{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T23:23:52Z","timestamp":1791329032058,"version":"4.3.1"},"reference-count":120,"publisher":"Bioscientifica","issue":"3","content-domain":{"domain":["joe.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,5,25]]},"abstract":"<jats:p>Testosterone acting via the androgen receptor, and via aromatisation to oestradiol, an activator of the oestrogen receptor, plays key roles in adipose tissue, bone and skeletal muscle biology. This is reflected in epidemiological studies associating obesity and disordered glucose metabolism with lower serum testosterone concentrations and an increased risk of type 2 diabetes (T2D) in men. Testosterone also modulates erythrocytosis and vascular endothelial and smooth muscle cell function, with potential impacts on haematocrit and the cardiovascular system. The Testosterone for the Prevention of Type 2 Diabetes (T4DM) study enrolled men aged 50 years and over with a waist circumference of 95 cm or over, impaired glucose tolerance or newly diagnosed T2D, and a serum testosterone concentration (as measured by chemiluminescence immunoassay) &lt;14.0 nmol\/L. The study reported that a 2-year treatment with testosterone undecanoate 1000 mg, administered 3-monthly intramuscularly, on the background of a lifestyle program, reduced the likelihood of T2D diagnosis by 40% compared to placebo. This effect was accompanied by a decrease in fasting serum glucose and associated with favourable changes in body composition, hand grip strength, bone mineral density and skeletal microarchitecture but not in HbA1c, a red blood cell-dependent measure of glycaemic control. There was no signal for cardiovascular adverse events. With the objective of informing translational science and future directions, this article discusses mechanistic studies underpinning the rationale for T4DM and translational implications of the key outcomes relating to glycaemia, and body composition, together with effects on erythrocytosis, cardiovascular risk and slow recovery of the hypothalamo\u2013pituitary\u2013testicular axis.<\/jats:p>","DOI":"10.1530\/joe-22-0223","type":"journal-article","created":{"date-parts":[[2023,5,25]],"date-time":"2023-05-25T09:18:51Z","timestamp":1685006331000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-5","source":"Crossref","is-referenced-by-count":9,"title":["Testosterone and type 2 diabetes prevention: translational lessons from the T4DM study"],"prefix":"10.1530","volume":"258","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6818-6065","authenticated-orcid":true,"given":"Gary A","family":"Wittert","sequence":"first","affiliation":[{"name":"Freemasons Centre for Male Health and Wellbeing, South Australian Health and Medical Research Institute, and University of Adelaide, Adelaide, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathis","family":"Grossmann","sequence":"additional","affiliation":[{"name":"Department of Medicine, The University of Melbourne and Department of Endocrinology Austin Health, Heidelberg, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bu B","family":"Yeap","sequence":"additional","affiliation":[{"name":"Medical School, University of Western Australia, and Department of Endocrinology and Diabetes, Fiona Stanley Hospital, Perth, Western Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J","family":"Handelsman","sequence":"additional","affiliation":[{"name":"ANZAC Research Institute, University of Sydney and Andrology Department, Concord Hospital, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Lancet. Respiratory Medicine","first-page":"e19","article-title":"Are the ICSD-3 criteria for sleep apnoea syndrome too inclusive?","volume":"4","author":"Adams","year":"2016","unstructured":"Adams RAppleton STaylor AMcEvoy D & Wittert G2016Are the ICSD-3 criteria for sleep apnoea syndrome too inclusive?Lancet. Respiratory Medicine4e19\u2013e20. (https:\/\/doi.org\/10.1016\/S2213-2600(1600109-0)"},{"key":"bib2","series-title":"Circulation Research","first-page":"813","article-title":"Natural androgens inhibit male atherosclerosis: a study in castrated, cholesterol-fed rabbits","volume":"84","author":"Alexandersen","year":"1999","unstructured":"Alexandersen PHaarbo JByrjalsen ILawaetz H & Christiansen C1999Natural androgens inhibit male atherosclerosis: a study in castrated, cholesterol-fed rabbits. Circulation Research84813\u2013819. (https:\/\/doi.org\/10.1161\/01.res.84.7.813)"},{"key":"bib3","series-title":"Sleep Science and Practice","article-title":"The prevalence of obstructive sleep apnea in patients with type 2 diabetes: a systematic review and meta-analysis","volume":"6","author":"Andayeshgar","year":"2022","unstructured":"Andayeshgar BJanatolmakan MSoroush AAzizi SM & Khatony A2022The prevalence of obstructive sleep apnea in patients with type 2 diabetes: a systematic review and meta-analysis. Sleep Science and Practice6 6. (https:\/\/doi.org\/10.1186\/s41606-022-00074-w)"},{"key":"bib4","series-title":"Journal of Endocrinological Investigation","first-page":"1133","article-title":"Testosterone insulin-like effects: an in vitro study on the short-term metabolic effects of testosterone in human skeletal muscle cells","volume":"40","author":"Antinozzi","year":"2017","unstructured":"Antinozzi CMarampon FCorinaldesi CVicini ESgro PVannelli GBLenzi ACrescioli C & Di Luigi L2017Testosterone insulin-like effects: an in vitro study on the short-term metabolic effects of testosterone in human skeletal muscle cells. Journal of Endocrinological Investigation401133\u20131143. (https:\/\/doi.org\/10.1007\/s40618-017-0686-y)"},{"key":"bib5","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"1400","article-title":"Association between sex steroid levels and bone microarchitecture in men: the STRAMBO study","volume":"99","author":"Argoud","year":"2014","unstructured":"Argoud TBoutroy SClaustrat BChapurlat R & Szulc P2014Association between sex steroid levels and bone microarchitecture in men: the STRAMBO study. Journal of Clinical Endocrinology and Metabolism991400\u20131410. (https:\/\/doi.org\/10.1210\/jc.2013-3233)"},{"key":"bib6","series-title":"European Journal of Haematology","first-page":"1","article-title":"Hepcidin--central regulator of iron metabolism","volume":"78","author":"Atanasiu","year":"2007","unstructured":"Atanasiu VManolescu B & Stoian I2007Hepcidin--central regulator of iron metabolism. European Journal of Haematology781\u201310. (https:\/\/doi.org\/10.1111\/j.1600-0609.2006.00772.x)"},{"key":"bib121","series-title":"Metabolism","first-page":"1013","article-title":"Inverse associations between muscle mass, strength, and the metabolic syndrome","volume":"58","year":"2009","unstructured":"Atlantis EMartin SAHaren MTTaylor AW & Wittert GA2009 Members of the Florey Adelaide male ageing study. Inverse associations between muscle mass, strength, and the metabolic syndrome. Metabolism581013\u20131022. (https:\/\/doi.org\/10.1016\/j.metabol.2009.02.027)"},{"key":"bib7","series-title":"BMC Endocrine Disorders","article-title":"Predictive value of serum testosterone for type 2 diabetes risk assessment in men","volume":"16","author":"Atlantis","year":"2016","unstructured":"Atlantis EFahey PMartin SO'Loughlin PTaylor AWAdams RJShi Z & Wittert G2016Predictive value of serum testosterone for type 2 diabetes risk assessment in men. BMC Endocrine Disorders16 26. (https:\/\/doi.org\/10.1186\/s12902-016-0109-7)"},{"key":"bib8","series-title":"Journals of Gerontology. Series A, Biological Sciences and Medical Sciences","first-page":"725","article-title":"Testosterone induces erythrocytosis via increased erythropoietin and suppressed hepcidin: evidence for a new erythropoietin\/hemoglobin set point","volume":"69","author":"Bachman","year":"2014","unstructured":"Bachman ETravison TGBasaria SDavda MNGuo WLi MConnor Westfall JBae HGordeuk V & Bhasin S2014Testosterone induces erythrocytosis via increased erythropoietin and suppressed hepcidin: evidence for a new erythropoietin\/hemoglobin set point. Journals of Gerontology. Series A, Biological Sciences and Medical Sciences69725\u2013735. (https:\/\/doi.org\/10.1093\/gerona\/glt154)"},{"key":"bib9","series-title":"New England Journal of Medicine","first-page":"109","article-title":"Adverse events associated with testosterone administration","volume":"363","author":"Basaria","year":"2010","unstructured":"Basaria SCoviello ADTravison TGStorer TWFarwell WRJette AMEder RTennstedt SUlloor JZhang A, 2010Adverse events associated with testosterone administration. New England Journal of Medicine363109\u2013122. (https:\/\/doi.org\/10.1056\/NEJMoa1000485)"},{"key":"bib10","series-title":"American Heart Journal","first-page":"41","article-title":"Effects of long-term testosterone treatment on cardiovascular outcomes in men with hypogonadism: rationale and design of the TRAVERSE study","volume":"245","author":"Bhasin","year":"2022","unstructured":"Bhasin SLincoff AMBasaria SBauer DCBoden WECunningham GRDavey DDubcenco EFukumoto SGarcia M, 2022Effects of long-term testosterone treatment on cardiovascular outcomes in men with hypogonadism: rationale and design of the TRAVERSE study. American Heart Journal24541\u201350. (https:\/\/doi.org\/10.1016\/j.ahj.2021.11.016)"},{"key":"bib11","series-title":"American Journal of Physiology. Endocrinology and Metabolism","first-page":"E1172","article-title":"Testosterone dose-response relationships in healthy young men","volume":"281","author":"Bhasin","year":"2001","unstructured":"Bhasin SWoodhouse LCasaburi RSingh ABBhasin DBerman NChen XYarasheski KEMagliano LDzekov C, 2001Testosterone dose-response relationships in healthy young men. American Journal of Physiology. Endocrinology and Metabolism281E1172\u2013E1181. (https:\/\/doi.org\/10.1152\/ajpendo.2001.281.6.E1172)"},{"key":"bib12","series-title":"Endocrinology","first-page":"5428","article-title":"Androgen receptor-dependent and independent atheroprotection by testosterone in male mice","volume":"151","author":"Bourghardt","year":"2010","unstructured":"Bourghardt JWilhelmson ASAlexanderson CDe Gendt KVerhoeven GKrettek AOhlsson C & Tivesten A2010Androgen receptor-dependent and independent atheroprotection by testosterone in male mice. Endocrinology1515428\u20135437. (https:\/\/doi.org\/10.1210\/en.2010-0663)"},{"key":"bib13","series-title":"PLoS One","article-title":"Testosterone, sex hormone-binding globulin and the metabolic syndrome in men: an individual participant data meta-analysis of observational studies","volume":"9","author":"Brand","year":"2014","unstructured":"Brand JSRovers MMYeap BBSchneider HJTuomainen TPHaring RCorona GOnat AMaggio MBouchard C, 2014Testosterone, sex hormone-binding globulin and the metabolic syndrome in men: an individual participant data meta-analysis of observational studies. PLoS One9 e100409. (https:\/\/doi.org\/10.1371\/journal.pone.0100409)"},{"key":"bib14","series-title":"American Heart Journal","first-page":"657","article-title":"Hematocrit and the risk of coronary heart disease mortality","volume":"142","author":"Brown","year":"2001","unstructured":"Brown DWGiles WH & Croft JB2001Hematocrit and the risk of coronary heart disease mortality. American Heart Journal142657\u2013663. (https:\/\/doi.org\/10.1067\/mhj.2001.118467)"},{"key":"bib15","series-title":"Arteriosclerosis, Thrombosis, and Vascular Biology","first-page":"2192","article-title":"Gender-specific differences in the effects of testosterone and estrogen on the development of atherosclerosis in rabbits","volume":"17","author":"Bruck","year":"1997","unstructured":"Bruck BBrehme UGugel NHanke SFinking GLutz CBenda NSchmahl FWHaasis R & Hanke H1997Gender-specific differences in the effects of testosterone and estrogen on the development of atherosclerosis in rabbits. Arteriosclerosis, Thrombosis, and Vascular Biology172192\u20132199. (https:\/\/doi.org\/10.1161\/01.atv.17.10.2192)"},{"key":"bib16","series-title":"JAMA","first-page":"708","article-title":"Testosterone treatment and coronary artery plaque volume in older men with low testosterone","volume":"317","author":"Budoff","year":"2017","unstructured":"Budoff MJEllenberg SSLewis CEMohler ER3rdWenger NKBhasin SBarrett-Connor ESwerdloff RSStephens-Shields ACauley JA, 2017Testosterone treatment and coronary artery plaque volume in older men with low testosterone. JAMA317708\u2013716. (https:\/\/doi.org\/10.1001\/jama.2016.21043)"},{"key":"bib17","series-title":"Journal of Bone and Mineral Research","first-page":"2558","article-title":"A longitudinal HR-pQCT study of alendronate treatment in postmenopausal women with low bone density: relations among density, cortical and trabecular microarchitecture, biomechanics, and bone turnover","volume":"25","author":"Burghardt","year":"2010","unstructured":"Burghardt AJKazakia GJSode Mde Papp AELink TM & Majumdar S2010A longitudinal HR-pQCT study of alendronate treatment in postmenopausal women with low bone density: relations among density, cortical and trabecular microarchitecture, biomechanics, and bone turnover. Journal of Bone and Mineral Research252558\u20132571. (https:\/\/doi.org\/10.1002\/jbmr.157)"},{"key":"bib18","series-title":"Clinical Endocrinology","first-page":"116","article-title":"Effects of aromatase inhibition in hypogonadal older men: a randomized, double-blind, placebo-controlled trial","volume":"70","author":"Burnett-Bowie","year":"2009","unstructured":"Burnett-Bowie SARoupenian KCDere MELee H & Leder BZ2009Effects of aromatase inhibition in hypogonadal older men: a randomized, double-blind, placebo-controlled trial. Clinical Endocrinology70116\u2013123. (https:\/\/doi.org\/10.1111\/j.1365-2265.2008.03327.x)"},{"key":"bib19","series-title":"Blood","first-page":"2236","article-title":"Sex hormones, acting on the tert gene, increase telomerase activity in human primary hematopoietic cells","volume":"114","author":"Calado","year":"2009","unstructured":"Calado RTYewdell WTWilkerson KLRegal JAKajigaya SStratakis CA & Young NS2009Sex hormones, acting on the tert gene, increase telomerase activity in human primary hematopoietic cells. Blood1142236\u20132243. (https:\/\/doi.org\/10.1182\/blood-2008-09-178871)"},{"key":"bib20","series-title":"Hypertension","first-page":"1095","article-title":"Testosterone and exercise in middle-to-older aged men: combined and independent effects on vascular function","volume":"77","author":"Chasland","year":"2021","unstructured":"Chasland LCNaylor LHYeap BBMaiorana AJ & Green DJ2021Testosterone and exercise in middle-to-older aged men: combined and independent effects on vascular function. Hypertension771095\u20131105. (https:\/\/doi.org\/10.1161\/HYPERTENSIONAHA.120.16411)"},{"key":"bib21","series-title":"Blood","first-page":"4284","article-title":"Red cell life span heterogeneity in hematologically normal people is sufficient to alter HbA1c","volume":"112","author":"Cohen","year":"2008","unstructured":"Cohen RMFranco RSKhera PKSmith EPLindsell CJCiraolo PJPalascak MB & Joiner CH2008Red cell life span heterogeneity in hematologically normal people is sufficient to alter HbA1c. Blood1124284\u20134291. (https:\/\/doi.org\/10.1182\/blood-2008-04-154112)"},{"key":"bib22","series-title":"Lancet. Diabetes and Endocrinology","first-page":"624","article-title":"Effects of diabetes definition on global surveillance of diabetes prevalence and diagnosis: a pooled analysis of 96 population-based studies with 331,288 participants","volume":"3","year":"2015","unstructured":"Collaboration NCDRF2015Effects of diabetes definition on global surveillance of diabetes prevalence and diagnosis: a pooled analysis of 96 population-based studies with 331,288 participants. Lancet. Diabetes and Endocrinology3624\u2013637. (https:\/\/doi.org\/10.1016\/S2213-8587(1500129-1)"},{"key":"bib23","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"914","article-title":"Effects of graded doses of testosterone on erythropoiesis in healthy young and older men","volume":"93","author":"Coviello","year":"2008","unstructured":"Coviello ADKaplan BLakshman KMChen TSingh AB & Bhasin S2008Effects of graded doses of testosterone on erythropoiesis in healthy young and older men. Journal of Clinical Endocrinology and Metabolism93914\u2013919. (https:\/\/doi.org\/10.1210\/jc.2007-1692)"},{"key":"bib24","series-title":"Reviews in Endocrine and Metabolic Disorders","first-page":"1173","article-title":"Bone health in ageing men","volume":"23","author":"David","year":"2022","unstructured":"David KNarinx NAntonio LEvenepoel PClaessens FDecallonne B & Vanderschueren D2022Bone health in ageing men. Reviews in Endocrine and Metabolic Disorders231173\u20131208. (https:\/\/doi.org\/10.1007\/s11154-022-09738-5)"},{"key":"bib25","series-title":"Biochemical Journal","first-page":"801","article-title":"Fructosamine 3-kinase is involved in an intracellular deglycation pathway in human erythrocytes","volume":"365","author":"Delpierre","year":"2002","unstructured":"Delpierre GCollard FFortpied J & Van Schaftingen E2002Fructosamine 3-kinase is involved in an intracellular deglycation pathway in human erythrocytes. Biochemical Journal365801\u2013808. (https:\/\/doi.org\/10.1042\/BJ20020325)"},{"key":"bib26","series-title":"Molecular and Cellular Biochemistry","first-page":"1245","article-title":"Testosterone deficiency accelerates early stage atherosclerosis in miniature pigs fed a high-fat and high-cholesterol diet: urine (1)H NMR metabolomics targeted analysis","volume":"476","author":"Deng","year":"2021","unstructured":"Deng LFu DZhu LHuang JLing Y & Cai Z2021Testosterone deficiency accelerates early stage atherosclerosis in miniature pigs fed a high-fat and high-cholesterol diet: urine (1)H NMR metabolomics targeted analysis. Molecular and Cellular Biochemistry4761245\u20131255. (https:\/\/doi.org\/10.1007\/s11010-020-03987-1)"},{"key":"bib27","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"1217","article-title":"The effects of testosterone and dihydrotestosterone on hypothalamic regulation of growth hormone secretion","volume":"81","author":"Eakman","year":"1996","unstructured":"Eakman GDDallas JSPonder SW & Keenan BS1996The effects of testosterone and dihydrotestosterone on hypothalamic regulation of growth hormone secretion. Journal of Clinical Endocrinology and Metabolism811217\u20131223. (https:\/\/doi.org\/10.1210\/jcem.81.3.8772602)"},{"key":"bib28","series-title":"Obesity Reviews","first-page":"333","article-title":"Attrition from randomized controlled trials of pharmacological weight loss agents: a systematic review and analysis","volume":"10","author":"Fabricatore","year":"2009","unstructured":"Fabricatore ANWadden TAMoore RHButryn MLGravallese EAErondu NEHeymsfield SB & Nguyen AM2009Attrition from randomized controlled trials of pharmacological weight loss agents: a systematic review and analysis. Obesity Reviews10333\u2013341. (https:\/\/doi.org\/10.1111\/j.1467-789X.2009.00567.x)"},{"key":"bib29","series-title":"Translational Andrology and Urology","first-page":"1108","article-title":"Failure of testosterone replacement therapy to improve symptoms correlates with burden of systemic conditions","volume":"9","author":"Farber","year":"2020","unstructured":"Farber NJVij SC & Shoskes DA2020Failure of testosterone replacement therapy to improve symptoms correlates with burden of systemic conditions. Translational Andrology and Urology91108\u20131112. (https:\/\/doi.org\/10.21037\/tau-19-848)"},{"key":"bib30","series-title":"American Journal of Physiology. Endocrinology and Metabolism","first-page":"E601","article-title":"Testosterone administration to older men improves muscle function: molecular and physiological mechanisms","volume":"282","author":"Ferrando","year":"2002","unstructured":"Ferrando AASheffield-Moore MYeckel CWGilkison CJiang JAchacosa ALieberman SATipton KWolfe RR & Urban RJ2002Testosterone administration to older men improves muscle function: molecular and physiological mechanisms. American Journal of Physiology. Endocrinology and Metabolism282E601\u2013E607. (https:\/\/doi.org\/10.1152\/ajpendo.00362.2001)"},{"key":"bib123","series-title":"Bone","first-page":"49","article-title":"Association of high-resolution peripheral quantitative computed tomography (HR-pQCT) bone microarchitectural parameters with previous clinical fracture in older men: the Osteoporotic Fractures in Men (MrOS) study","volume":"113","year":"2018","unstructured":"Fink HALangsetmo LVo TNOrwoll ESSchousboe JT & Ensrud KE for the Osteoporotic Fractures in Men (MrOS) Study Group 2018Association of high-resolution peripheral quantitative computed tomography (HR-pQCT) bone microarchitectural parameters with previous clinical fracture in older men: the Osteoporotic Fractures in Men (MrOS) study. Bone11349\u201356. (https:\/\/doi.org\/10.1016\/j.bone.2018.05.005)"},{"key":"bib31","series-title":"New England Journal of Medicine","first-page":"1011","article-title":"Gonadal steroids and body composition, strength, and sexual function in men","volume":"369","author":"Finkelstein","year":"2013","unstructured":"Finkelstein JSLee HBurnett-Bowie SAPallais JCYu EWBorges LFJones BFBarry CVWulczyn KEThomas BJ, 2013Gonadal steroids and body composition, strength, and sexual function in men. New England Journal of Medicine3691011\u20131022. (https:\/\/doi.org\/10.1056\/NEJMoa1206168)"},{"key":"bib32","series-title":"Journal of Clinical Investigation","first-page":"1114","article-title":"Gonadal steroid-dependent effects on bone turnover and bone mineral density in men","volume":"126","author":"Finkelstein","year":"2016","unstructured":"Finkelstein JSLee HLeder BZBurnett-Bowie SAGoldstein DWHahn CWHirsch SCLinker APerros NServais AB, 2016Gonadal steroid-dependent effects on bone turnover and bone mineral density in men. Journal of Clinical Investigation1261114\u20131125. (https:\/\/doi.org\/10.1172\/JCI84137)"},{"key":"bib33","series-title":"The Journal of Clinical Endocrinology & Metabolism","first-page":"e3143","article-title":"Effect of Testosterone Treatment on Bone Microarchitecture and Bone Mineral Density in Men: a 2-Year RCT","volume":"106","author":"Fui","year":"2021","unstructured":"Fui NTHoermann RBracken KHandelsman DJInder WJStuckey BGAYeap BBGhasem-Zadeh ARobledo KPJesudason D, 2021Effect of Testosterone Treatment on Bone Microarchitecture and Bone Mineral Density in Men: a 2-Year RCT. The Journal of Clinical Endocrinology & Metabolism106e3143\u2013e3158."},{"key":"bib34","series-title":"International Journal of Obesity","first-page":"828","article-title":"A within-trial cost-effectiveness analysis of primary care referral to a commercial provider for weight loss treatment, relative to standard care--an international randomised controlled trial","volume":"37","author":"Fuller","year":"2013","unstructured":"Fuller NRColagiuri SSchofield DOlson ADShrestha RHolzapfel CWolfenstetter SBHolle RAhern ALHauner H, 2013A within-trial cost-effectiveness analysis of primary care referral to a commercial provider for weight loss treatment, relative to standard care--an international randomised controlled trial. International Journal of Obesity37828\u2013834. (https:\/\/doi.org\/10.1038\/ijo.2012.139)"},{"key":"bib35","series-title":"American Heart Journal","first-page":"674","article-title":"Hematocrit and the risk of cardiovascular disease--the Framingham study: a 34-year follow-up","volume":"127","author":"Gagnon","year":"1994","unstructured":"Gagnon DRZhang TJBrand FN & Kannel WB1994Hematocrit and the risk of cardiovascular disease--the Framingham study: a 34-year follow-up. American Heart Journal127674\u2013682. (https:\/\/doi.org\/10.1016\/0002-8703(9490679-3)"},{"key":"bib36","series-title":"Diabetes Care","first-page":"2098","article-title":"Effect of testosterone treatment on glucose metabolism in men with type 2 diabetes: a randomized controlled trial","volume":"37","author":"Gianatti","year":"2014","unstructured":"Gianatti EJDupuis PHoermann RStrauss BJWentworth JMZajac JD & Grossmann M2014Effect of testosterone treatment on glucose metabolism in men with type 2 diabetes: a randomized controlled trial. Diabetes Care372098\u20132107. (https:\/\/doi.org\/10.2337\/dc13-2845)"},{"key":"bib37","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"3387","article-title":"Reciprocal relations of subcutaneous and visceral fat to bone structure and strength","volume":"94","author":"Gilsanz","year":"2009","unstructured":"Gilsanz VChalfant JMo AOLee DCDorey FJ & Mittelman SD2009Reciprocal relations of subcutaneous and visceral fat to bone structure and strength. Journal of Clinical Endocrinology and Metabolism943387\u20133393. (https:\/\/doi.org\/10.1210\/jc.2008-2422)"},{"key":"bib38","series-title":"International Urology and Nephrology","first-page":"2237","article-title":"Looking beyond hypogonadism: association between low testosterone and metabolic syndrome in men 20\u201359 years","volume":"52","author":"Gleicher","year":"2020","unstructured":"Gleicher SDaugherty MFerry E & Byler T2020Looking beyond hypogonadism: association between low testosterone and metabolic syndrome in men 20\u201359 years. International Urology and Nephrology522237\u20132244. (https:\/\/doi.org\/10.1007\/s11255-020-02557-0)"},{"key":"bib39","series-title":"Clinical Endocrinology","first-page":"11","article-title":"Hypogonadism and male obesity: focus on unresolved questions","volume":"89","author":"Grossmann","year":"2018","unstructured":"Grossmann M2018Hypogonadism and male obesity: focus on unresolved questions. Clinical Endocrinology8911\u201321. (https:\/\/doi.org\/10.1111\/cen.13723)"},{"key":"bib40","series-title":"Aging Cell","first-page":"280","article-title":"Testosterone administration inhibits hepcidin transcription and is associated with increased iron incorporation into red blood cells","volume":"12","author":"Guo","year":"2013","unstructured":"Guo WBachman ELi MRoy CNBlusztajn JWong SChan SYSerra CJasuja RTravison TG, 2013Testosterone administration inhibits hepcidin transcription and is associated with increased iron incorporation into red blood cells. Aging Cell12280\u2013291. (https:\/\/doi.org\/10.1111\/acel.12052)"},{"key":"bib41","series-title":"Andrology","first-page":"82","article-title":"Hepcidin is not essential for mediating testosterone's effects on erythropoiesis","volume":"8","author":"Guo","year":"2020","unstructured":"Guo WSchmidt PJFleming MD & Bhasin S2020Hepcidin is not essential for mediating testosterone's effects on erythropoiesis. Andrology882\u201390. (https:\/\/doi.org\/10.1111\/andr.12622)"},{"key":"bib42","series-title":"Journal of Sexual Medicine","first-page":"840","article-title":"Testosterone replacement therapy improves metabolic parameters in hypogonadal men with type 2 diabetes but not in men with coexisting depression: the BLAST study","volume":"11","author":"Hackett","year":"2014","unstructured":"Hackett GCole NBhartia MKennedy DRaju JWilkinson P & BLAST Study Group2014Testosterone replacement therapy improves metabolic parameters in hypogonadal men with type 2 diabetes but not in men with coexisting depression: the BLAST study. Journal of Sexual Medicine11840\u2013856. (https:\/\/doi.org\/10.1111\/jsm.12404)"},{"key":"bib43","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"E456","article-title":"Structural decay of bone microarchitecture in men with prostate cancer treated with androgen deprivation therapy","volume":"95","author":"Hamilton","year":"2010","unstructured":"Hamilton EJGhasem-Zadeh AGianatti ELim-Joon DBolton DZebaze RSeeman EZajac JD & Grossmann M2010Structural decay of bone microarchitecture in men with prostate cancer treated with androgen deprivation therapy. Journal of Clinical Endocrinology and Metabolism95E456\u2013E463. (https:\/\/doi.org\/10.1210\/jc.2010-0902)"},{"key":"bib44","series-title":"European Journal of Endocrinology","first-page":"307","article-title":"Recovery of male reproductive endocrine function after ceasing prolonged testosterone undecanoate injections","volume":"186","author":"Handelsman","year":"2022","unstructured":"Handelsman DJDesai RConway AJShankara-Narayana NStuckey BGAInder WJGrossmann MYeap BBJesudason DLy LP, 2022Recovery of male reproductive endocrine function after ceasing prolonged testosterone undecanoate injections. European Journal of Endocrinology186307\u2013318. (https:\/\/doi.org\/10.1530\/EJE-21-0608)"},{"key":"bib45","series-title":"European Journal of Endocrinology","first-page":"809","article-title":"Age-specific population centiles for androgen status in men","volume":"173","author":"Handelsman","year":"2015","unstructured":"Handelsman DJYeap BFlicker LMartin SWittert GA & Ly LP2015Age-specific population centiles for androgen status in men. European Journal of Endocrinology173809\u2013817. (https:\/\/doi.org\/10.1530\/EJE-15-0380)"},{"key":"bib46","series-title":"Endotext","article-title":"Androgen physiology, pharmacology, use and misuse","author":"Handelsman","year":"2000","unstructured":"Handelsman DJ2000Androgen physiology, pharmacology, use and misuse. In Endotext. Ed. FeingoldKRAnawalt BBoyce AChrousos Gde Herder WWDhatariya KDungan KHershman JMHofland JKalra S, South Dartmouth,MA: Endotext."},{"key":"bib47","series-title":"Circulation","first-page":"1382","article-title":"Effect of testosterone on plaque development and androgen receptor expression in the arterial vessel wall","volume":"103","author":"Hanke","year":"2001","unstructured":"Hanke HLenz CHess BSpindler KD & Weidemann W2001Effect of testosterone on plaque development and androgen receptor expression in the arterial vessel wall. Circulation1031382\u20131385. (https:\/\/doi.org\/10.1161\/01.cir.103.10.1382)"},{"key":"bib48","series-title":"Journal of Clinical Endocrinology and Metabolism","article-title":"Testosterone administration during energy deficit suppresses hepcidin and increases iron availability for erythropoiesis","volume":"105","author":"Hennigar","year":"2020","unstructured":"Hennigar SRBerryman CEHarris MNKarl JPLieberman HRMcClung JPRood JC & Pasiakos SM2020Testosterone administration during energy deficit suppresses hepcidin and increases iron availability for erythropoiesis. Journal of Clinical Endocrinology and Metabolism105. (https:\/\/doi.org\/10.1210\/clinem\/dgz316)"},{"key":"bib119","first-page":"271","year":"2004","unstructured":"Herbst KL & Bhasin S2004 Testosterone action on skeletal muscle. Current opinion in clinical nutrition and metabolic care7271\u20137. (https:\/\/doi.org\/10.1097\/00075197-200405000-00006)"},{"key":"bib49","series-title":"Lancet. Healthy Longevity","first-page":"e381","article-title":"Adverse cardiovascular events and mortality in men during testosterone treatment: an individual patient and aggregate data meta-analysis","volume":"3","author":"Hudson","year":"2022","unstructured":"Hudson JCruickshank MQuinton RAucott LAceves-Martins MGillies KBhasin SSnyder PJEllenberg SSGrossmann M, 2022Adverse cardiovascular events and mortality in men during testosterone treatment: an individual patient and aggregate data meta-analysis. Lancet. Healthy Longevity3e381\u2013e393. (https:\/\/doi.org\/10.1016\/S2666-7568(2200096-4)"},{"key":"bib50","series-title":"Annals of Internal Medicine","first-page":"621","article-title":"Long-term effects of dihydrotestosterone treatment on prostate growth in healthy, middle-aged men without prostate disease: a randomized, placebo-controlled trial","volume":"153","author":"Idan","year":"2010","unstructured":"Idan AGriffiths KAHarwood DTSeibel MJTurner LConway AJ & Handelsman DJ2010Long-term effects of dihydrotestosterone treatment on prostate growth in healthy, middle-aged men without prostate disease: a randomized, placebo-controlled trial. Annals of Internal Medicine153621\u2013632. (https:\/\/doi.org\/10.7326\/0003-4819-153-10-201011160-00004)"},{"key":"bib51","series-title":"Endocrinology","first-page":"4691","article-title":"Effects of 17beta-estradiol and androgen on glucose metabolism in skeletal muscle","volume":"157","author":"Inada","year":"2016","unstructured":"Inada AFujii NLInada OHigaki YFuruichi Y & Nabeshima YI2016Effects of 17beta-estradiol and androgen on glucose metabolism in skeletal muscle. Endocrinology1574691\u20134705. (https:\/\/doi.org\/10.1210\/en.2016-1261)"},{"key":"bib52","series-title":"European Journal of Endocrinology","first-page":"385","article-title":"Trough serum testosterone predicts the development of polycythemia in hypogonadal men treated for up to 21 years with subcutaneous testosterone pellets","volume":"162","author":"Ip","year":"2010","unstructured":"Ip FFdi Pierro IBrown RCunningham IHandelsman DJ & Liu PY2010Trough serum testosterone predicts the development of polycythemia in hypogonadal men treated for up to 21 years with subcutaneous testosterone pellets. European Journal of Endocrinology162385\u2013390. (https:\/\/doi.org\/10.1530\/EJE-09-0717)"},{"key":"bib53","series-title":"Clinical Endocrinology","first-page":"280","article-title":"Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle-aged men: a meta-analysis","volume":"63","author":"Isidori","year":"2005","unstructured":"Isidori AMGiannetta EGreco EAGianfrilli DBonifacio VIsidori ALenzi A & Fabbri A2005Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle-aged men: a meta-analysis. Clinical Endocrinology63280\u2013293. (https:\/\/doi.org\/10.1111\/j.1365-2265.2005.02339.x)"},{"key":"bib54","series-title":"Diabetes Care","first-page":"3105","article-title":"Does waist circumference predict diabetes and cardiovascular disease beyond commonly evaluated cardiometabolic risk factors?","volume":"30","author":"Janiszewski","year":"2007","unstructured":"Janiszewski PMJanssen I & Ross R2007Does waist circumference predict diabetes and cardiovascular disease beyond commonly evaluated cardiometabolic risk factors?Diabetes Care303105\u20133109. (https:\/\/doi.org\/10.2337\/dc07-0945)"},{"key":"bib55","series-title":"Diabetes Care","first-page":"485","article-title":"Macrovascular risk and diagnostic criteria for type 2 diabetes: implications for the use of FPG and HbA(1c) for cost-effective screening","volume":"26","author":"Jesudason","year":"2003","unstructured":"Jesudason DRDunstan KLeong D & Wittert GA2003Macrovascular risk and diagnostic criteria for type 2 diabetes: implications for the use of FPG and HbA(1c) for cost-effective screening. Diabetes Care26485\u2013490. (https:\/\/doi.org\/10.2337\/diacare.26.2.485)"},{"key":"bib56","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"4358","article-title":"Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism","volume":"81","author":"Katznelson","year":"1996","unstructured":"Katznelson LFinkelstein JSSchoenfeld DARosenthal DIAnderson EJ & Klibanski A1996Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism. Journal of Clinical Endocrinology and Metabolism814358\u20134365. (https:\/\/doi.org\/10.1210\/jcem.81.12.8954042)"},{"key":"bib57","series-title":"Nature Reviews. Endocrinology","first-page":"685","article-title":"Update on the pathogenesis and treatment of skeletal fragility in type 2 diabetes mellitus","volume":"17","author":"Khosla","year":"2021","unstructured":"Khosla SSamakkarnthai PMonroe DG & Farr JN2021Update on the pathogenesis and treatment of skeletal fragility in type 2 diabetes mellitus. Nature Reviews. Endocrinology17685\u2013697. (https:\/\/doi.org\/10.1038\/s41574-021-00555-5)"},{"key":"bib58","series-title":"Life Sciences","article-title":"Testosterone stimulates cholesterol clearance from human macrophages by stimulating LXRa","volume":"269","author":"Kilby","year":"2021","unstructured":"Kilby ELKelly DM & Jones TH2021Testosterone stimulates cholesterol clearance from human macrophages by stimulating LXRa. Life Sciences269 119040. (https:\/\/doi.org\/10.1016\/j.lfs.2021.119040)"},{"key":"bib59","series-title":"World Journal of Men\u2019s Health","first-page":"85","article-title":"Cross-sectional association of metabolic syndrome and its components with serum testosterone levels in a Korean-screened population","volume":"38","author":"Kim","year":"2020","unstructured":"Kim MKyung YS & Ahn TY2020Cross-sectional association of metabolic syndrome and its components with serum testosterone levels in a Korean-screened population. World Journal of Men\u2019s Health3885\u201394. (https:\/\/doi.org\/10.5534\/wjmh.190030)"},{"key":"bib60","series-title":"New England Journal of Medicine","first-page":"393","article-title":"Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin","volume":"346","author":"Knowler","year":"2002","unstructured":"Knowler WCBarrett-Connor EFowler SEHamman RFLachin JMWalker EANathan DM & Diabetes Prevention Program Research Group2002Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. New England Journal of Medicine346393\u2013403. (https:\/\/doi.org\/10.1056\/NEJMoa012512)"},{"key":"bib61","series-title":"Frontiers in Genetics","article-title":"Identification of variants associated with rare hematological disorder erythrocytosis using targeted next-generation sequencing analysis","volume":"12","author":"Kristan","year":"2021","unstructured":"Kristan APajic TMaver ARezen TKunej TKolic RVuga AFink MZula \u0160Podgornik H, 2021Identification of variants associated with rare hematological disorder erythrocytosis using targeted next-generation sequencing analysis. Frontiers in Genetics12 689868. (https:\/\/doi.org\/10.3389\/fgene.2021.689868)"},{"key":"bib62","series-title":"Preventive Medicine","first-page":"45","article-title":"Hematocrit and the risk of coronary heart disease mortality in the TAMRISK study, a 28-year follow-up","volume":"49","author":"Kunnas","year":"2009","unstructured":"Kunnas TSolakivi THuuskonen KKalela ARenko J & Nikkari ST2009Hematocrit and the risk of coronary heart disease mortality in the TAMRISK study, a 28-year follow-up. Preventive Medicine4945\u201347. (https:\/\/doi.org\/10.1016\/j.ypmed.2009.04.015)"},{"key":"bib63","series-title":"PLoS One","article-title":"Circulating Hepcidin-25 is reduced by endogenous estrogen in humans","volume":"11","author":"Lehtihet","year":"2016","unstructured":"Lehtihet MBonde YBeckman LBerinder KHoybye CRudling MSloan JHKonrad RJ & Angelin B2016Circulating Hepcidin-25 is reduced by endogenous estrogen in humans. PLoS One11 e0148802. (https:\/\/doi.org\/10.1371\/journal.pone.0148802)"},{"key":"bib64","series-title":"Metabolism: Clinical and Experimental","first-page":"883","article-title":"Muscle grip strength predicts incident type 2 diabetes: population-based cohort study","volume":"65","author":"Li","year":"2016","unstructured":"Li JJWittert GAVincent AAtlantis EShi ZAppleton SLHill CLJenkins AJJanuszewski AS & Adams RJ2016Muscle grip strength predicts incident type 2 diabetes: population-based cohort study. Metabolism: Clinical and Experimental65883\u2013892. (https:\/\/doi.org\/10.1016\/j.metabol.2016.03.011)"},{"key":"bib65","series-title":"American Journal of Physiology. Heart and Circulatory Physiology","first-page":"H1485","article-title":"Testosterone induces apoptosis in vascular smooth muscle cells via extrinsic apoptotic pathway with mitochondria-generated reactive oxygen species involvement","volume":"306","author":"Lopes","year":"2014","unstructured":"Lopes RANeves KBPestana CRQueiroz ALZanotto CZChignalia AZValim YMSilveira LRCurti C & Tostes RC2014Testosterone induces apoptosis in vascular smooth muscle cells via extrinsic apoptotic pathway with mitochondria-generated reactive oxygen species involvement. American Journal of Physiology. Heart and Circulatory Physiology306H1485\u2013H1494. (https:\/\/doi.org\/10.1152\/ajpheart.00809.2013)"},{"key":"bib66","series-title":"Andrology","first-page":"24","article-title":"Is the haematopoietic effect of testosterone mediated by erythropoietin? The results of a clinical trial in older men","volume":"1","author":"Maggio","year":"2013","unstructured":"Maggio MSnyder PJCeda GPMilaneschi YLuci MCattabiani CMasoni SVignali AVolpi RLauretani F, 2013Is the haematopoietic effect of testosterone mediated by erythropoietin? The results of a clinical trial in older men. Andrology124\u201328. (https:\/\/doi.org\/10.1111\/j.2047-2927.2012.00009.x)"},{"key":"bib67","series-title":"Clinical Endocrinology","first-page":"589","article-title":"Longitudinal changes in serum testosterone and sex hormone-binding globulin in men aged 40\u201369 years from the UK Biobank","volume":"96","author":"Marriott","year":"2022","unstructured":"Marriott RJMurray KHankey GJManning LDwivedi GWu FCW & Yeap BB2022Longitudinal changes in serum testosterone and sex hormone-binding globulin in men aged 40\u201369 years from the UK Biobank. Clinical Endocrinology96589\u2013598. (https:\/\/doi.org\/10.1111\/cen.14648)"},{"key":"bib68","series-title":"American Journal of Physiology. Cell Physiology","first-page":"C24","article-title":"Skeletal muscle wasting: the estrogen side of sexual dimorphism","volume":"322","author":"McMillin","year":"2022","unstructured":"McMillin SLMinchew ECLowe DA & Spangenburg EE2022Skeletal muscle wasting: the estrogen side of sexual dimorphism. American Journal of Physiology. Cell Physiology322C24\u2013C37. (https:\/\/doi.org\/10.1152\/ajpcell.00333.2021)"},{"key":"bib69","series-title":"Endocrinology","first-page":"841","article-title":"Androgen-induced progression of arterial calcification in apolipoprotein E-null mice is uncoupled from plaque growth and lipid levels","volume":"150","author":"McRobb","year":"2009","unstructured":"McRobb LHandelsman DJ & Heather AK2009Androgen-induced progression of arterial calcification in apolipoprotein E-null mice is uncoupled from plaque growth and lipid levels. Endocrinology150841\u2013848. (https:\/\/doi.org\/10.1210\/en.2008-0760)"},{"key":"bib70","series-title":"Proceedings of the National Academy of Sciences of the United States of America","first-page":"3589","article-title":"Testosterone inhibits early atherogenesis by conversion to estradiol: critical role of aromatase","volume":"98","author":"Nathan","year":"2001","unstructured":"Nathan LShi WDinh HMukherjee TKWang XLusis AJ & Chaudhuri G2001Testosterone inhibits early atherogenesis by conversion to estradiol: critical role of aromatase. Proceedings of the National Academy of Sciences of the United States of America983589\u20133593. (https:\/\/doi.org\/10.1073\/pnas.051003698)"},{"key":"bib71","series-title":"Circulation","first-page":"2427","article-title":"Physiological testosterone replacement therapy attenuates fatty streak formation and improves high-density lipoprotein cholesterol in the Tfm mouse: an effect that is independent of the classic androgen receptor","volume":"116","author":"Nettleship","year":"2007","unstructured":"Nettleship JEJones THChanner KS & Jones RD2007Physiological testosterone replacement therapy attenuates fatty streak formation and improves high-density lipoprotein cholesterol in the Tfm mouse: an effect that is independent of the classic androgen receptor. Circulation1162427\u20132434. (https:\/\/doi.org\/10.1161\/CIRCULATIONAHA.107.708768)"},{"key":"bib72","series-title":"Journal of Urology","first-page":"1295","article-title":"Secondary polycythemia in men receiving testosterone therapy increases risk of major adverse cardiovascular events and venous thromboembolism in the first year of therapy","volume":"207","author":"Ory","year":"2022","unstructured":"Ory JNackeeran SBalaji NCHare JM & Ramasamy AR2022Secondary polycythemia in men receiving testosterone therapy increases risk of major adverse cardiovascular events and venous thromboembolism in the first year of therapy. Journal of Urology2071295\u20131301. (https:\/\/doi.org\/10.1097\/JU.0000000000002437)"},{"key":"bib73","series-title":"Sports Medicine","first-page":"2853","article-title":"Mechanisms of estrogen influence on skeletal muscle: mass, regeneration, and mitochondrial function","volume":"52","author":"Pellegrino","year":"2022","unstructured":"Pellegrino ATiidus PM & Vandenboom R2022Mechanisms of estrogen influence on skeletal muscle: mass, regeneration, and mitochondrial function. Sports Medicine522853\u20132869. (https:\/\/doi.org\/10.1007\/s40279-022-01733-9)"},{"key":"bib74","series-title":"Acta Cardiologica","first-page":"177","article-title":"Red blood cell count in short-term prediction of cardiovascular disease incidence in the Gubbio population study","volume":"57","author":"Puddu","year":"2002","unstructured":"Puddu PELanti MMenotti AMancini MZanchetti ACirillo MAngeletti M & Gubbio Study Research Group2002Red blood cell count in short-term prediction of cardiovascular disease incidence in the Gubbio population study. Acta Cardiologica57177\u2013185. (https:\/\/doi.org\/10.2143\/AC.57.3.2005387)"},{"key":"bib75","series-title":"Sports Medicine \u2013 Open","article-title":"Effectiveness of resistance training and associated program characteristics in patients at risk for Type 2 diabetes: a systematic review and meta-analysis","volume":"7","author":"Qadir","year":"2021","unstructured":"Qadir RSculthorpe NFTodd T & Brown EC2021Effectiveness of resistance training and associated program characteristics in patients at risk for Type 2 diabetes: a systematic review and meta-analysis. Sports Medicine \u2013 Open7 38. (https:\/\/doi.org\/10.1186\/s40798-021-00321-x)"},{"key":"bib76","series-title":"Andrology","first-page":"1222","article-title":"Testosterone replacement therapy: pre-treatment sex hormone-binding globulin levels and age may identify clinical subgroups","volume":"8","author":"Ramachandran","year":"2020","unstructured":"Ramachandran SHackett GI & Strange RC2020Testosterone replacement therapy: pre-treatment sex hormone-binding globulin levels and age may identify clinical subgroups. Andrology81222\u20131232. (https:\/\/doi.org\/10.1111\/andr.12813)"},{"key":"bib77","series-title":"Archives of Pathology and Laboratory Medicine","first-page":"663","article-title":"Testis, epididymis, and spermatic cord in elderly men. Correlation of angiographic and histologic studies with systemic arteriosclerosis","volume":"109","author":"Regadera","year":"1985","unstructured":"Regadera JNistal M & Paniagua R1985Testis, epididymis, and spermatic cord in elderly men. Correlation of angiographic and histologic studies with systemic arteriosclerosis. Archives of Pathology and Laboratory Medicine109663\u2013667."},{"key":"bib78","series-title":"Laryngoscope Investigative Otolaryngology","first-page":"627","article-title":"Is obstructive sleep apnea associated with erythrocytosis? A systematic review and meta-analysis","volume":"7","author":"Rha","year":"2022","unstructured":"Rha MSJeong YKim JKim CHYoon JH & Cho HJ2022Is obstructive sleep apnea associated with erythrocytosis? A systematic review and meta-analysis. Laryngoscope Investigative Otolaryngology7627\u2013635. (https:\/\/doi.org\/10.1002\/lio2.751)"},{"key":"bib79","series-title":"Journal of Steroid Biochemistry and Molecular Biology","first-page":"189","article-title":"Testosterone action on erythropoiesis does not require its aromatization to estrogen: insights from the testosterone and estrogen treatment of two aromatase-deficient men","volume":"113","author":"Rochira","year":"2009","unstructured":"Rochira VZirilli LMadeo BMaffei L & Carani C2009Testosterone action on erythropoiesis does not require its aromatization to estrogen: insights from the testosterone and estrogen treatment of two aromatase-deficient men. Journal of Steroid Biochemistry and Molecular Biology113189\u2013194. (https:\/\/doi.org\/10.1016\/j.jsbmb.2008.12.007)"},{"key":"bib80","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"405","article-title":"Position statement: utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society position statement","volume":"92","author":"Rosner","year":"2007","unstructured":"Rosner WAuchus RJAzziz RSluss PM & Raff H2007Position statement: utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society position statement. Journal of Clinical Endocrinology and Metabolism92405\u2013413. (https:\/\/doi.org\/10.1210\/jc.2006-1864)"},{"key":"bib81","series-title":"Nature Reviews. Endocrinology","first-page":"177","article-title":"Waist circumference as a vital sign in clinical practice: a Consensus Statement from the IAS and ICCR Working Group on Visceral Obesity","volume":"16","author":"Ross","year":"2020","unstructured":"Ross RNeeland IJYamashita SShai ISeidell JMagni PSantos RDArsenault BCuevas AHu FB, 2020Waist circumference as a vital sign in clinical practice: a Consensus Statement from the IAS and ICCR Working Group on Visceral Obesity. Nature Reviews. Endocrinology16177\u2013189. (https:\/\/doi.org\/10.1038\/s41574-019-0310-7)"},{"key":"bib82","series-title":"Vitamins and Hormones","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/bs.vh.2019.01.005","article-title":"Regulators of hepcidin expression","volume":"110","author":"Roth","year":"2019","unstructured":"Roth MPMeynard D & Coppin H2019Regulators of hepcidin expression. Vitamins and Hormones110101\u2013129. (https:\/\/doi.org\/10.1016\/bs.vh.2019.01.005)"},{"key":"bib84","series-title":"European Journal of Endocrinology","first-page":"R23","article-title":"Mechanisms in endocrinology: estradiol as a male hormone","volume":"181","author":"Russell","year":"2019","unstructured":"Russell N & Grossmann M2019Mechanisms in endocrinology: estradiol as a male hormone. European Journal of Endocrinology181R23\u2013R43. (https:\/\/doi.org\/10.1530\/EJE-18-1000)"},{"key":"bib83","series-title":"European Journal of Endocrinology","first-page":"241","article-title":"Effects of estradiol on bone in men undergoing androgen deprivation therapy: a randomised placebo-controlled trial","volume":"187","author":"Russell","year":"2022","unstructured":"Russell NGhasem-Zadeh AHoermann RCheung ASZajac JDShore-Lorenti CEbeling PRHandelsman DJ & Grossmann M2022Effects of estradiol on bone in men undergoing androgen deprivation therapy: a randomised placebo-controlled trial. European Journal of Endocrinology187241\u2013256. (https:\/\/doi.org\/10.1530\/EJE-22-0227)"},{"key":"bib85","series-title":"Lancet. Diabetes and Endocrinology","first-page":"34","article-title":"Cortical and trabecular bone microarchitecture as an independent predictor of incident fracture risk in older women and men in the Bone Microarchitecture International Consortium (BoMIC): a prospective study","volume":"7","author":"Samelson","year":"2019","unstructured":"Samelson EJBroe KEXu HYang LBoyd SBiver ESzulc PAdachi JAmin SAtkinson E, 2019Cortical and trabecular bone microarchitecture as an independent predictor of incident fracture risk in older women and men in the Bone Microarchitecture International Consortium (BoMIC): a prospective study. Lancet. Diabetes and Endocrinology734\u201343. (https:\/\/doi.org\/10.1016\/S2213-8587(1830308-5)"},{"key":"bib86","series-title":"Clinical Endocrinology","first-page":"755","article-title":"Serum testosterone, dihydrotestosterone and estradiol concentrations in older men self-reporting very good health: the healthy man study","volume":"77","author":"Sartorius","year":"2012","unstructured":"Sartorius GSpasevska SIdan ATurner LForbes EZamojska AAllan CALy LPConway AJMcLachlan RI, 2012Serum testosterone, dihydrotestosterone and estradiol concentrations in older men self-reporting very good health: the healthy man study. Clinical Endocrinology77755\u2013763. (https:\/\/doi.org\/10.1111\/j.1365-2265.2012.04432.x)"},{"key":"bib87","series-title":"Journal of Clinical Investigation","first-page":"3979","article-title":"Monosaccharide-induced lipogenesis regulates the human hepatic sex hormone-binding globulin gene","volume":"117","author":"Selva","year":"2007","unstructured":"Selva DMHogeveen KNInnis SM & Hammond GL2007Monosaccharide-induced lipogenesis regulates the human hepatic sex hormone-binding globulin gene. Journal of Clinical Investigation1173979\u20133987. (https:\/\/doi.org\/10.1172\/JCI32249)"},{"key":"bib88","series-title":"Endocrinology","first-page":"193","article-title":"The role of GH and IGF-I in mediating anabolic effects of testosterone on androgen-responsive muscle","volume":"152","author":"Serra","year":"2011","unstructured":"Serra CBhasin STangherlini FBarton ERGanno MZhang AShansky JVandenburgh HHTravison TGJasuja R, 2011The role of GH and IGF-I in mediating anabolic effects of testosterone on androgen-responsive muscle. Endocrinology152193\u2013206. (https:\/\/doi.org\/10.1210\/en.2010-0802)"},{"key":"bib89","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"1827","article-title":"Rate and extent of recovery from reproductive and cardiac dysfunction due to androgen abuse in men","volume":"105","author":"Shankara-Narayana","year":"2020","unstructured":"Shankara-Narayana NYu CSavkovic SDesai RFennell CTurner LJayadev VConway AJKockx MRidley L, 2020Rate and extent of recovery from reproductive and cardiac dysfunction due to androgen abuse in men. Journal of Clinical Endocrinology and Metabolism1051827\u20131839. (https:\/\/doi.org\/10.1210\/clinem\/dgz324)"},{"key":"bib90","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"3289","article-title":"Longitudinal changes in testosterone over five years in community-dwelling men","volume":"98","author":"Shi","year":"2013","unstructured":"Shi ZAraujo ABMartin SO'Loughlin P & Wittert GA2013Longitudinal changes in testosterone over five years in community-dwelling men. Journal of Clinical Endocrinology and Metabolism983289\u20133297. (https:\/\/doi.org\/10.1210\/jc.2012-3842)"},{"key":"bib91","series-title":"Journal of Experimental Medicine","first-page":"345","article-title":"A sex-specific role for androgens in angiogenesis","volume":"207","author":"Sieveking","year":"2010","unstructured":"Sieveking DPLim PChow RWDunn LLBao SMcGrath KCHeather AKHandelsman DJCelermajer DS & Ng MK2010A sex-specific role for androgens in angiogenesis. Journal of Experimental Medicine207345\u2013352. (https:\/\/doi.org\/10.1084\/jem.20091924)"},{"key":"bib92","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"5928","article-title":"Reproductive hormone reference intervals for healthy fertile young men: evaluation of automated platform assays","volume":"90","author":"Sikaris","year":"2005","unstructured":"Sikaris KMcLachlan RIKazlauskas Rde Kretser DHolden CA & Handelsman DJ2005Reproductive hormone reference intervals for healthy fertile young men: evaluation of automated platform assays. Journal of Clinical Endocrinology and Metabolism905928\u20135936. (https:\/\/doi.org\/10.1210\/jc.2005-0962)"},{"key":"bib93","series-title":"Journal of Steroid Biochemistry and Molecular Biology","first-page":"3","article-title":"Estrogen, a fundamental player in energy homeostasis","volume":"95","author":"Simpson","year":"2005","unstructured":"Simpson EJones MMisso MHewitt KHill RMaffei LCarani C & Boon WC2005Estrogen, a fundamental player in energy homeostasis. Journal of Steroid Biochemistry and Molecular Biology953\u20138. (https:\/\/doi.org\/10.1016\/j.jsbmb.2005.04.018)"},{"key":"bib94","series-title":"BMC Public Health","article-title":"Waist circumference a good indicator of future risk for type 2 diabetes and cardiovascular disease","volume":"12","author":"Siren","year":"2012","unstructured":"Siren REriksson JG & Vanhanen H2012Waist circumference a good indicator of future risk for type 2 diabetes and cardiovascular disease. BMC Public Health12 631. (https:\/\/doi.org\/10.1186\/1471-2458-12-631)"},{"key":"bib95","series-title":"New England Journal of Medicine","first-page":"611","article-title":"Effects of testosterone treatment in older men","volume":"374","author":"Snyder","year":"2016","unstructured":"Snyder PJBhasin SCunningham GRMatsumoto AMStephens-Shields AJCauley JAGill TMBarrett-Connor ESwerdloff RSWang C, 2016Effects of testosterone treatment in older men. New England Journal of Medicine374611\u2013624. (https:\/\/doi.org\/10.1056\/NEJMoa1506119)"},{"key":"bib96","series-title":"JAMA Internal Medicine","first-page":"471","article-title":"Effect of testosterone treatment on volumetric bone density and strength in older men with low testosterone: a controlled clinical trial","volume":"177","author":"Snyder","year":"2017","unstructured":"Snyder PJKopperdahl DLStephens-Shields AJEllenberg SSCauley JAEnsrud KELewis CEBarrett-Connor ESchwartz AVLee DC, 2017Effect of testosterone treatment on volumetric bone density and strength in older men with low testosterone: a controlled clinical trial. JAMA Internal Medicine177471\u2013479. (https:\/\/doi.org\/10.1001\/jamainternmed.2016.9539)"},{"key":"bib97","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"2670","article-title":"Effects of testosterone replacement in hypogonadal men","volume":"85","author":"Snyder","year":"2000","unstructured":"Snyder PJPeachey HBerlin JAHannoush PHaddad GDlewati ASantanna JLoh LLenrow DAHolmes JH, 2000Effects of testosterone replacement in hypogonadal men. Journal of Clinical Endocrinology and Metabolism852670\u20132677. (https:\/\/doi.org\/10.1210\/jcem.85.8.6731)"},{"key":"bib98","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"639","article-title":"Effects of testosterone on muscle strength, physical function, body composition, and quality of life in intermediate-frail and frail elderly men: a randomized, double-blind, placebo-controlled study","volume":"95","author":"Srinivas-Shankar","year":"2010","unstructured":"Srinivas-Shankar URoberts SAConnolly MJO'Connell MDAdams JEOldham JA & Wu FC2010Effects of testosterone on muscle strength, physical function, body composition, and quality of life in intermediate-frail and frail elderly men: a randomized, double-blind, placebo-controlled study. Journal of Clinical Endocrinology and Metabolism95639\u2013650. (https:\/\/doi.org\/10.1210\/jc.2009-1251)"},{"key":"bib99","series-title":"International Journal of Impotence Research","first-page":"378","article-title":"Testosterone treatment in elderly men with subnormal testosterone levels improves body composition and BMD in the hip","volume":"20","author":"Svartberg","year":"2008","unstructured":"Svartberg JAgledahl IFigenschau YSildnes TWaterloo K & Jorde R2008Testosterone treatment in elderly men with subnormal testosterone levels improves body composition and BMD in the hip. International Journal of Impotence Research20378\u2013387. (https:\/\/doi.org\/10.1038\/ijir.2008.19)"},{"key":"bib122","series-title":"Journal of Bone and Mineral Reseach: the Official Journal","first-page":"1358","article-title":"Cross-sectional analysis of the association between fragility fractures and bone microarchitecture in older men: the STRAMBO study","volume":"26","year":"2011","unstructured":"Szulc PBoutroy SVilayphiou NChaitou ADelmas PD & Chapurlat R2011Cross-sectional analysis of the association between fragility fractures and bone microarchitecture in older men: the STRAMBO study. Journal of Bone and Mineral Reseach: the Official Journal for the American Society of Bone and Mineral Research 261358\u20131367. (https:\/\/doi.org\/10.1002\/jbmr.319)"},{"key":"bib100","series-title":"Biochemical Society Transactions","first-page":"1428","article-title":"Enzymatic deglycation--a new paradigm or an epiphenomenon?","volume":"31","author":"Szwergold","year":"2003","unstructured":"Szwergold BS & Beisswenger PJ2003Enzymatic deglycation--a new paradigm or an epiphenomenon?Biochemical Society Transactions311428\u20131432. (https:\/\/doi.org\/10.1042\/bst0311428)"},{"key":"bib101","series-title":"Diabetes","first-page":"2139","article-title":"Human fructosamine-3-kinase: purification, sequencing, substrate specificity, and evidence of activity in vivo","volume":"50","author":"Szwergold","year":"2001","unstructured":"Szwergold BSHowell S & Beisswenger PJ2001Human fructosamine-3-kinase: purification, sequencing, substrate specificity, and evidence of activity in vivo. Diabetes502139\u20132147. (https:\/\/doi.org\/10.2337\/diabetes.50.9.2139)"},{"key":"bib102","series-title":"Cardiovascular Research","first-page":"152","article-title":"Endogenous testosterone attenuates neointima formation after moderate coronary balloon injury in male swine","volume":"82","author":"Tharp","year":"2009","unstructured":"Tharp DLMasseau IIvey JGanjam VK & Bowles DK2009Endogenous testosterone attenuates neointima formation after moderate coronary balloon injury in male swine. Cardiovascular Research82152\u2013160. (https:\/\/doi.org\/10.1093\/cvr\/cvp038)"},{"key":"bib103","series-title":"Best Practice and Research. Clinical Endocrinology and Metabolism","article-title":"Effects of androgens on glucose metabolism","volume":"36","author":"Umapathysivam","year":"2022","unstructured":"Umapathysivam MGrossmann M & Wittert GA2022Effects of androgens on glucose metabolism. Best Practice and Research. Clinical Endocrinology and Metabolism36 101654. (https:\/\/doi.org\/10.1016\/j.beem.2022.101654)"},{"key":"bib104","series-title":"Endocrine Reviews","first-page":"906","article-title":"Sex steroid actions in male bone","volume":"35","author":"Vanderschueren","year":"2014","unstructured":"Vanderschueren DLaurent MRClaessens FGielen ELagerquist MKVandenput LB\u00f6rjesson AE & Ohlsson C2014Sex steroid actions in male bone. Endocrine Reviews35906\u2013960. (https:\/\/doi.org\/10.1210\/er.2014-1024)"},{"key":"bib105","series-title":"Best Practice and Research. Clinical Endocrinology and Metabolism","article-title":"Haematological actions of androgens","volume":"36","author":"Warren","year":"2022","unstructured":"Warren AM & Grossmann M2022Haematological actions of androgens. Best Practice and Research. Clinical Endocrinology and Metabolism36 101653. (https:\/\/doi.org\/10.1016\/j.beem.2022.101653)"},{"key":"bib106","series-title":"Diabetes, Obesity and Metabolism","first-page":"772","article-title":"Testosterone therapy to prevent type 2 diabetes mellitus in at-risk men (T4DM): design and implementation of a double-blind randomized controlled trial","volume":"21","author":"Wittert","year":"2019","unstructured":"Wittert GAtlantis EAllan CBracken KConway ADaniel MGebski VGrossmann MHague WHandelsman DJ, 2019Testosterone therapy to prevent type 2 diabetes mellitus in at-risk men (T4DM): design and implementation of a double-blind randomized controlled trial. Diabetes, Obesity and Metabolism21772\u2013780. (https:\/\/doi.org\/10.1111\/dom.13601)"},{"key":"bib107","series-title":"Lancet. Diabetes and Endocrinology","first-page":"32","article-title":"Testosterone treatment to prevent or revert type 2 diabetes in men enrolled in a lifestyle programme (T4DM): a randomised, double-blind, placebo-controlled, 2-year, phase 3b trial","volume":"9","author":"Wittert","year":"2021","unstructured":"Wittert GBracken KRobledo KPGrossmann MYeap BBHandelsman DJStuckey BConway AInder WMcLachlan R, 2021Testosterone treatment to prevent or revert type 2 diabetes in men enrolled in a lifestyle programme (T4DM): a randomised, double-blind, placebo-controlled, 2-year, phase 3b trial. Lancet. Diabetes and Endocrinology932\u201345. (https:\/\/doi.org\/10.1016\/S2213-8587(2030367-3)"},{"key":"bib108","series-title":"Reviews in Endocrine and Metabolic Disorders","first-page":"1233","article-title":"Obesity, type 2 diabetes, and testosterone in ageing men","volume":"23","author":"Wittert","year":"2022","unstructured":"Wittert G & Grossmann M2022Obesity, type 2 diabetes, and testosterone in ageing men. Reviews in Endocrine and Metabolic Disorders231233\u20131242. (https:\/\/doi.org\/10.1007\/s11154-022-09746-5)"},{"key":"bib118","year":"2022","unstructured":"Wittert G & Robledo K2022A mediation analysis of the effect of testosterone treatment in the T4DM trial. ESA-SRB-APEG-NZSE Annual Scientific Meeting, Te Pae, Christchurch, New Zealand, Nov 12-16, Abstract #172."},{"key":"bib110","series-title":"Blood Advances","first-page":"6353","article-title":"Erythrocytosis in the general population: clinical characteristics and association with clonal hematopoiesis","volume":"4","author":"Wouters","year":"2020","unstructured":"Wouters HJCMMulder Rvan Zeventer IASchuringa JJvan der Klauw MMvan der Harst PDiepstra AMulder AB & Huls G2020Erythrocytosis in the general population: clinical characteristics and association with clonal hematopoiesis. Blood Advances46353\u20136363. (https:\/\/doi.org\/10.1182\/bloodadvances.2020003323)"},{"key":"bib111","series-title":"Andrologia","first-page":"793","article-title":"Effects of continuous long-term testosterone therapy (TTh) on anthropometric, endocrine and metabolic parameters for up to 10 years in 115 hypogonadadal elderly men: real-life experience from an observational registry study","volume":"48","author":"Yassin","year":"2016","unstructured":"Yassin AANettleship JAlmehmadi YSalman M & Saad F2016Effects of continuous long-term testosterone therapy (TTh) on anthropometric, endocrine and metabolic parameters for up to 10 years in 115 hypogonadadal elderly men: real-life experience from an observational registry study. Andrologia48793\u2013799. (https:\/\/doi.org\/10.1111\/and.12514)"},{"key":"bib112","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"4565","article-title":"In older men, higher plasma testosterone or dihydrotestosterone is an independent predictor for reduced incidence of stroke but not myocardial infarction","volume":"99","author":"Yeap","year":"2014","unstructured":"Yeap BBAlfonso HChubb SAHankey GJHandelsman DJGolledge JAlmeida OPFlicker L & Norman PE2014In older men, higher plasma testosterone or dihydrotestosterone is an independent predictor for reduced incidence of stroke but not myocardial infarction. Journal of Clinical Endocrinology and Metabolism994565\u20134573. (https:\/\/doi.org\/10.1210\/jc.2014-2664)"},{"key":"bib114","series-title":"Clinical Endocrinology","first-page":"88","article-title":"Progressive impairment of testicular endocrine function in ageing men: testosterone and dihydrotestosterone decrease, and luteinizing hormone increases, in men transitioning from the 8th to 9th decades of life","volume":"88","author":"Yeap","year":"2018","unstructured":"Yeap BBManning LChubb SAPHandelsman DJAlmeida OPHankey GJ & Flicker L2018Progressive impairment of testicular endocrine function in ageing men: testosterone and dihydrotestosterone decrease, and luteinizing hormone increases, in men transitioning from the 8th to 9th decades of life. Clinical Endocrinology8888\u201395. (https:\/\/doi.org\/10.1111\/cen.13484)"},{"key":"bib115","series-title":"Annals of Internal Medicine","first-page":"159","article-title":"Associations of serum testosterone and sex hormone-binding globulin with incident cardiovascular events in middle-aged to older men","volume":"175","author":"Yeap","year":"2022","unstructured":"Yeap BBMarriott RJAntonio LRaj SDwivedi GReid CMAnawalt BDBhasin SDobs ASHandelsman DJ, 2022Associations of serum testosterone and sex hormone-binding globulin with incident cardiovascular events in middle-aged to older men. Annals of Internal Medicine175159\u2013170. (https:\/\/doi.org\/10.7326\/M21-0551)"},{"key":"bib116","series-title":"Journal of Breath Research","article-title":"Human erythrocyte lifespan measured by Levitt's CO breath test with newly developed automatic instrument","volume":"12","author":"Zhang","year":"2018","unstructured":"Zhang HDMa YJLiu QFYe TZMeng FYZhou YWYu GPYang JPJiang HWang QS, 2018Human erythrocyte lifespan measured by Levitt's CO breath test with newly developed automatic instrument. Journal of Breath Research12 036003. (https:\/\/doi.org\/10.1088\/1752-7163\/aaacf1)"},{"key":"bib117","series-title":"Aging (Albany NY)","first-page":"1962","article-title":"Impact of metabolic syndrome on sex hormones and reproductive function: a meta-analysis of 2923 cases and 14062 controls","volume":"13","author":"Zhou","year":"2020","unstructured":"Zhou LHan LLiu MLu J & Pan S2020Impact of metabolic syndrome on sex hormones and reproductive function: a meta-analysis of 2923 cases and 14062 controls. Aging (Albany NY)131962\u20131971. (https:\/\/doi.org\/10.18632\/aging.202160)"}],"container-title":["Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/joe.bioscientifica.com\/view\/journals\/joe\/258\/3\/JOE-22-0223.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/joe.bioscientifica.com\/view\/journals\/joe\/258\/3\/JOE-22-0223.xml","content-type":"text\/html","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/joe.bioscientifica.com\/view\/journals\/joe\/258\/3\/JOE-22-0223.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:57:46Z","timestamp":1784555866000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/joe\/article\/5578"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,25]]},"references-count":120,"journal-issue":{"issue":"3"},"URL":"https:\/\/doi.org\/10.1530\/joe-22-0223","relation":{},"ISSN":["0022-0795","1479-6805"],"issn-type":[{"value":"0022-0795","type":"print"},{"value":"1479-6805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,25]]}}}