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The human <jats:italic><jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content><\/jats:italic> gene (Xq11\u201012) spans 186,588\u00a0bp and eight exons. N\u2010terminal transactivation domain of the encoded <jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content> protein harbours two polymorphic stretches of identical amino acids, a polyglutamine tract (encoded by 8\u201037 <jats:styled-content style=\"fixed-case\">CAG<\/jats:styled-content>\u2010repeats) and a polyglycine tract (encoded by 10\u201030 <jats:styled-content style=\"fixed-case\">GGN<\/jats:styled-content>\u2010repeats). We set forward to analyse independent and combinatory effects of the length of these repetitive tracts on male reproductive hormones, testicular and sperm parameters in a population\u2010based cohort of Baltic young men (<jats:italic>n<\/jats:italic>\u00a0=\u00a0974; aged 20.1\u00a0\u00b1\u00a02.1\u00a0years). We designed an assay to amplify and detect simultaneously the variants of both polymorphic repeats. The study revealed that elongated <jats:italic><jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content><\/jats:italic> <jats:styled-content style=\"fixed-case\">CAG<\/jats:styled-content> tract was associated with lower <jats:styled-content style=\"fixed-case\">FSH<\/jats:styled-content> (linear regression: <jats:italic>p\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.0002, effect per repeat \u22120.056 <jats:styled-content style=\"fixed-case\">IU<\/jats:styled-content>\/L). As a novel finding, the carriers of <jats:styled-content style=\"fixed-case\">GGN<\/jats:styled-content>\u2010stretch with \u226524 repeats showed a trend for decreased sperm concentration (<jats:italic>p\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.027). Although neither of the variants exhibited an isolated effect on circulating T, their allelic combinations modulated serum T levels, as well as sperm concentration. The lowest T was measured for men carrying the <jats:italic><jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content><\/jats:italic> gene with long <jats:styled-content style=\"fixed-case\">CAG<\/jats:styled-content> (<jats:italic>n<\/jats:italic>\u00a0\u2265\u00a025) and short <jats:styled-content style=\"fixed-case\">GGN<\/jats:styled-content> (<jats:italic>n<\/jats:italic>\u00a0\u2264\u00a021) repeat tracts (mean 18.8 vs. 25.5\u201328.6 nmol\/L for the other <jats:italic><jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content><\/jats:italic> variants, <jats:italic>p\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.017). The lowest sperm concentration was detected among individuals with both elongated repetitive stretches (<jats:styled-content style=\"fixed-case\">CAG<\/jats:styled-content>,<jats:italic> n<\/jats:italic>\u00a0\u2265\u00a025 and <jats:styled-content style=\"fixed-case\">GGN<\/jats:styled-content>,<jats:italic> n<\/jats:italic>\u00a0\u2265\u00a024; mean 49.0 vs. 68.4\u201372.1 mill\/<jats:styled-content style=\"fixed-case\">mL<\/jats:styled-content> for the other variants; <jats:italic>p\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>0.00059). The innovative study design enabled to clearly demonstrate a combinatory impact of <jats:styled-content style=\"fixed-case\">CAG<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">GGN<\/jats:styled-content> repeat lengths at male reproductive parameters. As <jats:styled-content style=\"fixed-case\">AR<\/jats:styled-content> regulates transcription of over 900 genes in many tissues and organs, the combinatory effects of these common repeat\u2010length variants on male physiology in the wider context and across lifetime are still to be assessed.<\/jats:p><\/jats:sec>","DOI":"10.1111\/andr.12344","type":"journal-article","created":{"date-parts":[[2017,3,24]],"date-time":"2017-03-24T11:08:47Z","timestamp":1490353727000},"page":"495-504","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["The number of <scp>CAG<\/scp> and <scp>GGN<\/scp> triplet repeats in the <i>Androgen Receptor<\/i> gene exert combinatorial effect on hormonal and sperm parameters in young men"],"prefix":"10.1111","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8947-5816","authenticated-orcid":false,"given":"M.","family":"Grigorova","sequence":"first","affiliation":[{"name":"Institute of Biomedicine and Translational Medicine University of Tartu Tartu Estonia"},{"name":"Human Molecular Genetics Research Group Institute of Molecular and Cell Biology University of Tartu Tartu Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Punab","sequence":"additional","affiliation":[{"name":"Andrology Unit Tartu University Hospital Tartu Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Kahre","sequence":"additional","affiliation":[{"name":"Department of Genetics United Laboratories Tartu University Hospital Tartu Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Ivandi","sequence":"additional","affiliation":[{"name":"Department of Genetics United Laboratories Tartu University Hospital Tartu Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"T\u00f5nisson","sequence":"additional","affiliation":[{"name":"Department of Genetics United Laboratories Tartu University Hospital Tartu Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O.","family":"Poolamets","sequence":"additional","affiliation":[{"name":"Andrology Unit Tartu University Hospital Tartu Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Vihljajev","sequence":"additional","affiliation":[{"name":"Andrology Unit Tartu University Hospital Tartu Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"\u017dilaitien\u0117","sequence":"additional","affiliation":[{"name":"Medical Academy Institute of Endocrinology Lithuanian University of Health Sciences Kaunas Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Erenpreiss","sequence":"additional","affiliation":[{"name":"Latvian Biomedicine Research and Study center R\u012bga Latvia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Matulevi\u010dius","sequence":"additional","affiliation":[{"name":"Medical Academy Institute of Endocrinology Lithuanian University of Health Sciences Kaunas Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Laan","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine and Translational Medicine University of Tartu Tartu Estonia"},{"name":"Human Molecular Genetics Research Group Institute of Molecular and Cell Biology University of Tartu Tartu Estonia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,3,23]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.2164\/jandrol.110.012013"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-09-0123"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2013.03.005"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh181"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/22.15.3181"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.10.12.1527"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-0117"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2013-1391"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0086235"},{"key":"e_1_2_8_11_1","unstructured":"European Association of Urology(EAU) (2015)Guidelines on Male Infertility. 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