Oxandrolone in the treatment of HIV-associated weight loss in men: A randomized, double-blind, placebo-controlled study

Journal of Acquired Immune Deficiency Syndromes

Volumn 41, Issue 3, 2006, Pages 304-314

  Grunfeld, Carl ^a,f   Kotler, Donald P ^b   Dobs, Adrian ^c   Glesby, Marshall ^d   Bhasin, Shalender ^e  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b Columbia University School of Medicine ^*  (United States)

^c JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d Community Research Initiative on AIDS ^*  (United States)

^e CHARLES R DREW UNIVERSITY OF MEDICINE AND SCIENCE   (United States)

^f SAN FRANCISCO VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

Anabolic steroid; Anabolic therapy; Atherosclerosis; Body composition; Cachexia; Fat toxicity; Lean body mass; Lipoproteins; Liver function; Wasting syndrome

Indexed keywords

AMINOTRANSFERASE; ANABOLIC AGENT; FOLLITROPIN; HIGH DENSITY LIPOPROTEIN; LIPOPROTEIN; LOW DENSITY LIPOPROTEIN; LUTEINIZING HORMONE; OXANDROLONE; PLACEBO; SEX HORMONE BINDING GLOBULIN; STEROID;

ABNORMALLY HIGH SUBSTRATE CONCENTRATION IN BLOOD; ABNORMALLY LOW SUBSTRATE CONCENTRATION IN BLOOD; AMINOTRANSFERASE BLOOD LEVEL; ARTICLE; ATHEROSCLEROSIS; BODY COMPOSITION; BODY MASS; BODY WEIGHT DISORDER; CACHEXIA; CHOLESTEROL BLOOD LEVEL; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CORRELATION ANALYSIS; DISEASE SEVERITY; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; FOLLITROPIN BLOOD LEVEL; HORMONE BLOOD LEVEL; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; INNER CELL MASS; LIVER FUNCTION; LIVER TOXICITY; LUTEINIZING HORMONE BLOOD LEVEL; MAJOR CLINICAL STUDY; MALE; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; TESTOSTERONE BLOOD LEVEL; TIME SERIES ANALYSIS; WASTING SYNDROME; WEIGHT FLUCTUATION; WEIGHT GAIN; WEIGHT REDUCTION;

ADULT; ANABOLIC AGENTS; BODY MASS INDEX; DOUBLE-BLIND METHOD; FOLLICLE STIMULATING HORMONE; HIV INFECTIONS; HUMANS; LIPOPROTEINS, HDL; LUTEINIZING HORMONE; MALE; MIDDLE AGED; OXANDROLONE; PLACEBOS; SEX HORMONE-BINDING GLOBULIN; TESTOSTERONE; TRANSAMINASES; WEIGHT LOSS;

EID: 33645108179     PISSN: 15254135     EISSN: None     Source Type: Journal    
DOI: 10.1097/01.qai.0000197546.56131.40     Document Type: Article

References (68)

1. Hoover DR, Saah AJ, Bacellar H, et al. Clinical manifestations of AIDS in the era of pneumocystis prophylaxis. Multicenter AIDS Cohort Study. N Engl J Med. 1993;329:1922-1926.
2. Weiss PJ, Wallace MR, Olson PE, et al. Changes in the mix of AIDS-defining conditions. N Engl J Med. 1993;329:1962.
3. Nahlen BL, Chu SY, Nwanyanwu OC, et al. HIV wasting syndrome in the United States. AIDS. 1993;7:183-188.
4. Wanke CA, Silva M, Knox TA, et al. Weight loss and wasting remain common complications in individuals infected with human immunodeficiency virus in the era of highly active antiretroviral therapy. Clin Infect Dis. 2000;31:803-805.
5. Lindan CP, Allen S, Serufilira A, et al. Predictors of mortality among HIV-infected women in Kigali, Rwanda. Ann Intern Med. 1992;116:320-328.
6. Kotler DP, Tierney AR, Wang J, et al. Magnitude of body-cell-mass depletion and the timing of death from wasting in AIDS. Am J Clin Nutr. 1989;50:444-447.
7. Guenter P, Muurahainen N, Simons G, et al. Relationships among nutritional status, disease progression, and survival in HIV infection. J Acquir Immune Defic Syndr Hum Retrovirol. 1993;6:1130-1138.
8. Suttmann U, Ockenga J, Selberg O, et al. Incidence and prognostic value of malnutrition and wasting in human immunodeficiency virus-infected outpatients. J Acquir Immune Defic Syndr Hum Retrovirol. 1995;8:239-246.
9. Ott M, Fischer H, Polat H, et al. Bioelectrical impedance analysis as a predictor of survival in patients with human immunodeficiency virus infection. J Acquir Immune Defic Syndr Hum Retrovirol. 1995;9:20-25.
10. Palenicek JP, Graham NM, He YD, et al. Weight loss prior to clinical AIDS as a predictor of survival. Multicenter AIDS Cohort Study Investigators. J Acquir Immune Defic Syndr Hum Retrovirol. 1995; 10:366-373.
11. Melchior JC, Niyongabo T, Henzel D, et al. Malnutrition and wasting, immunodepression and chronic inflammation are independent predictors of survival in HIV-infected patients. Nutrition. 1999;15: 865-869.
12. Turner J, Muurahainen N, Graber TC, et al. Nutritional status and quality of life. Presented at: Xth International Conference on AIDS; Yokohama, Japan, 1994.
13. Cohan GR, Muurahainen N, Guenter P, et al. HIV-related hospitalization, CD4 percent and nutritional markers. Presented at: VIII International Conference on AIDS; 1992; Amsterdam.
14. Wilson IB, Roubenoff R, Knox T, et al. Relation of lean body mass to health-related quality of life in persons with HIV. J Acquir Immune Defic Syndr. 2000;24:137-146.
15. Wagner GJ, Ferrando SJ, Rabkin JG. Psychological and physical health correlates of body cell mass depletion among HIV+ men. J Psychosom Res. 2000;49:55-57.
16. Kotler DP, Wang J, Pierson RN. Body composition studies in patients with the acquired immunodeficiency syndrome. Am J Clin Nutr. 1985; 42:1255-1265.
17. Ott M, Lembcke B, Fischer H, et al. Early changes of body composition in human immunodeficiency virus-infected patients: tetrapolar body impedance analysis indicates significant malnutrition. Am J Clin Nutr. 1993;57:15-19.
18. Paton NI, Macallan DC, Jebb SA, et al. Longitudinal changes in body composition measured with a variety of methods in patients with AIDS. J Acquir Immune Defic Syndr Hum Retrovirol. 1997;14:119-127.
19. Mulligan K, Tai VW, Schambelan M. Cross-sectional and longitudinal evaluation of body composition in men with HIV infection. J Acquir Immune Defic Syndr Hum Retrovirol. 1997;15:43-48.
20. Grinspoon S, Corcoran C, Miller K, et al. Body composition and endocrine function in women with acquired immunodeficiency syndrome. J Clin Endocrinol Metab. 1997;82:1332-1337.
21. Swanson B, Hershow RC, Sha BE, et al. Body composition in HIV-infected women. Nutrition. 2000;16:1064-1068.
22. Kotler DP, Tierney AR, Culpepper-Morgan JA, et al. Effect of home total parenteral nutrition on body composition in patients with acquired immunodeficiency syndrome. JPRN J Parenter Enteral Nutr. 1990;14:454-458.
23. Kotler DP, Tierney AR, Ferraro R, et al. Enteral alimentation and repletion of body cell mass in malnourished patients with acquired immunodeficiency syndrome. Am J Clin Nutr. 1991;53:149-154.
24. Von Roenn JH, Armstrong D, Kotler DP, et al. Megestrol acetate in patients with AIDS-related cachexia. Ann Intern Med. 1994;121:393-399.
25. Oster MH, Enders SR, Samuels SJ, et al. Megestrol acetate in patients with AIDS and cachexia. Ann Intern Med. 1994;121:400-408.
26. Mulligan K, Grunfeld C, Hellerstein MK, et al. Anabolic effects of recombinant human growth hormone in patients with wasting associated with human immunodeficiency virus infection. J Clin Endocrinol Metab. 1993;77:956-962.
27. Krentz AJ, Koster FT, Crist DM, et al. Anthropometric, metabolic, and immunological effects of recombinant human growth hormone in AIDS and AIDS-related complex. J Acquir Immune Defic Syndr Hum Retrovirol. 1993;6:245-251.
28. Schambelan M, Mulligan K, Grunfeld C, et al. Recombinant human growth hormone in patients with HIV-associated wasting. A randomized, placebo-controlled trial. Serostim Study Group [see comments]. Ann Intern Med. 1996;125:873-882.
29. Moyle GJ, Daar E, Gertner J, et al. Growth hormone improves lean body mass, physical performance and quality of life in subjects with HIV-associated weight loss or wasting on highly active antiretroviral therapy. J Acquir Immune Defic Syndr. 2004;35:367-375.
30. Coodley GO, Coodley MK. A trial of testosterone therapy for HIV-associated weight loss. AIDS. 1997;11:1347-1352.
31. Grinspoon S, Corcoran C, Askari H, et al. Effects of androgen administration in men with the AIDS wasting syndrome. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1998;129:18-26.
32. Bhasin S, Storer TW, Asbel-Sethi N, et al. Effects of testosterone replacement with a nongenital, transdermal system, Androderm, in human immunodeficiency virus-infected men with low testosterone levels. J Clin Endocrinol Metab. 1998;83:3155-3162.
33. Dobs AS, Cofrancesco J, Nolten WE, et al. The use of a transscrotal testosterone delivery system in the treatment of patients with weight loss related to human immunodeficiency virus infection. Am J Med. 1999;107:126-132.
34. Grinspoon S, Corcoran C, Anderson E, et al. Sustained anabolic effects of long-term androgen administration in men with AIDS wasting. Clin Infect Dis. 1999;28:634-636.
35. Bhasin S, Storer TW, Javanbakht M, et al. Testosterone replacement and resistance exercise in HIV-infected men with weight loss and low testosterone levels. JAMA. 2000;283:763-770.
36. Grinspoon S, Corcoran C, Parlman K, et al. Effects of testosterone and progressive resistance training in eugonadal men with AIDS wasting. A randomized, controlled trial. Ann Intern Med. 2000;133:348-355.
37. Fairfield WP, Treat M, Rosenthal DI, et al. Effects of testosterone and exercise on muscle leanness in eugonadal men with AIDS wasting. J Appl Physiol. 2001;90:2166-2171.
38. Mendenhall CL, Anderson S, Garcia-Pont P, et al. Short-term and long-term survival in patients with alcoholic hepatitis treated with oxandrolone and prednisolone. N Engl J Med. 1984;311:1464-1470.
39. Chlebowski RT, Herrold J, Ali I, et al. Influence of nandrolone decanoate on weight loss in advanced non-small cell lung cancer. Cancer. 1986;58:183-186.
40. Mendenhall CL, Moritz TE, Roselle GA, et al. A study of oral nutritional support with oxandrolone in malnourished patients with alcoholic hepatitis: results of a Department of Veterans Affairs cooperative study. Hepatology. 1993;17:564-576.
41. Demling RH, Orgill DP. The anticatabolic and wound healing effects of the testosterone analog oxandrolone after severe burn injury. J Crit Care. 2000;15:12-17.
42. Orr R, Fiatarone Singh M. The anabolic androgen oxandrolone in the treatment of wasting and catabolic disorders: review of efficacy and safety. Drugs. 2004;64:725-750.
43. Berger JR, Pall L, Winfield D. Effect of anabolic steroids on HIV-related wasting myopathy. J South Med. 1993;86:865-866.
44. Gold J, High HA, Li Y, et al. Safety and efficacy of nandrolone decanoate for treatment of wasting in patients with HIV infection. AIDS. 1996;10:745-752.
45. Berger JR, Pall L, Hall CD, et al. Oxandrolone in AIDS-wasting myopathy. AIDS. 1996;10:1657-1662.
46. Strawford A, Barbieri T, Neese R, et al. Effects of nandrolone decanoate therapy in borderline hypogonadal men with HIV-associated weight loss. J Acquir Immune Defic Syndr. 1999;20:137-146.
47. Strawford A, Barbieri T, Van Loan M, et al. Resistance exercise and supraphysiologic androgen therapy in eugonadal men with HIV-related weight loss: a randomized controlled trial. JAMA. 1999;281:1282-1290.
48. Sattler FR, Jaque SV, Schroeder ET, et al. Effects of pharmacological doses of nandrolone decanoate and progressive resistance training in immunodeficient patients infected with human immunodeficiency virus. J Clin Endocrinol Metab. 1999;84:1268-1276.
49. Batterham MJ, Garsia R. A comparison of megestrol acetate, nandrolone decanoate and dietary counselling for HIV associated weight loss. Int J Androl. 2001;24:232-240.
50. Earthman CP, Reid PM, Harper IT, et al. Body cell mass repletion and improved quality of life in HIV-infected individuals receiving oxandrolone. JPEN J Parenter Enteral Nutr. 2002;26:357-365.
51. Hengge UR, Stocks K, Wiehler H, et al. Double-blind, randomized, placebo-controlled phase III trial of oxymetholone for treatment of HIV wasting. AIDS. 2003;17:699-710.
52. Wu AW, Rubin HR, Mathews WC, et al. A health status questionnaire using 30 items from the Medical Outcomes Study. Preliminary validation in persons with early HIV infection. Med Care. 1991;29:786-798.
53. Bhasin S, Storer TW, Berman N, et al. The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men. N Engl J Med. 1996;335:1-7.
54. Sinha-Hikim I, Arver S, Beall G, et al. The use of a sensitive equilibrium dialysis method for the measurement of free testosterone levels in healthy, cycling women and in human immunodeficiency virus-infected women. J Clin Endocrinol Metab. 1998;83:1312-1318.
55. Choi HH, Gray P, Calof O, et al. The effects of testosterone replacement in HIV-infected women with weight loss. J Clin Endocrinol Metab. 2005;90:1531-1541.
56. Wolf SE, Thomas SJ, Dasu MR, et al. Improved net protein balance, lean mass, and gene expression changes with oxandrolone treatment in the severely burned. Ann Surg. 2003;237:801-810.
57. Sheffield-Moore M, Wolfe RR, Gore DC, et al. Combined effects of hyperaminoacidemia and oxandrolone on skeletal muscle protein synthesis. Am J Physiol Endocrinol Metab. 2000;278:E273-E279.
58. Sheffield-Moore M, Urban RJ, Wolf SE, et al. Short-term oxandrolone administration stimulates net muscle protein synthesis in young men. J Clin Endocrinol Metab. 1999;84:2705-2711.
59. Schroeder ET, Zheng L, Ong MD, et al. Effects of androgen therapy on adipose tissue and metabolism in older men. J Clin Endocrinol Metab. 2004;89:4863-4872.
60. Schroeder ET, Zheng L, Yarasheski KE, et al. Treatment with oxandrolone and the durability of effects in older men. J Appl Physiol. 2004;96:1055-1062. [Epub 2003 Oct 24].
61. Kong A, Edmonds P. Testosterone therapy in HIV wasting syndrome: systematic review and meta-analysis. Lancet Infect Dis. 2002;2:692-699.
62. Bhasin S, Woodhouse L, Casaburi R, et al. Testosterone dose-response relationships in healthy young men. Am J Physiol Endocrinol Metab. 2001;281:E1172-E1181.
63. Bhasin S, Woodhouse L, Casaburi R, et al. Older men are as responsive as young men to the anabolic effects of graded doses of testosterone on the skeletal muscle. J Clin Endocrinol Metab. 2004;Nov 23. [Epub ahead of print].
64. Storer TW, Magliano L, Woodhouse L, et al. Testosterone dose-dependently increases maximal voluntary strength and leg power, but does not affect fatigability or specific tension. J Clin Endocrinol Metab. 2003;88:1478-1485.
65. Hickson RC, Ball KL, Falduto MT. Adverse effects of anabolic steroids. Med Toxicol Adverse Drug Exp. 1989;4:254-271.
66. Ishak KG, Zimmerman HJ. Hepatotoxic effects of the anabolic/androgenic steroids. Semin Liver Dis. 1987;7:230-236.
67. Storer TW, Woodhouse LJ, Sattler F, et al. A randomized, placebo-controlled trial of nandrolone decanoate in human immunodeficiency virus-infected men with mild to moderate weight loss with recombinant human growth hormone as active reference treatment. J Clin Endocrinol Metab. 2005;90:4474-4482. [Epub 2005 May 24].
68. Mulligan K, Zackin R, Clark RA, et al. AIDS Clinical Trials Group 329 Study Team; National Institute of Allergy and Infectious Diseases Adult AIDS Clinical Trials Group. Effect of nandrolone decanoate therapy on weight and lean body mass in HIV-infected women with weight loss: a randomized, double-blind, placebo-controlled, multicenter trial. Arch Intern Med. 2005;165:578-585.