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-20 -76 -20 -122 -20 -2618 0 -2810 -5 -2597 65 -2741 87 -180 227 -304 420 -372 l80 -28 2551 -3 2551 -2 98 25 c253 64 441 251 506 503 19 73 19 137 19 2617 0 2478 0 2544 -19 2617 -51 198 -181 361 -361 451 -53 26 -126 54 -165 62 -103 21 -5105 21 -5205 -1z m5055 -3129 l0 -2440 -2447 -3 -2448 -2 0 2445 0 2445 2448 -2 2447 -3 0 -2440z" /><path d="M1410 4893 c0 -2 0 -158 0 -348 l-1 -346 346 0 346 0 0 346 0 346 -346 2 c-190 1 -345 1 -345 0z" /><path d="M2460 4893 c0 -2 0 -158 0 -348 l-1 -345 1221 0 1221 0 0 345 0 345 -1221 3 c-671 1 -1220 1 -1220 0z" /><path d="M1407 3493 c-1 -1 -1 -157 1 -347 l3 -346 344 0 345 0 0 340 c0 187 0 342 0 345 0 5 -689 13 -693 8z" /><path d="M2457 3493 c-1 -1 -1 -157 1 -347 l3 -346 1219 0 1220 0 0 340 c0 187 -1 342 -2 345 -3 4 -2437 13 -2441 8z" /><path d="M1409 2096 c-2 -2 -3 -160 -1 -350 l3 -346 344 0 344 0 3 346 c2 190 1 348 -1 350 -6 5 -686 5 -692 0z" /><path d="M2459 2096 c-2 -2 -3 -160 -1 -350 l3 -346 1219 0 1219 0 3 346 c2 190 1 348 -1 350 -6 5 -2436 5 -2442 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-158 0 -348 l-1 -345 1221 0 1221 0 0 345 0 345 -1221 3 c-671 1 -1220 1 -1220 0z" /><path d="M1407 3493 c-1 -1 -1 -157 1 -347 l3 -346 344 0 345 0 0 340 c0 187 0 342 0 345 0 5 -689 13 -693 8z" /><path d="M2457 3493 c-1 -1 -1 -157 1 -347 l3 -346 1219 0 1220 0 0 340 c0 187 -1 342 -2 345 -3 4 -2437 13 -2441 8z" /><path d="M1409 2096 c-2 -2 -3 -160 -1 -350 l3 -346 344 0 344 0 3 346 c2 190 1 348 -1 350 -6 5 -686 5 -692 0z" /><path d="M2459 2096 c-2 -2 -3 -160 -1 -350 l3 -346 1219 0 1219 0 3 346 c2 190 1 348 -1 350 -6 5 -2436 5 -2442 0z" /></g></svg> </span> </button> <span id="sidebar-title">Contents</span></div><div id="sidebar-contents"><div class="toc-h1"><a id="heading-0" href="#top" class="toc-link">Top of page</a><div><div class="toc-h2"><a id="heading-1" href="#preface" class="toc-link">Preface</a></div><div class="toc-h2"><a id="heading-2" href="#table-of-comparable-estradiol-dosages" class="toc-link">Table of Comparable Estradiol Dosages</a><div><div class="toc-h3"><a id="heading-3" href="#notes" class="toc-link">Notes</a></div></div></div><div class="toc-h2"><a id="heading-4" href="#discussion" class="toc-link">Discussion</a></div><div class="toc-h2"><a id="heading-5" href="#references" class="toc-link">References</a><div><div class="toc-h3"><a id="heading-6" href="#general-sources" class="toc-link">General Sources</a></div><div class="toc-h3"><a id="heading-7" href="#inline-citations" class="toc-link">Inline Citations</a></div></div></div></div></div></div></div></div><div id="main-area"><div id="article"><h1 id="approximate-comparable-dosages-of-estradiol-by-different-routes"> <a href="#approximate-comparable-dosages-of-estradiol-by-different-routes" aria-labelledby="approximate-comparable-dosages-of-estradiol-by-different-routes" class="anchor-heading"><svg viewBox="0 0 16 16" aria-hidden="true"><use xlink:href="#svg-link"></use></svg></a> Approximate Comparable Dosages of Estradiol by Different Routes</h1><p>By <a href="/about/#aly">Aly</a> | First published April 19, 2020 | Last modified April 13, 2023</p><h2 id="preface"> <a href="#preface" aria-labelledby="preface" class="anchor-heading"><svg viewBox="0 0 16 16" aria-hidden="true"><use xlink:href="#svg-link"></use></svg></a> Preface</h2><p>Transfeminine people often ask about equivalent dosages of estradiol by different routes of administration. This page was put together to help facilitate answering these questions.</p><h2 id="table-of-comparable-estradiol-dosages"> <a href="#table-of-comparable-estradiol-dosages" aria-labelledby="table-of-comparable-estradiol-dosages" class="anchor-heading"><svg viewBox="0 0 16 16" aria-hidden="true"><use xlink:href="#svg-link"></use></svg></a> Table of Comparable Estradiol Dosages</h2><p>The following is a table of <em>estimated equivalent dosages</em> of estradiol by different routes:</p><div class="table-wrapper"><table><thead><tr><th>Route</th><th>Low dose</th><th>Moderate dose</th><th>High dose</th><th>Very high dose</th></tr></thead><tbody><tr><td><a href="https://en.wikipedia.org/wiki/Pharmacokinetics_of_estradiol#Oral_administration">Oral</a><sup>a</sup></td><td>2 mg/day</td><td>4 mg/day</td><td>8 mg/day</td><td>12 mg/day</td></tr><tr><td><a href="https://en.wikipedia.org/wiki/Pharmacokinetics_of_estradiol#Sublingual_administration">Sublingual</a>/<a href="https://en.wikipedia.org/wiki/Pharmacokinetics_of_estradiol#Buccal_administration">buccal</a><sup>b</sup></td><td>0.5–1 mg/day</td><td>1–2 mg/day</td><td>2–4 mg/day</td><td>3–6 mg/day</td></tr><tr><td><a href="https://en.wikipedia.org/wiki/Pharmacokinetics_of_estradiol#Transdermal_patches">Transdermal patch</a><sup>c,d</sup></td><td>50–100 μg/day</td><td>100–200 μg/day</td><td>200–400 μg/day</td><td>300–600 μg/day</td></tr><tr><td><a href="https://en.wikipedia.org/wiki/Pharmacokinetics_of_estradiol#Transdermal_gel">Transdermal gel</a><sup>c</sup></td><td>1.5 mg/day</td><td>3 mg/day</td><td>6 mg/day</td><td>9 mg/day</td></tr><tr><td><a href="https://en.wikipedia.org/wiki/Pharmacokinetics_of_estradiol#Intramuscular_injection">Injections</a> (<a href="https://en.wikipedia.org/wiki/Pharmacokinetics_of_estradiol#Intramuscular_injection">i.m.</a> or <a href="https://en.wikipedia.org/wiki/Pharmacokinetics_of_estradiol#Subcutaneous_injection">s.c.</a>)<sup>e</sup></td><td>1 mg/week</td><td>2 mg/week</td><td>4 mg/week</td><td>6 mg/week</td></tr><tr><td><a href="https://en.wikipedia.org/wiki/Pharmacokinetics_of_estradiol#Subcutaneous_implantation">Pellet implant (s.c.)</a></td><td>25 mg/6 months</td><td>50 mg/6 months</td><td>100 mg/6 months</td><td>150 mg/6 months</td></tr><tr><td>~Average estradiol level</td><td>50 pg/mL<br />(184 pmol/L)</td><td>100 pg/mL<br />(367 pmol/L)</td><td>200 pg/mL<br />(734 pmol/L)</td><td>300 pg/mL<br />(1101 pmol/L)</td></tr><tr><td>Equivalent <a href="https://en.wikipedia.org/wiki/Menstrual_cycle">cycle</a> phase</td><td><a href="https://en.wikipedia.org/wiki/Follicular_phase">Follicular</a></td><td>Whole cycle</td><td><a href="https://en.wikipedia.org/wiki/Luteal_phase">Luteal</a></td><td><a href="https://en.wikipedia.org/wiki/Ovulation">Ovulation</a></td></tr></tbody></table></div><p><small><sup>a</sup> For oral <em>estradiol</em>. Oral estradiol 1.5 mg is equivalent to about 2 mg oral <a href="https://en.wikipedia.org/wiki/Estradiol_valerate">estradiol valerate</a> (<a href="https://en.wikipedia.org/wiki/Estradiol_valerate#Oral_administration">Wiki</a>). <sup>b</sup> Based on sublingual estradiol having ~2- to 5-fold greater <a href="https://en.wikipedia.org/wiki/Bioavailability">bioavailability</a> than oral estradiol per studies (<a href="https://en.wikipedia.org/wiki/Pharmacokinetics_of_estradiol#Sublingual_administration">Wiki</a>; <a href="/articles/sublingual-e2-transfem/">Sam, 2021</a>). <sup>c</sup> Much lower doses of transdermal estradiol can be used in the case of genital application relative to conventional skin sites (potentially e.g. 5-fold lower doses for similar estradiol levels) (<a href="/articles/genital-e2-application/">Aly., 2019</a>). <sup>d</sup> Different patch brands may result in differing estradiol levels (<a href="https://doi.org/10.1016/S0378-5122(99)00039-0">Rohr, Nauert, & Stehle, 1999</a>; <a href="https://doi.org/10.1111/j.1464-410X.2008.07583.x">Langley et al., 2008</a>; <a href="https://doi.org/10.1016/j.ijpharm.2008.11.020">Farahmand & Maibach, 2009</a>; <a href="https://doi.org/10.1016/j.maturitas.2015.02.320">Langley et al., 2015</a>). <sup>e</sup> For i.m. or s.c. injection, total dose per week of an <a href="https://en.wikipedia.org/wiki/Estrogen_ester">estradiol ester</a> like estradiol valerate, <a href="https://en.wikipedia.org/wiki/Estradiol_cypionate">estradiol cypionate</a>, <a href="https://en.wikipedia.org/wiki/Estradiol_enantate">estradiol enanthate</a>, or <a href="https://en.wikipedia.org/wiki/Estradiol_benzoate">estradiol benzoate</a>. Differences in <a href="https://en.wikipedia.org/wiki/Molecular_weight">molecular weight</a> between these esters are minor (<a href="https://en.wikipedia.org/wiki/Template:Structural_properties_of_selected_estradiol_esters">Table</a>) and can be ignored for simplicity. Optimal injection intervals vary depending on the ester and doses should be scaled by injection interval to match the listed total dose per week (<a href="/articles/injectable-e2-meta-analysis/#insights-for-clinical-guidelines-and-dosing-recommendations">Aly, 2021</a>).</small></p><h3 id="notes"> <a href="#notes" aria-labelledby="notes" class="anchor-heading"><svg viewBox="0 0 16 16" aria-hidden="true"><use xlink:href="#svg-link"></use></svg></a> Notes</h3><ol><li>These doses are not absolute and should be considered only a rough guideline. They represent a generalized <em>model</em> based on many different studies with often very different individual findings. There is also an assumption that estradiol levels scale linearly or proportionally with dose, which may or may not actually be the case. One study found lower bioavailability of oral estradiol at high doses for instance (<a href="https://pubmed.ncbi.nlm.nih.gov/8240460/">Kuhnz, Gansau, & Mahler, 1993</a>).</li><li>These doses are approximate <em>equivalent</em> or <em>comparable</em> doses and don’t necessarily correspond to typical or recommended clinical doses. Injectable estradiol formulations are generally used at higher doses than other routes and forms of estradiol for instance (<a href="/articles/injectable-e2-meta-analysis/#insights-for-clinical-guidelines-and-dosing-recommendations">Aly, 2021</a>).</li><li>The comparable doses are based on total estradiol exposure rather than therapeutic estrogenic potency. Time-related variations in sex hormone levels have been reported to modify potency of sex hormone preparations (<a href="/articles/injectable-e2-meta-analysis/#estradiol-exposure-and-potency">Aly, 2021</a>). However, this has not been factored in to the table here due to a lack of available data and analysis on the influence. In any case, it may be relevant to routes with large fluctuations in estradiol levels like sublingual administration and shorter-acting injections.</li><li>A transdermal estradiol spray sold under the brand name Lenzetto is available. In a study in postmenopausal women, mean baseline-adjusted estradiol levels with Lenzetto over the course of a week following achievement of steady state were about 6 pg/mL pre-treatment, 13 pg/mL with 1 spray/day (1.53 mg/day), 19 pg/mL with 2 sprays/day (3.06 mg/day), and 26 pg/mL with 3 sprays/day (4.59 mg/day) (<a href="https://doi.org/10.1177/0091270009339187">Morton et al., 2009</a>; <a href="https://commons.wikimedia.org/wiki/File:Estradiol_levels_with_estradiol_transdermal_spray_(brand_name_Lenzetto)_in_postmenopausal_women.png">Graph</a>). Hence, this form of estradiol appears to achieve relatively low estradiol levels that likely aren’t well-suited for transfeminine people. No data are available on higher doses (i.e., more sprays per day) and so this formulation has not been included in the table.</li></ol><h2 id="discussion"> <a href="#discussion" aria-labelledby="discussion" class="anchor-heading"><svg viewBox="0 0 16 16" aria-hidden="true"><use xlink:href="#svg-link"></use></svg></a> Discussion</h2><p>For reference, mean integrated levels of estradiol during the normal <a href="https://en.wikipedia.org/wiki/Menstrual_cycle">menstrual cycle</a> in <a href="https://en.wikipedia.org/wiki/Menopause#Premenopause">premenopausal</a> cisgender women are about 100 pg/mL and during the <a href="https://en.wikipedia.org/wiki/Luteal_phase">luteal phase</a> (the latter half of the menstrual cycle) are around 150 pg/mL (<a href="https://commons.wikimedia.org/wiki/File:Estradiol_levels_across_the_normal_menstrual_cycle_in_women.png">Graph</a>; <a href="https://commons.wikimedia.org/wiki/File:Estradiol_levels_with_LC-MS-MS_during_the_normal_menstrual_cycle_in_women.png">Graph</a>; <a href="/articles/transfem-intro/#normal-hormone-levels">Aly, 2018</a>). The total production of estradiol over a single menstrual cycle (i.e., one month) is about 6 mg on average (<a href="https://doi.org/10.1016/b978-141604090-3.50019-3">Rosenfield et al., 2008</a>; <a href="/articles/transfem-intro/#normal-hormone-levels">Aly, 2018</a>). Slightly higher doses are required for injectable estradiol esters relative to endogenous production amounts since they contain less estradiol by weight due to the ester components (<a href="https://en.wikipedia.org/wiki/Template:Structural_properties_of_selected_estradiol_esters">Table</a>).</p><p>Note that there is high <a href="https://en.wikipedia.org/wiki/Interindividual_variability">interindividual variability</a> (i.e., variability between individuals) in terms of estradiol levels achieved with different forms and routes of estradiol. As an example, some people may get relatively low estradiol levels with the oral route and others may get relatively low levels with the transdermal route. Conversely, some people may get relatively high levels with the transdermal route or with injections. For data showing the substantial variability even with injections, see <a href="/articles/injectable-e2-meta-analysis/#variability-between-individuals">Aly (2021)</a>. Due to the variability in estradiol levels between individuals, the appropriate doses will often not be the same for different people. Doses should be adjusted as necessary based on blood work. It should also be noted that there are large time-dependent changes in estradiol levels with certain routes, namely sublingual or buccal administration (<a href="https://en.wikipedia.org/wiki/Template:Hormone_levels_with_sublingual_estradiol">Graphs</a>; <a href="https://commons.wikimedia.org/wiki/File:Estradiol_levels_during_therapy_with_0.25_mg_buccal_estradiol_in_postmenopausal_women.png">Graph</a>; <a href="/articles/sublingual-e2-transfem/">Sam, 2021</a>) and intramuscular or subcutaneous injection (<a href="https://en.wikipedia.org/wiki/Template:Hormone_levels_with_estradiol_esters_by_intramuscular_injection">Graphs</a>; <a href="/articles/injectable-e2-meta-analysis/">Aly, 2021</a>). Due to these fluctuations, estradiol levels will be vastly different when measured at different time points with these routes (e.g., around peak versus around trough).</p><p>For transfeminine people who have not yet undergone or do not plan to undergo <a href="https://en.wikipedia.org/wiki/Gonadectomy">gonadectomy</a>, a high to very high dose of estradiol can be used to achieve strong suppression of testosterone levels. On average, the high dose will suppress testosterone levels by about 90%, to around 50 ng/dL (<a href="https://en.wikipedia.org/wiki/Pharmacodynamics_of_estradiol#Antigonadotropic_effects">Wiki</a>; <a href="/articles/transfem-intro/#gonadal-suppression">Aly, 2018</a>). Hence, the high to very high doses are indicated for estradiol monotherapy (i.e., estradiol alone without an antiandrogen). After gonadectomy, testosterone suppression is no longer needed and lower doses of estradiol, such as the moderate doses, can be used instead. High doses of estradiol are not necessarily required if estradiol is used in combination with an adequately effective antiandrogen, for instance <a href="https://en.wikipedia.org/wiki/Cyproterone_acetate">cyproterone acetate</a>, <a href="https://en.wikipedia.org/wiki/Bicalutamide">bicalutamide</a>, or a <a href="https://en.wikipedia.org/wiki/Gonadotropin-releasing_hormone_agonist">gonadotropin-releasing hormone agonist</a> or <a href="https://en.wikipedia.org/wiki/Gonadotropin-releasing_hormone_antagonist">antagonist</a>. <a href="https://en.wikipedia.org/wiki/Spironolactone">Spironolactone</a>, on the other hand, may often not be fully effective for opposing androgens (<a href="/articles/spiro-testosterone/">Aly, 2018</a>).</p><h2 id="references"> <a href="#references" aria-labelledby="references" class="anchor-heading"><svg viewBox="0 0 16 16" aria-hidden="true"><use xlink:href="#svg-link"></use></svg></a> References</h2><h3 id="general-sources"> <a href="#general-sources" aria-labelledby="general-sources" class="anchor-heading"><svg viewBox="0 0 16 16" aria-hidden="true"><use xlink:href="#svg-link"></use></svg></a> General Sources</h3><ul><li>Aly. 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