Anabolic applications of androgens for functional limitations associated with aging and chronic illness

Frontiers of Hormone Research

Volumn 37, Issue , 2009, Pages 163-182

  Bhasin, S ^a   Storer, Thomas W ^a  

^a BOSTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANDROGEN; ANTIANDROGEN; ANTIRETROVIRUS AGENT; AROMATASE; BICALUTAMIDE; CYTOCHROME P450; DEXAMETHASONE; ERYTHROPOIETIN; ESTRATEST; ESTROGEN; GLUCOCORTICOID; GONADORELIN AGONIST; HUMAN GROWTH HORMONE; HYDANTOIN DERIVATIVE; HYDROXYFLUTAMIDE; METHYLTESTOSTERONE; MINERAL; MUSCLE PROTEIN; NANDROLONE; NANDROLONE DECANOATE; OXANDROLONE; OXYMETHOLONE; QUINOLINE; SELECTIVE ANDROGEN RECEPTOR MODULATOR; STEROID 5ALPHA REDUCTASE; STEROID 5ALPHA REDUCTASE INHIBITOR; TESTOSTERONE; TESTOSTERONE ENANTATE; TESTOSTERONE PROPIONATE; CHOLESTENONE 5ALPHA REDUCTASE;

ADVERSE DRUG REACTION; ADVERSE OUTCOME; AGED; AGING; ANDROGEN DEFICIENCY; ANDROGEN THERAPY; ANEMIA; ASTHMA; AXIS; BIOSYNTHESIS; BODY WEIGHT DISORDER; BONE DENSITY; BONE MASS; BONE MINERAL; CARDIOVASCULAR DISEASE; CHRONIC DISEASE; CHRONIC OBSTRUCTIVE LUNG DISEASE; CLINICAL TRIAL; DIABETES MELLITUS; DISABILITY; DISEASE ASSOCIATION; DISEASE COURSE; DRUG EFFECT; FALLING; FRACTURE; FUNCTIONAL ASSESSMENT; GRIP STRENGTH; HEALTH; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HORMONE SYNTHESIS; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HYPOGONADISM; HYPOTHALAMUS HYPOPHYSIS SYSTEM; INSULIN SENSITIVITY; KIDNEY DISEASE; MUSCLE ATROPHY; MUSCLE FATIGUE; MUSCLE MASS; MUSCLE STRENGTH; NONHUMAN; OSTEOPOROSIS; PHYSICAL CAPACITY; PRIORITY JOURNAL; PROSTATE; PROSTATE HYPERTROPHY; PROTEIN SYNTHESIS; QUADRICEPS FEMORIS MUSCLE; REVIEW; RISK; SIDE EFFECT; SKELETAL MUSCLE; TESTOSTERONE BLOOD LEVEL; TESTOSTERONE SYNTHESIS; VERTEBRA BODY; WEIGHT REDUCTION; ANIMAL; CHRONIC KIDNEY FAILURE; FEMALE; MALE; METABOLISM; PHYSIOLOGY;

AGED; AGING; ANIMALS; CHOLESTENONE 5 ALPHA-REDUCTASE; CHRONIC DISEASE; CLINICAL TRIALS AS TOPIC; FEMALE; GLUCOCORTICOIDS; HIV INFECTIONS; HUMANS; KIDNEY FAILURE, CHRONIC; MALE; MUSCLE, SKELETAL; PULMONARY DISEASE, CHRONIC OBSTRUCTIVE; TESTOSTERONE; WEIGHT LOSS;

EID: 59849101891     PISSN: 03013073     EISSN: None     Source Type: Book Series    
DOI: 10.1159/000176052     Document Type: Review

References (68)

1. Baumgartner RN, Koehler KM, Gallagher D, Romero L, Heymsfield SB, Ross RR, Garry PJ, Lindeman RD: Epidemiology of sarcopenia among the elderly in New Mexico. Am J Epidemiol 1998;147:755-763.
2. 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 Endocri -nol Metab 2002;283:E284-E294.
3. Guralnik JM, Ferrucci L, Simonsick EM, Salive ME, Wallace RB: Lower-extremity function in persons over the age of 70 years as a predictor of subsequent disability. N Engl J Med 1995;332:556-561.
4. Spillman BC: Changes in elderly disability rates and the implications for health care utilization and cost. Milbank Q 2004;82:157-194.
5. Kaufman JM, Vermeulen A: The decline of andro-gen levels in elderly men and its clinical and therapeutic implications. Endocr Rev 2005;26:833-876.
6. 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 Metab 2001;86:724-731.
7. Wu FCW: Subclinical hypogonadism. Endocrine Society Meetings, Philadelphia, 2003, abstr S22-23.
8. Travison TG, Araujo AB, O'Donnell AB, Kupelian V, McKinlay JB: A population-level decline in serum testosterone levels in American men. J Clin Endocrinol Metab 2007;92:196-202.
9. 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 Metab 1991;73:1016-1025.
10. Bhasin S, Buckwalter JG: Testosterone supplementation in older men: a rational idea whose time has not yet come. J Androl 2001;22:718-731.
11. Winters SJ, Sherins RJ, Troen P: The gonadotropin-suppressive activity of androgen is increased in elderly men. Metabolism 1984;33:1052-1059.
12. Veldhuis JD, Zwart A, Mulligan T, Iranmanesh A: Muting of androgen negative feedback unveils impoverished gonadotropin-releasing hormone/ luteinizing hormone secretory reactivity in healthy older men. J Clin Endocrinol Metab 2001;86: 529-535.
13. Pincus SM, Mulligan T, Iranmanesh A, Gheorghiu S, Godschalk M, Veldhuis JD: Older males secrete luteinizing hormone and testosterone more irregularly, and jointly more asynchronously, than younger males. Proc Natl Acad Sci USA 1996;93: 14100-14105.
14. Bonavera JJ, Swerdloff RS, Sinha Hakim AP, Lue YH, Wang C: Aging results in attenuated gonadotropin releasing hormone-luteinizing hormone axis respon -siveness to glutamate receptor agonist N-methyl-D-aspartate. J Neuroendocrinol 1998;10: 93-99.
15. Orwoll E, Lambert LC, Marshall LM, Blank J, Barrett-Connor E, Cauley J, Ensrud K, Cummings SR: Endogenous testosterone levels, physical performance, and fall risk in older men. Arch Intern Med 2006;166:2124-2131.
16. O'Donnell AB, Travison TG, Harris SS, Tenover JL, McKinlay JB: Testosterone, dehydroepiandroster -one and physical performance in older men: results from the Massachusetts Male Aging Study. J Clin Endocrinol Metab 2005;91:425-431.
17. Schaap LA, Pluijm SM, Smit JH, van Schoor NM, Visser M, Gooren LJ, Lips P: The association of sex hormone levels with poor mobility, low muscle strength and incidence of falls among older men and women. Clin Endocrinol (Oxf) 2005;63:152-160.
18. Dobs AS, Dempsey MA, Ladenson P W, Polk BF: Endocrine disorders in men infected with human immunodeficiency virus. Am J Med 1988;84: 611-616.
19. Arver S, Sinha-Hikim I, Beall G, Guerrero M, Shen R, Bhasin S: Serum dihydrotestosterone and testosterone concentrations in human immunodeficiency virus-infected men with and without weight loss. J Androl 1999;20:611-618.
20. Salehian B, Jacobson D, Swerdloff RS, Grafe MR, Sinha-Hikim I, McCutchan JA: Testicular pathologic changes and the pituitary-testicular axis during human immunodeficiency virus infection. Endocr Pract 1999;5:1-9.
21. Handelsman DJ: Hypothalamic-pituitary gonadal dysfunction in renal failure, dialysis and renal transplantation. Endocr Rev 1985;6:151-182.
22. Wilson J: Androgen abuse by athletes. Endocr Rev 1988;9:181-191.
23. Bhasin S, Woodhouse L, Storer TW: Proof of the effect of testosterone on skeletal muscle. J E ndo c rinol 2001;170:27-38.
24. Bhasin S, Calof OM, Storer T W, Lee ML, Mazer NA, Jasuja R, Montori VM, Gao W, Dalton JT: Drug insight: testosterone and selective androgen receptor modulators as anabolic therapies for chronic illness and aging. Nature Clin Pract 2006;2:146-159.
25. Katznelson L, Finkelstein JS, Schoenfeld DA, Rosen -thal DI, Anderson EJ, Klibanski A: Increase in bone density and lean body mass during testosterone adm -in istration in men with acquired hypogonadism. J Clin Endocrinol Metab 1996;81:4358-4365.
26. Mauras N, Hayes V, Welch S, Rini A, Helgeson K, Dokler M, Veldhuis JD, Urban RJ: Testosterone deficiency in young men: marked alterations in whole body protein kinetics, strength, and adiposity. J Clin Endocrinol Metab 1998;83:1886-1892.
27. Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, Montori VM: Testosterone therapy in adult men with androgen deficiency syndromes: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2006; 91:1995-2010.
28. Bhasin S, Storer T W, Berman N, Yarasheski KE, Clevenger B, Phillips J, Lee W P, Bunnell TJ, Casaburi R: Testosterone replacement increases fat-free mass and muscle size in hypogonadal men. J Clin Endocrinol Metab 1997;82:407-413.
29. Brodsky IG, Balagopal P, Nair KS: Effects of testosterone replacement on muscle mass and muscle protein synthesis in hypogonadal men: a clinical research center study. J Clin Endocrinol Metab 1996;81:3469-3475.
30. Bhasin S, Storer T W, Berman N, Callegari C, Clevenger B, Phillips J, Bunnell TJ, Tricker R, Shirazi A, Casaburi R: The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men. N Engl J Med 1996;335:1-7.
31. Bhasin S, Woodhouse L, Casaburi R, Singh AB, Bhasin D, Berman N, Chen X, Yarasheski KE, Magliano L, Dzekov C, Dzekov J, Bross R, Phillips J, Sinha-Hikim I, Shen R, Storer TW: Testosterone dose-response relationships in healthy young men. Am J Physiol Endocrinol Metab 2001;281: E1172-E1181.
32. Woodhouse LJ, Reisz-Porszasz S, Javanbakht M, Storer T W, Lee M, Zerounian H, Bhasin S: Development of models to predict anabolic response to testosterone administration in healthy young men. Am J Physiol Endocrinol Metab 2003;284: E1009-E1017.
33. Storer T W, Magliano L, Woodhouse L, Lee ML, Dzekov C, Dzekov J, Casaburi R, Bhasin S: Testosterone dose-dependently increases maximal voluntary strength and leg power, but does not affect fatigability or specific tension. J Clin Endo -crinol Metab 2003;88:1478-1485.
34. Snyder PJ, Peachey H, Hannoush P, Berlin JA, Loh L, Lenrow DA, Holmes JH, Dlewati A, Santanna J, Rosen CJ, Strom BL: Effect of testosterone treatment on body composition and muscle strength in men over 65 years of age. J Clin Endocrinol Metab 1999;84:2647-2653.
35. Page ST, Amory JK, Bowman FD, Anawalt BD, Matsumoto AM, Bremner WJ, Tenover JL: Exogenous testosterone (T) alone or with finasteride increases physical performance, grip strength, and lean body mass in older men with low serum T. J Clin Endocrinol Metab 2005;90:1502-1510.
36. Kong A, Edmonds P: Testosterone therapy in HIV wasting syndrome: systematic review and meta-analysis. Lancet Infect Dis 2002;2:692-699.
37. Bhasin S, Storer T W, Javanbakht M, Berman N, Yarasheski KE, Phillips J, Dike M, Sinha-Hikim I, Shen R, Hays RD, Beall G: Testosterone replacement and resistance exercise in HIV-infected men with weight loss and low testosterone levels. JAMA 2000;283:763-770.
38. Grinspoon S, Corcoran C, Parlman K, Costello M, Rosenthal D, Anderson E, Stanley T, Schoenfeld D, Burrows B, Hayden D, Basgoz N, Klibanski A: Effects of testosterone and progressive resistance training in eugonadal men with AIDS wasting: a randomized, controlled trial. Ann Intern Med 2000; 133:348-355.
39. Bhasin S, Storer T W, Asbel-Sethi N, Kilbourne A, Hays R, Sinha-Hikim I, Shen R, Arver S, Beall G: Effects of testosterone replacement with a nongeni-tal, transdermal system, Androderm, in human immunodeficiency virus-infected men with low testosterone levels. J Clin Endocrinol Metab 1998;83: 3155-3162.
40. Wang H, Kubica N, Ellisen LW, Jefferson LS, Kimball SR: Dexamethasone represses signaling through the mammalian target of rapamycin in muscle cells by enhancing expression of REDD1. J Biol Chem 2006;281:39128-39134.
41. Kamischke A, Kemper DE, Castel MA, Luthke M, Rolf C, Behre HM, Magnussen H, Nieschlag E: Testosterone levels in men with chronic obstructive pulmonary disease with or without glucocorticoid therapy. Eur Respir J 1998;11:41-45.
42. Crawford BA, Liu PY, Kean MT, Bleasel JF, Handelsman DJ: Randomized placebo-controlled trial of androgen effects on muscle and bone in men requiring long-term systemic glucocorticoid treatment. J Clin Endocrinol Metab 2003;88:3167-3176.
43. Reid IR, Wattie DJ, Evans MC, Stapleton JP: Testos -terone therapy in glucocorticoid-treated men. Arch Intern Med 1996;156:1173-1177.
44. Casaburi R, Bhasin S, Cosentino L, Porszasz J, Somfay A, Lewis MI, Fournier M, Storer TW: Effects of testosterone and resistance training in men with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2004;170:870-878.
45. Schols AM, Soeters PB, Mostert R, Pluymers RJ, Wouters EF: Physiologic effects of nutritional support and anabolic steroids in patients with chronic obstructive pulmonary disease: a placebo-controlled randomized trial. Am J Respir Crit Care Med 1995;152:1268-1274.
46. Johansen KL, Shubert T, Doyle J, Soher B, Sakkas GK, Kent-Braun JA: Muscle atrophy in patients receiving hemodialysis: effects on muscle strength, muscle quality, and physical function. Kidney Int 2003;63:291-297.
47. Johansen KL, Mulligan K, Schambelan M: Anabolic effects of nandrolone decanoate in patients receiving dialysis: a randomized controlled trial. JAMA 1999;281:1275-1281.
48. Johansen KL, Painter PL, Sakkas GK, Gordon P, Doyle J, Shubert T: Effects of resistance exercise training and nandrolone decanoate on body composition and muscle function among patients who receive hemodialysis: a randomized, controlled trial. J Am Soc Nephrol 2006;17:2307-2314.
49. Dolan S, Wilkie S, Aliabadi N, Sullivan MP, Basgoz N, Davis B, Grinspoon S: Effects of testosterone administration in human immunodeficiency virus-infected women with low weight: a randomized placebo-controlled study. Arch Intern Med 2004; 164:897-904.
50. Miller K, Corcoran C, Armstrong C, Caramelli K, Anderson E, Cotton D, Basgoz N, Hirschhorn L, Tuomala R, Schoenfeld D, Daugherty C, Mazer N, Grinspoon S: Transdermal testosterone administration in women with acquired immunodeficiency syndrome wasting: a pilot study. J Clin Endocrinol Metab 1998;83:2717-2725.
51. Choi HH, Gray PB, Storer T W, Calof OM, Woodhouse L, Singh AB, Padero C, Mac RP, Sinha-Hikim I, Shen R, Dzekov J, Dzekov C, Kushnir MM, Rockwood AL, Meikle AW, Lee ML, Hays RD, Bhasin S: Effects of testosterone replacement in human immunodeficiency virus-infected women with weight loss. J Clin Endocrinol Metab 2005;90: 1531-1541.
52. Dobs AS, Nguyen T, Pace C, Roberts CP: Differential effects of oral estrogen versus oral estrogen-andro-gen replacement therapy on body composition in postmenopausal women. J Clin Endocrinol Metab 2002;87:1509-1516.
53. Katznelson L, Rosenthal DI, Rosol MS, Anderson EJ, Hayden DL, Schoenfeld DA, Klibanski A: Using quantitative CT to assess adipose distribution in adult men with acquired hypogonadism. AJR Am J Roentgenol 1998;170:423-427.
54. Woodhouse LJ, Gupta N, Bhasin M, Singh AB, Ross R, Phillips J, Bhasin S: Dose-dependent effects of testosterone on regional adipose tissue distribution in healthy young men. J Clin Endocrinol Metab 2004;89:718-726.
55. Marin P, Holmang S, Jonsson L, Sjostrom L, Kvist H, Holm G, Lindstedt G, Bjorntorp P: The effects of testosterone treatment on body composition and metabolism in middle-aged obese men. Int J Obes Relat Metab Disord 1992;16:991-997.
56. Pitteloud N, Mootha VK, Dwyer AA, Hardin M, Lee H, Eriksson KF, Tripathy D, Yialamas M, Groop L, Elahi D, Hayes FJ: Relationship between testosterone levels, insulin sensitivity, and mitochondrial function in men. Diabetes Care 2005;28:1636-1642.
57. Kapoor D, Goodwin E, Channer KS, Jones TH: Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes. Eur J Endocrinol 2006;154:899-906.
58. Singh AB, Hsia S, Alaupovic P, Sinha-Hikim I, Woodhouse L, Buchanan TA, Shen R, Bross R, Berman N, Bhasin S: The effects of varying doses of T on insulin sensitivity, plasma lipids, apolipoproteins, and C-reactive protein in healthy young men. J Clin Endocrinol Metab 2002;87:136-143.
59. Holmang A, Bjorntorp P: The effects of testosterone on insulin sensitivity in male rats. Acta Physiol Scand 1992;146:505-510.
60. Sinha-Hikim I, Artaza J, Woodhouse L, Gonzalez-Cadavid N, Singh AB, Lee MI, Storer T W, Casaburi R, Shen R, Bhasin S: Testosterone-induced increase in muscle size in healthy young men is associated with muscle fiber hypertrophy. Am J Physiol Endocrinol Metab 2002;283:E154-E164.
61. Sinha-Hikim I, Roth SM, Lee MI, Bhasin S: Testo -sterone-induced muscle hypertrophy is associated with an increase in satellite cell number in healthy, young men. Am J Physiol Endocrinol Metab 2003; 285:E197-E205.
62. Singh R, Artaza JN, Taylor WE, Gonzalez-Cadavid N F, Bhasin S: Androgens stimulate myogenic differentiation and inhibit adipogenesis in C3H 10T1/2 pluripotent cells through an androgen receptor-mediated pathway. Endocrinology 2003;44:5081-5088.
63. Singh R, Artaza JN, Taylor WE, Braga M, Yuan X, Gonzalez-Cadavid NF, Bhasin S: Testosterone inhi -bits adipogenic differentiation in 3T3-L1 cells: nucl -ear translocation of androgen receptor complex with beta-catenin and T-cell factor 4 may bypass canonical Wnt signaling to down-regulate adipogenic trans -cription factors. Endocrinology 2006;147:141-154.
64. Wilson JD, Griffin JE, Russell DW: Steroid 5 alpha-reductase 2 deficiency. Endocr Rev 1993;14:577-593.
65. Jones ME, Thorburn AW, Britt KL, Hewitt KN, Wreford NG, Proietto J, Oz OK, Leury BJ, Robertson KM, Yao S, Simpson ER: Aromatase-deficient (ArKO) mice have a phenotype of increased adiposity. Proc Natl Acad Sci USA 2000;97:12735-12740.
66. Negro-Vilar A: Selective androgen receptor modulators (SARMs): a novel approach to androgen therapy for the new millennium. J Clin Endocrinol Metab 1999;84:3459-3462.
67. Dalton JT, Mukherjee A, Zhu Z, Kirkovsky L, Miller DD: Discovery of nonsteroidal androgens. Biochem Biophys Res Commun 1998;244:1-4.
68. Bohl CE, Miller DD, Chen J, Bell CE, Dalton JT: Structural basis for accommodation of nonsteroidal ligands in the androgen receptor. J Biol Chem 2005; 280:37747-37754.