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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EThe tissue-selective estrogen complex is a strategy to harness the benefits of estrogens while limiting their negative consequences, by combining an estrogen with a selective estrogen receptor modulator. This article reviews research with this new class of estrogen receptor-targeted therapy.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Ehormone therapy\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \n         \u003Cp id=\u0022p-2\u0022\u003EThe tissue-selective estrogen complex (TSEC) is a strategy to harness the benefits of estrogens while limiting their negative consequences, by combining an estrogen with a selective estrogen receptor modulator (SERM). Carolyn Smith, MD, Baylor College of Medicine, Houston, Texas, USA, reviewed research with this new class of estrogen receptor (ER)-targeted therapy.\u003C\/p\u003E\n         \u003Cp id=\u0022p-3\u0022\u003EEstrogen research is uncovering new concepts about its effects in different target tissues, and in the process it is clarifying the benefits of hormone replacement therapy, which can delay or improve many of the symptoms or diseases associated with menopause. The discovery of a second ER expands the potential for estrogen action.\u003C\/p\u003E\n         \u003Cp id=\u0022p-4\u0022\u003EBecause current concepts of estrogen action are extraordinarily complex, stated Dr. Smith, this translates clinically into a variety of actions, many of which are beneficial, in diverse tissues. Estrogen is a key hormone in maintaining skeletal integrity; improved cognition and protection against tooth loss and macular degeneration are also emerging as possible benefits of estrogen.\u003C\/p\u003E\n         \u003Cp id=\u0022p-5\u0022\u003EThe United States Food and Drug Administration has approved one TSEC, comprising conjugated estrogens (CE; 0.45 mg) and bazedoxifene (BAZ; 20 mg), as a treatment for moderate-to-severe vasomotor symptoms (VMS) associated with menopause and for the prevention of postmenopausal (PM) osteoporosis in women with a uterus. The estrogenic component provides relief of hot flashes and prevents bone loss, whereas the antiestrogenic component inhibits action in breast and endometrial tissue.\u003C\/p\u003E\n         \u003Cp id=\u0022p-6\u0022\u003EBasic science research has shown differential regulation of ER\u2013target gene expression in relation to the specific SERM that was combined with CE in the TSEC [Chang KCN et al. \u003Cem\u003EJ Steroid Biochem Mol Biol\u003C\/em\u003E 2010]. TSEC activates the transcriptional activity of ER\u2013heteroligand dimers, in which 1 receptor is bound to an agonist (CE or estradiol), and the other receptor is bound to an antagonist (tamoxifen, raloxifene, or BAZ). This activation has been shown in multiple cell types and requires both receptors to bind to DNA. TSEC stimulation of messenger RNA expression was gene specific, and it has been shown that different subsets are regulated by different combinations of agonist and antagonist [Chang KCN et al. \u003Cem\u003EJ Steroid Biochem Mol Biol\u003C\/em\u003E 2010]. Expression of ERs in breast and endometrial cells was downregulated with BAZ [Wardell SE et al. \u003Cem\u003EClin Cancer Res\u003C\/em\u003E 2013]. A program of 5 randomized, double-blind, placebo- and active-controlled Phase 3 trials called the Selective Estrogens, Menopause, and Response to Therapy [SMART; Komm BS et al. \u003Cem\u003ESteroids\u003C\/em\u003E 2014] trials evaluated the safety and efficacy of the CE\u2013BAZ TSEC in PM women with a uterus (\u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E). Together, the trials showed that this TSEC relieved VMS and vulvar-vaginal atrophy (VVA) symptoms, increased bone mineral density, exerted minimal breast stimulation, and provided adequate endometrial protection.\u003C\/p\u003E\n         \u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/16437\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/16437\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/16437\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \n               \u003Cp id=\u0022p-7\u0022 class=\u0022first-child\u0022\u003EDesign and Primary Outcomes of the SMART Trials\u003C\/p\u003E\n            \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-10\u0022\u003EThe preclinical work and evidence from the SMART trials support the ability of TSECs to blend the desirable ER agonist activity of estrogens and the tissue-selective ER agonist and ER antagonist properties of a SERM, stated Dr. Smith.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2014 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/14\/20\/20.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzoyj2\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_tables.js?nzoyj2\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}