{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T15:35:16Z","timestamp":1790868916832,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Low testosterone is common in men with type 2 diabetes and is associated with adverse metabolic outcomes. Our objective was to identify factors associated with low total and calculated free testosterone (CFT) in men with type 2 diabetes, with a focus on relative estrogen excess and subcutaneous adipose aromatase expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Cross\u2010sectional study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients<\/jats:title>\n                    <jats:p>One hundred eighty men with type 2 diabetes and 92 healthy men in the reference cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements<\/jats:title>\n                    <jats:p>Sex steroid hormones were measured alongside body composition, metabolic biomarkers, adipose tissue aromatase gene expression, and genetic variants of aromatase. T\u2010scores for testosterone and estradiol were calculated using a healthy reference cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      HbA1c (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), BMI (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.007), leptin (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.009) and insulin resistance (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.026) were associated with lower total testosterone (&lt;10\u2009nM). Lower CFT (&lt;220pM) was associated with age (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.049), BMI (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), interleukin\u20106 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), leptin (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.003) and insulin (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.020). Men with type 2 diabetes and low testosterone had relative estrogen excess (Estradiol T score\u2212Testosterone T score 1.63 [0.94, 2.76]) compared to healthy controls (0.06 [\u22120.74, 0.51],\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). A common CYP19A1 variant was associated with increased adipose CYP19A1 expression (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.044) and low CFT (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.042). Multivariable analysis identified BMI (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), CYP19A1 expression (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.020) and HbA1c (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.006) as independently associated with CFT.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In men with type 2 diabetes, low testosterone is associated with adiposity, glycaemic control, and increased adipose aromatase expression. Relative estrogen excess may contribute to hypothalamic\u2010pituitary\u2010testicular axis suppression and represents a novel target for diagnostic and therapeutic strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cen.70098","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T03:14:42Z","timestamp":1769051682000},"page":"362-371","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Low Testosterone in Men With Type 2 Diabetes: The Role of Estrogen Excess and Aromatase Activity"],"prefix":"10.1111","volume":"104","author":[{"given":"Nyo Nyo Z.","family":"Tun","sequence":"first","affiliation":[{"name":"Edinburgh Centre for Endocrinology &amp; Diabetes NHS Lothian Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawn E. W.","family":"Livingstone","sequence":"additional","affiliation":[{"name":"University\/BHF Centre for Cardiovascular Science, Queen's Medical Research Institute University of Edinburgh Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5576-6463","authenticated-orcid":false,"given":"Fraser W.","family":"Gibb","sequence":"additional","affiliation":[{"name":"Edinburgh Centre for Endocrinology &amp; Diabetes NHS Lothian Edinburgh UK"},{"name":"University\/BHF Centre for Cardiovascular Science, Queen's Medical Research Institute University of Edinburgh Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,21]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc06-1426"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-2177"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc17-2510"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-0804"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc10-1233"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-0760(03)00360-1"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-015-0563-4"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-2156"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/ejendo\/lvad099"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2265.2007.02755.x"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2009-2071"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2019.03.002"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/0004563215621096"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/0004563213501478"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.84.10.6079"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ijo.2014.94"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2008.112797"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2018-00229"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0911101"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-06-0737"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1262-3636(07)70086-1"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc11-0208"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgaf038"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/cen.14930"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-014-3223-0"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2003-0644"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.2337\/diacare.28.7.1636"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-67-3-460"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(20)30367-3"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-3375"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1206168"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2015-4146"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12958-025-01425-9"}],"container-title":["Clinical Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cen.70098","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cen.70098","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cen.70098","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T15:18:58Z","timestamp":1772983138000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cen.70098"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,21]]},"references-count":33,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1111\/cen.70098"],"URL":"https:\/\/doi.org\/10.1111\/cen.70098","archive":["Portico"],"relation":{},"ISSN":["0300-0664","1365-2265"],"issn-type":[{"value":"0300-0664","type":"print"},{"value":"1365-2265","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,21]]},"assertion":[{"value":"2025-11-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}