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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\u003ELuteinizing hormone and testosterone levels were significantly decreased by treatment with the neurokinin B receptor antagonist AZD4901 80 mg compared with placebo in women with polycystic ovary syndrome. The reductions were maintained throughout the 28 days of treatment. AZD4901 was safe and well tolerated in this group of patients.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Epolycystic ovary syndrome\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EAZD4901\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eneurokinin B receptor\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Eluteinizing hormone\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003Etestosterone\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EPCOS\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \n         \u003Cp id=\u0022p-2\u0022\u003EPolycystic ovary syndrome (PCOS) affects 5% to 10% of women of reproductive age. PCOS is characterized by accelerated luteinizing hormone (LH) pulse frequency and elevated serum testosterone concentrations, menstrual irregularity, and polycystic ovaries. Currently, there is no approved treatment for PCOS. Recently, hypothalamic neurokinin B (NKB) has been characterized as playing a key role in reproductive regulation, specifically as a modulator of gonadotropin-releasing hormone secretion [Topaloglu AK et al. \u003Cem\u003ENat Genet\u003C\/em\u003E. 2009]. The aim of this study [\u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01872078\u0026amp;atom=%2Fspmdc%2F15%2F4%2F16.1.atom\u0022\u003ENCT01872078\u003C\/a\u003E], presented by Jyothis T. George, PhD, University of Oxford, Oxford, United Kingdom, was to assess the effect of the NKB receptor antagonist, AZD4901, on LH secretion and testosterone levels in women with PCOS.\u003C\/p\u003E\n         \u003Cp id=\u0022p-3\u0022\u003EA total of 67 women with PCOS were randomized to receive AZD4901 20, 40, or 80 mg\/day, or placebo for 28 days. All of the patients had a clinical diagnosis of PCOS with polycystic ovarian morphology, free testosterone (\u0026gt;\u20050.85 upper limit of normal), and oligomenorrhea. The patients had intensive LH and testosterone sampling at baseline (day \u22121), day 7, and day 28. The primary end point was the change in 8-hour LH area under the curve (AUC) between baseline and day 7. The secondary end points were the change in total testosterone levels from baseline to days 7 and 28 and in LH pulse frequency at days 7 and 28.\u003C\/p\u003E\n         \u003Cp id=\u0022p-4\u0022\u003EThe LH AUC was 67.4\u2005\u00b1\u20051.6 IU\/L*h at baseline and 36\u2005\u00b1\u20052.3 IU\/L*h at day 7 in the AZD4901 80-mg group compared with 61.1\u2005\u00b1\u20051.9 IU\/L*h at baseline and 69.8\u2005\u00b1\u20051.7 IU\/L*h at day 7 in the placebo group (a 52% reduction relative to placebo, adjusted for baseline; 95% CI, 30% to 67%; \u003Cem\u003EP\u003C\/em\u003E\u2005=\u2005.0003). LH pulse frequency was 5.8\u2005\u00b1\u20052.1 pulses\/8 hours at baseline and 3.7\u2005\u00b1\u20052.1 pulses\/8 hours at day 7 in the AZD4901 80-mg group compared with 7.2\u2005\u00b1\u20052.3 pulses\/8 hours at baseline and 6.8\u2005\u00b1\u20052.6 pulses\/8 hours at day 7 in the placebo group, an adjusted mean change of \u22123.55 pulses\/8 hours vs placebo (\u003Cem\u003EP\u003C\/em\u003E\u2005\u0026lt;\u2005.0001).\u003C\/p\u003E\n         \u003Cp id=\u0022p-5\u0022\u003ETotal testosterone levels were 2.2\u2005\u00b1\u20051.3 nmol\/L at baseline and 1.6\u2005\u00b1\u20051.5 nmol\/L at day 7 in the AZD4901 80-mg group compared with 1.5\u2005\u00b1\u20051.7 nmol\/L at baseline and 1.6\u2005\u00b1\u20051.9 nmol\/L at day 7 in the placebo group (a 29% adjusted reduction relative to placebo; 95% CI, 14% to 41%; \u003Cem\u003EP\u003C\/em\u003E\u2005=\u2005.0006). At day 28, testosterone was reduced by 17% in the AZD4901 80-mg group.\u003C\/p\u003E\n         \u003Cp id=\u0022p-6\u0022\u003EA post hoc analysis in the anovulatory patients, defined as patients with serum P\u2005\u2265\u20056 ng\/mL throughout the study, showed that LH AUC was reduced in the ADZ4901 80-mg group by 46% at day 7 (\u003Cem\u003EP\u2005\u003C\/em\u003E=\u2005.0004) and by 35% at day 28 (\u003Cem\u003EP\u003C\/em\u003E\u2005=\u2005.0203); LH pulse frequency was \u22123.9 pulses\/8 hours at day 7 (\u003Cem\u003EP\u003C\/em\u003E\u2005\u0026lt;\u2005.0001) and \u22121.89 pulses\/8 hours at day 28 (\u003Cem\u003EP\u003C\/em\u003E\u2005=\u2005.0205); and testosterone was reduced by 27% at day 7 (\u003Cem\u003EP\u003C\/em\u003E\u2005=\u2005.0005) and by 20% at day 28 (\u003Cem\u003EP\u003C\/em\u003E\u2005=\u2005.0111) compared with placebo.\u003C\/p\u003E\n         \u003Cp id=\u0022p-7\u0022\u003EAfter 7 days of treatment with AZD4901 80 mg, women with PCOS had significant reductions in LH, LH pulse frequency, and total testosterone. These effects persisted for 28 days in nonovulating women. AZD4901 was safe and well tolerated. Longer-duration studies are needed to further evaluate its therapeutic potential, including metabolic responses.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2015 SAGE Publications\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\/15\/4\/16.1.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?nzlmuq\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}