mirror of
https://github.com/soapingtime/diyhrt.git
synced 2026-03-23 07:36:38 +00:00
1 line
No EOL
41 KiB
HTML
1 line
No EOL
41 KiB
HTML
<!doctype html><html lang="en-US"><head><meta charset="UTF-8"><meta name="viewport" content="width=device-width, initial-scale=1, minimum-scale=1"><title>The Possible Role of a Second X Chromosome in Breast Cancer Risk - Transfeminine Science</title><link rel="preload" href="../../assets/images/branding/logo.png" as="image" /><link rel="preload" href="../../assets/images/branding/logo-dark.png" as="image" /><link rel="stylesheet" href="../../assets/css/vendor/normalize.css"><link rel="stylesheet" href="../../assets/css/variables.css"><link rel="stylesheet" href="../../assets/css/site-layout.css"><link rel="stylesheet" href="../../assets/css/article-content.css"><link rel="stylesheet" href="../../assets/css/print.css"><meta name="robots" content="noarchive"><link rel="apple-touch-icon" sizes="180x180" href="../../apple-touch-icon.png"><link rel="icon" type="image/png" sizes="32x32" href="../../favicon-32x32.png"><link rel="icon" type="image/png" sizes="16x16" href="../../favicon-16x16.png"><link rel="icon" href="../../favicon.ico"><link rel="manifest" href="../../site.webmanifest"><meta name="msapplication-TileColor" content="#ece5ff"><meta name="theme-color" content="#ffffff"><link type="application/atom+xml" rel="alternate" href="../../feed-posts.xml" title="Transfeminine Science" /><link rel="alternate" type="application/atom+xml" title="The Possible Role of a Second X Chromosome in Breast Cancer Risk - Transfeminine Science" href="../../feed.xml"><link rel="canonical" href="index.html" /><meta property="og:title" content="The Possible Role of a Second X Chromosome in Breast Cancer Risk" /><meta property="og:image" content="https://transfemscience.org/assets/images/branding/logo-alt.png" /><meta name="twitter:image" content="https://transfemscience.org/assets/images/branding/logo-alt.png" /><meta property="og:url" content="https://transfemscience.org/articles/breast-cancer-suppl/" /><meta property="og:locale" content="en_US" /><meta property="og:site_name" content="Transfeminine Science" /><meta property="og:type" content="article" /><meta name="twitter:card" content="summary" /><meta name="publisher" content="Transfeminine Science"><meta name="description" content="The Possible Role of a Second X Chromosome in Breast Cancer Risk by Aly" /><meta property="og:description" content="The Possible Role of a Second X Chromosome in Breast Cancer Risk by Aly" /><meta name="author" content="Aly" /><meta name="citation_author" content="Aly"><meta name="citation_title" content="The Possible Role of a Second X Chromosome in Breast Cancer Risk"><meta name="citation_publication_date" content="2020/04/25"><meta name="citation_journal_title" content="Transfeminine Science"><meta name="citation_fulltext_html_url" content="https://transfemscience.org/articles/breast-cancer-suppl/"> <script type="application/ld+json"> { "@context": "https://schema.org", "name": "The Possible Role of a Second X Chromosome in Breast Cancer Risk", "mainEntityOfPage": "https://transfemscience.org/articles/breast-cancer-suppl/", "headline": "The Possible Role of a Second X Chromosome in Breast Cancer Risk", "url": "https://transfemscience.org/articles/breast-cancer-suppl/", "isAccessibleForFree": "True", "description": "The Possible Role of a Second X Chromosome in Breast Cancer Risk by Aly", "@type": "MedicalScholarlyArticle", "dateModified": "2023-03-01", "datePublished": "2020-04-25", "author": { "@type": "Person", "name": "Aly", "email": "", "url": "https://transfemscience.org/about/#aly" }, "publisher": { "@type": "Organization", "name": "Transfeminine Science", "url": "https://transfemscience.org", "email": "", "logo": "https://transfemscience.org/assets/images/branding/logo.png" } } </script><script type="application/ld+json"> { "@context": "https://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": 1, "name": "Home", "item": "https://transfemscience.org/" }, { "@type": "ListItem", "position": 2, "name": "Articles", "item": "https://transfemscience.org/articles/" }, { "@type": "ListItem", "position": 3, "name": "The Possible Role of a Second X Chromosome in Breast Cancer Risk" } ] }, { "@context": "https://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": 1, "name": "Home", "item": "https://transfemscience.org/" }, { "@type": "ListItem", "position": 2, "name": "Articles", "item": "https://transfemscience.org/articles/" }, { "@type": "ListItem", "position": 3, "name": "Articles by Date", "item": "https://transfemscience.org/articles-by-date/" }, { "@type": "ListItem", "position": 4, "name": "The Possible Role of a Second X Chromosome in Breast Cancer Risk" } ] } </script> <script src="../../assets/js/script.js"></script></head><body> <svg xmlns="http://www.w3.org/2000/svg" style="display: none;"> <symbol id="svg-link" viewBox="0 0 24 24"><title>Link</title><svg xmlns="http://www.w3.org/2000/svg" width="24" height="24" viewBox="0 0 24 24" fill="none" stroke="currentColor" stroke-width="2" stroke-linecap="round" stroke-linejoin="round" class="feather feather-link"><path d="M10 13a5 5 0 0 0 7.54.54l3-3a5 5 0 0 0-7.07-7.07l-1.72 1.71"></path><path d="M14 11a5 5 0 0 0-7.54-.54l-3 3a5 5 0 0 0 7.07 7.07l1.71-1.71"></path> </svg> </symbol> </svg><div id="header"><div id="header-subcontainer"> <a href="../../index.html" id="site-icon-and-title-container"> <span id="site-icon"> </span> <span id="site-title" translate="no" class="notranslate"> <span id="site-title-text-xs">TFS</span> <span id="site-title-text-sm">TFSci</span> <span id="site-title-text-md">Transfem Sci</span> <span id="site-title-text-lg">Transfeminine Science</span> </span> </a> <span id="top-links"> <a href="../index.html" class="top-link">Articles</a> <a href="../../articles-by-date/index.html" class="top-link">Latest</a> <a href="../../misc/index.html" class="top-link">Misc</a> <a href="../../about/index.html" class="top-link">About</a> </span> <span id="top-buttons"> <button id="theme-button" class="top-button" title="Theme (light/dark)"> <svg id="theme-button-light-svg" class="top-button-svg" width="20" height="20" viewBox="0 0 32 32"><path d="M16 12.005a4 4 0 1 1-4 4a4.005 4.005 0 0 1 4-4m0-2a6 6 0 1 0 6 6a6 6 0 0 0-6-6z"></path><path d="M5.394 6.813l1.414-1.415l3.506 3.506L8.9 10.318z"></path><path d="M2 15.005h5v2H2z"></path><path d="M5.394 25.197L8.9 21.691l1.414 1.415l-3.506 3.505z"></path><path d="M15 25.005h2v5h-2z"></path><path d="M21.687 23.106l1.414-1.415l3.506 3.506l-1.414 1.414z"></path><path d="M25 15.005h5v2h-5z"></path><path d="M21.687 8.904l3.506-3.506l1.414 1.415l-3.506 3.505z"></path><path d="M15 2.005h2v5h-2z"></path></svg> <svg id="theme-button-dark-svg" class="top-button-svg" width="20" height="20" viewBox="0 0 32 32"><path d="M13.502 5.414a15.075 15.075 0 0 0 11.594 18.194a11.113 11.113 0 0 1-7.975 3.39c-.138 0-.278.005-.418 0a11.094 11.094 0 0 1-3.2-21.584M14.98 3a1.002 1.002 0 0 0-.175.016a13.096 13.096 0 0 0 1.825 25.981c.164.006.328 0 .49 0a13.072 13.072 0 0 0 10.703-5.555a1.01 1.01 0 0 0-.783-1.565A13.08 13.08 0 0 1 15.89 4.38A1.015 1.015 0 0 0 14.98 3z"></path></svg> </button> <button id="language-button" class="top-button" title="Translate"> <svg class="top-button-svg" xmlns="http://www.w3.org/2000/svg" width="20" height="20" viewBox="0 0 24 24"><path d="M12.65 15.67c.14-.36.05-.77-.23-1.05l-2.09-2.06.03-.03c1.74-1.94 2.98-4.17 3.71-6.53h1.94c.54.0.99-.45.99-.99v-.02c0-.54-.45-.99-.99-.99H10V3c0-.55-.45-1-1-1s-1 .45-1 1v1H1.99c-.54.0-.99.45-.99.99.0.55.45.99.99.99h10.18C11.5 7.92 10.44 9.75 9 11.35c-.81-.89-1.49-1.86-2.06-2.88-.16-.29-.45-.47-.78-.47-.69.0-1.13.75-.79 1.35.63 1.13 1.4 2.21 2.3 3.21L3.3 16.87c-.4.39-.4 1.03.0 1.42.39.39 1.02.39 1.42.0L9 14l2.02 2.02c.51.51 1.38.32 1.63-.35zM17.5 10c-.6.0-1.14.37-1.35.94l-3.67 9.8c-.24.61.22 1.26.87 1.26.39.0.74-.24.88-.61l.89-2.39h4.75l.9 2.39c.14.36.49.61.88.61.65.0 1.11-.65.88-1.26l-3.67-9.8c-.22-.57-.76-.94-1.36-.94zm-1.62 7 1.62-4.33L19.12 17h-3.24z"></path></svg> </button> <button id="search-button" class="top-button" title="Search"> <svg version="1.1" class="top-button-svg" width="24" height="24" viewBox="0 0 32 32" xmlns="http://www.w3.org/2000/svg" xmlns:sketch="http://www.bohemiancoding.com/sketch/ns" xmlns:xlink="http://www.w3.org/1999/xlink"><g><path d="M19.4271164,21.4271164 C18.0372495,22.4174803 16.3366522,23 14.5,23 C9.80557939,23 6,19.1944206 6,14.5 C6,9.80557939 9.80557939,6 14.5,6 C19.1944206,6 23,9.80557939 23,14.5 C23,16.3366522 22.4174803,18.0372495 21.4271164,19.4271164 L27.0119176,25.0119176 C27.5621186,25.5621186 27.5575313,26.4424687 27.0117185,26.9882815 L26.9882815,27.0117185 C26.4438648,27.5561352 25.5576204,27.5576204 25.0119176,27.0119176 L19.4271164,21.4271164 L19.4271164,21.4271164 Z M14.5,21 C18.0898511,21 21,18.0898511 21,14.5 C21,10.9101489 18.0898511,8 14.5,8 C10.9101489,8 8,10.9101489 8,14.5 C8,18.0898511 10.9101489,21 14.5,21 L14.5,21 Z"></path></g></svg> </button> <button id="toc-button-mobile" class="top-button" title="Article contents (Ctrl+Shift+L)"> <svg class="top-button-svg" xmlns="http://www.w3.org/2000/svg" version="1.0" width="16" height="16" viewBox="0 0 16 16"><g transform="translate(0,16) scale(0.002536,-0.002540)"><path d="M550 6274 c-81 -17 -207 -79 -282 -139 -110 -87 -202 -230 -238 -371 -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 0z" /></g></svg> </button> <button id="menu-button-mobile-menu" class="top-button" title="Menu"> <svg class="top-button-svg" xmlns="http://www.w3.org/2000/svg" width="21" height="21" viewBox="0 0 24 24" fill="none" stroke="currentColor" stroke-width="2" stroke-linecap="round"><path d="M 3,12 L 21,12" /><path d="M 3,6 L 21,6" /><path d="M 3,18 L 21,18" /></svg> </button> <button id="hide-persistent-header-button" class="top-button" title="Hide top bar (Ctrl+Shift+H)"> <svg id="hide-persistent-header-button-svg" version="1.1" x="0px" y="0px" width="20px" height="20px" viewBox="0 0 24 24" enable-background="new 0 0 24 24" xml:space="preserve" fill="#5F6368"><path d="M8.59,16.59L13.17,12L8.59,7.41L10,6l6,6l-6,6L8.59,16.59z"></path><path fill="none" d="M0,0h24v24H0V0z"></path></svg> </button> </span></div><div id="mobile-menu"> <span id="top-links-mobile"> <a href="../index.html" class="top-link">Articles</a> <a href="../../articles-by-date/index.html" class="top-link">Latest</a> <a href="../../misc/index.html" class="top-link">Misc</a> <a href="../../about/index.html" class="top-link">About</a> </span></div></div><button id="restore-persistent-header-button" class="top-button" title="Show top bar (Ctrl+Shift+H)"> <svg id="restore-persistent-header-button-svg" version="1.1" x="0px" y="0px" width="20px" height="20px" viewBox="0 0 24 24" enable-background="new 0 0 24 24" xml:space="preserve" fill="#5F6368"><path d="M8.59,16.59L13.17,12L8.59,7.41L10,6l6,6l-6,6L8.59,16.59z"></path><path fill="none" d="M0,0h24v24H0V0z"></path></svg> </button> <button id="sidebar-button-standalone" class="sidebar-button" title="Article contents (Ctrl+Shift+L)"> <span id="sidebar-button-standalone-icon" class="sidebar-button-icon"> <svg id="sidebar-button-standalone-icon-svg" class="sidebar-button-icon-svg" xmlns="http://www.w3.org/2000/svg" version="1.0" width="16" height="16" viewBox="0 0 16 16"><g transform="translate(0,16) scale(0.002536,-0.002540)"><path d="M550 6274 c-81 -17 -207 -79 -282 -139 -110 -87 -202 -230 -238 -371 -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 0z" /></g></svg> </span> </button><div id="mid-section"><div id="sidebar"><div id="sidebar-subcontainer"><div id="sidebar-title-container"> <button id="sidebar-button" class="sidebar-button" title="Article contents (Ctrl+Shift+L)"> <span class="sidebar-button-icon"> <svg class="sidebar-button-icon-svg" xmlns="http://www.w3.org/2000/svg" version="1.0" width="16" height="16" viewBox="0 0 16 16"><g transform="translate(0,16) scale(0.002536,-0.002540)"><path d="M550 6274 c-81 -17 -207 -79 -282 -139 -110 -87 -202 -230 -238 -371 -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 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="index.html#top" class="toc-link">Top of page</a><div><div class="toc-h2"><a id="heading-1" href="index.html#preface" class="toc-link">Preface</a></div><div class="toc-h2"><a id="heading-2" href="index.html#introduction" class="toc-link">Introduction</a></div><div class="toc-h2"><a id="heading-3" href="index.html#x-chromosome-abnormalities-and-breast-cancer" class="toc-link">X Chromosome Abnormalities and Breast Cancer</a></div><div class="toc-h2"><a id="heading-4" href="index.html#x-chromosomes-and-breast-cancer-risk-in-chromosomal-disorders-and-intersexuality" class="toc-link">X Chromosomes and Breast Cancer Risk in Chromosomal Disorders and Intersexuality</a><div><div class="toc-h3"><a id="heading-5" href="index.html#klinefelters-syndrome-47xxy" class="toc-link">Klinefelter’s Syndrome (47,XXY)</a></div><div class="toc-h3"><a id="heading-6" href="index.html#complete-androgen-insensitivity-syndrome-46xy" class="toc-link">Complete Androgen Insensitivity Syndrome (46,XY)</a></div><div class="toc-h3"><a id="heading-7" href="index.html#turner-syndrome-45x-or-mixed-45x46xx" class="toc-link">Turner Syndrome (45,X or Mixed 45,X/46,XX)</a></div><div class="toc-h3"><a id="heading-8" href="index.html#xx-male-syndrome-46xx" class="toc-link">XX Male Syndrome (46,XX)</a></div><div class="toc-h3"><a id="heading-9" href="index.html#x-trisomy-47xxx-and-tetrasomy-48xxxx" class="toc-link">X Trisomy (47,XXX) and Tetrasomy (48,XXXX)</a></div></div></div><div class="toc-h2"><a id="heading-10" href="index.html#conclusions" class="toc-link">Conclusions</a></div><div class="toc-h2"><a id="heading-11" href="index.html#references" class="toc-link">References</a></div></div></div></div></div></div><div id="main-area"><div id="article"><h1 id="the-possible-role-of-a-second-x-chromosome-in-breast-cancer-risk"> <a href="index.html#the-possible-role-of-a-second-x-chromosome-in-breast-cancer-risk" aria-labelledby="the-possible-role-of-a-second-x-chromosome-in-breast-cancer-risk" class="anchor-heading"><svg viewBox="0 0 16 16" aria-hidden="true"><use xlink:href="#svg-link"></use></svg></a> The Possible Role of a Second X Chromosome in Breast Cancer Risk</h1><p>By <a href="../../about/index.html#aly">Aly</a> | First published April 25, 2020 | Last modified March 1, 2023</p><h2 id="preface"> <a href="index.html#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>This is a short supplement article to the section in the main article on breast cancer risk with hormone therapy in transfeminine people that can be found <a href="../breast-cancer/index.html">here</a>.</p><h2 id="introduction"> <a href="index.html#introduction" aria-labelledby="introduction" class="anchor-heading"><svg viewBox="0 0 16 16" aria-hidden="true"><use xlink:href="#svg-link"></use></svg></a> Introduction</h2><p>The <a href="https://en.wikipedia.org/wiki/Sex_chromosome">sex chromosomes</a> include the <a href="https://en.wikipedia.org/wiki/X_chromosome">X chromosome</a> and the <a href="https://en.wikipedia.org/wiki/Y_chromosome">Y chromosome</a>. Under normal biological circumstances, cisgender women have two X chromosomes (46,XX <a href="https://en.wikipedia.org/wiki/Karyotype">karyotype</a>) while cisgender men (and transfeminine people) have one X chromosome and one Y chromosome (46,XY karyotype). The sex chromosomes determine whether the gonads will differentiate into ovaries or testes, and hence mediate a large portion of physical sexual dimorphism. However, the sex chromosomes also have effects in terms of sexual dimorphism that are independent of gonadal differentiation. Although hormone therapy appears to increase the risk of breast cancer in transfeminine people, so far breast cancer risk in transfeminine people seems to be much lower than that in cisgender women. There are a variety of possible reasons for this, as touched on elsewhere. One reason may be our lack of a second X chromosome—there is indication that our absence of a second X chromosome may be partially protective against breast cancer.</p><h2 id="x-chromosome-abnormalities-and-breast-cancer"> <a href="index.html#x-chromosome-abnormalities-and-breast-cancer" aria-labelledby="x-chromosome-abnormalities-and-breast-cancer" class="anchor-heading"><svg viewBox="0 0 16 16" aria-hidden="true"><use xlink:href="#svg-link"></use></svg></a> X Chromosome Abnormalities and Breast Cancer</h2><p>The incidence of abnormal numbers of X chromosomes in cells (e.g., 45,X or 47,XXX karyotype) increases naturally with age (<a href="https://doi.org/10.1007/BF00204926">Barrios et al., 1991</a>; <a href="https://doi.org/10.1038/bjc.2012.577">Jacobs et al., 2013</a>). X-chromosome gain is associated with more aggressive and poorly prognostic female breast cancer (<a href="https://doi.org/10.1136/jcp.2006.037838">Nakopoulou et al., 2007</a>). Aberrant patterns of<a href="https://en.wikipedia.org/wiki/X-inactivation"> X-chromosome inactivation</a> have been observed in female breast cancer cell lines and tissue specimens and are associated with worse survival rates (<a href="https://doi.org/10.1371/journal.pone.0118453">Lin et al., 2015</a>; <a href="http://doi.org/10.1101/gr.185926.114">Chaligné et al., 2015</a>). High incidence of X-chromosome gain has been observed in male breast cancer but not in control gynecomastic breast tissue (<a href="https://doi.org/10.1016/j.humpath.2015.08.008">Di Oto et al., 2015</a>; <a href="https://doi.org/10.1007/s00428-018-2377-2">Di Oto et al., 2018</a>). Additional findings and readings on X-chromosome abnormalities in breast cancer also exist (e.g., <a href="https://doi.org/10.1038/nrc1413">Spatz, Borg, & Feunteun, 2004</a>; <a href="https://books.google.com/books?id=ZeInuazQ2cYC&pg=PA5">Sirchia, Tabano, & Miozzo, 2007</a>; <a href="https://doi.org/10.1016/j.febslet.2014.06.023">Chaligné & Heard, 2014</a>; <a href="https://doi.org/10.1016/j.ccr.2006.01.013">Richardson et al., 2006</a>; <a href="https://doi.org/10.1016/s1569-254x(98)80011-3">Dawson, 1998</a>).</p><h2 id="x-chromosomes-and-breast-cancer-risk-in-chromosomal-disorders-and-intersexuality"> <a href="index.html#x-chromosomes-and-breast-cancer-risk-in-chromosomal-disorders-and-intersexuality" aria-labelledby="x-chromosomes-and-breast-cancer-risk-in-chromosomal-disorders-and-intersexuality" class="anchor-heading"><svg viewBox="0 0 16 16" aria-hidden="true"><use xlink:href="#svg-link"></use></svg></a> X Chromosomes and Breast Cancer Risk in Chromosomal Disorders and Intersexuality</h2><p>A variety of genetic disorders involving abnormal sex-chromosome configurations and/or intersexuality also provide insight on the possible involvement of X chromosomes in breast cancer risk. These conditions include <a href="https://en.wikipedia.org/wiki/Klinefelter_syndrome">Klinefelter’s syndrome</a> (47,XXY male), <a href="https://en.wikipedia.org/wiki/Complete_androgen_insensitivity_syndrome">complete androgen insensitivity syndrome</a> (46,XY female), <a href="https://en.wikipedia.org/wiki/Turner_syndrome">Turner syndrome</a> (45,X or mixed 45,X/46,XX female), <a href="https://en.wikipedia.org/wiki/XX_male_syndrome">XX male syndrome</a> (46,XX male), and <a href="https://en.wikipedia.org/wiki/Triple_X_syndrome">X trisomy</a> and <a href="https://en.wikipedia.org/wiki/Tetrasomy_X">tetrasomy</a> (47,XXX and 48,XXXX female).</p><h3 id="klinefelters-syndrome-47xxy"> <a href="index.html#klinefelters-syndrome-47xxy" aria-labelledby="klinefelters-syndrome-47xxy" class="anchor-heading"><svg viewBox="0 0 16 16" aria-hidden="true"><use xlink:href="#svg-link"></use></svg></a> Klinefelter’s Syndrome (47,XXY)</h3><p>Men with <a href="https://en.wikipedia.org/wiki/Klinefelter_syndrome">Klinefelter’s syndrome</a> have a 47,XXY karyotype and hence an extra X chromosome. Because of their Y chromosome, men with Klinfelter’s syndrome have testes and develop normally as males. However, they have relatively low testosterone levels (about 260 ng/dL lower than usual), slightly increased estradiol levels (about 6 pg/mL more than normal), an increased ratio of estradiol to testosterone, and negligible progesterone (<a href="https://en.wikipedia.org/wiki/Klinefelter_syndrome#Endocrine">Wiki</a>). In addition, men with Klinefelter’s syndrome show undermasculinization and sometimes have mild gynecomastia. The risk of breast cancer in men with Klinefelter’s syndrome is strongly increased relative to 46,XY men (<a href="https://doi.org/10.1111/j.1651-2227.2010.02131.x">Brinton, 2011</a>; <a href="https://doi.org/10.1016/j.fertnstert.2012.05.026">Sokol, 2012</a>). The risk is estimated to be 20- to 60-fold higher in men with Klinefelter’s syndrome compared to 46,XY men and only 70% lower than the risk in 46,XX women (<a href="https://doi.org/10.1111/j.1651-2227.2010.02131.x">Brinton, 2011</a>; <a href="https://doi.org/10.1016/j.fertnstert.2012.05.026">Sokol, 2012</a>; <a href="https://doi.org/10.1093/jnci/dji240">Swerdlow et al., 2005</a>). The lifetime risk of breast cancer in men with Klinefelter’s syndrome is 4 to 8% (<a href="https://doi.org/10.1016/j.fertnstert.2012.05.026">Sokol, 2012</a>). Breast cancer risk in men with Klinefelter’s syndrome is much higher than that in almost any other known clinical situation in men. The typical age of diagnosis of breast cancer in men with Klinefelter’s syndrome is 58 years (<a href="https://doi.org/10.1007/s11912-015-0487-4">Ferzoco & Ruddy, 2016</a>). It is estimated that 7% of all men with breast cancer have Klinefelter’s syndrome (<a href="https://doi.org/10.1007/s11912-015-0487-4">Ferzoco & Ruddy, 2016</a>). Klinefelter’s syndrome suggests that breast cancer may be dependent on an extra X chromosome (<a href="https://doi.org/10.1038/nrc1413">Spatz, Borg, & Feunteun, 2004</a>; <a href="https://books.google.com/books?id=YKWGY21z14cC&pg=PA208">Sacchi, 1993</a>; <a href="https://doi.org/10.1016/s1569-254x(98)80011-3">Dawson, 1998</a>), although disordered hormone levels may also be involved.</p><h3 id="complete-androgen-insensitivity-syndrome-46xy"> <a href="index.html#complete-androgen-insensitivity-syndrome-46xy" aria-labelledby="complete-androgen-insensitivity-syndrome-46xy" class="anchor-heading"><svg viewBox="0 0 16 16" aria-hidden="true"><use xlink:href="#svg-link"></use></svg></a> Complete Androgen Insensitivity Syndrome (46,XY)</h3><p>Women with <a href="https://en.wikipedia.org/wiki/Complete_androgen_insensitivity_syndrome">complete androgen insensitivity syndrome</a> (CAIS) are individuals with a 46,XY karyotype and intra-abdominal testes who have a defective androgen receptor and hence are insensitive to the effects of androgens like testosterone. Due to their androgen insensitivity, CAIS women develop physically and behaviorally as females instead of as males. CAIS women naturally have male-range levels of sex hormones, including of testosterone, estradiol, and progesterone (<a href="https://en.wikipedia.org/wiki/Complete_androgen_insensitivity_syndrome#Endocrine">Wiki</a>). Relative to 46,XX women, testosterone levels are very high, estradiol levels relatively low (~35 pg/mL), and progesterone levels negligible. During adolescence, CAIS women undergo female puberty due to aromatization of testosterone into estradiol, and this results in feminization and excellent breast development, with breasts that are said to be somewhat above-average compared to those of 46,XX women.</p><p>After puberty, all clinically diagnosed CAIS women undergo gonadectomy due to a high risk of testicular cancer that’s associated with their intra-abdominal testes. Following gonadectomy, CAIS women receive estrogen replacement therapy, oftentimes if not usually only at menopausal doses. A progestogen is not usually included since CAIS women don’t have uteruses and hence don’t require the endometrial protection afforded by progestogens. Despite a 1 in 20,000 incidence of CAIS in 46,XY individuals and hence the estimated existence of hundreds of thousands of CAIS women throughout the world, breast cancer has never been reported in a CAIS woman (<a href="https://doi.org/10.1016/S0140-6736(12)60071-3">Hughes et al., 2012</a>; <a href="https://doi.org/10.1159/000158055">Tiefenbacher & Daxenbichler, 2008</a>; <a href="https://doi.org/10.1002/9781444316728.ch9">Hughes, 2009</a>). It’s unlikely that breast cancer <em>doesn’t occur</em> in women with CAIS, but rather it’s probable that it’s rare. It’s unknown why this is the case, but major possible reasons include the relatively low estrogen exposure, lack of progesterone, and the lack of a second X chromosome. Their androgen insensitivity is unlikely to be involved as androgens, via activation of the androgen receptor, are thought to be protective in terms of breast cancer risk (<a href="https://doi.org/10.1016/j.ecl.2011.05.007">Dimitrakakis, 2011</a>). CAIS women are fascinating because they suggest that considerable breast cancer incidence isn’t an inevitable companion of normal breast development.</p><h3 id="turner-syndrome-45x-or-mixed-45x46xx"> <a href="index.html#turner-syndrome-45x-or-mixed-45x46xx" aria-labelledby="turner-syndrome-45x-or-mixed-45x46xx" class="anchor-heading"><svg viewBox="0 0 16 16" aria-hidden="true"><use xlink:href="#svg-link"></use></svg></a> Turner Syndrome (45,X or Mixed 45,X/46,XX)</h3><p>Women with <a href="https://en.wikipedia.org/wiki/Turner_syndrome">Turner syndrome</a> have either a 45,X karyotype or a mosaic of 45,X and 46,XX karyotypes. They often though not always have gonadal failure and hence many of them fail to undergo puberty. Gonadal failure is much more prevalent in those with a 45,X karyotype than in mosaics. When gonadal failure occurs, hormone therapy is required. Women with Turner’s syndrome have uteruses, so those who have pubertal failure receive hormone replacement with both an estrogen and a progestogen. As with CAIS women, this is often with only menopausal replacement doses. The risk of breast cancer appears to be lower in women with Turner syndrome than in regular 46,XX women (<a href="https://doi.org/10.1016/S1470-2045(08)70033-0">Schoemaker et al., 2008</a>; <a href="http://doi.org/10.1056/NEJMc062795">Bösze, Tóth, & Török, 2006</a>; <a href="https://doi.org/10.1530/EJE-20-0702">Viuff et al., 2020</a>). For example, in one large cohort study of 3,425 women with Turner syndrome and an average of 17 years of follow up, the risk of breast cancer was significantly lower than in regular 46,XX women. Interestingly, the standardized incidence ratios were 0.2 (0.0–0.9) in those with a 45,X karyotype and 0.9 (0.3–2.0) in those with 45,X and 46,XX mosaicism. In other words, those with mosaicism had a risk of breast cancer similar to that of regular 46,XX women, whereas those with a 45,X chromosome had a significantly lower risk (<a href="https://doi.org/10.1016/S1470-2045(08)70045-7">Gravholt, 2008</a>).</p><h3 id="xx-male-syndrome-46xx"> <a href="index.html#xx-male-syndrome-46xx" aria-labelledby="xx-male-syndrome-46xx" class="anchor-heading"><svg viewBox="0 0 16 16" aria-hidden="true"><use xlink:href="#svg-link"></use></svg></a> XX Male Syndrome (46,XX)</h3><p><a href="https://en.wikipedia.org/wiki/XX_male_syndrome">XX males</a> have a 46,XX karyotype. In about 90% of cases, the condition is caused by translocation of the <em>SRY</em> gene, which encodes the protein <a href="https://en.wikipedia.org/wiki/Testis-determining_factor">testis-determining factor</a> (TDF), onto an X chromosome. As a result of this, XX males develop testes instead of ovaries, in turn developing as males instead of as females. Three case reports of breast cancer in 46,XX males exist (<a href="https://doi.org/10.1093/humrep/dex210">Berglund et al., 2017</a>). On the basis of these cases and the small total number of cases of XX male syndrome that have been reported, it has been said that XX males are at increased risk for breast cancer analogously to men with Klinefelter’s syndrome (<a href="https://doi.org/10.1038/nrc1413">Spatz, Borg, & Feunteun, 2004</a>; <a href="https://doi.org/10.1111/j.1399-0004.1980.tb01019.x">Giammarini, 1980</a>).</p><h3 id="x-trisomy-47xxx-and-tetrasomy-48xxxx"> <a href="index.html#x-trisomy-47xxx-and-tetrasomy-48xxxx" aria-labelledby="x-trisomy-47xxx-and-tetrasomy-48xxxx" class="anchor-heading"><svg viewBox="0 0 16 16" aria-hidden="true"><use xlink:href="#svg-link"></use></svg></a> X Trisomy (47,XXX) and Tetrasomy (48,XXXX)</h3><p>So far there is no evidence of increased breast cancer risk in <a href="https://en.wikipedia.org/wiki/Triple_X_syndrome">47,XXX</a> (X trisomy) or <a href="https://en.wikipedia.org/wiki/Tetrasomy_X">48,XXXX</a> (X tetrasomy) females (<a href="https://doi.org/10.1038/nrc1413">Spatz, Borg, & Feunteun, 2004</a>), although most cases of these syndromes go undetected and the conditions are understudied (<a href="http://www.scielo.org.ar/scielo.php?script=sci_arttext&pid=S0325-00752010000400012">Goldschmidt et al., 2010</a>; <a href="https://en.wikipedia.org/wiki/Triple_X_syndrome">Wiki</a>). Additional X chromosomes are inactivated in these individuals, limiting—although not fully eliminating—phenotypical abnormalities, possibly including greater breast cancer risk.</p><h2 id="conclusions"> <a href="index.html#conclusions" aria-labelledby="conclusions" class="anchor-heading"><svg viewBox="0 0 16 16" aria-hidden="true"><use xlink:href="#svg-link"></use></svg></a> Conclusions</h2><p>Taken together, these findings from chromosomal disorders and intersex conditions suggest that having at least two X chromosomes may greatly increase the risk of breast cancer. In addition, CAIS women suggest that normal breast development with very low breast cancer risk is possible, provided of course that the person has only one X chromosome.</p><h2 id="references"> <a href="index.html#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><ul><li>Barrios, L., Caballín, M., Miró, R., Fuster, C., Guedea, F., Subias, A., & Egozcue, J. (1991). Chromosomal instability in breast cancer patients. <em>Human Genetics</em>, <em>88</em>(1), 39–41. [DOI:<a href="https://doi.org/10.1007/bf00204926">10.1007/bf00204926</a>]</li><li>Berglund, A., Johannsen, T., Stochholm, K., Aksglaede, L., Fedder, J., Viuff, M., Main, K., & Gravholt, C. (2017). Incidence, prevalence, diagnostic delay, morbidity, mortality and socioeconomic status in males with 46,XX disorders of sex development: a nationwide study. <em>Human Reproduction</em>, <em>32</em>(8), 1751–1760. [DOI:<a href="https://doi.org/10.1093/humrep/dex210">10.1093/humrep/dex210</a>]</li><li>Bösze, P., Tóth, A., & Török, M. (2006). Hormone Replacement and the Risk of Breast Cancer in Turner’s Syndrome. <em>New England Journal of Medicine</em>, <em>355</em>(24), 2599–2600. [DOI:<a href="https://doi.org/10.1056/nejmc062795">10.1056/nejmc062795</a>]</li><li>Brinton, L. A. (2011). Breast cancer risk among patients with Klinefelter syndrome. <em>Acta Paediatrica</em>, <em>100</em>(6), 814–818. [DOI:<a href="https://doi.org/10.1111/j.1651-2227.2010.02131.x">10.1111/j.1651-2227.2010.02131.x</a>]</li><li>Chaligné, R., & Heard, E. (2014). X-chromosome inactivation in development and cancer. <em>FEBS Letters</em>, <em>588</em>(15), 2514–2522. [DOI:<a href="https://doi.org/10.1016/j.febslet.2014.06.023">10.1016/j.febslet.2014.06.023</a>]</li><li>Chaligné, R., Popova, T., Mendoza-Parra, M., Saleem, M. M., Gentien, D., Ban, K., Piolot, T., Leroy, O., Mariani, O., Gronemeyer, H., Vincent-Salomon, A., Stern, M., & Heard, E. (2015). The inactive X chromosome is epigenetically unstable and transcriptionally labile in breast cancer. <em>Genome Research</em>, <em>25</em>(4), 488–503. [DOI:<a href="https://doi.org/10.1101/gr.185926.114">10.1101/gr.185926.114</a>]</li><li>Dawson, P. J. (1998). A history of cancer of the male breast. In Peters, W. P., & Visscher, D. W. (Eds.). <em>Breast Cancer</em> (<em>Advances in Oncobiology, Volume 2</em>) (pp. 229–243). Stamford/London: Jai Press. [DOI:<a href="https://doi.org/10.1016/s1569-254x(98)80011-3">10.1016/s1569-254x(98)80011-3</a>] [<a href="https://books.google.com/books?id=85B9BFmek6wC&pg=PA238">Google Books</a>]</li><li>Di Oto, E., Monti, V., Cucchi, M. C., Masetti, R., Varga, Z., & Foschini, M. P. (2015). X chromosome gain in male breast cancer. <em>Human Pathology</em>, <em>46</em>(12), 1908–1912. [DOI:<a href="https://doi.org/10.1016/j.humpath.2015.08.008">10.1016/j.humpath.2015.08.008</a>]</li><li>Di Oto, E., Biserni, G. B., Varga, Z., Morandi, L., Cucchi, M. C., Masetti, R., & Foschini, M. P. (2018). X chromosome gain is related to increased androgen receptor expression in male breast cancer. <em>Virchows Archiv</em>, <em>473</em>(2), 155–163. [DOI:<a href="https://doi.org/10.1007/s00428-018-2377-2">10.1007/s00428-018-2377-2</a>]</li><li>Dimitrakakis, C. (2011). Androgens and Breast Cancer in Men and Women. <em>Endocrinology and Metabolism Clinics of North America</em>, <em>40</em>(3), 533–547. [DOI:<a href="https://doi.org/10.1016/j.ecl.2011.05.007">10.1016/j.ecl.2011.05.007</a>]</li><li>Ferzoco, R. M., & Ruddy, K. J. (2015). The Epidemiology of Male Breast Cancer. <em>Current Oncology Reports</em>, <em>18</em>(1), 1. [DOI:<a href="https://doi.org/10.1007/s11912-015-0487-4">10.1007/s11912-015-0487-4</a>]</li><li>Giammarini, A., Rocchi, M., Zennaro, W., & Filippi, G. (2008). XX Male with breast cancer. <em>Clinical Genetics</em>, <em>18</em>(2), 103–108. [DOI:<a href="https://doi.org/10.1111/j.1399-0004.1980.tb01019.x">10.1111/j.1399-0004.1980.tb01019.x</a>]</li><li>Goldschmidt, E., Márquez, M., Solari, A., Ziembar, M. I., & Laudicina, A. (2010). Variabilidad fenotípica en pacientes 47, XXX: Presentación de cuatro casos nuevos. [Phenotypic variability in 47, XXX patients. Clinical report of four new cases.] <em>Archivos Argentinos de Pediatría</em>, <em>108</em>(4), e88–e91. [<a href="http://www.scielo.org.ar/scielo.php?script=sci_arttext&pid=S0325-00752010000400012">URL</a>]</li><li>Gravholt, C. H. (2008). Epidemiology of Turner syndrome. <em>The Lancet Oncology</em>, <em>9</em>(3), 193–195. [DOI:<a href="https://doi.org/10.1016/s1470-2045(08)70045-7">10.1016/s1470-2045(08)70045-7</a>]</li><li>Hughes, I. A. (2010). Evaluation and Management of Disorders of Sex Development. In Brook, C. G. D., Clayton, P. E., & Brown, R. S. (Eds.). <em>Brook’s Clinical Pediatric Endocrinology, 6th Edition</em> (pp. 192–212). Oxford: Wiley-Blackwell. [DOI:<a href="https://doi.org/10.1002/9781444316728.ch9">10.1002/9781444316728.ch9</a>]</li><li>Hughes, I. A., Davies, J. D., Bunch, T. I., Pasterski, V., Mastroyannopoulou, K., & MacDougall, J. (2012). Androgen insensitivity syndrome. <em>The Lancet</em>, <em>380</em>(9851), 1419–1428. [DOI:<a href="https://doi.org/10.1016/s0140-6736(12)60071-3">10.1016/s0140-6736(12)60071-3</a>]</li><li>Jacobs, P. A., Maloney, V., Cooke, R., Crolla, J. A., Ashworth, A., & Swerdlow, A. J. (2013). Male breast cancer, age and sex chromosome aneuploidy. <em>British Journal of Cancer</em>, <em>108</em>(4), 959–963. [DOI:<a href="https://doi.org/10.1038/bjc.2012.577">10.1038/bjc.2012.577</a>]</li><li>Lin, I., Chen, D., Chang, Y., Lee, Y., Su, C., Cheng, C., Tsai, Y., Ng, S., Chen, H., Lee, M., Chen, H., Suen, S., Chen, Y., Liu, T., Chang, C., & Hsu, M. (2015). Hierarchical Clustering of Breast Cancer Methylomes Revealed Differentially Methylated and Expressed Breast Cancer Genes. <em>PLOS ONE</em>, <em>10</em>(2), e0118453. [DOI:<a href="https://doi.org/10.1371/journal.pone.0118453">10.1371/journal.pone.0118453</a>]</li><li>Nakopoulou, L., Panayotopoulou, E. G., Giannopoulou, I., Tsirmpa, I., Katsarou, S., Mylona, E., Alexandrou, P., & Keramopoulos, A. (2006). Extra copies of chromosomes 16 and X in invasive breast carcinomas are related to aggressive phenotype and poor prognosis. <em>Journal of Clinical Pathology</em>, <em>60</em>(7), 808–815. [DOI:<a href="https://doi.org/10.1136/jcp.2006.037838">10.1136/jcp.2006.037838</a>]</li><li>Richardson, A. L., Wang, Z. C., De Nicolo, A., Lu, X., Brown, M., Miron, A., Liao, X., Iglehart, J. D., Livingston, D. M., & Ganesan, S. (2006). X chromosomal abnormalities in basal-like human breast cancer. <em>Cancer Cell</em>, <em>9</em>(2), 121–132. [DOI:<a href="https://doi.org/10.1016/j.ccr.2006.01.013">10.1016/j.ccr.2006.01.013</a>]</li><li>Sacchi, N. (1993). Constitutional Chromosome Aneuploidy and Cancer. In Kirsch, I. R. (Ed.). <em>The Causes and Consequences of Chromosomal Aberrations</em> (pp. 191–222). Boca Raton: CRC Press. [<a href="https://books.google.com/books?id=YKWGY21z14cC&pg=PA208">Google Books</a>]</li><li>Schoemaker, M. J., Swerdlow, A. J., Higgins, C. D., Wright, A. F., & Jacobs, P. A. (2008). Cancer incidence in women with Turner syndrome in Great Britain: a national cohort study. <em>The Lancet Oncology</em>, <em>9</em>(3), 239–246. [DOI:<a href="https://doi.org/10.1016/s1470-2045(08)70033-0">10.1016/s1470-2045(08)70033-0</a>]</li><li>Sirchia, S. M., Tabano, S. M., & Miozzo, M. (2007). BRCA1 and X Chromosome Inactivation: Which is the Link? In Polinsky, K. R. (Ed.). <em>Tumor Suppressor Genes</em> (pp. 5–8). New York: Nova Biomedical Books. [<a href="https://books.google.com/books?id=ZeInuazQ2cYC&pg=PA5">Google Books</a>]</li><li>Sokol, R. Z. (2012). It’s not all about the testes: medical issues in Klinefelter patients. <em>Fertility and Sterility</em>, <em>98</em>(2), 261–265. [DOI:<a href="https://doi.org/10.1016/j.fertnstert.2012.05.026">10.1016/j.fertnstert.2012.05.026</a>]</li><li>Spatz, A., Borg, C., & Feunteun, J. (2004). X-Chromosome Genetics and Human Cancer. <em>Nature Reviews Cancer</em>, <em>4</em>(8), 617–629. [DOI:<a href="https://doi.org/10.1038/nrc1413">10.1038/nrc1413</a>]</li><li>Swerdlow, A. J., Schoemaker, M. J., Higgins, C. D., Wright, A. F., & Jacobs, P. A. (2005). Cancer Incidence and Mortality in Men with Klinefelter Syndrome: A Cohort Study. <em>JNCI: Journal of the National Cancer Institute</em>, <em>97</em>(16), 1204–1210. [DOI:<a href="https://doi.org/10.1093/jnci/dji240">10.1093/jnci/dji240</a>]</li><li>Tiefenbacher, K., & Daxenbichler, G. (2008). The Role of Androgens in Normal and Malignant Breast Tissue. <em>Breast Care</em>, <em>3</em>(5), 325–331. [DOI:<a href="https://doi.org/10.1159/000158055">10.1159/000158055</a>]</li><li>Viuff, M. H., Stochholm, K., Lin, A., Berglund, A., Juul, S., & Gravholt, C. H. (2021). Cancer occurrence in Turner syndrome and the effect of sex hormone substitution therapy. <em>European Journal of Endocrinology</em>, <em>184</em>(1), 79–88. [DOI:<a href="https://doi.org/10.1530/eje-20-0702">10.1530/eje-20-0702</a>]</li></ul></div></div><div id="footer"> <span id="footer-subcontainer"> <span id="site-copyright">© 2025 <span translate="no" class="notranslate">Transfeminine Science</span></span> </span></div></div></body></html> |