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@@ -433,114 +433,4 @@ Standard Adult Female Range: 0.8-3.1 nmol/L<br>
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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>
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<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 for the rest of your life and on that timescale they will almost certainly cause some level of permanent liver damage. Again while gender isn’t binary the endocrine system by our current understanding is, and if you’re uncomfortable with certain aspects of HRT it’s better to work through that with a therapist or close friends.</p>
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<h2 id="blood-tests">Blood Tests</h2>
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<h4 id="baseline">Baseline</h4>
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<p>There’s often an undue level of importance placed on baseline blood tests. If you have or suspect you may have any conditions that have contraindications with the HRT medications you plan to take then it’s worth getting tests for those conditions so they can be monitored, but there’s almost nothing actionable to derive from baseline sex hormone levels. Suppose your test shows you have unusually low Testosterone or higher than expected Estradiol levels for an AMAB person, what do you do with this information other than go “Huh, interesting”? It could indicate some sort of intersex condition or hypogonadism but it doesn’t imply any danger nor will it affect your starting dose, you’ll just keep an eye on it in later blood tests which you would have done anyway.</p>
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<p>If you have cheap and easy access to blood tests through a supportive doctor or a harm reduction organisation and it’s not going to significantly delay your start date then go for it, but if you’re going to be waiting months or it’s stressing an already tight financial situation then don’t worry about it.</p>
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<h4 id="units">Units</h4>
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<p>Several different units of measurement are used for different hormones and in different countries.</p>
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<p>Estradiol in North America is typically measured in picograms-per-milliliter (pg/mL) while internationally it’s measured in picomoles-per-liter (pmol/L). 100 pg/mL = 367 pmol/L or as a quick mental shortcut, “pmol/L is 3.5x pg/ml”.</p>
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<p>Testosterone in North America is typically measured in nanograms-per-decliliter (ng/dL) while internationally it’s measured in nanomoles-per-liter (nmol/L). 50 ng/dL = 1.73 nmol/L, no easy mental shortcut here.</p>
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<p>To further complicate this the molar concentrations (nmol and pmol) are dependent on the molecule being measured, so 2 nmol/L of Testosterone and 2 nmol/L of Estradiol refer to different amounts of the chemical.</p>
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<p>Transfemscience has a handy calculator <a href="https://transfemscience.org/misc/hormone-conc-unit-conv/">here</a> to convert between all of these units but our suggestion would simply be to memorise target levels in the unit used where you live and not worry about it unless advising someone else, in which case pull out the calculator and double check.</p>
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<h4 id="target-levels">Target Levels</h4>
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<p>Optimal target levels are a subject of vigorous debate both online within the trans community and offline within the medical establishment however it’s almost entirely conjecture, there isn’t a single study that objectively measures physical changes against hormone levels. All we have to go off are normal levels in AFAB people and anecdotes from within the community about what different levels have achieved for them. This isn’t to express doubt on the following recommendations nor cast aspersions on other recommendations, but simply to point out that all anyone has until those studies are performed are working theories, as evidenced by everyone recommending nice clean rounded numbers in their local unit of measurement. Any claim to authority on this subject should be treated with intense scepticism.</p>
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<h5 id="wpath-soc-v8">WPATH SoC v8</h5>
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<p>The <a href="https://www.wpath.org/soc8/chapters">WPATH Standards of Care Version 8</a> recommend a Serum Estradiol of 100-200 pg/mL (367-734 pmol/L) and Serum Testosterone of less than 50 ng/dL (1.73 nmol/L). Tests should be taken every 3 months for the first year, then 1-2 times per year thereafter. They also recommend monitoring potassium and kidney function depending on the blockers used and the method of administration.</p>
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<h5 id="ucsf">UCSF</h5>
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<p>The <a href="https://transcare.ucsf.edu/guidelines">UCSF Transgender and non-binary care guidelines</a> defer to <a href="https://www.endocrine.org/-/media/endocrine/files/cpg/gdgi-cpg-resource-page-13feb18.pdf">guidance from the Endocrine Society</a> which simply says to match mid-cycle levels in cis women. Depending on the reference ranges we look at this gives us a similar ~150 pg/mL (551 pmol/L) Estradiol target to the WPATH guidelines, but a lower ~40 ng/dL (1.39 nmol/L) target for Testosterone.</p>
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<p>Additional UCSF recommends a trough of 50 pg/mL (183 pmol/L) and a peak of 250 pg/mL (918 pmol/L) when using injections. This guidance is in light of the fact that many patients in North America use Estradiol Valerate injections on 2 weeks cycles, resulting in a large variance in levels across that time.</p>
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<h5 id="nhs-target-levels">NHS</h5>
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<p>In the UK the NHS Gender Identity Clinics use a variety of target numbers in different geographical locations, but they are all downstream of guidance from the Consultant Endocrinologist Dr Leighton Seal at Tavistock. These guidelines have at times included multiple false assertions such as reverse aromatase (the conversion of Estradiol back into Testosterone) which are easily refuted by any endocrinology textbook. They also make wildly unrealistic recommendations on starting dosages and suggest rates of titration that would result in most patients taking years to reach the 400-600 pmol/L (109-163 pg/mL) target guidelines.</p>
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<p>There are a wealth of credible accusations within the UK trans community that Seal, when challenged on this in private, believes that these long titration periods and lower levels result in better outcomes without any evidence and give a patient who shouldn’t be transitioning a chance to “prove” that it’s <em>really</em> right for them. These accusations are supported by it being almost standard practice in British private trans healthcare organisations for psychologists to order the patient’s dosage be limited to an almost placebo level until they’re satisfied with the progress of the patient’s social transition. This practice is completely unprecedented internationally, completely unfounded in evidence, rejected by WPATH internally and largely regarded as an attempt to appease transphobes espousing the <a href="https://juliaserano.medium.com/everything-you-need-to-know-about-rapid-onset-gender-dysphoria-1940b8afdeba">Rapid Onset Gender Dysphoria</a> conspiracy theory.</p>
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<p>As they are so far out of line with more rigorously achieved international guidance and a source of complaint for so many patients, the NHS guidelines can be entirely disregarded.</p>
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<h5 id="will-powers-target-levels">Dr Will Powers</h5>
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<p>Powers is a family doctor in Michigan who has produced many theories on trans medicine with varying degrees of credibility. His most popular guidance includes a target Estradiol range of 100-300 pg/mL (367-1101 pmol/L) and Testosterone of less than 50 ng/dL (1.73 nmol/L). While Powers has some more bombastic claims regarding Estrone and SHBG these suggestions are largely in line with more reputable guidance and there are plenty anecdotes online of patients benefiting at least psychologically from these higher levels.</p>
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<h5 id="female-reference-ranges">Female Reference Ranges</h5>
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<p>As a final consideration, it’s worth looking at female reference ranges. A Google search will turn up many slightly varying results, but we’d recommend <a href="https://www.hse.ie/eng/services/list/3/acutehospitals/hospitals/waterford/laboratoryservices/complex-reference-ranges.html">these values from the Irish Health Service Executive</a> as representative and reputable.</p>
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<h5 id="our-recommendation">Our Recommendation</h5>
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<p>Coming full circle we’re happy to endorse the WPATH guidelines of 100-200 pg/mL (367-734 pmol/L) for Estradiol and <50 ng/dL (1.73 nmol/L) for Testosterone. They’re known safe values in regards to broader health concerns, they clearly work given they’re what we see in cis women, and after seeing hundreds of blood tests and helping many trans people over the years, it’s clear to us that the overwhelming majority are happy with what they get from these levels in the long run. We would however add one caveat:</p>
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<p>You should aim for the upper end of this range and not be scared to exceed it at peak. In patients using transdermal patches where the level is essentially a flat line, it’s common to observe complaints of lethargy and low libido if the patient is sitting at the lower end of this spectrum, and then find those complaints are resolved when they titrate up to a higher dose. Rather than considering anywhere in that window the goal, treat it like an archery target where 200 pg/mL is the yellow center and 100 pg/mL is the edge of the target. If you hit the target it’s a good enough shot, but you’re always aiming for the center.</p>
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<h2 id="antiandrogens">Anti-androgens (AAs)</h2>
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<p>Most HRT regimens begin with the use of an antiandrogen (often known as a “blocker”) to suppress Androgens directly. It should be noted Estradiol alone functions as an AA by stimulating the Hypothalamus and slowing down the HPG axis. The amount required to achieve this varies wildly from person to person but it’s important to note that if Estradiol alone achieves this, an AA is usually unnecessary.</p>
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<h4 id="spironolactone">Spironolactone</h4>
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<p>Spiro is a widely used and extremely cheap drug first introduced in 1959, it is a potent anti-mineralocorticoid, a mild AA and a weak steroidogenesis inhibitor along with a few other minor interactions. It has been used successfully in the treatment of heart failure, high blood pressure and prostate cancer.</p>
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<p>Since its AA effects are quite weak compared to many alternatives it is typically taken at much higher doses. It functions primarily by blocking Androgen Receptors throughout the body, inhibiting Testosterone and other Androgens from successfully binding to and activating the receptors. Its function as a weak steroidogenesis inhibitor can also cause a reduction in overall sex hormone production, though the doses required to achieve this have only been tested in animals and results in human trials have been rather inconsistent. It has also been observed to slightly increase Estradiol levels through mechanisms that aren’t entirely clear.</p>
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<p>In feminising HRT Spironolactone is widely used for its AA properties, particularly in the United States where CPA isn’t FDA approved, and typically prescribed at dosages of 100-200mg/day.</p>
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<p>The <a href="https://books.google.co.uk/books?id=oeBgU3UwgZkC&pg=PA255&redir_esc=y#v=onepage&q&f=false">primary side effects of Spiro</a> are raised potassium levels in 10-15% of patients, weight gain and diuresis (increased urination).</p>
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<p>There is a growing consensus in transgender healthcare that Spiro - while being a generally safe drug - comes with greater associated risks and a wider range of side effects than other options while being no more effective. It has also been <a href="https://www.ncbi.nlm.nih.gov/pubmed/23055547">statistically linked</a> with reduced breast growth in transgender women.</p>
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<h4 id="cyproterone">Cyproterone Acetate (CPA)</h4>
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<p>CPA is a widely used and extremely cheap synthetic progestin used exclusively for its potent effects as an AA, first introduced in 1973. It has been widely used in AFAB birth control pills, used successfully to treat a variety of conditions relating to excessive androgen levels in both AMAB and AFAB individuals, and in Androgen Deprivation Therapy (ADT) to treat Prostate Cancer.</p>
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<p>As an AA, CPA functions by having a strong effect on the Hypothalamus, significantly reducing GnRH production and effectively shutting down the HPG axis.</p>
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<p>In Feminising HRT CPA is widely used in Europe, Australia and Latin America, typically at doses of 12.5-25mg/day.</p>
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<p>Though well tolerated, the primary side effects of CPA are mild depression, vitamin B12 deficiency, hepatotoxicity, increased prolactin levels and on rare occasions benign brain tumours. It is also worth noting that these side effects are mostly commonly found when used in ADT at significantly higher doses than the 12.5-25mg/day most commonly used in HRT.</p>
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<p>CPA is generally considered to be a safe and effective AA as part of an HRT regimen. When available it is generally considered a preferable alternative to Spironolactone due to its milder side effect profile.</p>
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<h4 id="bicalutamide">Bicalutamide</h4>
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<p>Bicalutamide is a Nonsteroidal antiandrogen (NSAA) first introduced in 1995. It is a derivative of Flutamide and appears on the World Health Organisation’s list of Essential Medicines, the safest and most effective medicines needed in a health system. It is most widely used as monotherapy ADT to treat Prostate Cancer.</p>
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<p>As an AA, Bicalutamide functions by indiscriminately blocking Androgen Receptors throughout the body. While this does not reduce Androgen levels in the blood, it almost entirely inhibits their ability to affect the body’s biological functions.</p>
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<p>Bicalutamide is remarkably well tolerated and except for Liver toxicity in less than 0.1% of patients, it comes with almost no significant risk of side effects. The side effects noted when used at higher doses of typically 150mg/day in ADT include Gynecomastia, reduced libido, and loss of erectile function, all directly attributed to lower Androgen levels and desired outcomes for our purposes in feminising HRT.</p>
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<p>There is a working theory that Bicalutamide’s AR blocking mechanism increases the sensitivity of Estrogen receptors due to its use at high doses as a monotherapy having Estrogen-like effects on the body, however there are currently no studies to support this.</p>
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<h4 id="gnrh-agonists">GnRH Agonists</h4>
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<p>Triptorelin, Goserelin and Leuprolide are all widely used GnRH agonists introduced in the mid-1980s that achieve a complete shutdown of the HPG axis by overstimulation of the Pituitary Gland, rendering it insensitive to the body’s naturally produced GnRH. They are used for a variety of conditions, most commonly androgen-sensitive cancers. They have also been used to chemically castrate sex offenders. The mechanism by which they work makes them equally effective in hormone shutdown for both AMAB and AFAB individuals.</p>
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<p>Triptorelin under the brand name Decapeptyl is the preferred Antiandrogen of the NHS’s network of Gender Identity Clinics. Leuprolide under the brand name Lupron is commonly used in the US as a “puberty blocker” for gender questioning children and teenagers.</p>
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<p>GnRH agonists are generally considered the most effective method of Androgen suppression, allowing for a complete shutdown of the HPG axis at safe and widely studied dosages. Unlike other Anti-Androgens discussed in this guide which are administered in the form of (usually daily) oral pills, GnRH agonists are delivered as monthly or quarterly Intramuscular injections. While largely interchangeable in safety and effectiveness, <a href="https://onlinelibrary.wiley.com/doi/full/10.1111/bju.14168">Triptorelin has shown to be slightly more effective in studies</a>.</p>
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<p>If available, a GnRH agonist is the preferred method of androgen suppression.</p>
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<h4 id="finasteride">Finasteride</h4>
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<p>Finasteride is a 5-alpha reductase inhibitor introduced in 1992 widely used against Prostate overgrowth and Androgen-sensitive cancers, but mostly commonly used as a palliative treatment to slow or stop male pattern baldness.</p>
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<p>As an AA, Finasteride functions in a limited capacity as a 5-alpha reductase inhibitor. As can be seen <a href="transfem-hrt-guide.html#steroidogensis-diagram">here</a> 5-alpha reductase is the process by which Testosterone is converted into Dihydrotestosterone (DHT).</p>
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<p>Finasteride is widely prescribed by several private Transgender healthcare providers in the UK (notably GenderGP) as a general Antiandrogen under the pretence that it will reduce Testosterone and all Androgens equally, <a href="https://www.ncbi.nlm.nih.gov/pubmed/14624915">this is entirely untrue</a>. It actually causes a minor <em>increase</em> in serum Testosterone levels, a finding replicated across a wide number of studies.</p>
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<p>While generally safe and well tolerated, Finasteride is widely associated with a <a href="https://zenodo.org/record/896024#.XjNZSGhKhaQ">high incidence of depression</a>. Given the already high levels of depression and suicidality in the transgender population this should give <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1622749/">serious food for thought</a> when considering the use of this drug.</p>
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<p>Finasteride is an effective method of treating male pattern baldness, a concern naturally important to transgender individuals interested in feminising HRT, however it should be understood that given the suppression of Testosterone and overall Androgen levels by Estrogens and/or other Antiandrogens, it is largely unnecessary as a component of feminising HRT regimen.</p>
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<h2 id="homebrew-vs-pharmaceuticals">“Homebrew” vs Pharmaceuticals</h2>
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<p>Homebrew drugs are manufactured by individuals or small groups of trans people looking to do their part to help the community. These groups will purchase Estradiol or another active ingredient from a wholesale supplier in its raw powder form and manufacture it into whatever form is ultimately taken by a person such as an injectable oil, a swallowable pill, etc. It’s important to understand the risks, there is a non-zero possibility of contamination or problems with the manufacturing process because these folks simply do not have the same resources that a multi-million dollar pharmaceutical company has.</p>
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<p>On the other hand, the most trusted suppliers are eminently educated on these subjects often working in or adjacent to the pharmaceutical industry, or at the very least operating on guidance from others who are. If you’re interested in reading more about this the guidance at <a href="https://hrtcafe.net/Homebrew/injection-tutorial.html"></a><a>hrtcafe.net</a> explains in intricate detail every single aspect of the process and most suppliers have a process largely comparable to that. At diyhrt.market we can vouch for having had this reviewed by a professional in the biomedical industry. Sites like this one and <a href="https://diyhrt.cafe/">diyhrt.cafe</a> vet suppliers, making sure there are months worth of satisfactory feedback from customers before listing anything from them. There have in the past been a very small handful of suppliers who have not reached that quality bar and been rejected by the community, so we know this community consensus approach works.</p>
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<p>Put simply, homebrew drugs from suppliers listed here are safe and effective within the constraints of reasonable concerns, but we do believe it’s important that you know what you’re getting.</p>
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<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
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