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Endometriosis: New Insights into Causes and Treatments – Gynecology

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tag-fertility-preservation tag-genetic-factors tag-hormonal-therapy tag-immune-dysfunction tag-infertility tag-inflammation tag-ivf tag-neuroangiogenesis tag-progesterone-resistance tag-targeted-therapy" itemtype="https://schema.org/CreativeWork" itemscope> <div class="inside-article"> <div class="featured-image page-header-image-single "> <img width="1200" height="628" src="https://gynecology.blog/archive/wp-content/uploads/2024/10/gynecology-min-scaled-e1727776088967.jpg" class="attachment-full size-full" alt="" itemprop="image" decoding="async" fetchpriority="high" /> </div> <header class="entry-header"> <h1 class="entry-title" itemprop="headline">Endometriosis: New Insights into Causes and Treatments</h1> <div class="entry-meta"> <span class="posted-on"><time class="entry-date published" datetime="2024-10-01T15:18:15+05:30" itemprop="datePublished">October 1, 2024</time></span> <span class="byline">by <span class="author vcard" itemprop="author" itemtype="https://schema.org/Person" itemscope><a class="url fn n" href="https://gynecology.blog/archive/author/gynecology/" title="View all posts by gynecology" rel="author" itemprop="url"><span class="author-name" itemprop="name">gynecology</span></a></span></span> </div> </header> <div class="entry-content" itemprop="text"> <p>Persistent gynecological disease endometriosis affects around 10% of women of childbearing age. Endometriosis, where tissue is present outside of the uterus that looks like endometrial tissue, has been linked to severe pelvic pain, dysmenorrhea, dyspareunia, and infertility. Even though endometriosis is a common disorder with a highly debilitating impact on life, the exact cause of endometriosis is not precisely known, and most treatments are palliative rather than etiological. New insights of the mechanisms behind the disease in terms of hereditary, environmental as well as immunological factors; also advances of more viable therapy options with a hope to increase the cure rate, have been achieved through recent research work done.</p> <h3><strong>Understanding the Causes of Endometriosis</strong></h3> <h4><strong>Genetic and Epigenetic Factors</strong></h4> <p>Investigation reveals that endometriosis carries considerable heritability. Many gene variations, for instance those affecting the progesterone receptor, have been associated with the development of the disease. For instance, resistance to progesterone in tissues lining the endometrium has been related to variability of the progesterone receptor gene. Because it leads to an inappropriate response to hormonal therapy that rely on progesterone activity in order to keep the proliferation of endometrial tissue within bounds, this resistance is the key factor in the pathogenesis of the disease.</p> <p>Epigenetic alterations have been found to be highly etiological contributors in endometriosis and other genetic mutations. Epigenetic changes, including DNA methylation, have been identified to alter gene expression without the sequence of DNA being altered. The authors report that such endometriosis-carrying women share aberrant DNA methylation profiles within their endometrial tissues, thus contributing to aberrantly expressed genes that play central roles in inflammation as well as hormone response.</p> <h4><strong>Environmental Toxins</strong></h4> <p>Exposure to chemicals is another environmental factor that may lead to endometriosis. Among the environmental toxins, dioxin is regarded as one of the best-studied ones in association with endometriosis. It has been proven that exposure to dioxin increases the rate of endometriosis progression, in which an inflammatory environment induces the growth and proliferation of the ectopic endometrial tissue. This toxin interferes with normal immune responses and hence will give the body a more difficult time in the removal of displaced endometrial cells from other locations outside the uterus.</p> <h4><strong>Immune Dysfunction</strong></h4> <p>Another important component in the pathophysiology of endometriosis is immune dysregulation. The immune system appears to fail to recognize and destroy ectopic endometrial cells, which immigrate outside the uterus in women who are diagnosed with endometriosis. This failure renders these cells the ability to proliferate, implant, and eventually cause chronic pelvic inflammation. Research has demonstrated that immune cells, such as macrophages, have the ability to secrete cytokines that stimulate inflammation and further perpetuate the survival and proliferation of ectopic endometrial cells. Research conducted on the aspects of neuroangiogenesis in lesions of endometriosis has also established that the tissue of endometriosis can tap its own existing neural connections and blood supply to enhance inflammation and pain.</p> <p></div></div> <div style="background: #f7f7f7;border: 1px solid rgba(0, 0, 0, 0.07);"> <div style="padding: 30px;"><div class="Adblock-main"> <div class="Adblock-head"> <h2>Yearwise Publication Trend on <b>“<a href="https://gynecology.blog/publication-trends/index/endometriosis" target="_blank" title="endometriosis - yearwise publication trends">endometriosis</a>”</b></h2> </div> </div><div class="results-container"><div class="chart-block" style="padding:15px;"> <div class="left"> <div id="results" class="results"></div> </div> <div class="right"> <div class="chart-container"><canvas id="publicationChart"></canvas></div> </div> <div class="keywordsdiv"> <div style="text-align:center;"><b>Find publication trends on relevant topics</b> </div> <span class="gp-icon icon-tags"><svg viewBox="0 0 512 512" aria-hidden="true" xmlns="http://www.w3.org/2000/svg" width="1em" height="1em"><path d="M20 39.5c-8.836 0-16 7.163-16 16v176c0 4.243 1.686 8.313 4.687 11.314l224 224c6.248 6.248 16.378 6.248 22.626 0l176-176c6.244-6.244 6.25-16.364.013-22.615l-223.5-224A15.999 15.999 0 00196.5 39.5H20zm56 96c0-13.255 10.745-24 24-24s24 10.745 24 24-10.745 24-24 24-24-10.745-24-24z"></path><path d="M259.515 43.015c4.686-4.687 12.284-4.687 16.97 0l228 228c4.686 4.686 4.686 12.284 0 16.97l-180 180c-4.686 4.687-12.284 4.687-16.97 0-4.686-4.686-4.686-12.284 0-16.97L479.029 279.5 259.515 59.985c-4.686-4.686-4.686-12.284 0-16.97z"></path></svg></span> <span id="keyword-stats"></span> </div> </div></div></div><div class="inside-article"><style> table { margin: 0 0 1.5em; 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if (!statistics || Object.keys(statistics).length === 0) { resultsContainer.innerHTML = '<p>No data found.</p>'; return; } var tableHTML = `<div class='pub-scroll'> <table class='tablediv' border='1' cellspacing='0' cellpadding='0'> <tr> <th>Year</th> <th>Publication Count</th> </tr>`; Object.entries(statistics).sort(([yearA], [yearB]) => yearB - yearA).forEach(([year, count]) => { const displayCount = count === 0 ? 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The drugs used majorly are progestins, GnRH agonists, and combination oral contraceptives. These treatments are utilized to suppress ovarian hormone production, hence slowing down the activity and proliferation of the lesions in the case of endometriosis. However, this cannot be said to be applicable for all patients due to the fact that progesterone resistance is a common feature for most endometriosis patients.</p> <p>Synthetic progestins, such as dienogest, upregulate expression of progesterone receptor and decrease inflammation-progressive course of the disease, thus being of interest as a novel approach. Dienogest may manage not only the symptoms of endometriosis but also act towards the underlying inflammatory processes that promote the course of the disease.</p> <p>Furthermore, GnRH antagonists are increasingly preferred nowadays as an alternative to GnRH agonists. Compared to agonists, GnRH antagonists allow for a quicker and more stable estrogen decrease without that initial rise in hormones before suppression, and thus might be more tolerable for long-term use.</p> <h4><strong>Non-Hormonal and Surgical Options</strong></h4> <p>In addition, non-hormonal treatments and surgery still remain viable alternatives for women who do not tolerate the hormonal treatments or cannot cope with their side effects. A number of patients can take non-steroidal anti-inflammatory medicines, more commonly referred to as NSAIDs, and utilize them to help alleviate pain but are not considered a treatment option for endometriosis. Patients experiencing severe endometriosis symptoms or infertility might undergo laparoscopic surgery as endometriotic lesions are removed or ablated. On the contrary, risks associated with surgical interventions are adhesion formation and recurrence of the disease.</p> <p>Such a radical surgical procedure would entail a hysterectomy, either as a standalone or in combination with an oophorectomy. Although the symptoms might be relieved, the disadvantages include serious side effects, most significantly to the woman of an older age who would want their reproductive functions. Additionally, the lesions could remain even after the removal of the uterus, and therefore, hysterectomy may not always be considered the remedy.</p> <h4><strong>Targeted Therapies</strong></h4> <p>The new developments in the pathophysiology of endometriosis now open the door for targeted treatments. Among them is the CXCL12/CXCR4 signaling pathway inhibitor, known to be involved in the recruitment of stem cells from bone marrow into endometriotic lesions. Use of such inhibitors may block the recruitment of cells and thus inhibit the development and spread of new endometriotic lesions.<br /> In addition to signaling pathways, there are now treatments of neuroangiogenesis. Here, researchers are going to decrease the pain and growth of lesions by blocking the neovascularization and neuronal growth within the endometriotic lesions. This is a singular approach towards the treatment of endometriosis.</p> <h4><strong>Fertility Preservation and Assisted Reproduction</strong></h4> <p>Fertility preservation through a technique such as egg freezing or ovarian tissue cryopreservation becomes much more relevant for endometriosis-affected women who intend to conceive. Endometriosis can greatly compromise fertility, and in severe cases, women are at risk of premature ovarian failure. Although there may be a decline in ovarian functions, fertility preservation gives women such an opportunity to conceive in the future.</p> <p>Today, on the other hand, IVF is still one of the best treatments for women whose infertility is caused by endometriosis. Progestin therapy has lately been reviewed in relation to controlled ovarian stimulation, known as CIFS, which has proven to improve treatment outcomes in women with advanced endometriosis.</p> <p></div></div> <div style="background: #f7f7f7;border: 1px solid rgba(0, 0, 0, 0.07);"> <div style="padding: 30px;"><div class="Adblock-main"> <div class="Adblock-head"> <h2>Recent Publications on <b>“<a href="https://gynecology.blog/recent-publications/index/endometriosis" target="_blank" rel="noopener" title="endometriosis - yearwise publication list">endometriosis</a>”</b></h2> </div> </div> <div class="pb-main"><div class="article-scroll"><div id="results_recent" class="results"></div></div><div class="keywordsdiv" style="margin: 0px 15px;margin-top:20px;"> <div style="text-align:center;"><b>Find publications on relevant topics</b> </div> <span class="gp-icon icon-tags"><svg viewBox="0 0 512 512" aria-hidden="true" xmlns="http://www.w3.org/2000/svg" width="1em" height="1em"><path d="M20 39.5c-8.836 0-16 7.163-16 16v176c0 4.243 1.686 8.313 4.687 11.314l224 224c6.248 6.248 16.378 6.248 22.626 0l176-176c6.244-6.244 6.25-16.364.013-22.615l-223.5-224A15.999 15.999 0 00196.5 39.5H20zm56 96c0-13.255 10.745-24 24-24s24 10.745 24 24-10.745 24-24 24-24-10.745-24-24z"></path><path d="M259.515 43.015c4.686-4.687 12.284-4.687 16.97 0l228 228c4.686 4.686 4.686 12.284 0 16.97l-180 180c-4.686 4.687-12.284 4.687-16.97 0-4.686-4.686-4.686-12.284 0-16.97L479.029 279.5 259.515 59.985c-4.686-4.686-4.686-12.284 0-16.97z"></path></svg></span> <span id="keyword-papers"></span> </div></div></div><div class="inside-article"> <style> .pb-main{ border: solid 1px #ccc; 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}); } function displayKeywordPapers(keywords) { var resultsContainer = document.getElementById('keyword-papers'); resultsContainer.innerHTML = ''; if (!keywords || keywords.length === 0) { resultsContainer.innerHTML = '<p>No data found.</p>'; return; } var keywordHTML = ''; keywords.forEach((key, index) => { let key_replace = key.replace(/ /g, '-'); key_replace = key_replace.toLowerCase(); keywordHTML += `<a href="https://gynecology.blog/recent-publications/index/${key_replace}" target="_blank" title="${key} - publication list">${key}</a>`; if (index < keywords.length - 1) { keywordHTML += ', '; } }); resultsContainer.innerHTML = keywordHTML; } // Call the function with the PHP data var recent_papers = [ { "title": "Indirect markers of oocyte quality in patients with ovarian endometriosis undergoing IVF\/ICSI: a systematic review and meta-analysis.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38943812", "publishedDate": "2024" }, { "title": "The prevalence of endometriosis in unexplained infertility: a systematic review.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38943813", "publishedDate": "2024" }, { "title": "Common Beverage Consumption and Benign Gynecological Conditions.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38948304", "publishedDate": "2024" }, { "title": "DNA methylation profiles of ovarian cysts resemble ovarian tissues but not endometrial tissues.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38844959", "publishedDate": "2024" }, { "title": "Retroperitoneal cystic endometriosis incidentally found at time of hysterectomy.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38885810", "publishedDate": "2024" }, { "title": "Correction: Comparison of microbial abundance and diversity in uterine and peritoneal fluid in infertile patients with or without endometriosis.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38877538", "publishedDate": "2024" }, { "title": "The Limitations of Endometriosis Research Need Not Be Self Imposed.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38885809", "publishedDate": "2024" }, { "title": "Investigating migraine phenotype and dynamics in women with endometriosis: an observational pilot study.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38878131", "publishedDate": "2024" }, { "title": "Clinical and Imaging Characteristics of Herlyn-Werner-Wunderlich Syndrome: a Comprehensive Analysis.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38907127", "publishedDate": "2024" }, { "title": "A Closer Look at Endometriosis.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38901896", "publishedDate": "2024" }, { "title": "Lysine acetyltransferase 14 mediates TGF-\u03b2-induced fibrosis in ovarian endometrioma via co-operation with serum response factor.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38867256", "publishedDate": "2024" }, { "title": "INTESTINAL ENDOMETRIOSIS: OUTCOMES FROM A MULTIDISCIPLINARY SPECIALIZED REFERRAL CENTER.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38958344", "publishedDate": "2024" }, { "title": "A mendelian randomization approach to study causal association between four types of endometriosis and immune cells: experimental studies.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38959091", "publishedDate": "2024" }, { "title": "Abnormal HCK\/glutamine\/autophagy axis promotes endometriosis development by impairing macrophage phagocytosis.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38956970", "publishedDate": "2024" }, { "title": "Efficacy, tolerability, and bone density outcomes of elagolix with add-back therapy for endometriosis-associated pain: 12 months of an ongoing randomized phase 3 trial.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38955323", "publishedDate": "2024" }, { "title": "Significant increased isolation of Escherichia coli in Iranian women with endometriosis: a case control - study.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38961459", "publishedDate": "2024" }, { "title": "A Comprehensive Review of the Efficacy and Safety of Dopamine Agonists for Women with Endometriosis-associated Infertility from Inception to July 31, 2022.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38939420", "publishedDate": "2024" }, { "title": "The PD-1\/PD-L1 Gateway: Peripheral Immune Regulation in the Pathogenesis of Endometriosis.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38928479", "publishedDate": "2024" }, { "title": "Transcriptomic Analysis of Hub Genes Reveals Associated Inflammatory Pathways in Estrogen-Dependent Gynecological Diseases.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38927277", "publishedDate": "2024" }, { "title": "Curative Effect of IKAP Nursing in Perioperative Nursing of Endometriosis Treated by Laparoscopic Surgery.", "url": "https:\/\/pubmed.ncbi.nlm.nih.gov\/38940808", "publishedDate": "2024" } ]; var keywordsArray = ["Endometriosis","chronic pain","infertility","neuroangiogenesis","progesterone resistance","genetic factors","environmental toxins","targeted therapy","hormonal therapy","surgery","fertility preservation","IVF","inflammation","immune dysfunction"]; displayResults_recent(recent_papers); displayKeywordPapers(keywordsArray); </script></p> <h3><strong>Conclusion</strong></h3> <p>The complexity of the disease is multi-dimensional and has led to very difficult diagnosis and therapy, thus this field remains poor in knowledge regarding the genetic, environmental, and immunological aspects of the disease though much progress has been achieved in this area. Promises are inevitable for better care of patients with endometriosis in the future through the development of tailored treatments as well as novel treatment modalities. A research would therefore find an ultimate goal in gaining insight that goes beyond the management of symptoms toward a better knowledge of mechanisms that cause this crippling disease.</p> <p></p> <h3><b>References</b></h3> <ol> <li>Barbara, G., Facchin, F., Buggio, L., Somigliana, E., Berlanda, N., Kustermann, A. and Vercellini, P., 2017. <a href="https://journals.sagepub.com/doi/abs/10.1177/1933719117707054">What is known and unknown about the association between endometriosis and sexual functioning: a systematic review of the literature.</a> <i>Reproductive sciences</i>, <i>24</i>(12), pp.1566-1576.</li> <li>Samani, E.N., Mamillapalli, R., Li, F., Mutlu, L., Hufnagel, D., Krikun, G. and Taylor, H.S., 2019. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6481344/">Micrometastasis of endometriosis to distant organs in a murine model</a>. <i>Oncotarget</i>, <i>10</i>(23), p.2282.</li> <li>Guo, H., Li, J., Shen, X., Cong, Y., Wang, Y., Wu, L., Li, B., Gao, H., Ma, M., Zhang, W. and Mao, X., 2020. <a href="https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2020.00129/full">Efficacy of different progestins in women with advanced endometriosis undergoing controlled ovarian hyperstimulation for in vitro fertilization-a single-center non-inferiority randomized controlled trial.</a> <i>Frontiers in endocrinology</i>, <i>11</i>, p.129.</li> <li>Asante, A. and Taylor, R.N., 2011. <a href="https://www.annualreviews.org/content/journals/10.1146/annurev-physiol-012110-142158">Endometriosis: the role of neuroangiogenesis.</a> <i>Annual review of physiology</i>, <i>73</i>(1), pp.163-182.</li> <li>Figueira, P.G.M., Abrão, M.S., Krikun, G. and Taylor, H., 2011. <a href="https://nyaspubs.onlinelibrary.wiley.com/doi/abs/10.1111/j.1749-6632.2011.05969.x">Stem cells in endometrium and their role in the pathogenesis of endometriosis.</a> <i>Annals of the New York academy of sciences</i>, <i>1221</i>(1), pp.10-17.</li> <li>Gupta, D., Hull, M.L., Fraser, I., Miller, L., Bossuyt, P.M., Johnson, N., Nisenblat, V. and Cochrane <a href="https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD012165/full">Gynaecology and Fertility Group, 1996. Endometrial biomarkers for the non‐invasive diagnosis of endometriosis.</a> <i>Cochrane Database of Systematic Reviews</i>, <i>2016</i>(4).</li> <li>Young, V.J., Brown, J.K., Saunders, P.T. and Horne, A.W., 2013. <a href="https://academic.oup.com/humupd/article/19/5/558/614030?login=false">The role of the peritoneum in the pathogenesis of endometriosis.</a> <i>Human reproduction update</i>, <i>19</i>(5), pp.558-569.</li> <li>Somigliana, E., Vigano, P., Filippi, F., Papaleo, E., Benaglia, L., Candiani, M. and Vercellini, P., 2015. <a href="https://academic.oup.com/humrep/article/30/6/1280/616968?login=false">Fertility preservation in women with endometriosis: for all, for some, for none?.</a> <i>Human Reproduction</i>, <i>30</i>(6), pp.1280-1286.</li> </ol> <p></div></div> <div style="background: #f7f7f7;border: 1px solid rgba(0, 0, 0, 0.07);"> <div style="padding: 30px;"><div class="Adblock-main"> <div class="Adblock-head"> <h2>Top Experts on “<b style="color:#000;font-size:22px;">endometriosis</b>“</h2> </div> </div><div class="author-main"><div id="results_author"></div><div style="text-align: center;"><a class="register-button" href="https://gynecology.blog/expert-search" target="_blank" rel="noopener">Find experts on any field</a></div></div><div class="inside-article" style="background: none;border: none;box-shadow: none;margin-top: -70px;"> <style> .author-block { padding: 15px; margin-bottom: 10px; text-align: left; font-size: 15px; line-height: 1.2; background: #FFF; border-bottom: solid 1px #ccc; margin-left: 15px; margin-right: 15px; } .author-block h3 { margin: 0 0 10px; color: #227cdc; } .author-block p { margin: 5px 0; } .author-b { display: flex; justify-content: space-between; flex-wrap: wrap; margin-bottom:10px; } .author-b .ainfo { flex: 1 1 30%; box-sizing: border-box; text-align: left; background: #dcdcdc; padding: 7px 14px; border-radius: 5px; margin-top: 3px; margin-right: 10px; } @media (max-width: 768px) { .author-b .ainfo { flex: 1 1 100%; margin: 10px 0; } } </style> <script> function displayResults_author(authors) { var resultsContainer = document.getElementById('results_author'); resultsContainer.innerHTML = ''; if (!authors || Object.keys(authors).length === 0) { resultsContainer.innerHTML = '<p>No authors found.</p>'; return; } Object.values(authors).slice(0, 10).forEach(author => { var authorBlock = document.createElement('div'); authorBlock.className = 'author-block'; var author_name=author.name; let key_replace = author_name.replace(/ /g, '-'); key_replace = key_replace.toLowerCase(); var authorHTML = ` <h3><a href="https://gynecology.blog/author/index/${key_replace}\/${author.aid}" target="_blank" title="${author.name}">${author.name}</a></h3> <div class="author-b"> <div class="ainfo"><strong>H-Index:</strong> ${author.hindex}</div> <div class="ainfo"><strong>Publication Count:</strong> ${author.paper_count}</div> <div class="ainfo"><strong>Citation Count:</strong> ${author.citation_count}</div> </div> <p><strong>Affiliation:</strong> ${author.affiliation}</p> `; authorBlock.innerHTML = authorHTML; resultsContainer.appendChild(authorBlock); }); } function displayKeywordAuthors(keywords) { var resultsContainer = document.getElementById('keyword-authors'); resultsContainer.innerHTML = ''; if (!keywords || keywords.length === 0) { resultsContainer.innerHTML = '<p>No data found.</p>'; return; } var keywordHTML = ''; keywords.forEach(key => { let key_replace = key.replace(/ /g, '-'); key_replace = key_replace.toLowerCase(); keywordHTML += `<a href="https://gynecology.blog/expert-search/index/${key_replace}" target="_blank" title="${key}">${key}</a>`; }); resultsContainer.innerHTML = keywordHTML; } // Call the function with the PHP data var authors_data = { "RLqYK4wBWBy50K-rs6xI": { "aid": "RLqYK4wBWBy50K-rs6xI", "name": "G. 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", "email": "udo.oppermann@sgc.ox.ac.uk", "slug_tail": "u-oppermann" } }; //console.log(authors_data); displayResults_author(authors_data); var keywordsArray = ["Endometriosis","chronic pain","infertility","neuroangiogenesis","progesterone resistance","genetic factors","environmental toxins","targeted therapy","hormonal therapy","surgery","fertility preservation","IVF","inflammation","immune dysfunction"]; displayKeywordAuthors(keywordsArray); </script></p> </div> <footer class="entry-meta" aria-label="Entry meta"> <span class="cat-links"><span class="gp-icon icon-categories"><svg viewBox="0 0 512 512" aria-hidden="true" xmlns="http://www.w3.org/2000/svg" width="1em" height="1em"><path d="M0 112c0-26.51 21.49-48 48-48h110.014a48 48 0 0143.592 27.907l12.349 26.791A16 16 0 00228.486 128H464c26.51 0 48 21.49 48 48v224c0 26.51-21.49 48-48 48H48c-26.51 0-48-21.49-48-48V112z" /></svg></span><span class="screen-reader-text">Categories </span><a 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