{"id":193,"date":"2019-10-07T22:17:42","date_gmt":"2019-10-07T16:47:42","guid":{"rendered":"https:\/\/medicineplexus.com\/?p=193"},"modified":"2019-10-07T22:17:42","modified_gmt":"2019-10-07T16:47:42","slug":"aromatase-inhibitors","status":"publish","type":"post","link":"https:\/\/medicineplexus.com\/aromatase-inhibitors\/","title":{"rendered":"Aromatase Inhibitors"},"content":{"rendered":"\n<p><strong>Aromatase Inhibitors<\/strong><\/p>\n\n\n\n<ul><li><strong>Androgens are converted to estrogen<\/strong> in\nthe peripheral tissue of <strong>post-menopausal\nfemales<\/strong> with the help of an <strong>enzyme,\naromatase.<\/strong> <\/li><li>The drugs inhibiting this\nenzyme will decrease the formation of estrogen <\/li><li>beneficial in the <strong>treatment of breast carcinoma<\/strong>. <\/li><\/ul>\n\n\n\n<p><strong>First-generation<\/strong> <\/p>\n\n\n\n<ul><li>aminoglutethimide <\/li><\/ul>\n\n\n\n<p><strong>second generation<\/strong> <\/p>\n\n\n\n<ul><li>letrozole, anastrozole, vorozole, fadrozole \u00e0 nonsteroidal or type II \u00e0 reversible inhibitors of aromatase<\/li><li>formestane, and exemestane \u00e0 steroidal or type I \u00e0 irreversible (suicide) inhibitor<\/li><\/ul>\n\n\n\n<figure class=\"wp-block-table\"><table class=\"\"><tbody><tr><td><strong>Generation<\/strong>   <\/td><td><strong>Steroidal (type 1)<\/strong>   <\/td><td><strong>Nonsteroidal (type 2)<\/strong>   <\/td><\/tr><tr><td>First (nonselective)   <\/td><td>\n  &#8211;\n  <\/td><td>Aminoglutethimide   <\/td><\/tr><tr><td>Second (selective)   <\/td><td>Formestane   <\/td><td>Fadrozole   <\/td><\/tr><tr><td>Third (super selective)   <\/td><td>Exemestane (Aromasin)   <\/td><td>Anastrozole, Letrozole   <\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n<p><strong>Letrozole<\/strong><\/p>\n\n\n\n<ul><li>orally active nonsteroidal (type\n2) compound <\/li><li>reversibly inhibits aromatization\nincluding that within the breast cancer cells, resulting in nearly total\nestrogen deprivation in postmenopausal women<\/li><li>Als are not recommended in\npremenopausal women unless ovaries are removed, or Gn secretion from pituitary\nis suppressed<\/li><li>The proliferation of estrogen-dependent\nbreast carcinoma cells is suppressed to a greater extent than with tamoxifen.<\/li><li>rapidly absorbed \u00e0 100% oral bioavailability, a large volume of distribution, t\u00bd of\n~40 hours. <\/li><\/ul>\n\n\n\n<p>Uses<\/p>\n\n\n\n<p><strong>Early breast cancer:<\/strong> <\/p>\n\n\n\n<ul><li>first-line drug for adjuvant\ntherapy after mastectomy in ER+ postmenopausal women. <\/li><li>Extended adjuvant therapy with\nletrozole beyond the standard 5-year tamoxifen treatment continues to afford\nprotection. <\/li><li><strong>Replacement of tamoxifen by an Al is now recommended after 2 years\n(sequential therapy) because Als do not predispose to thromboembolism and\nendometrial cancer<\/strong>. <\/li><li><strong>Survival is prolonged in patients who have positive axillary lymph\nnodes.<\/strong><\/li><\/ul>\n\n\n\n<p><strong>Advanced breast cancer:<\/strong> <\/p>\n\n\n\n<ul><li>Current guidelines recommend\nletrozole as first-line therapy because of a longer time to disease progression\nand higher response rate obtained with it compared to tamoxifen. <\/li><li><strong>also, effective as a second-line treatment when tamoxifen has\nfailed.<\/strong><\/li><\/ul>\n\n\n\n<p><strong>Adverse effects<\/strong> <\/p>\n\n\n\n<ul><li>Hot flashes, vaginal dryness,\nnausea, diarrhea, dyspepsia and thinning of hair are the side effects. <\/li><li>Joint pain and stiffness are\ncommon; <strong>bone loss may be accelerated<\/strong>.<\/li><li>However, there is no endometrial\nhyperplasia or an increased risk of endometrial carcinoma. <\/li><li>The risk of venous\nthromboembolism is also not increased, and there is no deterioration of the lipid\nprofile.<\/li><li>Dose: 2.5 mg OD oral.<\/li><li>The use of letrozole for\ninducing ovulation in infertile women has been banned in India since Oct. 20\n11.<\/li><\/ul>\n\n\n\n<p><strong>Anastrozole<\/strong> <\/p>\n\n\n\n<ul><li>Another nonsteroidal and\nreversible (Type 2) AI. <\/li><li><strong>more potent than letrozole and suitable for single daily dosing.<\/strong> <\/li><li>Accumulates in the body to\nproduce peak effect after 7- 10 days. <\/li><li>useful as adjuvant therapy in\nearly ER+ breast cancer as well as for palliation of advanced cases in\npostmenopausal women. <\/li><li>The risk of a new tumor\nappearing in the contralateral breast was also lower with anastrozole. <\/li><li>longer time to disease\nprogression compared to tamoxifen has been obtained in advanced ER+ive breast\ncancer. <\/li><li>Many tamoxifen-resistant cases\nresponded with increased survival.<\/li><li>Like letrozole. it is also a\nfirst-line drug for early as well as advanced breast carcinoma in postmenopausal\nwomen. Side effects are similar to those with letrozole.<\/li><li>Dose: 1 mg OD.<\/li><\/ul>\n\n\n\n<p><strong>Exemestane:<\/strong> <\/p>\n\n\n\n<ul><li>This <strong>steroidal and irreversible<\/strong> <strong>(Type I) inhibitor<\/strong> of aromatase acts like a suicide substrate by covalent binding to the enzyme. <\/li><li>As a result, <strong>&gt;90% suppression of estradiol production is obtained<\/strong>. <\/li><li>However, it has a weak androgenic activity similar to androstenedione.<\/li><li>found beneficial in early breast cancer by reducing the risk of disease progression when it was substituted for tamoxifen as adjuvant therapy. <\/li><li>In advanced breast cancer, longer survival, increased time to disease progression and fewer treatment failures have been obtained with exemestane.<\/li><li>It is administered orally and is well tolerated.<\/li><li>Adverse effects are similar to other Als.<\/li><li>Dose: 25 mg OD oral after meals; those receiving CYP3A4 inducer 50 mg OD.<\/li><\/ul>\n\n\n\n<figure class=\"wp-block-image size-large\"><img loading=\"lazy\" decoding=\"async\" width=\"685\" height=\"445\" src=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-43.png?w=685\" alt=\"\" class=\"wp-image-194\" srcset=\"https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-43.png 685w, https:\/\/medicineplexus.com\/wp-content\/uploads\/2019\/10\/image-43-300x195.png 300w\" sizes=\"(max-width: 685px) 100vw, 685px\" \/><\/figure>\n","protected":false},"excerpt":{"rendered":"<p>Aromatase Inhibitors Androgens are converted to estrogen in the peripheral tissue of post-menopausal females with the help of an enzyme, aromatase. The drugs inhibiting this enzyme will decrease the formation of estrogen beneficial in the treatment of breast carcinoma. First-generation aminoglutethimide second generation letrozole, anastrozole, vorozole, fadrozole \u00e0 nonsteroidal or type II \u00e0 reversible inhibitors[&#8230;]\n","protected":false},"author":3,"featured_media":194,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_seopress_robots_primary_cat":"","_seopress_titles_title":"","_seopress_titles_desc":"","_seopress_robots_index":"","footnotes":""},"categories":[3],"tags":[],"_links":{"self":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/193"}],"collection":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/comments?post=193"}],"version-history":[{"count":0,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/posts\/193\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/media\/194"}],"wp:attachment":[{"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/media?parent=193"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/categories?post=193"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/medicineplexus.com\/wp-json\/wp\/v2\/tags?post=193"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}