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@@ -133,8 +133,38 @@
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<a class="list-group-item" href="transfem-hrt-guide.html#honorable-mentions">
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  Honorable Mentions
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</a>
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<a class="list-group-item" href="transfem-hrt-guide.html#blood-tests">
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<strong>Blood Tests</strong>
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</a>
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<a class="list-group-item" href="transfem-hrt-guide.html#baseline">
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  Baseline
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</a>
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<a class="list-group-item" href="transfem-hrt-guide.html#units">
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  Units
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</a>
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<a class="list-group-item" href="transfem-hrt-guide.html#target-levels">
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  Target Levels
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</a>
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<a class="list-group-item" href="transfem-hrt-guide.html#wpath-soc-v8">
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   <i>WPATH SoC v8</i>
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</a>
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<a class="list-group-item" href="transfem-hrt-guide.html#ucsf">
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   <i>UCSF</i>
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</a>
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<a class="list-group-item" href="transfem-hrt-guide.html#nhs-target-levels">
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   <i>NHS</i>
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</a>
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<a class="list-group-item" href="transfem-hrt-guide.html#will-powers-target-levels">
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   <i>Dr Will Powers</i>
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</a>
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<a class="list-group-item" href="transfem-hrt-guide.html#female-reference-ranges">
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   <i>Female Reference Ranges</i>
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</a>
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<a class="list-group-item" href="transfem-hrt-guide.html#our-recommendation">
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   <i>Our Recommendation</i>
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</a>
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<a class="list-group-item" href="transfem-hrt-guide.html#antiandrogens">
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<strong>Antiandrogens (AAs)</strong>
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<strong>Anti-androgens (AAs)</strong>
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</a>
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<a class="list-group-item" href="transfem-hrt-guide.html#spironolactone">
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  Spironolactone
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@@ -266,7 +296,35 @@ Standard Adult Female Range: 0.8-3.1 nmol/L<br>
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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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</li>
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</ul>
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<h2 id="antiandrogens">Antiandrogens (AAs)</h2>
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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). 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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@@ -332,5 +390,5 @@ DIYHRT.Market 2022-2023
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