the democratization of the medical knowledge that is central to the lives of everyone—trans or cis—who is undergoing feminizing hormone replacement therapy, (3) I’ve seen a lot of trans people get stuck in very bad situations for a very long time due to an inequality of information and authority between themselves and their doctors, (4) with the United States having seen a steady increase in trans eliminationist policies for several years, knowing how to transition DIY is now the most important it’s been this century.
This is but one HRT guide in a sea of HRT guides, some good and some bad. There are a lot of very comprehensive and detailed guides out there (and thank you for your service!), so I wanted to write something a little more manageable and straight to the point. I only cover routes and medications that are commonly used by people I know, whether in person or over the internet. I cover topics that I tend to be asked about, that I see people misunderstanding, or that otherwise seem vital. Use multiple guides! I don’t know everything, and I am very busy with my PhD and cannot always update this page with new findings. Here are some people I trust and tend to agree with:
I want this page to become a living document. Please do not hesitate to reach out with questions or if you have objections to anything I have said here. Let’s be in conversation. As I learn more I will continue to update this essay, but as it stands now I think it serves as a handy overview of the basics. Edits made following publication will be reflected in the changelog down below.
The Big Three
Introduction to sex hormones
Estrogen, progesterone, and testosterone. These are the three hormones central to the trans woman’s experience. Despite some popular misconceptions, each of these hormones are present in all bodies, only in varying proportions. Yes, cis women have testosterone, and no, progesterone is not only “the pregnancy hormone.”
Adult cis men, for example, have testosterone levels roughly between 350-1200 ng/dL, estradiol1 levels between 8-35 pg/mL, and progesterone levels below 0.1 ng/mL.2
Because of menopause and the menstrual cycle, the picture is more complicated for adult cis women. During the follicular phase, or the first half of the cycle, estrogen levels are typically between 30-100 pg/mL. This then spikes to around 1000 pg/mL during ovulation, before dropping to between 70-300 pg/mL in the luteal phase, or the latter half of the cycle. Progesterone follows a less complicated trajectory, with typical levels of 0.1-1.5 ng/mL in the follicular phase and 15-25 ng/mL in the luteal phase.
Before menopause, cis women commonly have testosterone levels between 10-55 ng/dL. After menopause, this drops to between 7-40 ng/dL, while estradiol levels typically plunge to below 15 pg/mL and progesterone levels below 0.1 ng/mL.
What levels should I aim for?
The World Professional Association for Transgender Health (WPATH) recommends that trans women keep their estradiol levels between 100-200 pg/mL, comfortably within the luteal range, but they do not cite a rationale for this guideline. Many doctors caution against levels greater than 200 pg/mL based on real but overblown and largely outdated concerns about the relationship between estrogen and blood clots (more on this later).
While elevated estrogen levels are important for transfeminine hormone therapy (estrogen gives your body something to work with), higher estradiol levels have not been shown to be “more feminizing,” even if they can feminize you faster. What higher estradiol levels can accomplish, and what is significantly more important for feminization, is suppression of testosterone levels below about 55 ng/dL.3 This is usually accomplished through a combination of anti-androgens (testosterone blockers), estradiol, and progesterone. In short, whenever you take external (sometimes called exogenous) hormones, your body learns to produce less of its own. Your brain doesn’t care what hormones it has, it only cares how much.4 When a trans woman takes estradiol or progesterone, the body compensates by producing less testosterone. It is possible, then, with high enough estrogen and progesterone levels, to fully suppress your testosterone, even without using an anti-androgen.
A Note on Progesterone
You may have noticed that I have said very little about progesterone so far. This is because we know almost nothing for certain. Progesterone’s workings in trans women’s bodies have scarcely been studied aside from a single study in 1989.5 For a more candid description of what one Twitter user calls “the progesterone wars,” you can see this thread, but for the purposes of this article, it is just important to know that for one reason or another, doctors will not study what progesterone does for us.
However, the author of the 1989 study published a paper in 2019 which lists six discrete reasons that progesterone is likely to be beneficial for trans women, based on her decades of clinical experience and a review of the literature on progesterone in general. These reasons are as follows:
Progesterone reduces the conversion of testosterone into dihydrotestosterone (DHT), the hormone that masculinizes skin and hair follicles.
Progesterone slows the pulse rate of LH and lowers average LH levels, which leads to a decrease in gonadal testosterone production.
Progesterone is thought to be necessary for breast maturation and areola enlargement.
Progesterone promotes bone formation and can increase bone mass density.
Progesterone significantly improves deep sleep, decreases the time it takes to fall asleep, and decreases midsleep wakening.
Progesterone can lead to improved cardiovascular health and prevent against heart attacks.6
In my own experience, progesterone has dramatically lowered my testosterone, improved my breast development, and drastically aided my sleep. Some report changes in mood, anxiety, and libido, and anecdotally, adverse side effects can often be mitigated by changing your dose or using a different route of administration.
If you want my opinion: you should be taking progesterone.7
Routes of Administration
Estrogen and progesterone can be administered in various ways. The way you take these hormones determines the levels they will produce, how long they will stay in your system, and how often you need to take them, among other things.8
Estrogen
Everyone I know takes their estrogen via the oral, sublingual, or injectable routes. Each of these routes produces a different ratio of estradiol (E2) to estrone (E1), depending on how much estrogen is being metabolized by the liver.9 Estrone has weak feminizing effects compared to estradiol, and so it is a good idea to maintain a lower estrone/estradiol ratio, as a higher ratio can increase the health risks associated with estrogen with little feminization to show for it.10
Oral
Definition: Swallowing an estradiol tablet.
Levels: Lower than the sublingual and injectable routes, but more consistent.
Timing: Typically one dose per day.
Estrone/estradiol ratio: 9.28 (high, more risky).
Sublingual
Definition: Dissolving an estradiol tablet under your tongue.
Note: Most estradiol tablets made for oral use can be taken sublingually.
Levels: Considerably higher than the oral route, but dissipates much faster than the oral and injectable routes.
Timing: Two or more evenly-spaced doses per day are more effective at suppressing testosterone, owing to the “spikiness” of the sublingual route.
Estrone/estradiol ratio: 6.88 (medium-high).
Note: The sublingual route tends to result in higher estradiol levels than the oral route, meaning even though the estrone/estradiol ratio is lower, the total amount of estrone produced by each route may be about the same. Still, this means that for the same estradiol level, sublingual is safer than oral. In fact, it is likely that this number is inflated by the fact that you usually swallow some estradiol even when taking it sublingually. Try to do that as little as possible.
![Estradiol levels over a 24-hour period following a single 0.25, 0.5, or 1 mg dose of sublingual estradiol or a single 0.5 or 1 mg dose of oral estradiol in postmenopausal women.[1] Source: Price et al. (1997).[1]](https://substackcdn.com/image/fetch/$s_!yUB-!,f_auto,q_auto:good,fl_progressive:steep/https%3A%2F%2Fsubstack-post-media.s3.amazonaws.com%2Fpublic%2Fimages%2F6e5d2270-1b46-4894-a9f4-11b025732c19_300x274.png "Estradiol levels over a 24-hour period following a single 0.25, 0.5, or 1 mg dose of sublingual estradiol or a single 0.5 or 1 mg dose of oral estradiol in postmenopausal women.[1] Source: Price et al. (1997).[1]")
Injectable
Definition: Injecting a liquid estradiol ester into the muscle (intramuscular/IM), or just below the skin (subcutaneous/SubQ).
Note: IM and SubQ do not meaningfully differ in effectiveness.
Levels: Roughly the same as the sublingual route, but dissipate more slowly.
Timing: One dose every 4-7 days, depending on your levels and how you feel.
Estrone/estradiol ratio: 0.84 (low, less risky).
What do you recommend?
In general, injections are the gold standard, but they’re not for everyone! I currently take 4 mg sublingually, 2 in the morning and 2 at night, which has worked just fine. I typically advise against the oral route, but it is what many people start with.
Progesterone
I only know people taking their progesterone orally and rectally. Both routes can be accomplished with the same type of pill.
Oral
Definition: Swallowing a progesterone pill.
Levels: Lower than the rectal route and dissipates more quickly.
Timing: Once per day, ideally at night, as orally administered progesterone metabolizes into a few dozen other metabolites, some of which act as sedatives.
Rectal
Definition: Dissolving a progesterone pill in your rectum, as a suppository.
Levels: Higher than the oral route and dissipates more slowly.
Timing: Once a day, usually at night as you should try not to use the restroom within an hour of administration.
What do you recommend?
I know people who swallow, and I know people who boof. Personally, I swallow, as I like using progesterone as a sleep aid. It really is up to you and your goals, and if one way isn’t working, or is causing adverse effects, it’s super easy to switch!
What about blood clots?
The perennial question. Make no mistake: estrogen is procoagulatory (meaning, it has a clotting effect on the blood). This means that more estrogen equals more risk. With that said, the risk of blood clots is far more slim than your doctors may make it out to be, especially if you have an active lifestyle and don’t smoke.
The upper limit of the 100-200 pg/mL estradiol range prescribed by WPATH is, relatively speaking, still quite low. Recall that ovulation causes estrogen levels to spike to around 1000 pg/mL, and that estrogen levels during pregnancy are often well into the thousands. And yet, ovulating and pregnant women are not suffering from blood clots en masse. In addition, newer bioidentical (equivalent to what the body produces) estrogens are far safer than their predecessors.
A 2021 study found that blood clot incidence per 10,000 person-years was 42.8 for trans women, 34.8 for cis women, 11.1 for cis men, and 10.8 for trans men. When broken down by route of administration, the oral route had a higher incidence (34.0) than non-oral routes (11.2), and when broken down by type of estrogen, older formulations such as ethinyl estradiol and conjugated equine estrogens had a higher incidence (293.1 and 49.0, respectively) than bioidentical estrogens (31.5).11 Trans women’s cardiovascular risk is probably about equal to that of cis women, adjusting for lifestyle, so long as we are taking bioidentical estrogens via non-oral routes.
The truth is, the dolls have been saying this for years. As of June 2025, we finally have a study backing us up. The authors of a literature review in the journal LGBT Health found that, excluding studies that used non-bioidentical estrogens, there is no clinically documented association between estrogen levels outside the 100-200 pg/mL range and adverse health effects, including blood clots and cardiovascular disease.12
Let me put this simply, in no uncertain terms: the WPATH estradiol guideline range is not supported by the available evidence.
Anti-Androgens
The four main anti-androgens to know about are spironolactone, cyproterone acetate, bicalutamide, and finasteride. Unlike estrogen, anti-androgens are less of a sure science and there are downsides to each, meaning that there is no “gold standard” and treatment is more individualized. Another reason I recommend injections at high enough doses to fully suppress testosterone is to avoid having to deal with anti-androgens. However, if for whatever reason you don’t have access to injections, it may be useful to know the pros and cons to each anti-androgen. Each one has a cute little nickname, except for finasteride, because there’s no reason for us to be taking it.
Spironolactone
Spironolactone (cute nickname: spiro) is by far the most commonly prescribed anti-androgen in the United States. However, its effectiveness as a testosterone blocker for trans women is unclear.13 This is because while some anti-androgens reduce the total amount of testosterone in the blood, spiro largely leaves the amount of testosterone unchanged but prevents it from being used by the body.14 What this means is that with people taking spiro, blood tests are ineffective at determining how much testosterone is actually being used in the body, and so we have to resort to more qualitative markers such as facial and body hair growth.15 A 2024 study comparing user satisfaction of each anti-androgen found that trans women generally had more favorable experiences with cyproterone acetate than they did with spironolactone.16 In 2018, Aly at Transfeminine Science reviewed the existing data on spironolactone and found that, while spiro may be effective at preventing acne and facial hair growth in cis women, it is likely far less effective at promoting feminization in trans women.17 Recall that cis women tend to have far lower natural testosterone levels than trans women, and so spironolactone does not have to do as much work to suppress their testosterone.
While there are a variety of safety concerns about spiro, none of them are too severe. Spiro is a diuretic, meaning it can dehydrate you and make you have to pee more, but these effects vary from person to person. I notice some adverse side effects on 100 mg daily, but I am mostly fine. I know one girl who had to go from 100 mg to 50 mg after frequently losing her balance and nearly blacking out, and I know another girl who was completely unharmed by 300 mg daily. The most severe side effect of spironolactone is the risk of elevated potassium levels (hyperkalemia), but a recent study found that this risk was very low in people under 45 years old. The study authors recommend frequent potassium monitoring only for those older than 45 or those with other conditions such as hypertension, diabetes, renal disease, or heart failure.18 These risks aside, spiro appears to be safe for long-term use.
If you decide on using spironolactone, it may be beneficial to split the dose in half and take it twice a day, as it reaches peak effectiveness within the first two or three hours and then rapidly decreases, as can be seen in the chart below.
Cyproterone acetate
While cyproterone acetate (cypro) is likely a more effective anti-androgen than spironolactone and has also been used in trans medicine since the 1980s, it is not licensed for use in the United States. That said, for trans women in other parts of the world, it may be a better option than spiro. Cypro promotes feminization in two ways: it is similar to spiro in that it blocks existing testosterone from being used by the body, but it is also a progestogen, meaning it tells the body to produce less testosterone, as discussed above. When taken with estrogen, cyproterone acetate has been shown to fully suppress testosterone levels in trans women.
However, there are a number of safety concerns. For one, liver damage has been reported in patients treated with cypro, but this has only occurred at doses of at least 100 mg daily. Cypro use in trans women has also been associated with a four times higher incidence rate of meningiomas than in cis women not taking the drug, likely due to the presence of progesterone receptors in meningiomas. Both of these complications are associated with higher doses of cypro, and so research has been done to determine the lowest effective dose.
A 2021 study found that doses as low as 10 mg are just as effective as higher doses, with fewer associated health risks. While future research remains to be done on whether doses lower than 10 mg are still effective at suppressing testosterone, if you choose to use cyproterone acetate, I wouldn’t recommend any higher than 10 mg. Additionally, because cyproterone acetate is a progestogen, it is not necessary to take progesterone when on cypro.19
Bicalutamide
Bicalutamide (bica) is an anti-androgen typically used to treat prostate cancer, and it has only recently been considered for use with trans women. While bicalutamide is not recommended by the current standards of care, there has been increasing consideration of its use over the last few years, and so it warrants a discussion.
Bicalutamide works similarly to spironolactone and cyproterone acetate in that it prevents testosterone from being used by the body, but it is significantly stronger than the former medications. In fact, bicalutamide can even cause the body to overcorrect and produce more testosterone, even if this testosterone isn’t being metabolized, which means that as with spiro, it is difficult to assess its effectiveness by looking at the amount of testosterone in the blood. Still, trans women taking bicalutamide have reported a reduction in acne and facial hair growth.20
One notable effect of taking bicalutamide is the development of breasts even without taking estradiol. This likely happens for two reasons: bicalutamide reduces testosterone such that the ratio of estrogens to androgens causes the estrogens to take precedence, and by increasing the total testosterone in the body, some of that testosterone may be converted into estrogen through a process called aromatization.21
The primary safety risk with bicalutamide is liver damage, which is a rare but well-known phenomenon. While there has only been one official case report of liver damage in a transfem taking bicalutamide, this is an important risk to consider. The majority of liver damage cases with bicalutamide occur within the first three to four months of treatment, and so the FDA recommends that liver function is tested at regular intervals during the first four months of use. While severe liver damage and failure has been reported in prostate cancer patients taking bicalutamide, the risks may be lower in healthy trans youth taking a lower dosage.22
As shown by the chart below, bicalutamide levels increase steadily with dosage until about 300 mg, where they taper off. If you do choose to use bicalutamide, it may be wise to do so at a dose less than 300 mg.
Finasteride
Unlike the aforementioned anti-androgens, finasteride works by blocking the conversion of testosterone to the more potent dihydrotestosterone (DHT), which, as I mentioned above, is responsible for masculinizing skin and hair follicles.
While trans women are sometimes prescribed finasteride, it is unclear what benefit this has, especially considering that it has been shown to increase total testosterone levels. It makes more sense to focus on lowering testosterone itself so that less of it is available to be converted into DHT. As noted above, progesterone is also a DHT blocker. Additionally, a case report of a trans woman who saw a regrowth of scalp hair after six months of estradiol and spironolactone suggests that finasteride is not necessary to block DHT.23
Health Concerns
I’d like to conclude with a brief overview of some general health considerations when undergoing feminizing hormone therapy.
Cancer risk
Unsurprisingly, trans women’s breast cancer risk is higher than that of cis men, while comparable to or lower than that of cis women. However, when breast cancer does occur in trans women, it is often at a younger age than it is usually seen in cis women, and after a relatively short duration of HRT, though this may the effect of orally-administered non-bioidentical estrogens.
The risk of prostate cancer in trans women appears to be lower than in cis men, which may be due to lower levels of testosterone. However, many of the reported cases of prostate cancer in trans women had metastases at time of diagnoses. This could reflect a more aggressive form of prostate cancer in trans women, but it could also be a product of a delay in diagnosis due to improper screening techniques.24
A study published in 2020 by Sutherland et al. discusses and proposes ideas for medical care and cancer risk assessment of trans and nonbinary youth. They note that one’s experience of gender is prone to change over time, which makes it difficult to standardize when and how cancer risk assessment should be implemented. They say that cancer risk assessment and genetic testing may be medically necessary before 18 years of age if the patient meets certain criteria for consideration of risk, which is likely to inform decisions about hormone therapy.
They also discuss the fact that trans women may have longer exposure to estrogen and progesterone, as they are likely to take it at higher doses for proper suppression of gonadal function, and they are less likely to cease taking it at menopausal ages. Additionally, as trans people start to begin hormone therapy at younger ages, the data will begin to change.
Ultimately, the authors recommend organ-based routine cancer screening in accordance with the current general population guidelines.25
Fertility
Infertility due to hormone therapy is likely, though not guaranteed, and fertility desire should ideally be addressed prior to the administration of hormones.26
Periods
Many trans women on estrogen attest to feeling symptoms of premenstrual syndrome (such as sore breasts, mood swings, and irritability) on a semi-monthly basis, but the existence of a transfem period is far from an established fact. I have it on good word that there are enough unknowns about the interactions between exogenous hormones and hormone signaling dynamics in the brain, but ultimately, we don’t know for sure, and that’s okay.
There was a three-month period where I was logging my PMS-like symptoms in a tracking app, marking a period whenever they seemed to cluster together, and I was surprised to learn that these symptoms had a zero-day cycle variation. It’s possible this was a period! It’s important to remember, though, that premenstrual syndrome is a symptom of low estrogen, and it’s also possible that period symptoms are due to a poor regimen rather than a regular cycle. My boobs hurt when I forget to take my pills.
Changelog
March 20, 2023: Added “Periods” section under “Health Concerns” heading.
February 10, 2024: Significantly expanded the “Anti-Androgens” section.
September 23, 2024: Added information about estrone/estradiol ratios with different routes of administration; updated the “Anti-Androgens” section with recent findings; clarified confusing language about the subcutaneous and intramuscular routes of administering estrogen.
June 19, 2026: Did a long-overdue formatting and writing overhaul now that I am older and smarter. I was very guarded when I first wrote this essay, but now that pages like this are proliferating and DIY has become significantly more important, I feel I’m allowed to be more candid.
I use estrogen as an umbrella term, which includes estradiol and estrone. Similarly, progestogen is an umbrella term for hormones that bind to the progesterone receptor, including progesterone. I believe I’ve been fairly consistent with my usage of these terms, but there may be some mistakes scattered around.
This is because exogenous hormones have anti-gonadotropic effects, meaning they cause a decrease in the gonadotropins: luteinizing hormone (LH) and follicle-stimulating hormone (FSH). The gonadotropins signal to the gonads to produce whatever hormones the gonads are made to produce (testes primarily produce testosterone, ovaries primarily produce estrogen and progesterone). This is why, in the above diagram, LH and FSH follow a similar trajectory to estrogen and progesterone in cis women.
There are some fears about stunted breast development from beginning progesterone too early, but these have not been corroborated. If you’re worried, wait about 10-12 months after starting estrogen before getting on progesterone (this is what I did!)
The majority of this information is sourced from Kuhl, H. “Pharmacology of estrogens and progestogens: influence of different routes of administration.” Climacteric 8, sup1 (2005): 3-63. This data was gathered from cis women taking hormone therapy.
Higher estrone = more estrogenic activity in the liver.
Winston McPherson, Gabrielle N., Tiffany A. Thomas, Matthiew D. Krasowski, Sofia B. Ahmed, Lauren R. Cirrincione, Brooke M. Katzman, Christina C. Pierre, Chantal L. Rytz, Keila Turino Miranda, Zil Goldstein, Dina N. Greene. “Estradiol Concentrations for Adequate Gender-Affirming Feminizing Therapy: A Systematic Review.” LGBT Health (2025).
Spironolactone largely gets its positive reputation from the aforementioned 1989 study about progesterone, but the findings of that study have not been successfully replicated in the years since. I suspect this is because the study does not distinguish between the effects of progesterone and spironolactone, resulting in the anti-androgenic effects of the former being mistakenly attributed to the latter.
Spironolactone has weak anti-gonadotropic effects. If I understand correctly, this is because it prevents testosterone from binding to androgen receptors, thus increasing the amount of free testosterone in the blood, which the brain perceives as a total increase in hormones, resulting in diminished testosterone production. However, this is one of the places where I will readily admit that I am a little out of my depth.
Aromatization functions to maintain a balance of sex hormones. While excess testosterone can be converted into estrogen, excess estrogen cannot be converted into testosterone.