Defining 'relative' androgen deficiency in aging men: how should testosterone be measured and what are the relationships between androgen levels and physical, sexual and emotional health?

References

• Mitchell R, Hollis S, Rothwell C, Robertson WR. Age related changes in the pituitary—testicular axis in normal men; lower serum testosterone results from decreased bioactive LH drive. Clin Endocrinol (Oxf) 1995;42:501–7
   PubMed Web of Science ®Google Scholar
• Kaiser FE, Viosca SP, Morley JE, Mooradian AD, Davis P, Korenman SG. Impotence and aging: clinical and hormonal factors. J Am Geriatr Soc 1988;36:511–19
   PubMed Web of Science ®Google Scholar
• Maas D, Jochen A, Lalande B. Age-related changes in male gonadal function. Implications for therapy. Drugs Aging 1997;11:45–60
   Google Scholar
• Nankin HC, Calkins JH. Decreased bioavailable testosterone in aging normal and impotent men. J Clin Endocrinol Metab 1986;63:1418–20
   PubMed Web of Science ®Google Scholar
• Ferrini R, Barrett-Conner 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
   PubMed Web of Science ®Google Scholar
• Tenover JM, Matsumoto AM, Plymate SR, Bremner WJ. The effects of aging in normal men on bioavailable testosterone and luteinizing hor-mone secretion: response to clomiphene citrate. J Clin Endocrinol Metab 1987;65:1118–26
   PubMed Web of Science ®Google Scholar
• Morley JE, Kaiser FE, Perry HM III, et al. Longi-tudinal changes in testosterone, luteinizing hormone, and follicle-stimulating hormone in healthy older men. Metabolism 1997;46:410–13
   PubMed Web of Science ®Google Scholar
• Zmuda JC, Cauley JA, Kriska A, Glynn NW, Gutai JP, Kuller LH. Longitudinal relation between endogenous testosterone and cardio-vascular disease risk factors in middle-aged men. Am J Epidemiol 1997;146:609–17
   PubMed Web of Science ®Google Scholar
• Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab 2001;86:724–31
   PubMed Web of Science ®Google Scholar
• Morley JE. Androgens and aging. Maturitas 2001;38:61–73
   PubMed Web of Science ®Google Scholar
• Sih RM, Morley JE, Kaiser FE, Perry HM III, Patrick P, Ross C. Testosterone replacement in older hypogonadal men: a 12-month randomizedcontrolled trial. J Clin Endocrinol Metab 1997; 82:1661–7
   Google Scholar
• Mendel C. The free hormone hypothesis: a physiologically based mathematical model. Endocr Rev 1989;10:232–74
   PubMed Web of Science ®Google Scholar
• Manni AP, Pardridge WM, Cefalu W, et al. Bioavailability of albumin-bound testosterone. J Clin Endocrinol Metab 1985;61:705–10
   PubMed Web of Science ®Google Scholar
• Gray J, Nunez AA, Siegel LI, et al. Effects of testosterone on body weight and adipose tissue: role of aromatisation. Physiol Behav 1979;23: 465–9
   PubMed Web of Science ®Google Scholar
• Hryb Dj, Khan MS, Romas NA, Rosner W. Solubilization and partial characterization of the sex hormone-binding globulin receptor from human prostate. J Biol Chem 1989;264:5378–83
   PubMed Web of Science ®Google Scholar
• Hryb Dj, Khan MS, Romas NA, Rosner W. The control and interaction of sex hormone-binding globulin with its receptor by steroid hormones. J Biol Chem 1990:265:6048–54
   PubMed Web of Science ®Google Scholar
• Nakhla AM, Khan MS, Rosner W. Biologically active steroids activate receptor-bound human sex hormone-binding globulin to cause LNCaP cells to accumulate adenosine 3',5'-monophos-phate. J Clin Endocrinol Metab 1990;71: 398–404
   Google Scholar
• Schweikert H, Rulf W, Niederle N, Schafer HE, Keck E, Kruck F. Testosterone metabolism in human bone. Acta Endocrinol (Copenh ) 1980; 95:258
   PubMedGoogle Scholar
• Vittek J, Altman K, Gordon GG, Southren AL. The metabolism of 7-a-3H-testosterone by rat mandibular bone. Endocrinology 1974;94:325
   PubMed Web of Science ®Google Scholar
• Selby C. Sex hormone binding globulin: origin, function and clinical significance. Ann Clin Bio-chem 1990;27:532–41
   PubMed Web of Science ®Google Scholar
• Vermeulen A, Stoica T, Verdnock L. The apparent free testosterone concentration, an index of androgenicity. J Clin Endocrinol 1971; 33:759–67
   Google Scholar
• Vermeulen AV, Verdnock L, Kaufman JM. A critical evaluation of simple methods for theestimation of free testosterone in serum. J Gun Endocrinol Metab 1999;84:3666–72
   PubMed Web of Science ®Google Scholar
• Mathur R, Moody LO, Landgrebe S, Williamson HO. Plasma androgens and sex hormone-binding globulin in the evaluation of hirsute females. Fertil Steril 1981;35:29–35
   PubMed Web of Science ®Google Scholar
• Kapoor P, Luttrell BM, Williams D. The free androgen index is not valid for adult males. J Steroid Biochem Mol Biol 1993;45:325–6
   PubMed Web of Science ®Google Scholar
• O'Conner SB, Baker HWG, Dulmanis A, Hudson B. The measurement of sex steroid binding globulin by differential ammonium sulphate precipitation. J Steroid Biochem 1973:4:331–9
   PubMedGoogle Scholar
• Haren M, Nordin BEG, Pearce GEM, et al. The calculation of bioavailable testosterone. Andrology in the 21st Century [short communi-cation]. In Robiare B, Chemis H, Morales C, eds. Proceedings of the VII International Congress of Andrology. Englewood, NJ Medimond, 2001: 209–13
   Google Scholar
• 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 Gun Endocrinol Metab 1991;73:1016–25
   PubMed Web of Science ®Google Scholar
• Longcope CG, Goldfield SRW, Brambilla DJ, McKinlay J. Androgens, estrogens, and sex hormone-binding globulin in middle-aged men. J Gun Endocrinol Metab 1990;71:1442–6
   PubMed Web of Science ®Google Scholar
• Field AC, Colditz GA, Willet WC, Loncope C, McKinlay JB. The relation of smoking, age, relative weight, and dietery intake to serum adrenal steroids, sex hormones, and sex hormone-binding globulin in middle-aged men. J Gun Endocrinol Metab 1994;79:1310–16
   Google Scholar
• Nahoul KR, Roger M. Age-related decline of plasma bioavailable testosterone in adult men. J Steroid Biochem 1990;35:293–9
   PubMedGoogle Scholar
• Morley JE, Kaiser F, Raum WJ, et al. Potentially predictive and manipulable blood serum corre-lates of aging in the healthy human male: progres-sive decreases in bioavailable testosterone, dehydroepiandrosterone sulphate, and the ratio of insulin-like growth factor 1 to growth hormone. Proc Natl Acad Sci USA 1997;94: 7537–42
   PubMed Web of Science ®Google Scholar
• Simon D, Preziosi P, Barrett-Connor E, et al. The influence of aging on plasma sex hormones in men: the Telecom study. Am J Epidemiol 1992;135:783–91
   Google Scholar
• Baker HWG, Burger HG, de Krester DM, et al. Changes in the pituitary—testicular system with age. Clin Endocrinol 1976;5:349–72
   PubMed Web of Science ®Google Scholar
• Leifke E, Gorenoi V, Wichers C, Von Zur Muhlen A, Von Buren E, Brabant G. Age-related changes of serum sex hormones, insulin-like growth factor-1 and sex-hormone bindingglobulin levels in men: cross-sectional data from a healthy male cohort. Clin Endocrinol 2000; 53:689–95
   Google Scholar
• Maruyama Y, Aoki N, Suzuki Y, Sinohara H, Yamamuto T. Variation with age in the levels of sex-steroid-binding plasma protein as deter-mined by radioimmunoassay. Acta Endocrinol (Cope* 1984;106:428–32
   Google Scholar
• Tenover L. Testosterone and the aging male. J Androl 1997;18:103–6
   PubMed Web of Science ®Google Scholar
• Morley JE, Charlton E, Patrick P, et al. Valid-ation of a screening questionnnaire for androgen deficiency in aging males. Metabolism 2000; 49:1239–42
   PubMed Web of Science ®Google Scholar
• Smith KW, Feldman HA, McKinlay JB. Construction and field validation of a self-admin-istered screener for testosterone deficiency ( hypo-gonadism) in ageing men. Clin Endocrinol (Oxf) 2000;53:703–11
   Google Scholar
• Schiavi R, White D, Madeli J, Levine AC. Effect of testosterone administration on sexual behaviour and mood in men with erectile dysfunction. Arch Sex Behav 1997;26:231–41
   PubMed Web of Science ®Google Scholar
• Schiavi R, Schreiner-Engel P, White D, Mandeli J. The relationship between pituitary—gonadal function and sexual behaviour in healthy aging men. Psychosom Med 1991;53:363–74
   PubMed Web of Science ®Google Scholar
• Gladkova A. The regulation of male sexual behaviour by the sex hormones. Usp Fiziol Nauk 1999;30:97–105
   PubMedGoogle Scholar
• Sternbach H. Age-associated testosterone decline in men: clinical issues for psychiatry. Am J Psychiatry 1998;155:1310–18
   PubMed Web of Science ®Google Scholar
• Burris AS, Banks SM, Carter CS, Davidson JM, Sherins RJ. A long-term prospective study of the physiologic and behavioural effects of hormone replacement in untreated hypogonadal men. J Androl 1992;13:297–304
   Google Scholar
• Barrett-Connor E, Von Muhlen DG, Kritz-Silverstein D. Bioavailable testosterone and depressed mood in older men: the Rancho Bernardo study. J Clin Endocrinol Metab 1999; 84:573–7
   Google Scholar
• Yesavage JD, Davidson J, Widrow L, Berger PA. Plasma testosterone levels, depression, sexuality, and age. Biol Psychiatry 1985;20:199–228
   PubMed Web of Science ®Google Scholar
• Janowsky JO, Oviatt SK, Orwoll ES. Testos-terone influences spatial cognition in older men. Behav Neurosci 1994;108:325–32
   Google Scholar
• Barrett-Connor E, Goodman-Gruen D, Patay B. Endogenous sex hormones and cognitive function in older men. J Clin Endocrinol Metab 1999;84:3681–5
   PubMed Web of Science ®Google Scholar
• Moffat SD, Hampson E. A curvilinear relation-ship between testosterone and spatial cognition in humans: possible influence of hand preference. Psychoneuroendocrinology 1996;21:323–37
   PubMed Web of Science ®Google Scholar
• Tchernof A, Giagulli VA, Kaufman JM, Vermeulen A. Pathogenesis of the decreased androgen levels in obese men. J Gun Endocrinol Metab 1994;79:997–1000
   PubMed Web of Science ®Google Scholar
• Zumoff B, Strain GW, Miller LK, et al. Plasma free and non-sex-hormone binding-globulin-bound testosterone are decreased in obese men in proportion to their degree of obesity. J Gun Endocrinol Metab 1990;71:929–31
   PubMed Web of Science ®Google Scholar
• Tchernof A, Labrie F, Belanger A, Despres JP. Obesity and metabolic complications: contribu-tion of dehydroepiandrosterone and other steroid hormones. J Endocrinol 1996;150:S155–64
   PubMed Web of Science ®Google Scholar
• Mann P, Arver S. Androgens and abdominal obesity. Baillière's Clin Endocrinol Metab 1998; 12:441–51
   PubMed Web of Science ®Google Scholar
• Lovejoy J, Bray GA, Greeson CS, et al. Oral anabolic steroid treatment, but not parenteral androgen treatment, decreases abdominal fat in obese older men. Int J Obesity Relat Metab Disord 1995;19:614–24
   PubMed Web of Science ®Google Scholar
• Khaw K, Barrett-Conner E. Lower endogenous androgens predict central adiposity in men. Ann Epidemiol 1992;2:675–82
   PubMedGoogle Scholar
• Elbers J, Asscheman H, Seidell JC, Megens JA, Gooren IT Long-term testosterone admin-istration increases visceral fat in female to male transsexuals. J Gun Endocrinol Metab 1997; 82:2044–7
   PubMed Web of Science ®Google Scholar
• Clague JE, Wu FC, Horan MA. Difficulties in measuring the effect of testosterone replacement therapy on muscle function in older men. Int J Androl 1999;22:261–5
   Google Scholar
• Baumgartner RN, Waters DL, Gallagher D, Morley JE, Garry PJ. Predictors of skeletal muscle mass in elderly men and women. Med) Ageing Dev 1999;107:123–35
   Google Scholar
• Murphy S, Khaw KT, Cassidy A, Compston JE. Sex hormones and bone mineral density in elderly men. Bone Miner 1993;20:133–40
   PubMedGoogle Scholar
• Gillberg P, Johansson AG, Ljunghall S. Decreased estradiol levels and free androgen index and elevated sex hormone-binding globulin levels in male idiopathic osteoporosis. Calcif Tissue Int 1999;64:209–13
   Google Scholar
• Kenny AM, Gallagher JC, Prestwood KM, Gruman CA, Raisz LG. Bone density, bone turn-over, and hormone levels in men over age 75. J Gerontol A Biol Sci Med Sci 1998;53:M419–25
   Google Scholar
• Vanderschueren D, Van Herck E, De Costa R, Bouillon R. Aromatisation of androgens is important for skeletal maintenance of aged male rats. Calcif Tissue Int 1996;59:179–83
   PubMed Web of Science ®Google Scholar
• Falahati-Nini A, Riggs BL, Atkinson EJ, O'Fallon WM, Eastell R, Khosla S. Relative contributions of testosterone and estrogen in regulating boneresorption and formation in normal elderly men. J Clin Invest 2000;106:1553–60
   Google Scholar
• Centre JR, Nguyen TV, Sambrook PN, Eisman JA. Hormonal and biochemical parameters in the determination of osteoporosis in elderly men. J Gun Endocrinol Metab 1999;84:3626–35
   PubMed Web of Science ®Google Scholar
• Heller RF, Wheeler MJ, Micallef J, Miller NE, Lewis B. Relationship of high density lipoprotein cholesterol with total and free testosterone and sex hormone-binding globulin. Acta Endocrinol (Cope* 1983;104:253–6
   Google Scholar
• Hamalainen E, Adelcreutz H, Ehnholm C, Puska P. Relationships of serum lipoproteins and apo-proteins to sex hormones and to the binding capacity of sex hormone binding globulin in healthy Finnish men. Metabolism 1986;35: 535–41
   PubMed Web of Science ®Google Scholar
• Nanjee MN, Rajput WJ, Samuel L, Wootton R, Miller NE. Relationships of plasma lipoprotein concentrations to unbound, albumin-bound and sex hormone-binding globulin bound fractions of gonadal steroids in men. Eur J Clin Invest 1989;19:241–5
   Google Scholar
• Barrett-Connor E, Khaw KT. Endogenous sex hormones and cardiovascular disease in men: a prospective population based study. Circulation 1988;78:539–45
   Google Scholar
• Simon D, Charles MA, Nahoul K, et al. Associa-tions between plasma total testosterone and cardiovascular risk factors in healthy adult men: the Telecom study. J Clin Endocrinol Metab 1997;82:682–5
   PubMed Web of Science ®Google Scholar
• van Kesteren P, Asscherman H, Megens JA, Gooren U. Mortality and morbidity in trans-sexual subjects treated with cross-sex hormones. Clin Endocrinol (Oxf) 1997;47:337–42
   PubMed Web of Science ®Google Scholar
• Snyder P, Peachy H, Hannoush P, et al. Effect of testosterone treatment on bone mineral density in men over 65 years of age. J Clin Endocrinol Metab 1999;84:1966–72
   PubMed Web of Science ®Google Scholar
• Hajjar RR, Kaiser FE, Morley JE. Outcomes of long-term testosterone replacement in older hypogonadal males: a retrospective analysis. J Clin Endocrinol Metab 1997;82:3793–6
   Google Scholar
• Wang C, Swerdloff RS, Iranmanesh A, et al. Transdermal testosterone gel improves sexual function, mood, muscle strength and body composition parameters in hypogonadal men. Testosterone Gel Study Group. J Clin Endocrinol Metab 2000;85:2839–53
   PubMed Web of Science ®Google Scholar
• Arver S, Dobs AS, Meikle AW, et al. Long-term efficacy and safety of a permeation enhanced testosterone transdermal system in hypogonadal men. Clin Endocrinol (Oxf) 1997;47:727–37
   PubMed Web of Science ®Google Scholar
• Morley JE, Perry HM III, Kaiser FE, et al. Effects of testosterone replacement therapy in oldhypogonadal males: a preliminary study. J Am Geriatr Soc 1993;41:149–52
   PubMed Web of Science ®Google Scholar
• Urban R, Bodenburg YH, Gilkison 0, et al. Testosterone administration to elderly men increases skeletal muscle strength and protein synthesis. Am J Physiol 1995;269: E820–6
   Google Scholar
• Snyder P, Peachy H, Hannoush P, et al. Effect of testosterone treatment on body composition and muscle strength in men over 65 years of age. J Gun Endocrinol Metab 1999;84:2647–53
   PubMed Web of Science ®Google Scholar
• Katznelson L, Finklestein JS, Schoenfeld DA, Rosenthal DI, Anderson EJ, Klibanski A. Increase in bone density and lean body mass during testos-terone administration in men with acquired hypogonadism. J Gun Endocrinol Metab 1996; 81:4358–65
   PubMed Web of Science ®Google Scholar
• Bhasin S, Storer TW, Berman N, et al. A replace-ment dose of testosterone increases muscle mass and size in hypogonadal men. J Gun Endocrinol Metab 1997;82:407–13
   PubMed Web of Science ®Google Scholar
• Brodsky I, Balagopal P, Nair KS. Effects of testos-terone replacement on muscle mass and muscle protein synthesis in hypogonadal men — a Clinical Research Centre study. J Gun Endocrinol Metab 1996;81:3469–75
   Google Scholar
• Wang CA, Alexander G, Berman N, et al. Testos-terone replacement therapy improves mood in hypogonadal men — a Clinical Research Centre study. J Gun Endocrinol Metab 1996;81: 3578–83
   PubMed Web of Science ®Google Scholar
• Behre H, Bohmeyer J, Nieschlag E. Prostate volume in testosterone-treated and untreated hypogonadal men in comparison to age-matched normal controls. Clin Endocrinol (Oxf) 1994; 40:341–9
   Google Scholar
• Douglas T, Connelly RR, McLeod DG, Erickson SJ, Barren R, Murphy GP. Effect of exogenous testosterone replacement on prostate-specific antigen and prostate-specific membrane antigen levels in hypogonadal men. J Surg Oncol 1995; 59:246–50
   PubMed Web of Science ®Google Scholar
• Jin B, Turner L, Walters WA, Handelsman DJ. The effects of chronic high dose androgen or oestrogen treatment on the human prostate. J Gun Endocrinol Metab 1996;82:413
   Web of Science ®Google Scholar
• Ellyin FM. The long-term beneficial effects of low dose testosterone in the aging male. Presented at the 77th Annual Meeting of the Endocrine Society (USA) Washington DC, June 1995: abstr P2–127
   Google Scholar
• O'Carroll RB, Bancroft J. Testosterone therapy for low sexual interest and erectile dysfunction in men: a controlled study. Br Psychiatry 1984;145: 146–51
   PubMed Web of Science ®Google Scholar
• Anderson RA, Bancroft J, Wu FCW. The effects of exogenous testosterone on sexuality and mood of normal men. J Clin Endocrinol Metab 1992; 75:1503–7
   Google Scholar
• Morales A, Johnston B, Heaton JP, Lundie M. Testosterone supplementation for hypogonadal impotence: assessment of biochemical measures and therapy outcomes. J Urol 1997;157:849–54
   PubMed Web of Science ®Google Scholar
• Tenover J. Effects of testosterone supple-mentation in the aging male. J Clin Endocrinol Metab 1992;75:1092–8
   PubMed Web of Science ®Google Scholar
• Haddad G, Peachy H, Lipman C, Snyder PJ. Testosterone treatment improves body compo-sition and muscle strength in hypogonadal men. In Proceedings of the 76th Annual Meeting of the Endocrine Society, Anaheim, California, June 1994
   Google Scholar
• Alexander GM, Swerdloff RS, Wang C, et al. Androgen—behaviour correlations in hypo-gonadal men and eugonadal men. Cognitive abilities. Horm Behav 1998;33:85–94
   PubMed Web of Science ®Google Scholar
• Holmang S, Mann P, Lindstedt G, Hendelin H. Effect of long-term oral testosterone undecanoate treatment on prostate volume and serum pros-tate-specific antigen concentration in eugonadal middle-aged men. Prostate 1993;23:99–106
   PubMed Web of Science ®Google Scholar
• Mann P, Holmang S, Gustafsson C, et al. Andro-gen treatment of abdominally obese men. Obesity Res 1993;1:245–51
   PubMedGoogle Scholar
• Gann P, Hennekens CH, Ma J, Longcope C, Stampfer MJ. Prospective study of sex hormone levels and risk of prostate cancer. J Natl Cancer Inst 1996;88:1118–26
   PubMed Web of Science ®Google Scholar
• Eaton N, Reeves GK, Appleby PN, Key TJ. Endogenous sex-hormones and prostate cancer: a quantitative review of prospective studies. Br J Cancer 1999;80:930–4
   PubMed Web of Science ®Google Scholar