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<?xml version="1.0" encoding="utf-8"?><feed xmlns="http://www.w3.org/2005/Atom" ><generator uri="https://jekyllrb.com/" version="3.9.5">Jekyll</generator><link href="https://transfemscience.org/feed-posts.xml" rel="self" type="application/atom+xml" /><link href="https://transfemscience.org/" rel="alternate" type="text/html" /><updated>2024-05-14T20:18:28-07:00</updated><id>https://transfemscience.org/feed-posts.xml</id><title type="html">Transfeminine Science</title><subtitle>Transfeminine Science is a site for information on hormone therapy for transfeminine people.</subtitle><author><name>Transfeminine Science</name></author></feed> <?xml version="1.0" encoding="utf-8"?><feed xmlns="http://www.w3.org/2005/Atom" ><generator uri="https://jekyllrb.com/" version="3.9.5">Jekyll</generator><link href="https://transfemscience.org/feed-posts.xml" rel="self" type="application/atom+xml" /><link href="https://transfemscience.org/" rel="alternate" type="text/html" /><updated>2024-06-27T01:10:55-07:00</updated><id>https://transfemscience.org/feed-posts.xml</id><title type="html">Transfeminine Science</title><subtitle>Transfeminine Science is a site for information on hormone therapy for transfeminine people.</subtitle><author><name>Transfeminine Science</name></author></feed>

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<?xml version="1.0" encoding="utf-8"?><feed xmlns="http://www.w3.org/2005/Atom" ><generator uri="https://jekyllrb.com/" version="3.9.5">Jekyll</generator><link href="https://transfemscience.org/feed.xml" rel="self" type="application/atom+xml" /><link href="https://transfemscience.org/" rel="alternate" type="text/html" /><updated>2024-05-14T20:18:28-07:00</updated><id>https://transfemscience.org/feed.xml</id><title type="html">Transfeminine Science | Articles</title><subtitle>Transfeminine Science is a site for information on hormone therapy for transfeminine people.</subtitle><author><name>Transfeminine Science</name></author><entry><title type="html">Puberty Blockers: A Review of GnRH Analogues in Transgender Youth</title><link href="https://transfemscience.org/articles/puberty-blockers/" rel="alternate" type="text/html" title="Puberty Blockers: A Review of GnRH Analogues in Transgender Youth" /><published>2022-01-30T15:04:00-08:00</published><updated>2022-01-31T00:00:00-08:00</updated><id>https://transfemscience.org/articles/puberty-blockers</id><content type="html" xml:base="https://transfemscience.org/articles/puberty-blockers/"><![CDATA[<h1 id="puberty-blockers-a-review-of-gnrh-analogues-in-transgender-youth">Puberty Blockers: A Review of GnRH Analogues in Transgender Youth</h1> <?xml version="1.0" encoding="utf-8"?><feed xmlns="http://www.w3.org/2005/Atom" ><generator uri="https://jekyllrb.com/" version="3.9.5">Jekyll</generator><link href="https://transfemscience.org/feed.xml" rel="self" type="application/atom+xml" /><link href="https://transfemscience.org/" rel="alternate" type="text/html" /><updated>2024-06-27T01:10:55-07:00</updated><id>https://transfemscience.org/feed.xml</id><title type="html">Transfeminine Science | Articles</title><subtitle>Transfeminine Science is a site for information on hormone therapy for transfeminine people.</subtitle><author><name>Transfeminine Science</name></author><entry><title type="html">Puberty Blockers: A Review of GnRH Analogues in Transgender Youth</title><link href="https://transfemscience.org/articles/puberty-blockers/" rel="alternate" type="text/html" title="Puberty Blockers: A Review of GnRH Analogues in Transgender Youth" /><published>2022-01-30T15:04:00-08:00</published><updated>2022-01-31T00:00:00-08:00</updated><id>https://transfemscience.org/articles/puberty-blockers</id><content type="html" xml:base="https://transfemscience.org/articles/puberty-blockers/"><![CDATA[<h1 id="puberty-blockers-a-review-of-gnrh-analogues-in-transgender-youth">Puberty Blockers: A Review of GnRH Analogues in Transgender Youth</h1>
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@ -467,13 +467,13 @@ Using the term desistence in this way does not imply anything about the identity
<ul> <ul>
<li>Abbott Laboratories. (2009). <em>Estradiol. Architect System.</em> Abbott Park, Illinois/Wiesbaden, Germany: Abbott Laboratories. [<a href="https://web.archive.org/web/20200127014925/http://www.ilexmedical.com/files/PDF/Estradiol_ARC.pdf">PDF</a>]</li> <li>Abbott Laboratories. (2009). <em>Estradiol. Architect System.</em> Abbott Park, Illinois/Wiesbaden, Germany: Abbott Laboratories. [<a href="https://web.archive.org/web/20200127014925/http://www.ilexmedical.com/files/PDF/Estradiol_ARC.pdf">PDF</a>]</li>
<li>Behre, H. M., Abshagen, K., Oettel, M., Hubler, D., &amp; Nieschlag, E. (1999). Intramuscular injection of testosterone undecanoate for the treatment of male hypogonadism: phase I studies. <em>European Journal of Endocrinology</em>, <em>140</em>(5), 414–419. [DOI:<a href="https://doi.org/10.1530/eje.0.1400414">10.1530/eje.0.1400414</a>]</li> <li>Behre, H. M., Abshagen, K., Oettel, M., Hubler, D., &amp; Nieschlag, E. (1999). Intramuscular injection of testosterone undecanoate for the treatment of male hypogonadism: phase I studies. <em>European Journal of Endocrinology</em>, <em>140</em>(5), 414–419. [DOI:<a href="https://doi.org/10.1530/eje.0.1400414">10.1530/eje.0.1400414</a>]</li>
</ul>]]></content><author><name>{&quot;first_name&quot;=&gt;&quot;Aly&quot;, &quot;last_name&quot;=&gt;&quot;W.&quot;, &quot;author-link&quot;=&gt;&quot;/about/#aly&quot;, &quot;articles-link&quot;=&gt;&quot;/articles-by-author/aly/&quot;}</name></author><category term="github" /><category term="workspace" /><summary type="html"><![CDATA[An Interactive Web Simulator for Estradiol Levels with Injectable Estradiol Esters By Aly | First published July 16, 2021 | Last modified April 12, 2023]]></summary><media:thumbnail xmlns:media="http://search.yahoo.com/mrss/" url="https://transfemscience.org/assets/images/injectable-e2/simulator-screenie.png" /><media:content medium="image" url="https://transfemscience.org/assets/images/injectable-e2/simulator-screenie.png" xmlns:media="http://search.yahoo.com/mrss/" /></entry><entry><title type="html">An Informal Meta-Analysis of Estradiol Curves with Injectable Estradiol Preparations</title><link href="https://transfemscience.org/articles/injectable-e2-meta-analysis/" rel="alternate" type="text/html" title="An Informal Meta-Analysis of Estradiol Curves with Injectable Estradiol Preparations" /><published>2021-07-16T12:00:00-07:00</published><updated>2024-04-03T00:00:00-07:00</updated><id>https://transfemscience.org/articles/injectable-e2-meta-analysis</id><content type="html" xml:base="https://transfemscience.org/articles/injectable-e2-meta-analysis/"><![CDATA[<h1 id="an-informal-meta-analysis-of-estradiol-curves-with-injectable-estradiol-preparations">An Informal Meta-Analysis of Estradiol Curves with Injectable Estradiol Preparations</h1> </ul>]]></content><author><name>{&quot;first_name&quot;=&gt;&quot;Aly&quot;, &quot;last_name&quot;=&gt;&quot;W.&quot;, &quot;author-link&quot;=&gt;&quot;/about/#aly&quot;, &quot;articles-link&quot;=&gt;&quot;/articles-by-author/aly/&quot;}</name></author><category term="github" /><category term="workspace" /><summary type="html"><![CDATA[An Interactive Web Simulator for Estradiol Levels with Injectable Estradiol Esters By Aly | First published July 16, 2021 | Last modified April 12, 2023]]></summary><media:thumbnail xmlns:media="http://search.yahoo.com/mrss/" url="https://transfemscience.org/assets/images/injectable-e2/simulator-screenie.png" /><media:content medium="image" url="https://transfemscience.org/assets/images/injectable-e2/simulator-screenie.png" xmlns:media="http://search.yahoo.com/mrss/" /></entry><entry><title type="html">An Informal Meta-Analysis of Estradiol Curves with Injectable Estradiol Preparations</title><link href="https://transfemscience.org/articles/injectable-e2-meta-analysis/" rel="alternate" type="text/html" title="An Informal Meta-Analysis of Estradiol Curves with Injectable Estradiol Preparations" /><published>2021-07-16T12:00:00-07:00</published><updated>2024-06-27T00:00:00-07:00</updated><id>https://transfemscience.org/articles/injectable-e2-meta-analysis</id><content type="html" xml:base="https://transfemscience.org/articles/injectable-e2-meta-analysis/"><![CDATA[<h1 id="an-informal-meta-analysis-of-estradiol-curves-with-injectable-estradiol-preparations">An Informal Meta-Analysis of Estradiol Curves with Injectable Estradiol Preparations</h1>
<!-- Supports up to four authors per article currently (author, author2, author3, author4) --> <!-- Supports up to four authors per article currently (author, author2, author3, author4) -->
<p>By <p>By
<!-- First author --><a href="/about/#aly">Aly</a><!-- Second author --><!-- Third author --><!-- Fourth author --> | First published July 16, 2021 <!-- First author --><a href="/about/#aly">Aly</a><!-- Second author --><!-- Third author --><!-- Fourth author --> | First published July 16, 2021
| Last modified April 3, 2024</p> | Last modified June 27, 2024</p>
<h2 id="abstract--tldr">Abstract / TL;DR</h2> <h2 id="abstract--tldr">Abstract / TL;DR</h2>
@ -1866,7 +1866,7 @@ Using the term desistence in this way does not imply anything about the identity
<p>With the preceding concerns about the doses and intervals of injectable estradiol preparations recommended by transgender care guidelines considered, the question of how these recommendations were determined arises. Unfortunately, current guidelines do not generally describe how they arrived at their recommendations nor do they usually cite sources to support them. It is notable that the UCSF guidelines recommend doses and intervals for injectable estradiol preparations that are nearly identical to those advised by <a href="https://en.wikipedia.org/wiki/Christian_Hamburger">Christian Hamburger</a> and <a href="https://en.wikipedia.org/wiki/Harry_Benjamin">Harry Benjamin</a> in the late 1960s in the first medical textbook on transgender people (<a href="https://scholar.google.com/scholar?cluster=17287240145299798098">Hamburger &amp; Benjamin, 1969</a>). These authors recommended a dose of 10–40 mg/2 weeks for estradiol valerate and of 2–5 mg/2 weeks for estradiol cypionate (although Benjamin additionally stated that after 4–8 months, the same doses could be used at a longer injection interval of once every 4 weeks). These recommendations were notably made before estradiol blood tests became practicably available and were prior to the advent of modern pharmacokinetic studies. Hence, the recommendations for at least these guidelines appear to be based mainly on past expert opinion and long-standing historical precedent rather than on pharmacokinetic or clinical data. The same is likely to also be true for most other guidelines. High doses with certain injectable estradiol preparations (namely estradiol valerate) were probably originally employed for the purpose of achieving longer durations and more convenient injection intervals. This was notably prior to the risks of excessive estrogenic exposure like blood clots becoming known, and these doses may simply have never been revised.</p> <p>With the preceding concerns about the doses and intervals of injectable estradiol preparations recommended by transgender care guidelines considered, the question of how these recommendations were determined arises. Unfortunately, current guidelines do not generally describe how they arrived at their recommendations nor do they usually cite sources to support them. It is notable that the UCSF guidelines recommend doses and intervals for injectable estradiol preparations that are nearly identical to those advised by <a href="https://en.wikipedia.org/wiki/Christian_Hamburger">Christian Hamburger</a> and <a href="https://en.wikipedia.org/wiki/Harry_Benjamin">Harry Benjamin</a> in the late 1960s in the first medical textbook on transgender people (<a href="https://scholar.google.com/scholar?cluster=17287240145299798098">Hamburger &amp; Benjamin, 1969</a>). These authors recommended a dose of 10–40 mg/2 weeks for estradiol valerate and of 2–5 mg/2 weeks for estradiol cypionate (although Benjamin additionally stated that after 4–8 months, the same doses could be used at a longer injection interval of once every 4 weeks). These recommendations were notably made before estradiol blood tests became practicably available and were prior to the advent of modern pharmacokinetic studies. Hence, the recommendations for at least these guidelines appear to be based mainly on past expert opinion and long-standing historical precedent rather than on pharmacokinetic or clinical data. The same is likely to also be true for most other guidelines. High doses with certain injectable estradiol preparations (namely estradiol valerate) were probably originally employed for the purpose of achieving longer durations and more convenient injection intervals. This was notably prior to the risks of excessive estrogenic exposure like blood clots becoming known, and these doses may simply have never been revised.</p>
<p>The reasons that dose recommendations for injectable estradiol in transfeminine people have remained as they have for so long may be related to several factors. These include (1) a long-standing lack of research and funding in transgender health; (2) injectable estradiol not being widely available or as commonly used as other forms of estradiol; and (3) many clinicians only testing estradiol levels at trough (right before the next injection) with injectable estradiol preparations (e.g., <a href="https://doi.org/10.1055/s-0030-1255074">Mueller et al., 2011</a>; <a href="https://doi.org/10.4158/EP-2020-0414">Chantrapanichkul et al., 2021</a>; <a href="https://doi.org/10.1089/lgbt.2020.0249">Cirrincione et al., 2021</a>). The latter point is noteworthy as trough levels only describe the lowest point of the estradiol concentration–time curve with injectable estradiol preparations, and can give a very misleading impression of average or total estradiol exposure. In any case, the very high estradiol levels with currently recommended doses of injectable estradiol forms for transfeminine people have not gone unnoticed in the literature (e.g., <a href="https://doi.org/10.1159/000087751">Gooren, 2005</a>; <a href="https://doi.org/10.1001/jama.2012.165234">Spack, 2013</a>; <a href="https://books.google.com/books?id=EuB_AwAAQBAJ&amp;pg=PA241">Deutsch, 2014</a>; <a href="https://doi.org/10.1530/EJE-21-0059">Glintborg et al., 2021</a>; <a href="https://doi.org/10.3390/ijerph182312640">Tassinari &amp; Maranghi, 2021</a>; <a href="https://doi.org/10.1016/j.tips.2022.03.006">Le, Huang, &amp; Cirrincione, 2022</a>). Additionally, clinical studies in transfeminine people have reported high to very high estradiol levels with typical clinical doses of injectable estradiol (e.g., <a href="https://doi.org/10.1530/EJE-09-0265">Kronawitter et al., 2009</a> [<a href="https://archive.is/k2HTe">Table</a>]; <a href="https://doi.org/10.1055/s-0030-1255074">Mueller et al., 2011</a> [<a href="https://archive.is/cXyD5">Table</a>]; <a href="https://doi.org/10.1111/j.1447-0756.2011.01815.x">Sharula et al., 2012</a> [<a href="https://files.transfemscience.org/pdfs/docs/Sharula%20et%20al.%20(2012)%20Tables%201%20and%202%20Clinical%20Features%20+%20Laboratory%20Data.pdf">Data</a>]; <a href="https://doi.org/10.1089/trgh.2016.0016">Nelson et al., 2016</a> [<a href="https://archive.is/MlUU5">Table</a>]; <a href="https://doi.org/10.1016/j.fertnstert.2020.08.277">LaBudde, Craig, &amp; Spratt, 2020</a>; <a href="https://doi.org/10.4158/EP-2020-0414">Chantrapanichkul et al., 2021</a> [<a href="https://archive.is/arQvz">Table</a>]; <a href="https://doi.org/10.1089/lgbt.2020.0249">Cirrincione et al., 2021</a> [<a href="https://archive.is/Gk8Y5">Table</a>]).</p> <p>The reasons that dose recommendations for injectable estradiol in transfeminine people have remained as they have for so long may be related to several factors. These include (1) a long-standing lack of research and funding in transgender health; (2) injectable estradiol not being widely available or as commonly used as other forms of estradiol; and (3) many clinicians only testing estradiol levels at trough (right before the next injection) with injectable estradiol preparations (e.g., <a href="https://doi.org/10.1055/s-0030-1255074">Mueller et al., 2011</a>; <a href="https://doi.org/10.4158/EP-2020-0414">Chantrapanichkul et al., 2021</a>; <a href="https://doi.org/10.1089/lgbt.2020.0249">Cirrincione et al., 2021</a>). The latter point is noteworthy as trough levels only describe the lowest point of the estradiol concentration–time curve with injectable estradiol preparations, and can give a very misleading impression of average or total estradiol exposure. In any case, the very high estradiol levels with currently recommended doses of injectable estradiol forms for transfeminine people have not gone unnoticed in the literature (e.g., <a href="https://doi.org/10.1159/000087751">Gooren, 2005</a>; <a href="https://doi.org/10.1001/jama.2012.165234">Spack, 2013</a>; <a href="https://books.google.com/books?id=EuB_AwAAQBAJ&amp;pg=PA241">Deutsch, 2014</a>; <a href="https://doi.org/10.1530/EJE-21-0059">Glintborg et al., 2021</a>; <a href="https://doi.org/10.3390/ijerph182312640">Tassinari &amp; Maranghi, 2021</a>; <a href="https://doi.org/10.1016/j.tips.2022.03.006">Le, Huang, &amp; Cirrincione, 2022</a>). Additionally, studies in transfeminine people have reported high to very high estradiol levels with typical clinical doses of injectable estradiol (e.g., <a href="https://doi.org/10.1016/0026-0495(84)90248-8">Futterweit, Gabrilove, &amp; Smith, 1984</a> [<a href="https://archive.is/Pa6r3">Figure</a>]; <a href="https://doi.org/10.1530/EJE-09-0265">Kronawitter et al., 2009</a> [<a href="https://archive.is/k2HTe">Table</a>]; <a href="https://doi.org/10.1055/s-0030-1255074">Mueller et al., 2011</a> [<a href="https://archive.is/cXyD5">Table</a>]; <a href="https://doi.org/10.1111/j.1447-0756.2011.01815.x">Sharula et al., 2012</a> [<a href="https://files.transfemscience.org/pdfs/docs/Sharula%20et%20al.%20(2012)%20Tables%201%20and%202%20Clinical%20Features%20+%20Laboratory%20Data.pdf">Data</a>]; <a href="https://doi.org/10.1089/trgh.2016.0016">Nelson et al., 2016</a> [<a href="https://archive.is/MlUU5">Table</a>]; <a href="https://doi.org/10.1016/j.fertnstert.2020.08.277">LaBudde, Craig, &amp; Spratt, 2020</a>; <a href="https://doi.org/10.4158/EP-2020-0414">Chantrapanichkul et al., 2021</a> [<a href="https://archive.is/arQvz">Table</a>]; <a href="https://doi.org/10.1089/lgbt.2020.0249">Cirrincione et al., 2021</a> [<a href="https://archive.is/Gk8Y5">Table</a>]).</p>
<p>Among the surveyed guidelines for transgender hormone therapy, only the UCSF guidelines (<a href="https://transcare.ucsf.edu/guidelines/feminizing-hormone-therapy">Deutsch, 2016b</a>) and the <a href="https://sherbourne.on.ca/">Sherbourne Health</a>/<a href="https://www.rainbowhealthontario.ca/">Rainbow Health Ontario</a> guidelines (<a href="https://www.rainbowhealthontario.ca/product/4th-edition-sherbournes-guidelines-for-gender-affirming-primary-care-with-trans-and-non-binary-patients/">Bourns, 2019</a>) referenced pharmacokinetic literature in their discussion of injectable estradiol. The specific publications cited by these guidelines were <a href="https://doi.org/10.1016/0378-5122(82)90064-0">Düsterberg &amp; Nishino (1982)</a>, <a href="https://doi.org/10.1016/j.contraception.2011.03.014">Sierra-Ramírez et al. (2011)</a>, and <a href="https://doi.org/10.1016/j.contraception.2012.11.010">Thurman et al. (2013)</a>. Although it is favorable to see guidelines considering published pharmacokinetic data for informing use of these preparations, there are a few concerns about the studies that were cited. <a href="https://doi.org/10.1016/0378-5122(82)90064-0">Düsterberg &amp; Nishino (1982)</a> in its study of injectable estradiol valerate had a very small sample size (n=2), and this study was excluded as an outlier in the present meta-analysis due to unusually high estradiol levels. The findings of <a href="https://doi.org/10.1016/0378-5122(82)90064-0">Düsterberg &amp; Nishino (1982)</a> also do not seem to have actually been used to guide dosing recommendations in the case of the UCSF guidelines, since if this were the case, the recommended doses should have been much lower. On the other hand, <a href="https://www.rainbowhealthontario.ca/product/4th-edition-sherbournes-guidelines-for-gender-affirming-primary-care-with-trans-and-non-binary-patients/">Bourns (2019)</a> cited the same study and recommended injectable estradiol valerate at doses of 3–4 mg/week or 6–8 mg/2 weeks. These doses are well below those recommended by other transgender care guidelines and appear to be more appropriate for use in transfeminine people in light of the present meta-analysis. <a href="https://doi.org/10.1016/j.contraception.2011.03.014">Sierra-Ramírez et al. (2011)</a> and <a href="https://doi.org/10.1016/j.contraception.2012.11.010">Thurman et al. (2013)</a>, although better-quality studies than <a href="https://doi.org/10.1016/0378-5122(82)90064-0">Düsterberg &amp; Nishino (1982)</a>, described injectable estradiol cypionate suspension rather than estradiol cypionate in oil. The oil-based version of estradiol cypionate is the form normally used in transfeminine hormone therapy, and there are important differences between these estradiol cypionate preparations such that pharmacokinetic studies for the suspension can’t necessarily be generalized to the oil solution. These preparations do in any case produce similar total estradiol levels however and hence doses should be comparable for them.</p> <p>Among the surveyed guidelines for transgender hormone therapy, only the UCSF guidelines (<a href="https://transcare.ucsf.edu/guidelines/feminizing-hormone-therapy">Deutsch, 2016b</a>) and the <a href="https://sherbourne.on.ca/">Sherbourne Health</a>/<a href="https://www.rainbowhealthontario.ca/">Rainbow Health Ontario</a> guidelines (<a href="https://www.rainbowhealthontario.ca/product/4th-edition-sherbournes-guidelines-for-gender-affirming-primary-care-with-trans-and-non-binary-patients/">Bourns, 2019</a>) referenced pharmacokinetic literature in their discussion of injectable estradiol. The specific publications cited by these guidelines were <a href="https://doi.org/10.1016/0378-5122(82)90064-0">Düsterberg &amp; Nishino (1982)</a>, <a href="https://doi.org/10.1016/j.contraception.2011.03.014">Sierra-Ramírez et al. (2011)</a>, and <a href="https://doi.org/10.1016/j.contraception.2012.11.010">Thurman et al. (2013)</a>. Although it is favorable to see guidelines considering published pharmacokinetic data for informing use of these preparations, there are a few concerns about the studies that were cited. <a href="https://doi.org/10.1016/0378-5122(82)90064-0">Düsterberg &amp; Nishino (1982)</a> in its study of injectable estradiol valerate had a very small sample size (n=2), and this study was excluded as an outlier in the present meta-analysis due to unusually high estradiol levels. The findings of <a href="https://doi.org/10.1016/0378-5122(82)90064-0">Düsterberg &amp; Nishino (1982)</a> also do not seem to have actually been used to guide dosing recommendations in the case of the UCSF guidelines, since if this were the case, the recommended doses should have been much lower. On the other hand, <a href="https://www.rainbowhealthontario.ca/product/4th-edition-sherbournes-guidelines-for-gender-affirming-primary-care-with-trans-and-non-binary-patients/">Bourns (2019)</a> cited the same study and recommended injectable estradiol valerate at doses of 3–4 mg/week or 6–8 mg/2 weeks. These doses are well below those recommended by other transgender care guidelines and appear to be more appropriate for use in transfeminine people in light of the present meta-analysis. <a href="https://doi.org/10.1016/j.contraception.2011.03.014">Sierra-Ramírez et al. (2011)</a> and <a href="https://doi.org/10.1016/j.contraception.2012.11.010">Thurman et al. (2013)</a>, although better-quality studies than <a href="https://doi.org/10.1016/0378-5122(82)90064-0">Düsterberg &amp; Nishino (1982)</a>, described injectable estradiol cypionate suspension rather than estradiol cypionate in oil. The oil-based version of estradiol cypionate is the form normally used in transfeminine hormone therapy, and there are important differences between these estradiol cypionate preparations such that pharmacokinetic studies for the suspension can’t necessarily be generalized to the oil solution. These preparations do in any case produce similar total estradiol levels however and hence doses should be comparable for them.</p>
@ -1898,7 +1898,7 @@ Using the term desistence in this way does not imply anything about the identity
<h3 id="update-1-wpath-soc8-guidelines">Update 1: WPATH SOC8 Guidelines</h3> <h3 id="update-1-wpath-soc8-guidelines">Update 1: WPATH SOC8 Guidelines</h3>
<p>In September 2022, the <a href="https://en.wikipedia.org/wiki/World_Professional_Association_for_Transgender_Health">World Professional Association for Transgender Health</a> (WPATH) <a href="https://en.wikipedia.org/wiki/Standards_of_Care_for_the_Health_of_Transgender_and_Gender_Diverse_People">Standards of Care for the Health of Transgender and Gender Diverse People</a> Version 8 (SOC8) were published and made recommendations on transgender hormone therapy for the first time (<a href="https://doi.org/10.1080/26895269.2022.2100644">Coleman et al., 2022</a>). These guidelines are among the most highly regarded and consulted transgender care guidelines. In terms of the recommended doses of hormonal medications for transgender people, the WPATH SOC8 appear to have largely copied the <a href="https://en.wikipedia.org/wiki/Endocrine_Society">Endocrine Society’s</a> 2017 guidelines on transgender hormone therapy (<a href="https://doi.org/10.1210/jc.2017-01658">Hembree et al., 2017</a>). More specifically, in the case of injectable estradiol preparations for transfeminine people, doses of 5–30 mg/2 weeks or 2–10 mg/week estradiol valerate or estradiol cypionate were recommended. There was no discussion of injectable estradiol in the guidelines besides the preceding doses and intervals being included in a table, and no literature citations were included to support these doses. As described in the present work, these recommendations include doses and intervals that appear to be highly excessive, too widely spaced, and are likely unsafe. As such, major transgender care guidelines unfortunately continue to make uncited recommendations for injectable estradiol in transfeminine people that are out of step with insights available from abundant published pharmacokinetic data. These recommendations are likely inadvisable, with the possibility of substantial safety risks.</p> <p>In September 2022, the <a href="https://en.wikipedia.org/wiki/World_Professional_Association_for_Transgender_Health">World Professional Association for Transgender Health</a> (WPATH) <a href="https://en.wikipedia.org/wiki/Standards_of_Care_for_the_Health_of_Transgender_and_Gender_Diverse_People">Standards of Care for the Health of Transgender and Gender Diverse People</a> Version 8 (SOC8) were published and made recommendations on transgender hormone therapy for the first time (<a href="https://doi.org/10.1080/26895269.2022.2100644">Coleman et al., 2022</a>). These guidelines are among the most highly regarded and consulted transgender care guidelines. In terms of the recommended doses of hormonal medications for transgender people, the WPATH SOC8 appear to have largely copied the <a href="https://en.wikipedia.org/wiki/Endocrine_Society">Endocrine Society’s</a> 2017 guidelines on transgender hormone therapy (<a href="https://doi.org/10.1210/jc.2017-01658">Hembree et al., 2017</a>). More specifically, in the case of injectable estradiol preparations for transfeminine people, doses of 5–30 mg/2 weeks or 2–10 mg/week estradiol valerate or estradiol cypionate were recommended. There was no discussion of injectable estradiol in the guidelines besides the preceding doses and intervals being included in a table, and no literature citations were included to support these doses. As described in the present work, these recommendations include doses and intervals that appear to be highly excessive, too widely spaced, and are likely unsafe. As such, major transgender care guidelines unfortunately continue to make uncited recommendations for injectable estradiol that are out of step with insights available from abundant published pharmacokinetic data. These recommendations are likely inadvisable, with the possibility of substantial health risks.</p>
<h3 id="update-2-literature-mentions">Update 2: Literature Mentions</h3> <h3 id="update-2-literature-mentions">Update 2: Literature Mentions</h3>
@ -1942,6 +1942,26 @@ Using the term desistence in this way does not imply anything about the identity
<p>It may happen in consultation that the person does not wish to use the prescribed estrogens and wishes to continue the self-prescription of injectable estrogens. It is then possible to evaluate with them the most suitable dosage using the Transfem Science Injection Simulator (https://transfemscience.org/misc/injectable-e2-simulator/). Risk prevention related to injections (needles) can be done. Associations can help the person find 25 G needles of 40 mm useful this type of treatment.</p> <p>It may happen in consultation that the person does not wish to use the prescribed estrogens and wishes to continue the self-prescription of injectable estrogens. It is then possible to evaluate with them the most suitable dosage using the Transfem Science Injection Simulator (https://transfemscience.org/misc/injectable-e2-simulator/). Risk prevention related to injections (needles) can be done. Associations can help the person find 25 G needles of 40 mm useful this type of treatment.</p>
</blockquote> </blockquote>
<h4 id="rothman-et-al-2024">Rothman et al. (2024)</h4>
<p>Rothman, M. S., Ariel, D., Kelley, C., Hamnvik, O. R., Abramowitz, J., Irwig, M. S., Soe, K., Davidge-Pitts, C., Misakian, A. L., Safer, J. D., &amp; Iwamoto, S. J. (2024). The Use of Injectable Estradiol in Transgender and Gender Diverse Adults: A Scoping Review of Dose and Serum Estradiol Levels. <em>Endocrine Practice</em>, ahead of print. [DOI:<a href="https://doi.org/10.1016/j.eprac.2024.05.008">10.1016/j.eprac.2024.05.008</a>]:</p>
<blockquote>
<p>In recent years, we have noted trends in our clinical practices with TGD adults requesting injectable estradiol, particularly in the United States. The reasons given can vary; it may be due to ease of weekly or every two weeks administration, fatigue of taking daily oral medications and skin reactions to or cost of transdermal preparations. There have been discussions as to the roles of estrone/estradiol ratios in feminization and whether injectable estradiol might lead to more favorable results, however research has not supported a role for estrone in optimizing feminizing outcomes [13]. There is also a belief that higher levels can be attained with 82 injections and may lead to faster and more complete feminization; however, there is a lack of data in the literature to support these conclusions. Such conversations occurring on reddit.com and even some hormone provider websites, are perhaps related to the historical use of high dose injectable estradiol noted above [14]. However, there is a paucity of data to guide clinicians on what dose, type and at what interval estradiol esters should be injected and when levels should be measured to ensure physiologic range estradiol levels. In fact, recent reports and clinical observations have raised concerns that the dosing suggested in guidelines may result in supraphysiological estradiol levels and that higher doses and levels may put patients at elevated risk of thromboembolic events [15-18]. This scoping review examines the available data on levels achieved with various dosages of estradiol injections in TGD adults. We also report on testosterone suppression, route (i.e., SC vs. IM), and type of estradiol ester as well as timing of blood draw relative to dose, where available.</p>
</blockquote>
<blockquote>
<p>Acknowledgment</p>
<p>[…] [We] thank Aly from Transfemscience for community representation and correspondence.</p>
</blockquote>
<blockquote>
<ol>
<li>https://transfemscience.org/articles/injectable-e2-meta-analysis/. [March 16, 2024].</li>
</ol>
</blockquote>
<h3 id="update-3-herndon-et-al-2023">Update 3: Herndon et al. (2023)</h3> <h3 id="update-3-herndon-et-al-2023">Update 3: Herndon et al. (2023)</h3>
<p>In March 2023, the following study on injectable estradiol in transfeminine people was published online:</p> <p>In March 2023, the following study on injectable estradiol in transfeminine people was published online:</p>
@ -1980,9 +2000,9 @@ Using the term desistence in this way does not imply anything about the identity
<p>The findings of Herndon et al. (2023) are pleasingly consistent with the results of the present meta-analysis. Based on the findings of this meta-analysis, assuming a linear relationship between dose and estradiol levels, estradiol levels with non-polymeric injectable estradiol esters, like estradiol valerate and estradiol cypionate in oil via intramuscular injection, increase by around 60 pg/mL on average for each 1 mg per week in dose (with Herndon et al. (2023) finding a value of 57 pg/mL per 1 mg using a multiple linear regression model). In relation to this, mean integrated estradiol levels of around 250 pg/mL on average would be expected at a dosage of 4 mg once per week. Accordingly, Herndon et al. (2023) found median estradiol levels of 190 to 196 pg/mL at per-week median doses of 3.75 to 4 mg. Similarly, the present work recommended injectable estradiol doses with non-polymeric esters of 1 to 6 mg per week (to achieve mean integrated estradiol levels of roughly 50–300 pg/mL), which is comparable to the range of about 2 to 6 mg per week used in most transfeminine people in Herndon et al. (2023) (to achieve estradiol levels of at least 100 pg/mL, along with adequate testosterone suppression). Additionally, it was noted in this meta-analysis—based on clinical research in cisgender men with prostate cancer—that only modestly supraphysiological estradiol levels, of no more than approximately 200 to 300 pg/mL, are likely to be needed for strong testosterone suppression in transfeminine people. This has likewise been confirmed with solid clinical data in transfeminine people by Herndon et al. (2023), with 88% of those on injectable estradiol monotherapy having testosterone levels of &lt;50 ng/dL at a median injectable estradiol dose of 4 mg/week and with median estradiol levels of 220 pg/mL. It is the opinion of the present author that Herndon et al. (2023) is a very important and formative study, with clinical implications that go far beyond merely supporting the s.c. use of injectable estradiol. The study represents the first major step in the published literature to correcting the dosing and intervals of injectable estradiol in transgender care guidelines and in transgender health generally. I commend the researchers for their work.</p> <p>The findings of Herndon et al. (2023) are pleasingly consistent with the results of the present meta-analysis. Based on the findings of this meta-analysis, assuming a linear relationship between dose and estradiol levels, estradiol levels with non-polymeric injectable estradiol esters, like estradiol valerate and estradiol cypionate in oil via intramuscular injection, increase by around 60 pg/mL on average for each 1 mg per week in dose (with Herndon et al. (2023) finding a value of 57 pg/mL per 1 mg using a multiple linear regression model). In relation to this, mean integrated estradiol levels of around 250 pg/mL on average would be expected at a dosage of 4 mg once per week. Accordingly, Herndon et al. (2023) found median estradiol levels of 190 to 196 pg/mL at per-week median doses of 3.75 to 4 mg. Similarly, the present work recommended injectable estradiol doses with non-polymeric esters of 1 to 6 mg per week (to achieve mean integrated estradiol levels of roughly 50–300 pg/mL), which is comparable to the range of about 2 to 6 mg per week used in most transfeminine people in Herndon et al. (2023) (to achieve estradiol levels of at least 100 pg/mL, along with adequate testosterone suppression). Additionally, it was noted in this meta-analysis—based on clinical research in cisgender men with prostate cancer—that only modestly supraphysiological estradiol levels, of no more than approximately 200 to 300 pg/mL, are likely to be needed for strong testosterone suppression in transfeminine people. This has likewise been confirmed with solid clinical data in transfeminine people by Herndon et al. (2023), with 88% of those on injectable estradiol monotherapy having testosterone levels of &lt;50 ng/dL at a median injectable estradiol dose of 4 mg/week and with median estradiol levels of 220 pg/mL. It is the opinion of the present author that Herndon et al. (2023) is a very important and formative study, with clinical implications that go far beyond merely supporting the s.c. use of injectable estradiol. The study represents the first major step in the published literature to correcting the dosing and intervals of injectable estradiol in transgender care guidelines and in transgender health generally. I commend the researchers for their work.</p>
<h3 id="update-4-rothman-et-al-2024">Update 4: Rothman et al. (2024)</h3> <h3 id="update-4-rothman-et-al-2024a-and-rothman-et-al-2024b">Update 4: Rothman et al. (2024a) and Rothman et al. (2024b)</h3>
<p>In February 2024, the following review on injectable estradiol in transfeminine people was published online:</p> <p>In February 2024, the following short review on injectable estradiol dosing in transfeminine people by Micol Rothman and colleagues was published online:</p>
<ul> <ul>
<li>Rothman, M. S., Hamnvik, O. P. R., Davidge-Pitts, C., Safer, J. D., Ariel, D., Tangpricha, V., Abramowitz, J., Soe, K., Sarvaideo, J., Kelley, C., Irwig, M. S., &amp; Iwamoto, S. J. (2024). Revisiting Injectable Estrogen Dosing Recommendations for Gender-Affirming Hormone Therapy. <em>Transgender Health</em>, ahead of print. [DOI:<a href="https://doi.org/10.1089/trgh.2023.0209">10.1089/trgh.2023.0209</a>]</li> <li>Rothman, M. S., Hamnvik, O. P. R., Davidge-Pitts, C., Safer, J. D., Ariel, D., Tangpricha, V., Abramowitz, J., Soe, K., Sarvaideo, J., Kelley, C., Irwig, M. S., &amp; Iwamoto, S. J. (2024). Revisiting Injectable Estrogen Dosing Recommendations for Gender-Affirming Hormone Therapy. <em>Transgender Health</em>, ahead of print. [DOI:<a href="https://doi.org/10.1089/trgh.2023.0209">10.1089/trgh.2023.0209</a>]</li>
@ -1994,6 +2014,56 @@ Using the term desistence in this way does not imply anything about the identity
<p>Injectable estrogens are options for gender-affirming hormone therapy per guidelines, which suggest intramuscular dosages of 5–30 mg every 2 weeks or 2–10 mg weekly with estradiol cypionate or valerate interchangeably. Data among transgender and gender-diverse patients are limited due to local unavailability and concerns around laboratory assay variability and estradiol (E2) level fluctuation. We note a concerning trend where patients are prescribed high-dose injections based on the guidelines leading to serum E2 levels well above the range recommended in the same guidelines. Our review indicates that 5 mg weekly or lower should be prescribed when initiating injectable estrogens to avoid supraphysiologic E2 levels.</p> <p>Injectable estrogens are options for gender-affirming hormone therapy per guidelines, which suggest intramuscular dosages of 5–30 mg every 2 weeks or 2–10 mg weekly with estradiol cypionate or valerate interchangeably. Data among transgender and gender-diverse patients are limited due to local unavailability and concerns around laboratory assay variability and estradiol (E2) level fluctuation. We note a concerning trend where patients are prescribed high-dose injections based on the guidelines leading to serum E2 levels well above the range recommended in the same guidelines. Our review indicates that 5 mg weekly or lower should be prescribed when initiating injectable estrogens to avoid supraphysiologic E2 levels.</p>
</blockquote> </blockquote>
<p>Then, in May 2024, the following longer and more comprehensive review on injectable estradiol dosing in transfeminine people by Rothman and most of the same other academics was published online:</p>
<ul>
<li>Rothman, M. S., Ariel, D., Kelley, C., Hamnvik, O. R., Abramowitz, J., Irwig, M. S., Soe, K., Davidge-Pitts, C., Misakian, A. L., Safer, J. D., &amp; Iwamoto, S. J. (2024). The Use of Injectable Estradiol in Transgender and Gender Diverse Adults: A Scoping Review of Dose and Serum Estradiol Levels. <em>Endocrine Practice</em>, ahead of print. [DOI:<a href="https://doi.org/10.1016/j.eprac.2024.05.008">10.1016/j.eprac.2024.05.008</a>]</li>
</ul>
<p>Here is the abstract of this paper:</p>
<blockquote>
<p>Objective: Feminizing gender-affirming hormone therapy is the mainstay of treatment for many transgender and gender diverse people. Injectable estradiol preparations are recommended by the World Professional Association for Transgender Health Standards of Care 8 and the Endocrine Society guidelines. Many patients prefer this route of administration, but few studies have rigorously assessed optimal dosing or route.</p>
<p>Methods: We performed a scoping review of the available data on estradiol levels achieved with various dosages of estradiol injections in transgender and gender diverse adults on feminizing gender-affirming hormone therapy. We also report on testosterone suppression, route (ie, subcutaneous vs intramuscular), and type of injectable estradiol ester as well as timing of blood draw relative to the most recent dose, where available.</p>
<p>Results: The data we reviewed suggest that the current guidelines, which recommend starting doses 2 to 10 mg weekly or 5 to 30 mg every 2 weeks of estradiol cypionate or valerate, are too high and likely lead to patients having supraphysiologic levels across much of their injection cycle.</p>
<p>Conclusions: The optimal starting dose for injectable estradiol remains unclear and whether it should differ for cypionate and valerate. Based on the data available, we suggest that clinicians start injectable estradiol cypionate or valerate via subcutaneous or intramuscular injections at a dose ≤5 mg weekly and then titrate accordingly to keep levels within guideline-recommended range. Future studies should assess timing of injections and subsequent levels more precisely across the injection cycle and between esters.</p>
</blockquote>
<p>This paper notably also cited the present Transfeminine Science article as raising concerns about guideline-based dosing for injectable estradiol and potential health complications from these doses.</p>
<p>Aside from Micol Rothman herself, these reviews were also authored by other well-known experts in transgender health. For instance, two of the coauthors, Joshua Safer and Michael Irwig, were authors for the WPATH SOC8 hormone therapy chapter (<a href="https://www.wpath.org/media/cms/Documents/SOC%20v8/SOC8%20Full%20Contributor%20List%20-%20FINAL%20UPDATED%2009232021.pdf">WPATH SOC8 Full Contributor List</a>). Additionally, Safer was one of the authors for the Endocrine Society’s transgender hormone therapy guidelines (<a href="https://doi.org/10.1210/jc.2017-01658">Hembree et al., 2017</a>). As such, it would appear that transgender medicine has finally started to seriously correct injectable estradiol dosing. This is a very important development. Now, the appropriate dosing and intervals of injectable estradiol will need to be more precisely established and the corrections will need to make their way into updated transgender hormone therapy guidelines and general clinical practice.</p>
<h2 id="update-5-kariyawasam-et-al-2024">Update 5: Kariyawasam et al. (2024)</h2>
<p>In March 2024, the following study of estradiol levels with different routes of estradiol in transfeminine people, including injectable estradiol, was published:</p>
<ul>
<li>Kariyawasam, N. M., Ahmad, T., Sarma, S., &amp; Fung, R. (2024). Comparison of Estrone/Estradiol Ratio and Levels in Transfeminine Individuals on Different Routes of Estradiol. <em>Transgender Health</em>, ahead of print. [DOI:<a href="https://doi.org/10.1089/trgh.2023.0138">10.1089/trgh.2023.0138</a>]</li>
</ul>
<p>The study stratified injectable estradiol doses into different dosing levels, accounted for timing of blood draws, and compared injectable estradiol to other estradiol routes. The other routes included oral estradiol, sublingual estradiol, and transdermal estradiol. The form of injectable estradiol used was estradiol valerate in dose groups including ≤4 mg/week (“low-dose”), &gt;4 mg/week to ≤8 mg/week (“medium-dose”), and &gt;8 mg/week (“high-dose”). In the study, this injectable estradiol regimen resulted in supraphysiological estradiol levels in the medium- to high-dose groups (&gt;4 mg/week) and dramatically higher estradiol levels than with the other estradiol routes (<a href="https://archive.is/yDHV0">Data</a>). Median estradiol levels were reported in a subsequent paper as follows: “Figure 2 from the paper shows estradiol levels across the 3 groups. Although exact numbers are not given in this figure, we learned through correspondence with the authors that the low dose injection group [n=8] had a median level of 202.7 ± SD 232.6 pg/mL, the medium group [n=22] 465.2 ± SD 466.3 pg/mL, and the high group [n=3] 574.4 ± SD147.3 pg/mL (converted from SI units)” (<a href="https://doi.org/10.1016/j.eprac.2024.05.008">Rothman et al., 2024b</a>). Although the sample sizes for the different dose groups were small, this study, along with <a href="https://doi.org/10.1016/j.eprac.2023.02.006">Herndon et al. (2023)</a>, provides some of the best clinical data on estradiol levels with injectable estradiol in transfeminine people that have so far been published.</p>
<h2 id="update-6-patel-et-al-2024">Update 6: Patel et al. (2024)</h2>
<p>In June 2024, the following open-access review discussing injectable estradiol in transfeminine people and calling for updated transgender health guidelines was published:</p>
<ul>
<li>Patel, R., Korenman, S., Weimer, A., &amp; Grock, S. (2024). A Call for Updates to Hormone Therapy Guidelines for Gender-Diverse Adults Assigned Male at Birth. <em>Cureus</em>, <em>16</em>(6), e62262. [DOI:<a href="https://doi.org/10.7759/cureus.62262">10.7759/cureus.62262</a>] [<a href="https://assets.cureus.com/uploads/editorial/pdf/256537/20240612-31130-lgqwyn.pdf">PDF</a>]</li>
</ul>
<p>The following quote is the relevant excerpt on injectable estradiol from the review:</p>
<blockquote>
<p>The current guideline-based dosing recommendations for estradiol vary considerably, which is problematic for clinicians and patients who rely on guidelines to initiate treatment. Most notably, the conversion rates between parenteral estradiol valerate and estradiol cypionate vary drastically between the UCSF Guidelines for the Primary and Gender-Affirming Care of Transgender and Gender Nonbinary People (UCSF Guidelines) and The Endocrine Society Clinical Practice Guidelines for Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons (the Endocrine Society Guidelines). The UCSF Guidelines indicate the conversion between estradiol valerate and cypionate to be as high as a 4:1 ratio [2], while the Endocrine Society Guidelines provide no dosing differentiations [1]. Herndon and colleagues demonstrated that the conversion between estradiol cypionate and estradiol valerate is closer to 1:1 [4]. Further equivalence studies are needed to clarify ideal dosing conversions.</p>
<p>The Endocrine Society Guidelines recommend titrating estradiol to 100-200 pg/mL [1]. The UCSF Guidelines recommend 2-4 mg daily as the starting dose for oral estradiol and 5 mg weekly for parenteral estradiol valerate [2]. The Endocrine Society Guidelines suggest oral estradiol 2-6 mg daily and parenteral estradiol 2- 10 mg weekly [1]. However, Chantrapanichkul et al. found that intramuscular injections of estradiol valerate greater than 5 mg weekly led to mean estradiol concentrations well above 200 pg/mL, while 4-5 mg of oral estradiol daily only led to minimum desired concentrations [5]. Similarly, Herndon et al. found that subcutaneous estradiol at a median dose of 3.75 mg per week led to a median estradiol level of 196 pg/mL [4]. Thus, current guideline-based dosing may lead providers to choose doses of injectable estradiol that would result in supratherapeutic serum estradiol levels. In light of these recent publications, it is clear that guideline-based dosing for estradiol needs updating. In our clinical experience, parenteral estradiol valerate at doses of 2-4 mg weekly typically leads to physiologic estradiol levels. Estradiol cypionate should likely be dosed in a 1:1 ratio with estradiol valerate until future data are obtained.</p>
<p>Lastly, while estradiol valerate and cypionate are only FDA-approved for intramuscular administration, many patients prefer subcutaneous administration. There are small studies that suggest the pharmacokinetics of intramuscular and subcutaneous estradiol are similar [4]. While the UCSF Guidelines comment on the use of subcutaneous estradiol, other guidelines should be updated to include this option for patients [2].</p>
</blockquote>
<h2 id="supplementary-material">Supplementary Material</h2> <h2 id="supplementary-material">Supplementary Material</h2>
<ul> <ul>
@ -2051,6 +2121,7 @@ Using the term desistence in this way does not imply anything about the identity
<li>Fisher, D., &amp; Shafer, S. (2007). <em>Fisher/Shafer NONMEM Workshop Pharmacokinetic and Pharmacodynamic Analysis with NONMEM. Basic Concepts.</em> [<a href="https://web.archive.org/web/20210717084442if_/https://wiki.ucl.ac.uk/download/attachments/23206987/Shafer%20NONMEM.pdf">PDF</a>]</li> <li>Fisher, D., &amp; Shafer, S. (2007). <em>Fisher/Shafer NONMEM Workshop Pharmacokinetic and Pharmacodynamic Analysis with NONMEM. Basic Concepts.</em> [<a href="https://web.archive.org/web/20210717084442if_/https://wiki.ucl.ac.uk/download/attachments/23206987/Shafer%20NONMEM.pdf">PDF</a>]</li>
<li>Florence, A. T. (2010). Looking at Formulations. In Florence, A. T. <em>An Introduction to Clinical Pharmaceutics</em> (pp. 69–100). London/Chicago: Pharmaceutical Press. [<a href="https://scholar.google.com/scholar?cluster=10923988500882019865">Google Scholar</a>] [<a href="https://books.google.com/books?id=5wcyP2OBPhoC&amp;pg=PA69">Google Books</a>]</li> <li>Florence, A. T. (2010). Looking at Formulations. In Florence, A. T. <em>An Introduction to Clinical Pharmaceutics</em> (pp. 69–100). London/Chicago: Pharmaceutical Press. [<a href="https://scholar.google.com/scholar?cluster=10923988500882019865">Google Scholar</a>] [<a href="https://books.google.com/books?id=5wcyP2OBPhoC&amp;pg=PA69">Google Books</a>]</li>
<li>Fotherby, K., Benagiano, G., Toppozada, H. K., Abdel-Rahman, A., Navaroli, F., Arce, B., Ramos-Cordero, R., Gual, C., Landgren, B. M., &amp; Johannisson, E. (1982). A preliminary pharmacological trial of the monthly injectable contraceptive Cycloprovera. <em>Contraception</em>, <em>25</em>(3), 261–272. [DOI:<a href="https://doi.org/10.1016/0010-7824(82)90049-X">10.1016/0010-7824(82)90049-X</a>]</li> <li>Fotherby, K., Benagiano, G., Toppozada, H. K., Abdel-Rahman, A., Navaroli, F., Arce, B., Ramos-Cordero, R., Gual, C., Landgren, B. M., &amp; Johannisson, E. (1982). A preliminary pharmacological trial of the monthly injectable contraceptive Cycloprovera. <em>Contraception</em>, <em>25</em>(3), 261–272. [DOI:<a href="https://doi.org/10.1016/0010-7824(82)90049-X">10.1016/0010-7824(82)90049-X</a>]</li>
<li>Futterweit, W., Gabrilove, J., &amp; Smith, H. (1984). Testicular steroidogenic response to human chorionic gonadotropin of fifteen male transsexuals on chronic estrogen treatment. <em>Metabolism</em>, <em>33</em>(10), 936–942. [DOI:<a href="https://doi.org/10.1016/0026-0495(84)90248-8">10.1016/0026-0495(84)90248-8</a>] [<a href="https://archive.is/Pa6r3">Figure</a>]</li>
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@ -2128,6 +2201,7 @@ Using the term desistence in this way does not imply anything about the identity
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<li>Zhou, X. F., Shao, Q. X., Han, X. J., Weng, L. J., &amp; Sang, G. W. (1998). Pharmacokinetics of medroxyprogesterone acetate after single and multiple injection of Cyclofem<sup>®</sup> in Chinese women. <em>Contraception</em>, <em>57</em>(6), 405–411. [DOI:<a href="https://doi.org/10.1016/S0010-7824(98)00048-1">10.1016/S0010-7824(98)00048-1</a>]</li> <li>Zhou, X. F., Shao, Q. X., Han, X. J., Weng, L. J., &amp; Sang, G. W. (1998). Pharmacokinetics of medroxyprogesterone acetate after single and multiple injection of Cyclofem<sup>®</sup> in Chinese women. <em>Contraception</em>, <em>57</em>(6), 405–411. [DOI:<a href="https://doi.org/10.1016/S0010-7824(98)00048-1">10.1016/S0010-7824(98)00048-1</a>]</li>
</ul>]]></content><author><name>{&quot;first_name&quot;=&gt;&quot;Aly&quot;, &quot;last_name&quot;=&gt;&quot;W.&quot;, &quot;author-link&quot;=&gt;&quot;/about/#aly&quot;, &quot;articles-link&quot;=&gt;&quot;/articles-by-author/aly/&quot;}</name></author><category term="github" /><category term="workspace" /><summary type="html"><![CDATA[An Informal Meta-Analysis of Estradiol Curves with Injectable Estradiol Preparations By Aly | First published July 16, 2021 | Last modified April 3, 2024]]></summary></entry><entry><title type="html">An Exploration of Sublingual Estradiol as an Alternative to Oral Estradiol in Transfeminine People</title><link href="https://transfemscience.org/articles/sublingual-e2-transfem/" rel="alternate" type="text/html" title="An Exploration of Sublingual Estradiol as an Alternative to Oral Estradiol in Transfeminine People" /><published>2021-06-11T20:26:25-07:00</published><updated>2024-03-30T00:00:00-07:00</updated><id>https://transfemscience.org/articles/sublingual-e2-transfem</id><content type="html" xml:base="https://transfemscience.org/articles/sublingual-e2-transfem/"><![CDATA[<h1 id="an-exploration-of-sublingual-estradiol-as-an-alternative-to-oral-estradiol-in-transfeminine-people">An Exploration of Sublingual Estradiol as an Alternative to Oral Estradiol in Transfeminine People</h1> </ul>]]></content><author><name>{&quot;first_name&quot;=&gt;&quot;Aly&quot;, &quot;last_name&quot;=&gt;&quot;W.&quot;, &quot;author-link&quot;=&gt;&quot;/about/#aly&quot;, &quot;articles-link&quot;=&gt;&quot;/articles-by-author/aly/&quot;}</name></author><category term="github" /><category term="workspace" /><summary type="html"><![CDATA[An Informal Meta-Analysis of Estradiol Curves with Injectable Estradiol Preparations By Aly | First published July 16, 2021 | Last modified June 27, 2024]]></summary></entry><entry><title type="html">An Exploration of Sublingual Estradiol as an Alternative to Oral Estradiol in Transfeminine People</title><link href="https://transfemscience.org/articles/sublingual-e2-transfem/" rel="alternate" type="text/html" title="An Exploration of Sublingual Estradiol as an Alternative to Oral Estradiol in Transfeminine People" /><published>2021-06-11T20:26:25-07:00</published><updated>2024-03-30T00:00:00-07:00</updated><id>https://transfemscience.org/articles/sublingual-e2-transfem</id><content type="html" xml:base="https://transfemscience.org/articles/sublingual-e2-transfem/"><![CDATA[<h1 id="an-exploration-of-sublingual-estradiol-as-an-alternative-to-oral-estradiol-in-transfeminine-people">An Exploration of Sublingual Estradiol as an Alternative to Oral Estradiol in Transfeminine People</h1>
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@ -2437,13 +2511,13 @@ Using the term desistence in this way does not imply anything about the identity
<li>Wren, B. G., Day, R. O., McLachlan, A. J., &amp; Williams, K. M. (2003). Pharmacokinetics of estradiol, progesterone, testosterone and dehydroepiandrosterone after transbuccal administration to postmenopausal women. <em>Climacteric</em>, <em>6</em>(2), 104–111. [DOI:<a href="https://doi.org/10.1080/cmt.6.2.104.111">10.1080/cmt.6.2.104.111</a>]</li> <li>Wren, B. G., Day, R. O., McLachlan, A. J., &amp; Williams, K. M. (2003). Pharmacokinetics of estradiol, progesterone, testosterone and dehydroepiandrosterone after transbuccal administration to postmenopausal women. <em>Climacteric</em>, <em>6</em>(2), 104–111. [DOI:<a href="https://doi.org/10.1080/cmt.6.2.104.111">10.1080/cmt.6.2.104.111</a>]</li>
<li>Yaish, I., Gindis, G., Greenman, Y., Moshe, Y., Arbiv, M., Buch, A., Sofer, Y., Shefer, G., &amp; Tordjman, K. (2023). Sublingual Estradiol Offers No Apparent Advantage Over Combined Oral Estradiol and Cyproterone Acetate for Gender-Affirming Hormone Therapy of Treatment-Naive Trans Women: Results of a Prospective Pilot Study. <em>Transgender Health</em>, <em>8</em>(6), 485–493. [DOI:<a href="https://doi.org/10.1089/trgh.2023.0022">10.1089/trgh.2023.0022</a>]</li> <li>Yaish, I., Gindis, G., Greenman, Y., Moshe, Y., Arbiv, M., Buch, A., Sofer, Y., Shefer, G., &amp; Tordjman, K. (2023). Sublingual Estradiol Offers No Apparent Advantage Over Combined Oral Estradiol and Cyproterone Acetate for Gender-Affirming Hormone Therapy of Treatment-Naive Trans Women: Results of a Prospective Pilot Study. <em>Transgender Health</em>, <em>8</em>(6), 485–493. [DOI:<a href="https://doi.org/10.1089/trgh.2023.0022">10.1089/trgh.2023.0022</a>]</li>
<li>Yaish, I., Gindis, G., Greenman, Y., Shefer, G., Buch, A., Arbiv, M., Moshe, Y., Sofer, Y., &amp; Tordjman, K. M. (2023). Sublingual Estradiol Only, Compared To Combined Oral Estradiol And Cyproterone Acetate,Offers No Apparent Advantage For Gender Affirming Hormone Therapy (GHAT), In Treatment Naïve Transwomen: Results Of A Prospective Pilot Study. <em>Journal of the Endocrine Society</em>, <em>7</em>(Suppl 1) [<em>ENDO 2023 Abstracts Annual Meeting of the Endocrine Society</em>], A1104–A1105 (abstract no. SAT409/bvad114.2080). [DOI:<a href="https://doi.org/10.1210/jendso/bvad114.2080">10.1210/jendso/bvad114.2080</a>] [<a href="https://academic.oup.com/jes/article-pdf/7/Supplement_1/bvad114.2080/51899408/bvad114.2080.pdf">PDF</a>]</li> <li>Yaish, I., Gindis, G., Greenman, Y., Shefer, G., Buch, A., Arbiv, M., Moshe, Y., Sofer, Y., &amp; Tordjman, K. M. (2023). Sublingual Estradiol Only, Compared To Combined Oral Estradiol And Cyproterone Acetate,Offers No Apparent Advantage For Gender Affirming Hormone Therapy (GHAT), In Treatment Naïve Transwomen: Results Of A Prospective Pilot Study. <em>Journal of the Endocrine Society</em>, <em>7</em>(Suppl 1) [<em>ENDO 2023 Abstracts Annual Meeting of the Endocrine Society</em>], A1104–A1105 (abstract no. SAT409/bvad114.2080). [DOI:<a href="https://doi.org/10.1210/jendso/bvad114.2080">10.1210/jendso/bvad114.2080</a>] [<a href="https://academic.oup.com/jes/article-pdf/7/Supplement_1/bvad114.2080/51899408/bvad114.2080.pdf">PDF</a>]</li>
</ul>]]></content><author><name>{&quot;first_name&quot;=&gt;&quot;Sam&quot;, &quot;last_name&quot;=&gt;&quot;S.&quot;, &quot;author-link&quot;=&gt;&quot;/about/#sam&quot;, &quot;articles-link&quot;=&gt;&quot;/articles-by-author/sam/&quot;}</name></author><category term="github" /><category term="workspace" /><summary type="html"><![CDATA[An Exploration of Sublingual Estradiol as an Alternative to Oral Estradiol in Transfeminine People By Sam | First published June 11, 2021 | Last modified March 30, 2024]]></summary></entry><entry><title type="html">Clinical Guidelines with Information on Transfeminine Hormone Therapy</title><link href="https://transfemscience.org/articles/transfem-hormone-guidelines/" rel="alternate" type="text/html" title="Clinical Guidelines with Information on Transfeminine Hormone Therapy" /><published>2020-11-20T10:00:00-08:00</published><updated>2024-03-21T00:00:00-07:00</updated><id>https://transfemscience.org/articles/transfem-hormone-guidelines</id><content type="html" xml:base="https://transfemscience.org/articles/transfem-hormone-guidelines/"><![CDATA[<h1 id="clinical-guidelines-with-information-on-transfeminine-hormone-therapy">Clinical Guidelines with Information on Transfeminine Hormone Therapy</h1> </ul>]]></content><author><name>{&quot;first_name&quot;=&gt;&quot;Sam&quot;, &quot;last_name&quot;=&gt;&quot;S.&quot;, &quot;author-link&quot;=&gt;&quot;/about/#sam&quot;, &quot;articles-link&quot;=&gt;&quot;/articles-by-author/sam/&quot;}</name></author><category term="github" /><category term="workspace" /><summary type="html"><![CDATA[An Exploration of Sublingual Estradiol as an Alternative to Oral Estradiol in Transfeminine People By Sam | First published June 11, 2021 | Last modified March 30, 2024]]></summary></entry><entry><title type="html">Clinical Guidelines with Information on Transfeminine Hormone Therapy</title><link href="https://transfemscience.org/articles/transfem-hormone-guidelines/" rel="alternate" type="text/html" title="Clinical Guidelines with Information on Transfeminine Hormone Therapy" /><published>2020-11-20T10:00:00-08:00</published><updated>2024-06-26T00:00:00-07:00</updated><id>https://transfemscience.org/articles/transfem-hormone-guidelines</id><content type="html" xml:base="https://transfemscience.org/articles/transfem-hormone-guidelines/"><![CDATA[<h1 id="clinical-guidelines-with-information-on-transfeminine-hormone-therapy">Clinical Guidelines with Information on Transfeminine Hormone Therapy</h1>
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<p>By <p>By
<!-- First author --><a href="/about/#aly">Aly</a><!-- Second author --><!-- Third author --><!-- Fourth author --> | First published November 20, 2020 <!-- First author --><a href="/about/#aly">Aly</a><!-- Second author --><!-- Third author --><!-- Fourth author --> | First published November 20, 2020
| Last modified March 21, 2024</p> | Last modified June 26, 2024</p>
<h2 id="abstract--tldr">Abstract / TL;DR</h2> <h2 id="abstract--tldr">Abstract / TL;DR</h2>
@ -2476,7 +2550,7 @@ Using the term desistence in this way does not imply anything about the identity
<td>Published article</td> <td>Published article</td>
</tr> </tr>
<tr> <tr>
<td><a href="https://doi.org/10.1080/26895269.2022.2100644">Standards of Care for the Health of Transgender and Gender Diverse People, Version 8</a> (<a href="https://www.wpath.org/publications/soc">Alt</a>; <a href="https://www.tandfonline.com/doi/pdf/10.1080/26895269.2022.2100644">PDF</a>) [See also: <a href="https://doi.org/10.1080/15532739.2011.700873">Version 7/2012 edition</a> ([<a href="https://www.wpath.org/media/cms/Documents/SOC%20v7/Standards%20of%20Care%20V7%20-%202011%20WPATH.pdf">PDF</a>])]</td> <td><a href="https://doi.org/10.1080/26895269.2022.2100644">Standards of Care for the Health of Transgender and Gender Diverse People, Version 8</a> (<a href="https://www.wpath.org/publications/soc">Alt</a>; <a href="https://www.tandfonline.com/doi/pdf/10.1080/26895269.2022.2100644">PDF</a>) [See also all previous versions <a href="#wpath-standards-of-care-previous-versions">below</a>]</td>
<td>Coleman et al. / World Professional Association for Transgender Health (WPATH)</td> <td>Coleman et al. / World Professional Association for Transgender Health (WPATH)</td>
<td>2022</td> <td>2022</td>
<td>Published article</td> <td>Published article</td>
@ -2502,6 +2576,18 @@ Using the term desistence in this way does not imply anything about the identity
</tbody> </tbody>
</table> </table>
<h3 id="wpath-standards-of-care-previous-versions">WPATH <em>Standards of Care</em> Previous Versions</h3>
<ul>
<li><strong>1st/1979:</strong> Walker, P. A., Berger, J. C., Green, R., Laub, D. R., Reynolds, C. L., &amp; Wollman, L. (1979 February 13). <em>Standards of Care: The Hormonal and Surgical Sex Reassignment of Gender Dysphoric Persons</em> [<em>1st Edition/1979 Original Draft</em>]. Palo Alto, California: The Harry Benjamin International Gender Dysphoria Association, Inc. [<a href="https://scholar.google.com/scholar?cluster=3937857535576528085">Google Scholar</a>]</li>
<li><strong>2nd/1980:</strong> Walker, P. A., Berger, J. C., Green, R., Laub, D. R., Reynolds, C. L., &amp; Wollman, L. (1980 January 20). <em>Standards of Care: The Hormonal and Surgical Sex Reassignment of Gender Dysphoric Persons</em> [<em>2nd Edition/1980 Revised Draft</em>]. Stanford, California: The Harry Benjamin International Gender Dysphoria Association, Inc. [<a href="https://scholar.google.com/scholar?cluster=4070995568726990498">Google Scholar 1</a>] [<a href="https://scholar.google.com/scholar?cluster=4070995568726990498">Google Scholar 2</a>]</li>
<li><strong>3rd/1981:</strong> Walker, P. A., Berger, J. C., Green, R., Laub, D. R., Reynolds, C. L., &amp; Wollman, L. (1981 March 9). <em>Standards of Care: The Hormonal and Surgical Sex Reassignment of Gender Dysphoric Persons</em> [<em>3rd Edition/1981 Revised Draft</em>]. San Francisco, California: <em>The Harry Benjamin International Gender Dysphoria Association, Inc.</em> [<a href="https://archive.org/details/sexgendertheolog0000unse/page/284/">URL 1</a>] [<a href="https://archive.org/details/frommasculinetof0000stev/page/124/">URL 2</a>] [DOI:<a href="https://doi.org/10.1007/BF01541354">10.1007/BF01541354</a>—1985 reprint in <em>Archives of Sexual Behavior</em>, <em>14</em>(1), 79–90)]</li>
<li><strong>4th/1990:</strong> Walker, P. A., Berger, J. C., Green, R., Laub, D. R., Reynolds, C. L., &amp; Wollman, L. (1990 January 25). <em>Standards of Care: The Hormonal and Surgical Sex Reassignment of Gender Dysphoric Persons</em> [<em>4th Edition/1990 Revised Draft</em>]. Palo Alto/Sonoma, California: The Harry Benjamin International Gender Dysphoria Association, Inc. [<a href="https://scholar.google.com/scholar?cluster=17048419947031216406">Google Scholar 1</a>] [<a href="https://scholar.google.com/scholar?cluster=15855587737212682288">Google Scholar 2</a>] [<a href="http://www.genderpsychology.org/transsexual/hbsoc_1990.html">URL 1</a>] [<a href="https://web.archive.org/web/20011123075249/http://pfc.org.uk/medical/soc1990.htm">URL 2</a>] [<a href="https://archive.org/details/counselingingend0000niel/page/187/">URL 3</a>] [<a href="https://archive.org/details/genderblending0000unse_i4y3/page/505/">URL 4</a>] [<a href="https://archive.org/details/genderblending0000unse/page/504/">URL 5</a>] [<a href="https://archive.org/details/transsexualslife0000hubs/page/139/">URL 6</a>]</li>
<li><strong>5th/1998:</strong> Levine, S. B., Brown, G., Coleman, E., Cohen-Kettenis, P., Joris Hage, J., Van Maasdam, J., Petersen, M., Pfaefflin, F., &amp; Schaefer, L. C. (June 1998). [<em>The Harry Benjamin International Gender Dysphoria Association’s</em>] <em>The Standards of Care for Gender Identity Disorders</em> [<em>5th Edition</em>]. <em>International Journal of Transgenderism</em>, <em>2</em>(2). [Consultants: Denny, D., DiCeglie, D., Eicher, W., Green, J., Green, R., Gooren, L., Laub, D., Lawrence, A., Meyer, W., &amp; Wheeler, C.] [<a href="https://web.archive.org/web/19981205104251/http://www.symposion.com/ijt/ijtc0405.htm">URL 1</a>] [<a href="http://www.genderpsychology.org/transsexual/hbsoc_1998.html">URL 2</a>] [<a href="https://web.archive.org/web/20011102092848/http://www.pfc.org.uk/medical/soc1998.htm">URL 3</a>] [<a href="https://web.archive.org/web/20070221165442/http://www.pfc.org.uk:80/files/medical/soc1998.pdf">PDF</a>]</li>
<li><strong>6th/2001:</strong> Meyer, W., Bockting, W. O., Cohen-Kettenis, P., Coleman, E., DiCeglie, D., Devor, H., Gooren, L., Joris Hage, J., Kirk, S., Kuiper, B., Laub, D., Lawrence, A., Menard, Y., Patton, J., Schaefer, L., Webb, A., &amp; Wheeler, C. C. (February 2001). [<em>The Harry Benjamin International Gender Dysphoria Association’s</em>] <em>The Standards of Care for Gender Identity Disorders – Sixth Version</em>. <em>International Journal of Transgenderism</em>, <em>5</em>(1). [<a href="https://scholar.google.com/scholar?cluster=12867487738445343345">Google Scholar 1</a>] [<a href="https://scholar.google.com/scholar?cluster=6358061019204855170">Google Scholar 2</a>] [<a href="https://scholar.google.com/scholar?cluster=17782708118245621163">Google Scholar 3</a>] [<a href="https://web.archive.org/web/20010709084442/http://www.symposion.com/ijt/soc_2001/">URL 1</a>] [<a href="http://www.genderpsychology.org/transsexual/hbsoc_2001.html">URL 2</a>] [DOI:<a href="https://doi.org/10.1300/J056v13n01_01">10.1300/J056v13n01_01</a>—2001/2002 reprint in <em>Journal of Psychology &amp; Human Sexuality</em>, <em>13</em>(1), 1–30] [<a href="https://web.archive.org/web/20240511220027/https://www.cpath.ca/wp-content/uploads/2009/12/WPATHsocv6.pdf">PDF 1</a>] [<a href="https://web.archive.org/web/20240317223231/https://onlineacademiccommunity.uvic.ca/ahdevor/wp-content/uploads/sites/2247/2020/04/The-Harry-Benjamin-International-Gender-Dysphoria-Association-s-Standards-of-Care-for-Gender-Identity-Disorders-Sixth-Version.pdf">PDF 2</a>]</li>
<li><strong>7th/2012:</strong> Coleman, E., Bockting, W., Botzer, M., Cohen-Kettenis, P., DeCuypere, G., Feldman, J., Fraser, L., Green, J., Knudson, G., Meyer, W. J., Monstrey, S., Adler, R. K., Brown, G. R., Devor, A. H., Ehrbar, R., Ettner, R., Eyler, E., Garofalo, R., Karasic, D. H., … &amp; Zucker, K. (2012). [World Professional Association for Transgender Health (WPATH)] Standards of Care for the Health of Transsexual, Transgender, and Gender-Nonconforming People, Version 7. <em>International Journal of Transgenderism</em>, <em>13</em>(4), 165–232. [DOI:<a href="https://doi.org/10.1080/15532739.2011.700873">10.1080/15532739.2011.700873</a>] [<a href="https://www.wpath.org/publications/soc">URL</a>] [<a href="https://www.wpath.org/media/cms/Documents/SOC%20v7/SOC%20V7_English2012.pdf">PDF</a>]</li>
</ul>
<h2 id="united-states">United States</h2> <h2 id="united-states">United States</h2>
<table> <table>
@ -2807,7 +2893,9 @@ Using the term desistence in this way does not imply anything about the identity
<li>Hembree, W. C., Cohen-Kettenis, P. T., Gooren, L., Hannema, S. E., Meyer, W. J., Murad, M. H., Rosenthal, S. M., Safer, J. D., Tangpricha, V., &amp; T’Sjoen, G. G. (2017). Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons: An Endocrine Society Clinical Practice Guideline. <em>The Journal of Clinical Endocrinology and Metabolism</em>, <em>102</em>(11), 3869–3903. [DOI:<a href="https://doi.org/10.1210/jc.2017-01658">10.1210/jc.2017-01658</a>] [<a href="https://academic.oup.com/jcem/article-pdf/102/11/3869/21533864/jc.2017-01658.pdf">PDF</a>]</li> <li>Hembree, W. C., Cohen-Kettenis, P. T., Gooren, L., Hannema, S. E., Meyer, W. J., Murad, M. H., Rosenthal, S. M., Safer, J. D., Tangpricha, V., &amp; T’Sjoen, G. G. (2017). Endocrine Treatment of Gender-Dysphoric/Gender-Incongruent Persons: An Endocrine Society Clinical Practice Guideline. <em>The Journal of Clinical Endocrinology and Metabolism</em>, <em>102</em>(11), 3869–3903. [DOI:<a href="https://doi.org/10.1210/jc.2017-01658">10.1210/jc.2017-01658</a>] [<a href="https://academic.oup.com/jcem/article-pdf/102/11/3869/21533864/jc.2017-01658.pdf">PDF</a>]</li>
<li>International Planned Parenthood Federation (IPPF). (2015). <em>IMAP Statement on Hormone Therapy for Transgender People.</em> International Medical Advisory Panel/International Planned Parenthood Federation. [<a href="https://www.ippf.org/resource/imap-statement-hormone-therapy-transgender-people">URL</a>] [<a href="https://www.ippf.org/sites/default/files/ippf_imap_transgender.pdf">PDF</a>]</li> <li>International Planned Parenthood Federation (IPPF). (2015). <em>IMAP Statement on Hormone Therapy for Transgender People.</em> International Medical Advisory Panel/International Planned Parenthood Federation. [<a href="https://www.ippf.org/resource/imap-statement-hormone-therapy-transgender-people">URL</a>] [<a href="https://www.ippf.org/sites/default/files/ippf_imap_transgender.pdf">PDF</a>]</li>
<li>Latkin, S., &amp; Coakley, G. (2017). <em>[Transgender Women] Prescribing Guidelines.</em> Doncaster/Bassetlaw: Doncaster and Bassetlaw Teaching Hospitals NHS Foundation Trust. [<a href="https://medicinesmanagement.doncasterccg.nhs.uk/wp-content/uploads/2018/06/Doncaster-and-Bassetlaw-Transgender-women-prescribing-guidance.pdf">PDF</a>]</li> <li>Latkin, S., &amp; Coakley, G. (2017). <em>[Transgender Women] Prescribing Guidelines.</em> Doncaster/Bassetlaw: Doncaster and Bassetlaw Teaching Hospitals NHS Foundation Trust. [<a href="https://medicinesmanagement.doncasterccg.nhs.uk/wp-content/uploads/2018/06/Doncaster-and-Bassetlaw-Transgender-women-prescribing-guidance.pdf">PDF</a>]</li>
<li>Levine, S. B., Brown, G., Coleman, E., Cohen-Kettenis, P., Joris Hage, J., Van Maasdam, J., Petersen, M., Pfaefflin, F., &amp; Schaefer, L. C. (June 1998). [<em>The Harry Benjamin International Gender Dysphoria Association’s</em>] <em>The Standards of Care for Gender Identity Disorders</em> [<em>5th Edition</em>]. <em>International Journal of Transgenderism</em>, <em>2</em>(2). [Consultants: Denny, D., DiCeglie, D., Eicher, W., Green, J., Green, R., Gooren, L., Laub, D., Lawrence, A., Meyer, W., &amp; Wheeler, C.] [<a href="https://web.archive.org/web/19981205104251/http://www.symposion.com/ijt/ijtc0405.htm">URL 1</a>] [<a href="http://www.genderpsychology.org/transsexual/hbsoc_1998.html">URL 2</a>] [<a href="https://web.archive.org/web/20011102092848/http://www.pfc.org.uk/medical/soc1998.htm">URL 3</a>] [<a href="https://web.archive.org/web/20070221165442/http://www.pfc.org.uk:80/files/medical/soc1998.pdf">PDF</a>]</li>
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</ul>]]></content><author><name>{&quot;first_name&quot;=&gt;&quot;Aly&quot;, &quot;last_name&quot;=&gt;&quot;W.&quot;, &quot;author-link&quot;=&gt;&quot;/about/#aly&quot;, &quot;articles-link&quot;=&gt;&quot;/articles-by-author/aly/&quot;}</name></author><category term="github" /><category term="workspace" /><summary type="html"><![CDATA[Clinical Guidelines with Information on Transfeminine Hormone Therapy By Aly | First published November 20, 2020 | Last modified March 21, 2024]]></summary></entry><entry><title type="html">Spironolactone and Claims About Increased Visceral Fat in Transfeminine People</title><link href="https://transfemscience.org/articles/spiro-visceral-fat/" rel="alternate" type="text/html" title="Spironolactone and Claims About Increased Visceral Fat in Transfeminine People" /><published>2020-10-25T09:56:15-07:00</published><updated>2022-10-02T00:00:00-07:00</updated><id>https://transfemscience.org/articles/spiro-visceral-fat</id><content type="html" xml:base="https://transfemscience.org/articles/spiro-visceral-fat/"><![CDATA[<h1 id="spironolactone-and-claims-about-increased-visceral-fat-in-transfeminine-people">Spironolactone and Claims About Increased Visceral Fat in Transfeminine People</h1> </ul>]]></content><author><name>{&quot;first_name&quot;=&gt;&quot;Aly&quot;, &quot;last_name&quot;=&gt;&quot;W.&quot;, &quot;author-link&quot;=&gt;&quot;/about/#aly&quot;, &quot;articles-link&quot;=&gt;&quot;/articles-by-author/aly/&quot;}</name></author><category term="github" /><category term="workspace" /><summary type="html"><![CDATA[Clinical Guidelines with Information on Transfeminine Hormone Therapy By Aly | First published November 20, 2020 | Last modified June 26, 2024]]></summary></entry><entry><title type="html">Spironolactone and Claims About Increased Visceral Fat in Transfeminine People</title><link href="https://transfemscience.org/articles/spiro-visceral-fat/" rel="alternate" type="text/html" title="Spironolactone and Claims About Increased Visceral Fat in Transfeminine People" /><published>2020-10-25T09:56:15-07:00</published><updated>2022-10-02T00:00:00-07:00</updated><id>https://transfemscience.org/articles/spiro-visceral-fat</id><content type="html" xml:base="https://transfemscience.org/articles/spiro-visceral-fat/"><![CDATA[<h1 id="spironolactone-and-claims-about-increased-visceral-fat-in-transfeminine-people">Spironolactone and Claims About Increased Visceral Fat in Transfeminine People</h1>
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<!-- First author --><a href="/about/#aly">Aly</a><!-- Second author --><!-- Third author --><!-- Fourth author --> | First published October 25, 2020 <!-- First author --><a href="/about/#aly">Aly</a><!-- Second author --><!-- Third author --><!-- Fourth author --> | First published October 25, 2020
| Last modified October 2, 2022</p> | Last modified October 2, 2022</p>
<p>A <a href="https://moderntranshormones.com/2018/01/01/whats-wrong-with-spironolactone/">claim has been originated by some in the online transgender community</a> that the antiandrogen <a href="https://en.wikipedia.org/wiki/Spironolactone">spironolactone</a> increases <a href="https://en.wikipedia.org/wiki/Visceral_fat">visceral fat</a> in transfeminine people and that this effect is irreversible. Visceral fat is a type of adipose tissue located in the intra-abdominal region which surrounds the internal organs (viscera) in that area. In excess, visceral fat causes the abdomen to look bloated and unattractive. The supposed phenomenon of visceral fat accumulation with spironolactone has sometimes been referred to by people in the transgender community as “spiro belly”. The claim is based on theory—specifically that spironolactone has been found to increase levels of the <a href="https://en.wikipedia.org/wiki/Corticosteroid">corticosteroid</a> hormone <a href="https://en.wikipedia.org/wiki/Cortisol">cortisol</a> due to its <a href="https://en.wikipedia.org/wiki/Antimineralocorticoid">antimineralocorticoid</a> activity and cortisol is known to increase visceral fat, which together imply that spironolactone might likewise be able to increase visceral fat. It is also based on claimed <a href="https://en.wikipedia.org/wiki/Anecdotal_evidence">anecdotal observations</a> of transfeminine people taking spironolactone, which are said to corroborate the hypothesis. Despite these claims owever, there is no actual direct scientific or medical literature to support the idea that spironolactone increases visceral fat, and there is considerable evidence contradicting it.</p> <p>A <a href="https://moderntranshormones.com/2018/01/01/whats-wrong-with-spironolactone/">claim has been originated by some in the online transgender community</a> that the antiandrogen <a href="https://en.wikipedia.org/wiki/Spironolactone">spironolactone</a> increases <a href="https://en.wikipedia.org/wiki/Visceral_fat">visceral fat</a> in transfeminine people and that this effect is irreversible. Visceral fat is a type of adipose tissue located in the intra-abdominal region which surrounds the internal organs (viscera) in that area. In excess, visceral fat causes the abdomen to look bloated and unattractive. The supposed phenomenon of visceral fat accumulation with spironolactone has sometimes been referred to by people in the transgender community as “spiro belly”. The claim is based on theory—specifically that spironolactone has been found to increase levels of the <a href="https://en.wikipedia.org/wiki/Corticosteroid">corticosteroid</a> hormone <a href="https://en.wikipedia.org/wiki/Cortisol">cortisol</a> due to its <a href="https://en.wikipedia.org/wiki/Antimineralocorticoid">antimineralocorticoid</a> activity and cortisol is known to increase visceral fat, which together imply that spironolactone might likewise be able to increase visceral fat. It is also based on claimed <a href="https://en.wikipedia.org/wiki/Anecdotal_evidence">anecdotal observations</a> of transfeminine people taking spironolactone, which are said to corroborate the hypothesis. Despite these claims however, there is no actual direct scientific or medical literature to support the idea that spironolactone increases visceral fat, and there is considerable evidence contradicting it.</p>
<p>The influence of spironolactone on cortisol levels in clinical studies is variable and the magnitude of effect is limited. Hence, the clinical significance of increased cortisol levels with spironolactone is uncertain. Moreover, cortisol is an <a href="https://en.wikipedia.org/wiki/Agonist">agonist</a> of the <a href="https://en.wikipedia.org/wiki/Glucocorticoid_receptor">glucocorticoid receptor</a> (thereby producing <a href="https://en.wikipedia.org/wiki/Glucocorticoid">glucocorticoid</a> effects) and of the <a href="https://en.wikipedia.org/wiki/Mineralocorticoid_receptor">mineralocorticoid receptor</a> (thereby producing <a href="http://en.wikipedia.org/wiki/Mineralocorticoid">mineralocorticoid</a> effects). As already touched on, spironolactone has potent antimineralocorticoid activity (that is, mineralocorticoid receptor <a href="https://en.wikipedia.org/wiki/Receptor_antagonist">antagonism</a>). Hence, even if spironolactone did increase cortisol levels enough to potentially increase visceral fat, its antimineralocorticoid activity could modify the capacity of cortisol to produce this effect. In relation to this, there is accumulating research to suggest that spironolactone may actually <em>decrease</em> visceral fat via its antimineralocorticoid activity. Antimineralocorticoids like spironolactone show <a href="https://en.wiktionary.org/wiki/antiadipogenic">antiadipogenic</a> (anti-fat-accumulation) effects <em>in vitro</em> (<a href="https://doi.org/10.1096/fj.06-7970com">Caprio et al., 2007</a>; <a href="https://doi.org/10.1210/en.2010-0674">Caprio et al., 2011</a>) and have been shown to decrease visceral fat in animals (<a href="https://doi.org/10.1007/s12325-008-0039-5">Karakurt, 2008</a>; <a href="https://doi.org/10.1096/fj.13-245415">Armani et al., 2014</a>; <a href="https://doi.org/10.1038/ijo.2016.13">Mammi et al., 2016</a>; <a href="https://doi.org/10.1139/cjpp-2018-0416">Olatunji et al., 2018</a>). It is possible that they may also be able to do so in humans. Here are some notable literature excerpts relevant to this topic (<a href="https://doi.org/10.1016/bs.vh.2018.10.005">Infante et al., 2019</a>; <a href="https://doi.org/10.1038/nrd.2016.31">Giordano, Frontini, &amp; Cinti, 2016</a>):</p> <p>The influence of spironolactone on cortisol levels in clinical studies is variable and the magnitude of effect is limited. Hence, the clinical significance of increased cortisol levels with spironolactone is uncertain. Moreover, cortisol is an <a href="https://en.wikipedia.org/wiki/Agonist">agonist</a> of the <a href="https://en.wikipedia.org/wiki/Glucocorticoid_receptor">glucocorticoid receptor</a> (thereby producing <a href="https://en.wikipedia.org/wiki/Glucocorticoid">glucocorticoid</a> effects) and of the <a href="https://en.wikipedia.org/wiki/Mineralocorticoid_receptor">mineralocorticoid receptor</a> (thereby producing <a href="http://en.wikipedia.org/wiki/Mineralocorticoid">mineralocorticoid</a> effects). As already touched on, spironolactone has potent antimineralocorticoid activity (that is, mineralocorticoid receptor <a href="https://en.wikipedia.org/wiki/Receptor_antagonist">antagonism</a>). Hence, even if spironolactone did increase cortisol levels enough to potentially increase visceral fat, its antimineralocorticoid activity could modify the capacity of cortisol to produce this effect. In relation to this, there is accumulating research to suggest that spironolactone may actually <em>decrease</em> visceral fat via its antimineralocorticoid activity. Antimineralocorticoids like spironolactone show <a href="https://en.wiktionary.org/wiki/antiadipogenic">antiadipogenic</a> (anti-fat-accumulation) effects <em>in vitro</em> (<a href="https://doi.org/10.1096/fj.06-7970com">Caprio et al., 2007</a>; <a href="https://doi.org/10.1210/en.2010-0674">Caprio et al., 2011</a>) and have been shown to decrease visceral fat in animals (<a href="https://doi.org/10.1007/s12325-008-0039-5">Karakurt, 2008</a>; <a href="https://doi.org/10.1096/fj.13-245415">Armani et al., 2014</a>; <a href="https://doi.org/10.1038/ijo.2016.13">Mammi et al., 2016</a>; <a href="https://doi.org/10.1139/cjpp-2018-0416">Olatunji et al., 2018</a>). It is possible that they may also be able to do so in humans. Here are some notable literature excerpts relevant to this topic (<a href="https://doi.org/10.1016/bs.vh.2018.10.005">Infante et al., 2019</a>; <a href="https://doi.org/10.1038/nrd.2016.31">Giordano, Frontini, &amp; Cinti, 2016</a>):</p>

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