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Review

Aging and sex hormones in males

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Pages 545-570 | Received 13 May 2016, Accepted 07 Nov 2016, Published online: 18 Dec 2016

References

  • Veldhuis JD. Changes in pituitary function with ageing and implications for patient care. Nat Rev Endocrinol 2013; 9:205-15; PMID:23438832; https://doi.org/10.1038/nrendo.2013.38
  • Al-Safi Z, Santoro N. The Postmenopausal Woman. In: De Groot LJ, Beck-Peccoz P, Chrousos G, Dungan K, Grossman A, Hershman JM, Koch C, McLachlan R, New M, Rebar R, et al., eds. Endotext. South Dartmouth MA: MDText.com, Inc., 2000.
  • Wu FC, Tajar A, Beynon JM, Pye SR, Silman AJ, Finn JD, O'Neill TW, Bartfai G, Casanueva FF, Forti G, et al. Identification of late-onset hypogonadism in middle-aged and elderly men. N Engl J Med 2010; 363:123-35; PMID:20554979; https://doi.org/10.1056/NEJMoa0911101
  • Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metabolism 2001; 86:724-31; https://doi.org/10.1210/jcem.86.2.7219
  • Kaufman JM, Vermeulen A. The decline of androgen levels in elderly men and its clinical and therapeutic implications. Endocr Rev 2005; 26:833-76; PMID:15901667; https://doi.org/10.1210/er.2004-0013
  • Zmuda JM, Cauley JA, Kriska A, Glynn NW, Gutai JP, Kuller LH. Longitudinal relation between endogenous testosterone and cardiovascular disease risk factors in middle-aged men. A 13-year follow-up of former Multiple Risk Factor Intervention Trial participants. Am J Epidemiol 1997; 146:609-17; PMID:9345114; https://doi.org/10.1093/oxfordjournals.aje.a009326
  • Vermeulen A, Kaufman JM, Giagulli VA. Influence of some biological indexes on sex hormone-binding globulin and androgen levels in aging or obese males. J Clin Endocrinol Metabol 1996; 81:1821-6.
  • Araujo AB, O'Donnell AB, Brambilla DJ, Simpson WB, Longcope C, Matsumoto AM, McKinlay JB. Prevalence and incidence of androgen deficiency in middle-aged and older men: estimates from the Massachusetts Male Aging Study. J Clin Endocrinol Metabol 2004; 89:5920-6; https://doi.org/10.1210/jc.2003-031719
  • Mulligan T, Frick MF, Zuraw QC, Stemhagen A, McWhirter C. Prevalence of hypogonadism in males aged at least 45 years: the HIM study. Int J Clin Pract 2006; 60:762-9; PMID:16846397; https://doi.org/10.1111/j.1742-1241.2006.00992.x
  • Schneider HJ, Sievers C, Klotsche J, Bohler S, Pittrow D, Lehnert H, Wittchen HU, Stalla GK. Prevalence of low male testosterone levels in primary care in Germany: cross-sectional results from the DETECT study. Clin Endocrinol 2009; 70:446-54; https://doi.org/10.1111/j.1365-2265.2008.03370.x
  • Handelsman DJ. Androgen Physiology, Pharmacology and Abuse. In: De Groot LJ, Beck-Peccoz P, Chrousos G, Dungan K, Grossman A, Hershman JM, Koch C, McLachlan R, New M, Rebar R, et al., eds. Endotext. South Dartmouth MA: MDText.com, Inc., 2000.
  • Wang C, Nieschlag E, Swerdloff R, Behre HM, Hellstrom WJ, Gooren LJ, Kaufman JM, Legros JJ, Lunenfeld B, Morales A, et al. Investigation, treatment, and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA, and ASA recommendations. J Androl 2009; 30:1-9; PMID:18772485; https://doi.org/10.2164/jandrol.108.006486
  • Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metabol 1999; 84:3666-72; https://doi.org/10.1210/jcem.84.10.6079
  • Ly LP, Sartorius G, Hull L, Leung A, Swerdloff RS, Wang C, Handelsman DJ. Accuracy of calculated free testosterone formulae in men. Clin Endocrinol 2010; 73:382-8; https://doi.org/10.1111/j.1365-2265.2010.03804.x
  • Travison TG, Araujo AB, Kupelian V, O'Donnell AB, McKinlay JB. The relative contributions of aging, health, and lifestyle factors to serum testosterone decline in men. J Clin Endocrinol Metabol 2007; 92:549-55; https://doi.org/10.1210/jc.2006-1859
  • Lapauw B, Goemaere S, Zmierczak H, Van Pottelbergh I, Mahmoud A, Taes Y, De Bacquer D, Vansteelandt S, Kaufman JM. The decline of serum testosterone levels in community-dwelling men over 70 years of age: descriptive data and predictors of longitudinal changes. Eur J Endocrinol/Eur Federat Endocrine Soc 2008; 159:459-68; https://doi.org/10.1530/EJE-07-0873
  • Tajar A, O'Connell MD, Mitnitski AB, O'Neill TW, Searle SD, Huhtaniemi IT, Finn JD, Bartfai G, Boonen S, Casanueva FF, et al. Frailty in relation to variations in hormone levels of the hypothalamic-pituitary-testicular axis in older men: results from the European male aging study. J Am Geriatrics Soc 2011; 59:814-21; https://doi.org/10.1111/j.1532-5415.2011.03398.x
  • Antonio L, Wu FC, O'Neill TW, Pye SR, Carter EL, Finn JD, Rutter MK, Laurent MR, Huhtaniemi IT, Han TS, et al. Associations between sex steroids and the development of metabolic syndrome: a longitudinal study in European men. J Clin Endocrinol Metabol 2015; 100:1396-404; https://doi.org/10.1210/jc.2014-4184
  • Brand JS, Rovers MM, Yeap BB, Schneider HJ, Tuomainen TP, Haring R, Corona G, Onat A, Maggio M, Bouchard C, et al. Testosterone, sex hormone-binding globulin and the metabolic syndrome in men: an individual participant data meta-analysis of observational studies. PloS One 2014; 9:e100409; PMID:25019163; https://doi.org/10.1371/journal.pone.0100409
  • Corona G, Rastrelli G, Monami M, Saad F, Luconi M, Lucchese M, Facchiano E, Sforza A, Forti G, Mannucci E, et al. Body weight loss reverts obesity-associated hypogonadotropic hypogonadism: a systematic review and meta-analysis. Eur J Endocrinol/Euro Federat Endocrine Soc 2013; 168:829-43; https://doi.org/10.1530/EJE-12-0955
  • Palmer BF, Clegg DJ. Gonadal dysfunction in chronic kidney disease. Rev Endoc Metab Dis 2016.
  • Karagiannis A, Harsoulis F. Gonadal dysfunction in systemic diseases. Eur J Endocrinol/Euro Federat Endocrine Soc 2005; 152:501-13; https://doi.org/10.1530/eje.1.01886
  • Simoni MFF, Roli L, Pagotto U. Methodology for measuring testosterone, dihydrotestosterone and sex hormone-binding globulin in a clinical setting. In: Behre ENHM, ed. Testosterone Action, Deficiency, Substitution. Cambridge, UK: Cambridge University Press, 2012:60-86.
  • Winters SJ. Laboratory Assessment of Testicular Function. In: De Groot LJ, Beck-Peccoz P, Chrousos G, Dungan K, Grossman A, Hershman JM, Koch C, McLachlan R, New M, Rebar R, et al., eds. Endotext. South Dartmouth MA: MDText.com, Inc., 2000.
  • Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, Montori VM. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metabol 2010; 95:2536-59; https://doi.org/10.1210/jc.2009-2354
  • Wang Y, Gay GD, Botelho JC, Caudill SP, Vesper HW. Total testosterone quantitative measurement in serum by LC-MS/MS. Clinica Chimica Acta; Int J Clin Chem 2014; 436:263-7; PMID:24960363; https://doi.org/10.1016/j.cca.2014.06.009
  • Wang C, Catlin DH, Demers LM, Starcevic B, Swerdloff RS. Measurement of total serum testosterone in adult men: comparison of current laboratory methods versus liquid chromatography-tandem mass spectrometry. J Clin Endocrinol Metabol 2004; 89:534-43; https://doi.org/10.1210/jc.2003-031287
  • Fanelli F, Belluomo I, Di Lallo VD, Cuomo G, De Iasio R, Baccini M, Casadio E, Casetta B, Vicennati V, Gambineri A, et al. Serum steroid profiling by isotopic dilution-liquid chromatography-mass spectrometry: comparison with current immunoassays and reference intervals in healthy adults. Steroids 2011; 76:244-53; PMID:21112348; https://doi.org/10.1016/j.steroids.2010.11.005
  • Rosner W, Auchus RJ, Azziz R, Sluss PM, Raff H. Position statement: utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society position statement. J Clin Endocrinol Metabol 2007; 92:405-13; https://doi.org/10.1210/jc.2006-1864
  • Rosner W, Vesper H. Toward excellence in testosterone testing: a consensus statement. J Clin Endocrinol Metabol 2010; 95:4542-8; https://doi.org/10.1210/jc.2010-1314
  • Ketha H, Kaur S, Grebe SK, Singh RJ. Clinical applications of LC-MS sex steroid assays: evolution of methodologies in the 21st century. Curr Opin Endocrinol, Diab Obes 2014; 21:217-26; PMID:24739314; https://doi.org/10.1097/MED.0000000000000068
  • Huhtaniemi IT, Tajar A, Lee DM, O'Neill TW, Finn JD, Bartfai G, Boonen S, Casanueva FF, Giwercman A, Han TS, et al. Comparison of serum testosterone and estradiol measurements in 3174 European men using platform immunoassay and mass spectrometry; relevance for the diagnostics in aging men. Euro J Endocrinol/ Euro Federat Endocrine Soc 2012; 166:983-91; https://doi.org/10.1530/EJE-11-1051
  • Morales A, Bebb RA, Manjoo P, Assimakopoulos P, Axler J, Collier C, Elliott S, Goldenberg L, Gottesman I, Grober ED, et al. Diagnosis and management of testosterone deficiency syndrome in men: clinical practice guideline. CMAJ: Canadian Med Assoc J = J de l'Assoc Med Canadienne 2015; 187:1369-77; PMID:26504097; https://doi.org/10.1503/cmaj.150033
  • Bremner WJ, Vitiello MV, Prinz PN. Loss of circadian rhythmicity in blood testosterone levels with aging in normal men. J Clin Endocrinol Metabol 1983; 56:1278-81; https://doi.org/10.1210/jcem-56-6-1278
  • Brambilla DJ, O'Donnell AB, Matsumoto AM, McKinlay JB. Intraindividual variation in levels of serum testosterone and other reproductive and adrenal hormones in men. Clin Endocrinol 2007; 67:853-62; PMID:18052942; https://doi.org/10.1111/j.1365-2265.2007.02976.x
  • Gonzalez-Sales M, Barriere O, Tremblay PO, Nekka F, Desrochers J, Tanguay M. Modeling testosterone circadian rhythm in hypogonadal males: effect of age and circannual variations. AAPS J 2016; 18:217-27; PMID:26553482; https://doi.org/10.1208/s12248-015-9841-6
  • Feldman HA, Longcope C, Derby CA, Johannes CB, Araujo AB, Coviello AD, Bremner WJ, McKinlay JB. Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male aging study. J Clin Endocrinol Metabol 2002; 87:589-98; https://doi.org/10.1210/jcem.87.2.8201
  • Huhtaniemi I. Late-onset hypogonadism: current concepts and controversies of pathogenesis, diagnosis and treatment. Asian J Androl 2014; 16:192-202; PMID:24407185; https://doi.org/10.4103/1008-682X.122336
  • Corona G, Rastrelli G, Vignozzi L, Mannucci E, Maggi M. How to recognize late-onset hypogonadism in men with sexual dysfunction. Asian J Androl 2012; 14:251-9; PMID:22286862; https://doi.org/10.1038/aja.2011.138
  • Corona G, Maseroli E, Rastrelli G, Francomano D, Aversa A, Hackett G, Ferri S, Sforza A, Maggi M. Is late-onset hypogonadotropic hypogonadism a specific age-dependent disease, or merely an epiphenomenon caused by accumulating disease-burden? Focusing on metabolic diseases. Minerva Endocrinol 2016; PMID:26883937
  • Rodriguez A, Muller DC, Metter EJ, Maggio M, Harman SM, Blackman MR, Andres R. Aging, androgens, and the metabolic syndrome in a longitudinal study of aging. J Clin Endocrinol Metabol 2007; 92:3568-72; https://doi.org/10.1210/jc.2006-2764
  • Rochira V, Kara E, Carani C. The endocrine role of estrogens on human male skeleton. Int J Endocrinol 2015; 2015:165215; PMID:25873947; https://doi.org/10.1155/2015/165215
  • Mellstrom D, Vandenput L, Mallmin H, Holmberg AH, Lorentzon M, Oden A, Johansson H, Orwoll ES, Labrie F, Karlsson MK, et al. Older men with low serum estradiol and high serum SHBG have an increased risk of fractures. J Bone Mineral Res: Off J Am Soc Bone Min Res 2008; 23:1552-60; PMID:18518773; https://doi.org/10.1359/jbmr.080518
  • Rochira V, Zirilli L, Genazzani AD, Balestrieri A, Aranda C, Fabre B, Antunez P, Diazzi C, Carani C, Maffei L. Hypothalamic-pituitary-gonadal axis in two men with aromatase deficiency: evidence that circulating estrogens are required at the hypothalamic level for the integrity of gonadotropin negative feedback. Euro J Endocrinol/ Eur Federat Endocrine Soc 2006; 155:513-22; https://doi.org/10.1530/eje.1.02254
  • Finkelstein JS, Lee H, Burnett-Bowie SA, Pallais JC, Yu EW, Borges LF, Jones BF, Barry CV, Wulczyn KE, Thomas BJ, et al. Gonadal steroids and body composition, strength, and sexual function in men. N Engl J Med 2013; 369:1011-22; PMID:24024838; https://doi.org/10.1056/NEJMoa1206168
  • Carani C, Rochira V, Faustini-Fustini M, Balestrieri A, Granata AR. Role of oestrogen in male sexual behaviour: insights from the natural model of aromatase deficiency. Clin Endocrinol 1999; 51:517-24; PMID:10583321; https://doi.org/10.1046/j.1365-2265.1999.00849.x
  • Cunningham GR, Stephens-Shields AJ, Rosen RC, Wang C, Ellenberg SS, Matsumoto AM, Bhasin S, Molitch ME, Farrar JT, Cella D, et al. Association of sex hormones with sexual function, vitality, and physical function of symptomatic older men with low testosterone levels at baseline in the testosterone trials. J Clin Endocrinol Metabol 2015; 100:1146-55; https://doi.org/10.1210/jc.2014-3818
  • Rochira V, Balestrieri A, Madeo B, Zirilli L, Granata AR, Carani C. Osteoporosis and male age-related hypogonadism: role of sex steroids on bone (patho)physiology. Euro J Endocrinol / Euro Federat Endocrine Soc 2006; 154:175-85; https://doi.org/10.1530/eje.1.02088
  • Buvat J, Maggi M, Guay A, Torres LO. Testosterone deficiency in men: systematic review and standard operating procedures for diagnosis and treatment. J Sex Med 2013; 10:245-84; PMID:22971200; https://doi.org/10.1111/j.1743-6109.2012.02783.x
  • Rochira V, Guaraldi G. Hypogonadism in the HIV-infected man. Endocrinol Metab Clin North Am 2014; 43:709-30; PMID:25169563; https://doi.org/10.1016/j.ecl.2014.06.005
  • Rosner W, Hankinson SE, Sluss PM, Vesper HW, Wierman ME. Challenges to the measurement of estradiol: an endocrine society position statement. J Clin Endocrinol Metabol 2013; 98:1376-87; https://doi.org/10.1210/jc.2012-3780
  • Morley JE, Kaiser FE, Perry HM, 3rd, Patrick P, Morley PM, Stauber PM, Vellas B, Baumgartner RN, Garry PJ. Longitudinal changes in testosterone, luteinizing hormone, and follicle-stimulating hormone in healthy older men. Metabol: Clin Exp 1997; 46:410-3; PMID:9109845; https://doi.org/10.1016/S0026-0495(97)90057-3
  • Gray A, Feldman HA, McKinlay JB, Longcope C. Age, disease, and changing sex hormone levels in middle-aged men: results of the Massachusetts Male Aging Study. J. Clin. Endocrinol. Metabol. 1991; 73:1016-25; https://doi.org/10.1210/jcem-73-5-1016
  • Gray A, Berlin JA, McKinlay JB, Longcope C. An examination of research design effects on the association of testosterone and male aging: results of a meta-analysis. J Clin Epidemiol 1991; 44:671-84; PMID:1829756; https://doi.org/10.1016/0895-4356(91)90028-8
  • Deslypere JP, Vermeulen A. Leydig cell function in normal men: effect of age, life-style, residence, diet, and activity. J Clin Endocrinol Metabol 1984; 59:955-62; https://doi.org/10.1210/jcem-59-5-955
  • Baker HW, Burger HG, de Kretser DM, Hudson B, O'Connor S, Wang C, Mirovics A, Court J, Dunlop M, Rennie GC. Changes in the pituitary-testicular system with age. Clin Endocrinol 1976; 5:349-72; PMID:971543; https://doi.org/10.1111/j.1365-2265.1976.tb01964.x
  • Seftel AD. Male hypogonadism. Part I: epidemiology of hypogonadism. Int J Impot Res 2006; 18:115-20.
  • Stone JL, Norris AH. Activities and attitudes of participants in the Baltimore longitudinal study. J Gerontol 1966; 21:575-80; PMID:5918312; https://doi.org/10.1093/geronj/21.4.575
  • Greendale GA, Edelstein S, Barrett-Connor E. Endogenous sex steroids and bone mineral density in older women and men: the Rancho Bernardo Study. J Bone Min Res: Off J Am Soc Bone Min Res 1997; 12:1833-43; PMID:9383688; https://doi.org/10.1359/jbmr.1997.12.11.1833
  • Bjornerem A, Straume B, Midtby M, Fonnebo V, Sundsfjord J, Svartberg J, Acharya G, Oian P, Berntsen GK. Endogenous sex hormones in relation to age, sex, lifestyle factors, and chronic diseases in a general population: the Tromso Study. J Clin Endocrinol Metabol 2004; 89:6039-47; https://doi.org/10.1210/jc.2004-0735
  • Mohr BA, Guay AT, O'Donnell AB, McKinlay JB. Normal, bound and nonbound testosterone levels in normally ageing men: results from the Massachusetts Male Ageing Study. Clin Endocrinol 2005; 62:64-73; PMID:15638872; https://doi.org/10.1111/j.1365-2265.2004.02174.x
  • Orwoll E, Blank JB, Barrett-Connor E, Cauley J, Cummings S, Ensrud K, Lewis C, Cawthon PM, Marcus R, Marshall LM, et al. Design and baseline characteristics of the osteoporotic fractures in men (MrOS) study–a large observational study of the determinants of fracture in older men. Contemp Clin Trials 2005; 26:569-85; PMID:16084776; https://doi.org/10.1016/j.cct.2005.05.006
  • Lee DM, O'Neill TW, Pye SR, Silman AJ, Finn JD, Pendleton N, Tajar A, Bartfai G, Casanueva F, Forti G, et al. The European Male Ageing Study (EMAS): design, methods and recruitment. Int J Androl 2009; 32:11-24; PMID:18328041; https://doi.org/10.1111/j.1365-2605.2008.00879.x
  • Lee DM, Pye SR, Tajar A, O'Neill TW, Finn JD, Boonen S, Bartfai G, Casanueva FF, Forti G, Giwercman A, et al. Cohort profile: the European male ageing study. Int J Epidemiol 2013; 42:391-401; PMID:22314965; https://doi.org/10.1093/ije/dyr234
  • Barrett-Connor E. The Rancho Bernardo Study: 40 years studying why women have less heart disease than men and how diabetes modifies women's usual cardiac protection. Global heart 2013; 8; PMID:24187655; https://doi.org/10.1016/j.gheart.2012.12.002
  • Maggio M, Lauretani F, Ceda GP, Bandinelli S, Ling SM, Metter EJ, Artoni A, Carassale L, Cazzato A, Ceresini G, et al. Relationship between low levels of anabolic hormones and 6-year mortality in older men: the aging in the Chianti Area (InCHIANTI) study. Arch Int Med 2007; 167:2249-54; PMID:17998499; https://doi.org/10.1001/archinte.167.20.2249
  • Maggio M, Lauretani F, Ceda GP, Bandinelli S, Basaria S, Paolisso G, Giumelli C, Luci M, Najjar SS, Metter EJ, et al. Estradiol and metabolic syndrome in older italian men: the InCHIANTI Study. J Androl 2010; 31:155-62; PMID:19059904; https://doi.org/10.2164/jandrol.108.006098
  • Maggio M, Lauretani F, Ceda GP, Bandinelli S, Basaria S, Ble A, Egan J, Paolisso G, Najjar S, Jeffrey Metter E, et al. Association between hormones and metabolic syndrome in older Italian men. Journal of the American Geriatrics Society 2006; 54:1832-8; PMID:17198487; https://doi.org/10.1111/j.1532-5415.2006.00963.x
  • Maggio M, Ceda GP, Lauretani F, Bandinelli S, Metter EJ, Guralnik JM, Basaria S, Cattabiani C, Luci M, Dall'Aglio E, et al. Gonadal status and physical performance in older men. Aging Male: Off J Int Soc Study Aging Male 2011; 14:42-7; PMID:20937007; https://doi.org/10.3109/13685538.2010.518179
  • Maggio M, Cattabiani C, Lauretani F, Artoni A, Bandinelli S, Schiavi G, Vignali A, Volpi R, Ceresini G, Lippi G, et al. The relationship between sex hormones, sex hormone binding globulin and peripheral artery disease in older persons. Atherosclerosis 2012; 225:469-74; PMID:23102785; https://doi.org/10.1016/j.atherosclerosis.2012.09.014
  • Bjornerem A, Emaus N, Berntsen GK, Joakimsen RM, Fonnebo V, Wilsgaard T, Oian P, Seeman E, Straume B. Circulating sex steroids, sex hormone-binding globulin, and longitudinal changes in forearm bone mineral density in postmenopausal women and men: the Tromso study. Calcified Tissue Int 2007; 81:65-72; PMID:17612780; https://doi.org/10.1007/s00223-007-9035-z
  • Bjornerem A, Ahmed LA, Joakimsen RM, Berntsen GK, Fonnebo V, Jorgensen L, Oian P, Seeman E, Straume B. A prospective study of sex steroids, sex hormone-binding globulin, and non-vertebral fractures in women and men: the Tromso Study. Euro Endocrinol / Euro Federat Endocrine Soc 2007; 157:119-25; https://doi.org/10.1530/EJE-07-0032
  • Cumming RG, Handelsman D, Seibel MJ, Creasey H, Sambrook P, Waite L, Naganathan V, Le Couteur D, Litchfield M. Cohort profile: the concord health and ageing in Men project (CHAMP). Int J Epidemiol 2009; 38:374-8; PMID:18480109; https://doi.org/10.1093/ije/dyn071
  • Hsu B, Cumming RG, Blyth FM, Naganathan V, Le Couteur DG, Seibel MJ, Waite LM, Handelsman DJ. The longitudinal relationship of sexual function and androgen status in older men: the Concord Health and Ageing in Men Project. J Clin Endocrinol Metabol 2015; 100:1350-8; https://doi.org/10.1210/jc.2014-4104
  • Hsu B, Cumming RG, Blyth FM, Naganathan V, Le Couteur DG, Seibel MJ, Waite LM, Handelsman DJ. Longitudinal and cross-sectional relationships of circulating reproductive hormone levels to self-rated health and health-related quality of life in community-dwelling older men. J Clin Endocrinol Metabol 2014; 99:1638-47; https://doi.org/10.1210/jc.2013-3984
  • Hsu B, Cumming RG, Naganathan V, Blyth FM, Le Couteur DG, Seibel MJ, Waite LM, Handelsman DJ. Associations between circulating reproductive hormones and SHBG and prevalent and incident metabolic syndrome in community-dwelling older men: the Concord Health and Ageing in Men Project. J Clin Endocrinol Metabol 2014; 99:E2686-91; https://doi.org/10.1210/jc.2014-2464
  • Hsu B, Cumming RG, Hirani V, Blyth FM, Naganathan V, Le Couteur DG, Seibel MJ, Waite LM, Handelsman DJ. Temporal trend in androgen status and androgen-sensitive outcomes in older Men. J Clin Endocrinol Metabol 2016; 101:1836-46; https://doi.org/10.1210/jc.2015-3810
  • Norman PE, Flicker L, Almeida OP, Hankey GJ, Hyde Z, Jamrozik K. Cohort profile: the health in Men study (HIMS). Int J Epidemiol 2009; 38:48-52; PMID:18316347; https://doi.org/10.1093/ije/dyn041
  • Fabbri E, An Y, Gonzalez-Freire M, Zoli M, Maggio M, Studenski SA, Egan JM, Chia CW, Ferrucci L. Bioavailable testosterone linearly declines over a wide age spectrum in Men and Women from the baltimore longitudinal study of aging. J Gerontol A Biol Sci Med Sci 2016.
  • Ferrini RL, Barrett-Connor E. Sex hormones and age: a cross-sectional study of testosterone and estradiol and their bioavailable fractions in community-dwelling men. Am J Epidemiol 1998; 147:750-4; PMID:9554416; https://doi.org/10.1093/oxfordjournals.aje.a009519
  • Hsu B, Cumming RG, Naganathan V, Blyth FM, Le Couteur DG, Hirani V, Waite LM, Seibel MJ, Handelsman DJ. Temporal changes in androgens and estrogens are associated with all-cause and cause-specific mortality in older Men. J Clin Endocrinol Metabol 2016; 101:2201-10; https://doi.org/10.1210/jc.2016-1025
  • Camacho EM, Huhtaniemi IT, O'Neill TW, Finn JD, Pye SR, Lee DM, Tajar A, Bartfai G, Boonen S, Casanueva FF, et al. Age-associated changes in hypothalamic-pituitary-testicular function in middle-aged and older men are modified by weight change and lifestyle factors: longitudinal results from the European Male Ageing Study. Euro J Endocrinol / Euro Federat Endocrine Soc 2013; 168:445-55; https://doi.org/10.1530/EJE-12-0890
  • Antonio L, Wu FC, O'Neill TW, Pye SR, Ahern TB, Laurent MR, Huhtaniemi IT, Lean ME, Keevil BG, Rastrelli G, et al. Low free testosterone is associated with hypogonadal signs and symptoms in Men with normal total testosterone. J Clin Endocrinol Metabol 2016:jc20154106.
  • Yeap BB, Almeida OP, Hyde Z, Norman PE, Chubb SA, Jamrozik K, Flicker L. In men older than 70 years, total testosterone remains stable while free testosterone declines with age. The Health Men Study. Euro J Endocrinol / Euro Federat Endocrine Soc 2007; 156:585-94; https://doi.org/10.1530/EJE-06-0714
  • Oh JY, Barrett-Connor E, Wedick NM, Wingard DL. Endogenous sex hormones and the development of type 2 diabetes in older men and women: the Rancho Bernardo study. Diab Care 2002; 25:55-60; PMID:11772901; https://doi.org/10.2337/diacare.25.1.55
  • Mellstrom D, Johnell O, Ljunggren O, Eriksson AL, Lorentzon M, Mallmin H, Holmberg A, Redlund-Johnell I, Orwoll E, Ohlsson C. Free testosterone is an independent predictor of BMD and prevalent fractures in elderly men: MrOS Sweden. J Bone Mineral Res: Off J Am Soc Bone Min Res 2006; 21:529-35; PMID:16598372; https://doi.org/10.1359/jbmr.060110
  • Cauley JA, Ewing SK, Taylor BC, Fink HA, Ensrud KE, Bauer DC, Barrett-Connor E, Marshall L, Orwoll ES. Sex steroid hormones in older men: longitudinal associations with 4.5-year change in hip bone mineral density–the osteoporotic fractures in men study. J Clin Endocrinol Metabol 2010; 95:4314-23; https://doi.org/10.1210/jc.2009-2635
  • Cawthon PM, Schousboe JT, Harrison SL, Ensrud KE, Black D, Cauley JA, Cummings SR, LeBlanc ES, Laughlin GA, Nielson CM, et al. Sex hormones, sex hormone binding globulin, and vertebral fractures in older men. Bone 2016; 84:271-8; PMID:26778261; https://doi.org/10.1016/j.bone.2016.01.009
  • Tajar A, Huhtaniemi IT, O'Neill TW, Finn JD, Pye SR, Lee DM, Bartfai G, Boonen S, Casanueva FF, Forti G, et al. Characteristics of androgen deficiency in late-onset hypogonadism: results from the European Male Aging Study (EMAS). J Clin Endocrinol Metabol 2012; 97:1508-16; https://doi.org/10.1210/jc.2011-2513
  • Tajar A, Forti G, O'Neill TW, Lee DM, Silman AJ, Finn JD, Bartfai G, Boonen S, Casanueva FF, Giwercman A, et al. Characteristics of secondary, primary, and compensated hypogonadism in aging men: evidence from the European Male Ageing Study. J Clin Endocrinol Metabol 2010; 95:1810-8; https://doi.org/10.1210/jc.2009-1796
  • Svartberg J, Midtby M, Bonaa KH, Sundsfjord J, Joakimsen RM, Jorde R. The associations of age, lifestyle factors and chronic disease with testosterone in men: the Tromso Study. Euro J Endocrinol / Euro Federat Endocrine Soc 2003; 149:145-52; https://doi.org/10.1530/eje.0.1490145
  • O'Connor DB, Lee DM, Corona G, Forti G, Tajar A, O'Neill TW, Pendleton N, Bartfai G, Boonen S, Casanueva FF, et al. The relationships between sex hormones and sexual function in middle-aged and older European men. J Clin Endocrinol Metabol 2011; 96:E1577-87; https://doi.org/10.1210/jc.2010-2216
  • Kupelian V, Shabsigh R, Travison TG, Page ST, Araujo AB, McKinlay JB. Is there a relationship between sex hormones and erectile dysfunction? Results from the Massachusetts Male Aging Study. J Urol 2006; 176:2584-8; PMID:17085164; https://doi.org/10.1016/j.juro.2006.08.020
  • Hall SA, Shackelton R, Rosen RC, Araujo AB. Risk factors for incident erectile dysfunction among community-dwelling men. J Sex Med 2010; 7:712-22; PMID:19929915; https://doi.org/10.1111/j.1743-6109.2009.01600.x
  • Pye SR, Huhtaniemi IT, Finn JD, Lee DM, O'Neill TW, Tajar A, Bartfai G, Boonen S, Casanueva FF, Forti G, et al. Late-onset hypogonadism and mortality in aging men. J Clin Endocrinol Metabol 2014; 99:1357-66; https://doi.org/10.1210/jc.2013-2052
  • Travison TG, Morley JE, Araujo AB, O'Donnell AB, McKinlay JB. The relationship between libido and testosterone levels in aging men. J Clin Endocrinol Metabol 2006; 91:2509-13; https://doi.org/10.1210/jc.2005-2508
  • LeBlanc ES, Wang PY, Janowsky JS, Neiss MB, Fink HA, Yaffe K, Marshall LM, Lapidus JA, Stefanick ML, Orwoll ES. Association between sex steroids and cognition in elderly men. Clin Endocrinol 2010; 72:393-403; PMID:19744108; https://doi.org/10.1111/j.1365-2265.2009.03692.x
  • Mohr BA, Bhasin S, Link CL, O'Donnell AB, McKinlay JB. The effect of changes in adiposity on testosterone levels in older men: longitudinal results from the Massachusetts Male Aging Study. Euro J Endocrinol / Euro Federat Endocrine Soc 2006; 155:443-52; https://doi.org/10.1530/eje.1.02241
  • Derby CA, Zilber S, Brambilla D, Morales KH, McKinlay JB. Body mass index, waist circumference and waist to hip ratio and change in sex steroid hormones: the Massachusetts Male Ageing Study. Clin Endocrinol 2006; 65:125-31; PMID:16817831; https://doi.org/10.1111/j.1365-2265.2006.02560.x
  • Wu FC, Tajar A, Pye SR, Silman AJ, Finn JD, O'Neill TW, Bartfai G, Casanueva F, Forti G, Giwercman A, et al. Hypothalamic-pituitary-testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: the European Male Aging Study. J Clin Endocrinol Metabol 2008; 93:2737-45; https://doi.org/10.1210/jc.2007-1972
  • Vikan T, Schirmer H, Njolstad I, Svartberg J. Low testosterone and sex hormone-binding globulin levels and high estradiol levels are independent predictors of type 2 diabetes in men. European journal of endocrinology; European Federation of Endocrine Societies 2010; 162:747-54
  • Svartberg J, Jenssen T, Sundsfjord J, Jorde R. The associations of endogenous testosterone and sex hormone-binding globulin with glycosylated hemoglobin levels, in community dwelling men. Tromso Study. Diab Metab 2004; 30:29-34; https://doi.org/10.1016/S1262-3636(07)70086-1
  • Agledahl I, Skjaerpe PA, Hansen JB, Svartberg J. Low serum testosterone in men is inversely associated with non-fasting serum triglycerides: the Tromso study. Nutrit Metab Cardiovasc Dis: NMCD 2008; 18:256-62; PMID:17560771; https://doi.org/10.1016/j.numecd.2007.01.014
  • Kupelian V, Page ST, Araujo AB, Travison TG, Bremner WJ, McKinlay JB. Low sex hormone-binding globulin, total testosterone, and symptomatic androgen deficiency are associated with development of the metabolic syndrome in nonobese men. J. Clin. Endocrinol. Metabol. 2006; 91:843-50; https://doi.org/10.1210/jc.2005-1326
  • Barrett-Connor E. Lower endogenous androgen levels and dyslipidemia in men with non-insulin-dependent diabetes mellitus. Annals of internal medicine 1992; 117:807-11; PMID:1416554; https://doi.org/10.7326/0003-4819-117-10-807
  • Barrett-Connor E, Von Muhlen DG, Kritz-Silverstein D. Bioavailable testosterone and depressed mood in older men: the Rancho Bernardo Study. J. Clin. Endocrinol. Metabol. 1999; 84:573-7; https://doi.org/10.1210/jcem.84.2.5495
  • Stellato RK, Feldman HA, Hamdy O, Horton ES, McKinlay JB. Testosterone, sex hormone-binding globulin, and the development of type 2 diabetes in middle-aged men: prospective results from the Massachusetts male aging study. Diabetes care 2000; 23:490-4; PMID:10857940; https://doi.org/10.2337/diacare.23.4.490
  • Chubb SA, Hyde Z, Almeida OP, Flicker L, Norman PE, Jamrozik K, Hankey GJ, Yeap BB. Lower sex hormone-binding globulin is more strongly associated with metabolic syndrome than lower total testosterone in older men: the Health in Men Study. Euro J Endocrinol / Euro Federat Endocrine Soc 2008; 158:785-92; https://doi.org/10.1530/EJE-07-0893
  • Yeap BB, Almeida OP, Hyde Z, Norman PE, Chubb SA, Jamrozik K, Hankey GJ, Flicker L. Healthier lifestyle predicts higher circulating testosterone in older men: the Health In Men Study. Clin Endocrinol 2009; 70:455-63; PMID:18691270; https://doi.org/10.1111/j.1365-2265.2008.03372.x
  • Svartberg J, von Muhlen D, Schirmer H, Barrett-Connor E, Sundfjord J, Jorde R. Association of endogenous testosterone with blood pressure and left ventricular mass in men. The Tromso Study. Euro J Endocrinol / Euro Federat Endocrine Soc 2004; 150:65-71; https://doi.org/10.1530/eje.0.1500065
  • Svartberg J, von Muhlen D, Mathiesen E, Joakimsen O, Bonaa KH, Stensland-Bugge E. Low testosterone levels are associated with carotid atherosclerosis in men. J Int Med 2006; 259:576-82; PMID:16704558; https://doi.org/10.1111/j.1365-2796.2006.01637.x
  • Vikan T, Johnsen SH, Schirmer H, Njolstad I, Svartberg J. Endogenous testosterone and the prospective association with carotid atherosclerosis in men: the Tromso study. Euro J Epidemiol 2009; 24:289-95; PMID:19263227; https://doi.org/10.1007/s10654-009-9322-2
  • Hougaku H, Fleg JL, Najjar SS, Lakatta EG, Harman SM, Blackman MR, Metter EJ. Relationship between androgenic hormones and arterial stiffness, based on longitudinal hormone measurements. Am J Physiol Endocrinol Metab 2006; 290:E234-42; PMID:16159908; https://doi.org/10.1152/ajpendo.00059.2005
  • Ohlsson C, Barrett-Connor E, Bhasin S, Orwoll E, Labrie F, Karlsson MK, Ljunggren O, Vandenput L, Mellstrom D, Tivesten A. High serum testosterone is associated with reduced risk of cardiovascular events in elderly men. The MrOS (Osteoporotic Fractures in Men) study in Sweden. J Am College Card 2011; 58:1674-81; https://doi.org/10.1016/j.jacc.2011.07.019
  • Khaw KT, Barrett-Connor E. Blood pressure and endogenous testosterone in men: an inverse relationship. J Hypertension 1988; 6:329-32; PMID:3379300; https://doi.org/10.1097/00004872-198804000-00010
  • Svartberg J, Jorde R. Endogenous testosterone levels and smoking in men. The fifth Tromso study. Int J Androl 2007; 30:137-43; https://doi.org/10.1111/j.1365-2605.2006.00720.x
  • LeBlanc ES, Nielson CM, Marshall LM, Lapidus JA, Barrett-Connor E, Ensrud KE, Hoffman AR, Laughlin G, Ohlsson C, Orwoll ES. The effects of serum testosterone, estradiol, and sex hormone binding globulin levels on fracture risk in older men. J Clin Endocrinol Metabol 2009; 94:3337-46; https://doi.org/10.1210/jc.2009-0206
  • Vanderschueren D, Pye SR, Venken K, Borghs H, Gaytant J, Huhtaniemi IT, Adams JE, Ward KA, Bartfai G, Casanueva FF, et al. Gonadal sex steroid status and bone health in middle-aged and elderly European men. Osteoporos Int 2010; 21:1331-9; PMID:20012940; https://doi.org/10.1007/s00198-009-1144-2
  • Laughlin GA, Barrett-Connor E, Bergstrom J. Low serum testosterone and mortality in older men. J Clin Endocrinol Metabol 2008; 93:68-75; https://doi.org/10.1210/jc.2007-1792
  • Barrett-Connor E, Laughlin GA, Li H, Nielson CM, Wang PY, Dam TT, Cauley JA, Ensrud KE, Stefanick ML, Lau E, et al. The association of concurrent vitamin D and sex hormone deficiency with bone loss and fracture risk in older men: the osteoporotic fractures in men (MrOS) study. J Bone Min Res: Off J Am Soc Bone Min Res 2012; 27:2306-13; PMID:22777902; https://doi.org/10.1002/jbmr.1697
  • Ward KA, Pye SR, Adams JE, Boonen S, Vanderschueren D, Borghs H, Gaytant J, Gielen E, Bartfai G, Casanueva FF, et al. Influence of age and sex steroids on bone density and geometry in middle-aged and elderly European men. Osteoporos Int 2011; 22:1513-23; PMID:21052641; https://doi.org/10.1007/s00198-010-1437-5
  • Hsu B, Cumming RG, Seibel MJ, Naganathan V, Blyth FM, Bleicher K, Dave A, Le Couteur DG, Waite LM, Handelsman DJ. Reproductive hormones and longitudinal change in bone mineral density and incident fracture risk in older Men: the concord health and aging in Men project. J Bone Min Res: Off J Am Soc Bone Min Res 2015; 30:1701-8; PMID:25736139; https://doi.org/10.1002/jbmr.2493
  • Roy TA, Blackman MR, Harman SM, Tobin JD, Schrager M, Metter EJ. Interrelationships of serum testosterone and free testosterone index with FFM and strength in aging men. Am J Physiol Endocrinol Metab 2002; 283:E284-94; PMID:12110533; https://doi.org/10.1152/ajpendo.00334.2001
  • Hsu B, Cumming RG, Naganathan V, Blyth FM, Le Couteur DG, Seibel MJ, Waite LM, Handelsman DJ. Longitudinal relationships of circulating reproductive hormone with functional disability, muscle mass, and strength in community-dwelling older men: the Concord Health and Ageing in Men project. J Clin Endocrinol Metabol 2014; 99:3310-8; https://doi.org/10.1210/jc.2014-1124
  • O'Donnell AB, Travison TG, Harris SS, Tenover JL, McKinlay JB. Testosterone, dehydroepiandrosterone, and physical performance in older men: results from the Massachusetts Male Aging Study. J Clin Endocrinol Metabol 2006; 91:425-31; https://doi.org/10.1210/jc.2005-1227
  • LeBlanc ES, Wang PY, Lee CG, Barrett-Connor E, Cauley JA, Hoffman AR, Laughlin GA, Marshall LM, Orwoll ES. Higher testosterone levels are associated with less loss of lean body mass in older men. J Clin Endocrinol Metabol 2011; 96:3855-63; https://doi.org/10.1210/jc.2011-0312
  • Hyde Z, Flicker L, Almeida OP, Hankey GJ, McCaul KA, Chubb SA, Yeap BB. Low free testosterone predicts frailty in older men: the health in men study. J Clin Endocrinol Metabol 2010; 95:3165-72; https://doi.org/10.1210/jc.2009-2754
  • Travison TG, Nguyen AH, Naganathan V, Stanaway FF, Blyth FM, Cumming RG, Le Couteur DG, Sambrook PN, Handelsman DJ. Changes in reproductive hormone concentrations predict the prevalence and progression of the frailty syndrome in older men: the concord health and ageing in men project. J Clin Endocrinol Metabol 2011; 96:2464-74; https://doi.org/10.1210/jc.2011-0143
  • Cawthon PM, Ensrud KE, Laughlin GA, Cauley JA, Dam TT, Barrett-Connor E, Fink HA, Hoffman AR, Lau E, Lane NE, et al. Sex hormones and frailty in older men: the osteoporotic fractures in men (MrOS) study. J Clin Endocrinol Metabol 2009; 94:3806-15; https://doi.org/10.1210/jc.2009-0417
  • Moffat SD, Zonderman AB, Metter EJ, Blackman MR, Harman SM, Resnick SM. Longitudinal assessment of serum free testosterone concentration predicts memory performance and cognitive status in elderly men. J Clin Endocrinol Metabol 2002; 87:5001-7; https://doi.org/10.1210/jc.2002-020419
  • Zonderman AB. Predicting Alzheimer's disease in the Baltimore longitudinal study of aging. J Geriatr Psychiatry Neurol 2005; 18:192-5; PMID:16306238; https://doi.org/10.1177/0891988705281863
  • Moffat SD, Zonderman AB, Metter EJ, Kawas C, Blackman MR, Harman SM, Resnick SM. Free testosterone and risk for Alzheimer disease in older men. Neurology 2004; 62:188-93; PMID:14745052; https://doi.org/10.1212/WNL.62.2.188
  • Barrett-Connor E, Goodman-Gruen D, Patay B. Endogenous sex hormones and cognitive function in older men. J Clin Endocrinol Metabol 1999; 84:3681-5.
  • Yeap BB, Almeida OP, Hyde Z, Chubb SA, Hankey GJ, Jamrozik K, Flicker L. Higher serum free testosterone is associated with better cognitive function in older men, while total testosterone is not. The Health In Men Study. Clin Endocrinol 2008; 68:404-12.
  • Ford AH, Yeap BB, Flicker L, Hankey GJ, Chubb SA, Handelsman DJ, Golledge J, Almeida OP. Prospective longitudinal study of testosterone and incident depression in older men: the health in Men study. Psychoneuroendocrinology 2016; 64:57-65; PMID:26615472; https://doi.org/10.1016/j.psyneuen.2015.11.012
  • Fonda SJ, Bertrand R, O'Donnell A, Longcope C, McKinlay JB. Age, hormones, and cognitive functioning among middle-aged and elderly men: cross-sectional evidence from the Massachusetts Male Aging Study. J Gerontol A Biol Sci Med Sci 2005; 60:385-90; PMID:15860479; https://doi.org/10.1093/gerona/60.3.385
  • Hsu B, Cumming RG, Waite LM, Blyth FM, Naganathan V, Le Couteur DG, Seibel MJ, Handelsman DJ. Longitudinal relationships between reproductive hormones and cognitive decline in older Men: the concord health and ageing in Men project. J Clin Endocrinol Metabol 2015; 100:2223-30; https://doi.org/10.1210/jc.2015-1016
  • Hyde Z, Norman PE, Flicker L, Hankey GJ, Almeida OP, McCaul KA, Chubb SA, Yeap BB. Low free testosterone predicts mortality from cardiovascular disease but not other causes: the Health in Men Study. J Clin Endocrinol Metabol 2012; 97:179-89; https://doi.org/10.1210/jc.2011-1617
  • Araujo AB, Kupelian V, Page ST, Handelsman DJ, Bremner WJ, McKinlay JB. Sex steroids and all-cause and cause-specific mortality in men. Arch Int Med 2007; 167:1252-60; PMID:17592098; https://doi.org/10.1001/archinte.167.12.1252
  • Vikan T, Schirmer H, Njolstad I, Svartberg J. Endogenous sex hormones and the prospective association with cardiovascular disease and mortality in men: the tromso study. Euro J Endocrinol/ Euro Federat Endocrine Soc 2009; 161:435-42; https://doi.org/10.1530/EJE-09-0284
  • Tivesten A, Vandenput L, Labrie F, Karlsson MK, Ljunggren O, Mellstrom D, Ohlsson C. Low serum testosterone and estradiol predict mortality in elderly men. J Clin Endocrinol Metabol 2009; 94:2482-8; https://doi.org/10.1210/jc.2008-2650
  • Harman SM, Tsitouras PD. Reproductive hormones in aging men. I. Measurement of sex steroids, basal luteinizing hormone, and Leydig cell response to human chorionic gonadotropin. J Clin Endocrinol Metabol 1980; 51:35-40.
  • Burns-Cox N, Gingell C. The andropause: fact or fiction? Postgrad Med J 1997; 73:553-6; PMID:9373594; https://doi.org/10.1136/pgmj.73.863.553
  • Featherstone M, Hepworth M. The history of the male menopause 1848-1936. Maturitas 1985; 7:249-57; PMID:3908882; https://doi.org/10.1016/0378-5122(85)90047-7
  • Schultheiss D, Jonas U, Musitelli S. Some historical reflections on the ageing male. World J Urol 2002; 20:40-4; PMID:12088189; https://doi.org/10.1007/s00345-002-0254-7
  • Snyder PJ. Hypogonadism in elderly men–what to do until the evidence comes. N Engl J Med 2004; 350:440-2; PMID:14749451; https://doi.org/10.1056/NEJMp038207
  • Corona G, Rastrelli G, Maggi M. Diagnosis and treatment of late-onset hypogonadism: systematic review and meta-analysis of TRT outcomes. Best Pract Res Clin Endocrinol Metab 2013; 27:557-79; PMID:24054931; https://doi.org/10.1016/j.beem.2013.05.002
  • Petak SM, Nankin HR, Spark RF, Swerdloff RS, Rodriguez-Rigau LJ. American Association of Clinical Endocrinologists Medical Guidelines for clinical practice for the evaluation and treatment of hypogonadism in adult male patients–2002 update. Endocr Pract 2002; 8:440-56; PMID:15260010
  • Nieschlag EB. H.M. Anamnesis and Physical Examination. In: Nieschlag EB,   HM, Nieschlag S, ed. Andrology. Berlin: Springer, 2010:93-100.
  • Ross A, Bhasin S. Hypogonadism: its prevalence and diagnosis. Urologic Clin North America 2016; 43:163-76; PMID:27132573; https://doi.org/10.1016/j.ucl.2016.01.002
  • Ahern T, Swiecicka A, Eendebak RJ, Carter EL, Finn JD, Pye SR, O'Neill TW, Antonio L, Keevil B, Bartfai G, et al. Natural history, risk factors and clinical features of primary hypogonadism in ageing men: longitudinal data from the European male ageing study. Clin Endocrinol 2016; PMID:27374987
  • Rastrelli G, Carter EL, Ahern T, Finn JD, Antonio L, O'Neill TW, Bartfai G, Casanueva FF, Forti G, Keevil B, et al. Development of and recovery from secondary hypogonadism in aging Men: prospective results from the EMAS. J Clin Endocrinol Metabol 2015; 100:3172-82; https://doi.org/10.1210/jc.2015-1571
  • Kalyani RR, Gavini S, Dobs AS. Male hypogonadism in systemic disease. Endocrinol Metab Clin North Am 2007; 36:333-48; PMID:17543722; https://doi.org/10.1016/j.ecl.2007.03.014
  • Lunenfeld B, Mskhalaya G, Zitzmann M, Arver S, Kalinchenko S, Tishova Y, Morgentaler A. Recommendations on the diagnosis, treatment and monitoring of hypogonadism in men. Aging Male: Off J Int Soc Study Aging Male 2015; 18:5-15; PMID:25657080; https://doi.org/10.3109/13685538.2015.1004049
  • Kim S, Kwon H, Park JH, Cho B, Kim D, Oh SW, Lee CM, Choi HC. A low level of serum total testosterone is independently associated with nonalcoholic fatty liver disease. BMC Gastroenterol 2012; 12:69; PMID:22691278; https://doi.org/10.1186/1471-230X-12-69
  • Balasubramanian V, Naing S. Hypogonadism in chronic obstructive pulmonary disease: incidence and effects. Curr Opin Pulmonary Med 2012; 18:112-7; PMID:22234275; https://doi.org/10.1097/MCP.0b013e32834feb37
  • Mousavi SA, Kouchari MR, Samdani-Fard SH, Gilvaee ZN, Arabi M. Relationship between serum levels of testosterone and the severity of chronic obstructive pulmonary disease. Tanaffos 2012; 11:32-5; PMID:25191426
  • Svartberg J, Schirmer H, Medbo A, Melbye H, Aasebo U. Reduced pulmonary function is associated with lower levels of endogenous total and free testosterone. The Tromso study. Euro J Epidemiol 2007; 22:107-12; https://doi.org/10.1007/s10654-006-9095-9
  • Iglesias P, Carrero JJ, Diez JJ. Gonadal dysfunction in men with chronic kidney disease: clinical features, prognostic implications and therapeutic options. J Nephrol 2012; 25:31-42; PMID:21748720; https://doi.org/10.5301/JN.2011.8481
  • Prem AR, Punekar SV, Kalpana M, Kelkar AR, Acharya VN. Male reproductive function in uraemia: efficacy of haemodialysis and renal transplantation. Brit J Urol 1996; 78:635-8; PMID:8944524; https://doi.org/10.1046/j.1464-410X.1996.14624.x
  • Albu A, Barbu CG, Antonie L, Vladareanu F, Fica S. Risk factors associated with hypogonadism in beta-thalassemia major patients: predictors for a frequent complication of a rare disease. Postgraduate Med 2014; 126:121-7; PMID:25295656; https://doi.org/10.3810/pgm.2014.09.2806
  • Pelusi C, Gasparini DI, Bianchi N, Pasquali R. Endocrine dysfunction in hereditary hemochromatosis. J Endocrinol Investigat 2016; 39:837-47; PMID:26951056; https://doi.org/10.1007/s40618-016-0451-7
  • Luppa P, Munker R, Nagel D, Weber M, Engelhardt D. Serum androgens in intensive-care patients: correlations with clinical findings. Clin Endocrinol 1991; 34:305-10; PMID:1831739; https://doi.org/10.1111/j.1365-2265.1991.tb03771.x
  • Woolf PD, Hamill RW, McDonald JV, Lee LA, Kelly M. Transient hypogonadotropic hypogonadism caused by critical illness. J Clin Endocrinol Metabol 1985; 60:444-50; https://doi.org/10.1210/jcem-60-3-444
  • Corona G, Rastrelli G, Maseroli E, Fralassi N, Sforza A, Forti G, Mannucci E, Maggi M. Low testosterone syndrome protects subjects with high cardiovascular risk burden from major adverse cardiovascular events. Andrology 2014; 2:741-7; PMID:25044637; https://doi.org/10.1111/j.2047-2927.2014.00241.x
  • Rochira V, Diazzi C, Santi D, Brigante G, Ansaloni A, Decaroli MC, De Vincentis S, Stentarelli C, Zona S, Guaraldi G. Low testosterone is associated with poor health status in men with human immunodeficiency virus infection: a retrospective study. Andrology 2015; 3:298-308; PMID:25704864; https://doi.org/10.1111/andr.310
  • Morley JE, Melmed S. Gonadal dysfunction in systemic disorders. Metabol: Clin Exp 1979; 28:1051-73; PMID:386028; https://doi.org/10.1016/0026-0495(79)90010-6
  • Spratt DI, Cox P, Orav J, Moloney J, Bigos T. Reproductive axis suppression in acute illness is related to disease severity. J Clin Endocrinol Metabol 1993; 76:1548-54.
  • Fourrier F, Jallot A, Leclerc L, Jourdain M, Racadot A, Chagnon JL, Rime A, Chopin C. Sex steroid hormones in circulatory shock, sepsis syndrome, and septic shock. Circ Shock 1994; 43:171-8; PMID:7895322
  • Christeff N, Benassayag C, Carli-Vielle C, Carli A, Nunez EA. Elevated oestrogen and reduced testosterone levels in the serum of male septic shock patients. J Steroid Biochem 1988; 29:435-40; PMID:3374133; https://doi.org/10.1016/0022-4731(88)90254-3
  • Travison TG, Shackelton R, Araujo AB, Hall SA, Williams RE, Clark RV, O'Donnell AB, McKinlay JB. The natural history of symptomatic androgen deficiency in men: onset, progression, and spontaneous remission. J Am Geriat Soc 2008; 56:831-9; PMID:18454749; https://doi.org/10.1111/j.1532-5415.2008.01679.x
  • Rockwood K, Mitnitski A. Frailty defined by deficit accumulation and geriatric medicine defined by frailty. Clin Geriat Med 2011; 27:17-26; PMID:21093719; https://doi.org/10.1016/j.cger.2010.08.008
  • Mitnitski A, Collerton J, Martin-Ruiz C, Jagger C, von Zglinicki T, Rockwood K, Kirkwood TB. Age-related frailty and its association with biological markers of ageing. BMC Med 2015; 13:161; PMID:26166298; https://doi.org/10.1186/s12916-015-0400-x
  • Armstrong JJ, Mitnitski A, Andrew MK, Launer LJ, White LR, Rockwood K. Cumulative impact of health deficits, social vulnerabilities, and protective factors on cognitive dynamics in late life: a multistate modeling approach. Alzheimer's Res Ther 2015; 7:38; PMID:26052349; https://doi.org/10.1186/s13195-015-0120-7
  • Eichholzer M, Barbir A, Basaria S, Dobs AS, Feinleib M, Guallar E, Menke A, Nelson WG, Rifai N, Platz EA, et al. Serum sex steroid hormones and frailty in older American men of the Third National Health and Nutrition Examination Survey (NHANES III). Aging Male: The Off J Int Soc Study Aging Male 2012; 15:208-15; PMID:22822787; https://doi.org/10.3109/13685538.2012.705366
  • Tajar A, Lee DM, Pye SR, O'Connell MD, Ravindrarajah R, Gielen E, Boonen S, Vanderschueren D, Pendleton N, Finn JD, et al. The association of frailty with serum 25-hydroxyvitamin D and parathyroid hormone levels in older European men. Age Ageing 2013; 42:352-9; PMID:23111338; https://doi.org/10.1093/ageing/afs162
  • Ravindrarajah R, Lee DM, Pye SR, Gielen E, Boonen S, Vanderschueren D, Pendleton N, Finn JD, Tajar A, O'Connell MD, et al. The ability of three different models of frailty to predict all-cause mortality: results from the European Male Aging Study (EMAS). Arch Gerontol Geriat 2013; 57:360-8; PMID:23871598; https://doi.org/10.1016/j.archger.2013.06.010
  • Vitale G, Cesari M, Mari D. Aging of the endocrine system and its potential impact on sarcopenia. Euro J Int Med 2016.
  • Keevil VL, Romero-Ortuno R. Ageing well: a review of sarcopenia and frailty. Proc Nutrit Soc 2015; 74:337-47; PMID:26004622; https://doi.org/10.1017/S0029665115002037
  • Angulo J, El Assar M, Rodriguez-Manas L. Frailty and sarcopenia as the basis for the phenotypic manifestation of chronic diseases in older adults. Mol Aspects Med 2016; 50:1-32; PMID:27370407; https://doi.org/10.1016/j.mam.2016.06.001
  • Basualto-Alarcon C, Varela D, Duran J, Maass R, Estrada M. Sarcopenia and androgens: a Link between Pathology and Treatment. Front Endocrinol 2014; 5:217; PMID:25566189
  • Kizilarslanoglu MC, Kuyumcu ME, Yesil Y, Halil M. Sarcopenia in critically ill patients. J Anesthesia 2016; 30:884-90; PMID:27376823; https://doi.org/10.1007/s00540-016-2211-4
  • Trojian TH, Lishnak TS, Heiman D. Epididymitis and orchitis: an overview. Am Fam Physician 2009; 79:583-7; PMID:19378875
  • El-Serafi AT, Osama S, El-Zalat H. IM EL-D. Dysregulation of male sex hormones in chronic hepatitis C patients. Andrologia 2016; 48:82-6; PMID:25912488; https://doi.org/10.1111/and.12425
  • Deeks SG. HIV infection, inflammation, immunosenescence, and aging. Annu Rev Med 2011; 62:141-55; PMID:21090961; https://doi.org/10.1146/annurev-med-042909-093756
  • Rochira V, Zirilli L, Orlando G, Santi D, Brigante G, Diazzi C, Carli F, Carani C, Guaraldi G. Premature decline of serum total testosterone in HIV-infected men in the HAART-era. PloS One 2011; 6:e28512; PMID:22174826; https://doi.org/10.1371/journal.pone.0028512
  • Sikaris K, McLachlan RI, Kazlauskas R, de Kretser D, Holden CA, Handelsman DJ. Reproductive hormone reference intervals for healthy fertile young men: evaluation of automated platform assays. J Clin Endocrinol Metabol 2005; 90:5928-36; https://doi.org/10.1210/jc.2005-0962
  • Yeap BB, Alfonso H, Chubb SA, Handelsman DJ, Hankey GJ, Norman PE, Flicker L. Reference ranges and determinants of testosterone, dihydrotestosterone, and estradiol levels measured using liquid chromatography-tandem mass spectrometry in a population-based cohort of older men. J Clin Endocrinol Metabol 2012; 97:4030-9; https://doi.org/10.1210/jc.2012-2265
  • Kloner RA, Carson C, 3rd Dobs A, Kopecky S, Mohler ER, 3rd. Testosterone and cardiovascular disease. J Am College Cardiol 2016; 67:545-57; PMID:26846952; https://doi.org/10.1016/j.jacc.2015.12.005
  • Corona G, Isidori AM, Buvat J, Aversa A, Rastrelli G, Hackett G, Rochira V, Sforza A, Lenzi A, Mannucci E, et al. Testosterone supplementation and sexual function: a meta-analysis study. J Sex Med 2014; 11:1577-92; PMID:24697970; https://doi.org/10.1111/jsm.12536
  • Basaria S, Coviello AD, Travison TG, Storer TW, Farwell WR, Jette AM, Eder R, Tennstedt S, Ulloor J, Zhang A, et al. Adverse events associated with testosterone administration. N Engl J Med 2010; 363:109-22; PMID:20592293; https://doi.org/10.1056/NEJMoa1000485
  • Finkle WD, Greenland S, Ridgeway GK, Adams JL, Frasco MA, Cook MB, Fraumeni JF, Jr., Hoover RN. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PloS One 2014; 9:e85805; PMID:24489673; https://doi.org/10.1371/journal.pone.0085805
  • Vigen R, O'Donnell CI, Baron AE, Grunwald GK, Maddox TM, Bradley SM, Barqawi A, Woning G, Wierman ME, Plomondon ME, et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA 2013; 310:1829-36; PMID:24193080; https://doi.org/10.1001/jama.2013.280386
  • Corona G, Maseroli E, Rastrelli G, Isidori AM, Sforza A, Mannucci E, Maggi M. Cardiovascular risk associated with testosterone-boosting medications: a systematic review and meta-analysis. Expert Opin Drug Saf 2014; 13:1327-51; PMID:25139126; https://doi.org/10.1517/14740338.2014.950653
  • Calof OM, Singh AB, Lee ML, Kenny AM, Urban RJ, Tenover JL, Bhasin S. Adverse events associated with testosterone replacement in middle-aged and older men: a meta-analysis of randomized, placebo-controlled trials. J Gerontol A Biol Sci Med Sci 2005; 60:1451-7; PMID:16339333; https://doi.org/10.1093/gerona/60.11.1451
  • Haddad RM, Kennedy CC, Caples SM, Tracz MJ, Bolona ER, Sideras K, Uraga MV, Erwin PJ, Montori VM. Testosterone and cardiovascular risk in men: a systematic review and meta-analysis of randomized placebo-controlled trials. Mayo Clin Proc 2007; 82:29-39; PMID:17285783; https://doi.org/10.1016/S0025-6196(11)60964-6
  • Fernandez-Balsells MM, Murad MH, Lane M, Lampropulos JF, Albuquerque F, Mullan RJ, Agrwal N, Elamin MB, Gallegos-Orozco JF, Wang AT, et al. Clinical review 1: adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis. J Clin Endocrinol Metabol 2010; 95:2560-75; https://doi.org/10.1210/jc.2009-2575
  • Xu L, Freeman G, Cowling BJ, Schooling CM. Testosterone therapy and cardiovascular events among men: a systematic review and meta-analysis of placebo-controlled randomized trials. BMC Med 2013; 11:108; PMID:23597181; https://doi.org/10.1186/1741-7015-11-108
  • Same RV, Bell DL, Rosenthal SL, Marcell AV. Sexual and reproductive health care: adolescent and adult men's willingness to talk and preferred approach. Am J Prevent Med 2014; 47:175-81; PMID:24951042; https://doi.org/10.1016/j.amepre.2014.03.009
  • Hughes AK, Wittmann D. Aging sexuality: knowledge and perceptions of preparation among U.S. primary care providers. J Sex Marital Ther 2015; 41:304-13; PMID:24512220; https://doi.org/10.1080/0092623X.2014.889056
  • Stenholm S, Metter EJ, Roth GS, Ingram DK, Mattison JA, Taub DD, Ferrucci L. Relationship between plasma ghrelin, insulin, leptin, interleukin 6, adiponectin, testosterone and longevity in the Baltimore Longitudinal Study of Aging. Aging Clin Exp Res 2011; 23:153-8; PMID:21743292; https://doi.org/10.1007/BF03351078
  • Austad SN, Fischer KE. Sex Differences in Lifespan. Cell Metabol 2016; 23:1022-33; PMID:27304504; https://doi.org/10.1016/j.cmet.2016.05.019
  • Nieschlag E, Nieschlag S, Behre HM. Lifespan and testosterone. Nature 1993; 366:215; PMID:8232579; https://doi.org/10.1038/366215a0
  • Bale TL, Epperson CN. Sex differences and stress across the lifespan. Nat Neurosc. 2015; 18:1413-20; https://doi.org/10.1038/nn.4112

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