<h4id="what-is-hrt">What is Hormone Replacement Therapy (HRT)?</h4>
<p>Hormone Replacement Therapy is a broad range of treatments using a variety of drugs that all have one simple goal: to reduce Androgens (such as Testosterone) and increase Estrogen to standard female levels. Originally pioneered in the early 1940s to counteract the effects of menopause in older women, significant research didn’t begin until the early 1970s when it was found that existing options came with significant cancer and clotting risks. It was around this time doctors started to realise the process could be used in AMAB Transgender people for its feminising effects.</p>
<h4id="is-hrt-dangerous">Is HRT dangerous?</h4>
<p>No drug or medical procedure comes without risks, however, using modern best practices the chance of side effects and rate of adverse events is extremely low. Weighed in a cost/benefit analysis against the <ahref="https://williamsinstitute.law.ucla.edu/wp-content/uploads/AFSP-Williams-Suicide-Report-Final.pdf">high transgender suicide rate</a>, <ahref="https://www.ncbi.nlm.nih.gov/pubmed/29665513">incidence of depression</a> and other mental health issues common in transgender individuals, and the extremely low rates of regret it is - to put it mildly - <ahref="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354936/">unquestionably beneficial</a>.</p>
<p>The risks that have been found to occur at statistically observable rates in studies fall broadly into 3 categories:</p>
<p>These are not general risks of the process, but instead of individual drugs used. Older drugs used in the 70’s and 80’s no longer prescribed today are mostly responsible for the negative reputation. All of these risks have been largely eliminated through the use of <ahref="https://www.ncbi.nlm.nih.gov/pubmed/17217322">bioidentical hormones</a>, <ahref="https://www.bmj.com/content/364/bmj.l157">non-oral administration</a> and screening via blood tests.</p>
<p>A wealth of studies over the last few decades have concluded that the clotting risks are almost entirely associated with the use of Conjugated Estrogens originally introduced in the 1940s, to a lesser degree with Synthetic Estrogens such as Ethinylestradiol, and are almost (though not entirely) eliminated by using Bioidentical Estrogens and further reduced through non-oral (particularly transdermal) administration.</p>
<p>Cancer risks largely follow the same theme, meanwhile the Thyroid, Kidney and Liver risks are mostly associated with high doses of particular antiandrogens such as <ahref="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4087608/">Cyproterone Acetate</a> and <ahref="https://www.ncbi.nlm.nih.gov/books/NBK547921/">Spironolactone</a>.</p>
<h4id="what-does-hrt-do">What does HRT do?</h4>
<p>Achieving female hormone levels will have an overall feminising effect on the body. This includes changes to skin, hair, nails, sweat, facial features, fat distribution and breast growth.</p>
<p>Often understated however are the <ahref="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5010234/">mental effects</a>. Though not well studied in the micro there is a wealth of anecdotes within the transgender community describing positive changes to aggression, emotions, thinking patterns, sexuality, and even sexual orientation. In the macro there is <ahref="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5010234/">clear statistical evidence</a> that there are overwhelmingly positive outcomes on mental health and an overall improvement in quality of life.</p>
<h4id="how-long-does-it-take">How long does it take?</h4>
<p>Due to a lack of consistency in regimens, targets and recording by medical professionals, it is almost impossible to judge this objectively. Based on experiences shared within transgender internet communities a good rule of thumb is that many of the visceral mental effects such as reduced aggression and libido occur within the first couple of weeks and other mental changes follow over the next few months, while the physical effects develop gradually over 2-3 years, finalising around the 5-year mark.</p>
<h2id="sex-hormones">Sex Hormones</h2>
<p>Since HRT involves manipulating sex hormone levels it’s good to have a brief high-level understanding of them.</p>
<p>At a basic level, there are three primary groups we are interested in: Progestogens, Androgens and Estrogens. Estrogens are female hormones, Androgens are male hormones, while Progestogens are a more complicated family that play an important role in - among other things - reproductive function in AFAB individuals. We generally discuss Estradiol and Testosterone levels specifically when talking about HRT, but it should be understood that we are suppressing the group as a whole. This is particularly important when discussing 5-alpha reductase inhibitors and DHT, the main exception to this rule.</p>
<p>Estrone has 4-8% of the Estrogenic activity of Estradiol. Estrone levels are regularly increased by using oral administration and there is some limited evidence linking increased amounts of it with <ahref="https://www.ncbi.nlm.nih.gov/pubmed/20553380">VTE</a> and <ahref="https://clincancerres.aacrjournals.org/content/9/6/2229">Cancer</a> risks.</p>
<h4id="androgens-info">Androgens</h4>
<h5id="testosterone-info">Testosterone</h5>
<p>Testosterone is the primary male hormone and the primary source of androgenic activity.</p>
<p>DHT has 200-300% of the androgenic activity of Testosterone. Its primary role in the human body is in sperm production within the Testes, however, it is also strongly associated with male hair patterns including both the development of facial/pubic/body hair and male pattern baldness. DHT represents a small and generally quite localised portion of the overall androgenic activity within the body and in the context of HRT, its reduction should not be seen as a goal in and of itself beyond attempting to reverse male pattern baldness.</p>
<h4id="progestogens">Progestogens</h4>
<h5id="progesterone-info">Progesterone</h5>
<p>Progesterone is a key signalling agent in AFAB reproductive function. Most female birth control takes the form of high-dose Progesterone. It has anecdotally been observed to have some positive effects on breast development in HRT, though hard evidence for this is lacking.</p>
<p>Based on level stability, safety, compliance and cost there’s a fairly clear hierarchy of optimal regimens. You can choose any of these regimens and be happy with them, but if you plan to use one further down the list it should only be done after carefully considering the downsides in regards to your personal circumstances.</p>
<p>A subcutaneous injection of estered Estradiol approx weekly. Estradiol has a biological half-life of ~4 hours and will be entirely out of your system within 24-36 hours however <ahref="https://en.wikipedia.org/wiki/Estrogen_ester">esterification</a> extends this making it a slow-release dose, Estradiol Enanthate (EEn) for example has a biological half-life of ~6.5 days and takes 4-5 weeks to be entirely flushed out of your system. A weekly injection of 4mg EEn will bring almost anyone to Estradiol levels high enough to shut down Testosterone production without the use of a blocker by taking advantage of the HPG axis we discussed above, acting on the Hypothalamus and satisfying its target for sex hormone levels.</p>
<p>This regimen ticks a lot of boxes. First, the injection is done with a tiny needle not into a vein but into the fat layer right underneath the skin, typically in the buttocks or abdomen <ahref="https://www.youtube.com/watch?v=YeyFSMHfVgQ">just like the insulin injections that many diabetics perform as a normal part of their daily routine</a>. While self-injecting can seem scary at first it’s just a simple 5-minute routine once per week, easily maintained and not a big deal if it’s missed by a few hours or even a day or two.</p>
<p>While other administration methods will see large variations throughout the day and a huge spread from person to person in what dose is required to reach certain levels, injections provide highly stable and predictable results. This makes recommended starting doses and judging blood tests very simple, perfect for DIY where many are paying out-of-pocket for every test and trying to minimise how many are needed.</p>
<p>Lastly, <ahref="meds/groups/estradiol-injections.html">it’s cheap</a>. DIY injectables are almost always homebrew and 2 years of supplies can easily be bought for around $150. Many in our community struggle financially, given the importance of HRT this cheapness is life and death for many.</p>
<h4id="transdermal-gel-plus-blockers">Transdermal Gel + Blockers</h4>
<p>Transdermal gels are rubbed on the skin and absorbed within a few minutes, done daily. This is combined with an oral blocker also taken daily, usually <ahref="meds/groups/cyproterone.html">Cyproterone Acetate</a> though <ahref="meds/groups/bicalutamide.html">Bicalutamide</a> or <ahref="meds/groups/spironolactone.html">Spironolactone</a> work well too.</p>
<p>While it lacks the stability and predictable dosages of injections it has no problem achieving good enough levels and avoids the liver conversion issues of pills. Theoretically, monotherapy is practical with gel but in practice the margin of error for letting them get too low is so thin that it’s not taking the chance. Miss your dose by half a day or get into a habit of spreading it too thin and you can find your Testosterone levels starting to rise again.</p>
<p>It’s also physically safer since no needles are involved and <ahref="meds/groups/estradiol-gels.html">similarly cheap</a> since Gels are increasingly sold by the same homebrew providers that make the injectables.</p>
<p>A starting Estradiol dose of 3-4mg/day will work for most though this should be tweaked in response to blood tests. For blockers 12.5mg/day Cyproterone, 50mg/day Bicalutamide or 200mg Spironolactone will do the job, no testing necessary.</p>
<p>As a final note there’s <ahref="https://transfemscience.org/articles/genital-e2-application/">a common suggestion</a> floating around the community that gels can be applied to the scrotum for optimal absorption. This isn’t an old wive’s tail, there is a study showing higher absorption and it’s well studied with Testosterone however it also results in a much greater spike. It’s a higher level shortly after, but it also falls off a lot faster which works against our goal of stable levels. If you want higher levels then just take a higher dose, it’s that simple, there’s no need to cheat.</p>
<p>The main downsides of Estradiol pills compared to other administration methods are extremely poor absorption and rapid elimination from your system, most of it is destroyed in the liver and it’s entirely out of your system within 24-36 hours. This results in needing to take relatively large doses multiple times per day to maintain target levels.</p>
<p>Pills should be taken at least twice per day, ideally thrice. If taken once per day in the morning you’ll find yourself towards the end of the day feeling quite lethargic and though it’s not been studied or quantified this almost certainly negatively impacts feminisation since you’re below target levels for most of the day.</p>
<p>Sublingual pills (allowing them to dissolve under the tongue and be absorbed) aren’t recommended for essentially the same reason as explained above with scrotal gel application. It does circumvent much of the destruction in the liver but it also flushes through the system even faster which is already a problem with pills. Again if you want higher levels it’s better to just take a higher oral dose.</p>
<p>An Estradiol dose of 4-6mg/day is a good starting point. The pills are almost universally 2mg, so one pill every 12 hours or every 8 hours is the way to go. When getting blood tests try to get it taken as close to the trough as possible, right before your next pill.</p>
<p>Blockers are the same as recommended for gels. 12.5mg/day Cyproterone Acetate, 50mg/day Bicalutamide or 200mg/day Spironolactone.</p>
<p>Transdermal Patches + Blocker: This regimen is in many ways superior to gel as patches release Estradiol at a stable rate and are more easily complied with assuming no sensory issues. However, as of late 2023, patches have been <ahref="meds/groups/estradiol-patches.html">almost entirely out of stock through</a> most grey market sellers for over a year and even regular pharmacies are having massive supply issues. It’s a result of a manufacturing shortage that isn’t likely to be fixed any time soon so the reliable access simply isn’t there.</p>
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<p>Any Method + GnRH agonist: GnRH agonists are the ideal blockers, however they are extremely expensive and difficult to source from grey market sources. Their upsides simply don’t merit the cost when your wallet is footing the bill.</p>
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<p>Any Method + Finasteride/Dutasteride: As explained <ahref="transfem-hrt-guide.html#finasteride">further down</a> these 5-Alpha Reductase Inhibitors are not proper blockers. You can take them if you have reason to do so, but it should be in addition to a real blocker or a monotherapy regimen.</p>
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<p>Progesterone + Anything: Likewise Progesterone is not a substitute for Estradiol or a blocker, it should be taken in addition to these things, not as a substitute.</p>
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<p>Ethinylestradiol: This is a synthetic Estrogen that comes with statistically significant health risks and based on the well-studied fact that it has different potencies in different areas of the body it’s likely not even as effective for feminisation as bioidentical Estradiol. There’s no reason to take this.</p>
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<p>Premarin: Similar to Ethinylestradiol, higher risks for no upside. Do not take this.</p>
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<p>Blocker-only: While this is the common approach for puberty blockers it has both long and short-term health effects. The goal with these regimens is usually some form of non-binary HRT but the endocrine system just doesn’t work that way. Your body needs one dominant sex hormone to function properly.</p>
<p>Tamoxifen/Clomifene/Raloxifene (SERMs): There are stories within the community of using these drugs as part of a non-binary or femboy regimen to prevent breast growth. While in theory this should work these drugs are too toxic to the liver to take long term. Transition is different for everyone but starting HRT is ostensibly a commitment f
