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Oxymetholone promotes weight gain in patients with advanced human immunodeficiency virus (HIV-1) infection*

Published online by Cambridge University Press:  09 March 2007

Ulrich R. Hengge ,
Mathias Baumann ,
Rolf Maleba ,
Norbert H. Brockmeyer  and
Manfred Goos
Ulrich R. Hengge
Affiliation:
Department of Dermatology, Venerology and Allergy, STD Unit, University of Essen, Germany
Mathias Baumann
Affiliation:
Department of Dermatology, Venerology and Allergy, STD Unit, University of Essen, Germany
Rolf Maleba
Affiliation:
Department of Neurology, University of Essen, Germany
Norbert H. Brockmeyer
Affiliation:
Department of Dermatology, Venerology and Allergy, STD Unit, University of Essen, Germany
Manfred Goos
Affiliation:
Department of Dermatology, Venerology and Allergy, STD Unit, University of Essen, Germany
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Abstract

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The effect of the testosterone derivative oxymetholone alone or in combination with the H1receptor antagonist ketotifen, which has recently been shown to block tumour necrosis factor α (TNFα), on weight gain and performance status in human immunodeficiency virus (HIV) patients with chronic cachexia was evaluated in a 30 week prospective pilot study. Thirty patients were randomly assigned to either oxymetholone monotherapy (n 14) or oxymetholone plus ketotifen (n 16). Patients receiving treatment were compared with a group of thirty untreated matched controls, who met the same inclusion criteria. Body weight and the Karnofsky index, which assessesthe ability to perform activities of daily life, and several quality-of-life variables were measured to evaluate response to therapy. The average weight gain at peak was 8. 2 (SD 6. 2) kg ( + 14. 5 % of body weight at study entry) in the oxymetholone group (P<0·0.001), and 6.1 (SD 4.6) kg (+ 10.9 %) in the combination group (P<0·005), compared with an average weight loss of 1.8 (SD 0.7) kg in the untreated controls. The mean time to peak weight was 196 weeks in the monotherapy group and 20.8 weeks in the combination group. The Karnofsky index improved equally in both groups from 56% before to 67% after 20 weeks of treatment (P< 0·05). The quality of life variables (activities of daily life, and appetite/nutrition) improved in 68 % (P<0·05)and 91%(P< 0·01) of the treated patients respectively. Oxymetholone was safe and promoted weight gain in cachectic patients with advanced HIV-1 infection. The addition of ketotifendid not further support weight gain. These results suggest the need for a randomized, double-blind, placebo-controlled multicentre trial.

Keywords

CachexiaHuman immunodeficiency virusOxymetholone
Type
Oxymetholone for weight gain in HIV infection
Information
British Journal of Nutrition , Volume 75 , Issue 1 , January 1996 , pp. 129 - 138
Copyright
Copyright © The Nutrition Society 1996

References

REFERENCES

Allen, B. J., Blagojevic, N., Delaney, I., Pollock, C. A., Ibels, L. S., Allman, M. A., Tiller, DJ., Gaskin, K. J., Baur, L. A., Waters, D. L., Cowell, C., Ambler, G., Quigley, C. & Fletcher, J. P. (1990). The role of body protein in clinical trials. In In Vivo Body Composition Studies, pp. 155–169 [Yasumura, S., Harrison, J. E., McNeill, K. G., Woodhead, A. D. and Dilmanian, F. A., editors] New York: Plenum Press.Google Scholar
Arnold, A., Potts, G. O. & Beyler, A. L. (1963). Evaluation of the protein anabolic properties of certain orally active anabolic agents based on nitrogen balance studies in rats. Endocrinology 72, 408–417.CrossRefGoogle Scholar
Beisel, W. R., Edelmann, R., Nauss, K. & Suskind, R. M. (1981). Single-nutrient effects on immunologic functions. Journal of the American Medical Association 245, 53–58.CrossRefGoogle ScholarPubMed
Camerino, B. & Sala, G. (1960). Anabolic steroids. Progress in Drug Research 2, 71–134.Google Scholar
Chandra, R. K. (1983). Nutrition, immunity, and infection: present knowledge and future directions. Lancet 1, 688–691.CrossRefGoogle ScholarPubMed
Coodley, G. O., Loveless, M. O., Nelson, H. D. & Coodley, M. K. (1994). Endocrine function in the HIV wasting syndrome. Journal of the Acquired Immune Deficiency Syndrome 7, 46–51.Google Scholar
Dobs, A. S., Dempsey, M. A., Ladenson, P. W. & Polk, B. F. (1988). Endocrine disorders in men infected with the human immunodeficiency virus. American Journal of Medicine 84, 611–616.Google Scholar
Doney, K., Pepe, M., Storb, R., Bryant, E., Anasetti, C., Appelbaum, F. R., Buckner, C. D. & Sanders, J. (1992). Immunosuppressive therapy of aplastic anemia: results of a prospective, randomized trial of antithymocyte globulin (ATG), methylprednisolone, and oxymetholone to ATG, very high methylprednisolone, and oxymetholone. Blood 79, 2566–2571.CrossRefGoogle ScholarPubMed
Engelson, E. S., Pisunyer, F. X. & Kotler, D. P. (1995). Effects of megestrol acetate therapy on bodycomposition and circulating testosterone concentrations in patients with AIDS. AIDS 9, 1107–1108.Google Scholar
Escaich, S., Ritter, J., Rougier, P., Lepot, D., Lamelin, J. P., Sepetjan, M. & Trepo, C. (1991). Plasma viraemia as a marker of viral replication in HIV-infected individuals. AIDS 5, 118–1194.CrossRefGoogle ScholarPubMed
Forbes, G. B. (1985). The effect of anabolic steroids on lean body mass: the dose response curve. Metabolism 34, 571–573.Google Scholar
Forbes, G. B., Porta, C. R., Herr, B. E. & Griggs, R. C. (1992). Sequence of changes in body composition induced by testosterone and reversal of changes after drug is stopped. Journal of the American Medical Association 267, 397–399.Google Scholar
Freed, D. F. J., Banks, A. J., Longson, D. & Burley, D. M. (1975). Anabolic steroids in athletics: crossover double-blind trial on weightlifters. British Medical Journal 2, 471–473.Google Scholar
Grunfeld, C. & Feingold, K. R. (1991). The metabolic effects of tumor necrosis factor and other cytokines. Biotherapy 3, 143–158.CrossRefGoogle ScholarPubMed
Grunfeld, C. & Feingold, K. R. (1992). Metabolic disturbances and wasting in the acquired immunodeficiency syndrome. New England Journal of Medicine 327, 329–337.Google Scholar
Hervey, G. R., Knibbs, A. V., Burkinshaw, L., ?Morgan, D. B., Jones, P. R., Chettle, D. R. & Vartsky, D. (1981). Effects of methandienone on the performance and body composition of men undergoing athletic training. Clinical Science 60, 457–461.Google Scholar
Hommes, M. J. T., Romijn, J. A., Endert, E. & Sauerwein, H. P. (1991). Resting energy expenditure and substrate oxidation in human immunodeficiency virus (HIV)-infected asymptomatic men: HIV affects host metabolism in the early asymptomatic stage. American Journal of Clinical Nutrition 54, 311–315.Google Scholar
Hughes, W. T., Price, R. A., Sisko, F., Havron, W. S., Kafatos, A. G., Schonland, M. & Smythe, P. M. (1974). Protein-calorie malnutrition: a host determinant for Pneumocystis carinii infection. American Journal of Diseases of Children 128, 44–52.Google Scholar
Kochakian, C. D. (1976). Mechanism of action: regulation of protein synthesis by anabolic-androgenic steroids. In Anabolic-androgenic Steroids, pp. 211–228 [Kochakian, C. D., editor]. New York: Springer.Google Scholar
Kotler, D. P., Tierney, A. R., Altilio, D., Wang, J. & Pierson, R. N. (1989a). Body mass repletion during ganciclovir therapy of cytomegalovirus infection in patients with the acquired immunodeficiency syndrome. Archives of Internal Medicine 149, 901–905.CrossRefGoogle ScholarPubMed
Kotler, D. P., Tierney, A. R., Brenner, S. K., Couture, S., Wang, J. & Pierson, R. N. Jr (1991). Preservation of short-term energy balance in clinically stable AIDS patients. American Journal of Clinical Nutrition 51, 17–23.Google Scholar
Kotler, D. P., Tierney, A. R., Wang, J. & Pierson, R. N. (1989b). Magnitude of body cell-mass depletion and the timing of death from wasting in AIDS. American Journal of Clinical Nutrition 50, 444–447.CrossRefGoogle ScholarPubMed
Krentz, A. J., Koster, F. T., Crist, D. M., Finn, K., Johnson, L. Z., Boyle, P. J. & Schade, D. S. (1993). Anthropometric, metabolic, and immunological effects of recombinant human growth hormone in AIDS and AIDS-related complex. Journal of the Acquired Immune Deficiency Syndrome 6, 245–251.Google Scholar
Kupfer, S. R., Underwood, L. E., Baxter, R. C. & Clemmons, D. R. (1993). Enhancement of the anabolic effects of growth hormone and insulin-like growth factor I by use of both agents simultaneously. Journal of Clinical Investigation 91, 391–396.Google Scholar
Lahdvirta, J., Maury, C. P. J., Teppo, A. M. & Repo, H. (1988). Elevated levels of circulating cachectin/tumor necrosis factor in patients with acquired immunodeficiency syndrome. American Journal of Medicine 85, 289–291.Google Scholar
Liebermann, S. A., Butterfield, G. E., Harrison, D. & Hoffman, A. R. (1993). Anabolic effects of recombinant insulin-like growth factor I in AIDS-associated cachexia. Proceedings of the 75th Annual Meeting of the Endocrine Society, 1664 Abstr.Bethesda:The Endocrine Society.Google Scholar
Loprinzi, C. L. (1992). Effect of megestrol acetate on the human pituitary-adrenal axis. Mayo Clinics Proceedings 67, 1160–1162.CrossRefGoogle ScholarPubMed
Loprinzi, C. L., Schaid, D. J., Dose, A. M., Burnham, N. L. & Jensen, M. D. (1993). Body-composition changes in patients who gain weight while receiving megestrol acetate. Journal of Clinical Oncology 11, 152–154.Google Scholar
Macallan, D. C., Noble, C., Baldwin, C., Foskett, M., McManus, T. & Griffin, G. E. (1993). Prospective analysis of patterns of weight change in stage IV human immunodeficiency virus infection. American Journal of Clinical Nutrition 58, 417–424.Google Scholar
Mayer, M. & Rosen, F. (1975). Interaction of anabolic steroids with glucocorticoid receptor sites in rat muscle cytosol. American Journal of Physiology 229, 1381–1386.Google Scholar
Micozzi, M. S., Albdnes, D., Jones, Y. & Chumlea, W. C. (1986). Correlations of body mass indices with weight, stature, and body composition in men and women in NHANES I and II. American Journal of Clinical Nutrition 44, 723–731.Google Scholar
Mor, V., Laliberte, L., Morris, J. N. &; Wiemann, M. (1984). The Karnofsky performance status scale. Cancer 53, 2002–2007.3.0.CO;2-W>CrossRefGoogle ScholarPubMed
Mulligan, K., Grunfeld, C., Hellerstein, M. K., Neese, R. A. & Schambelan, M. (1993). Anabolic effects of recombinant human growth hormone in patients with wasting associated with human immunodeficiency virus infection. Journal of Clinical Endocrinology and Metabolism 71, 956–962.Google Scholar
Navia, B. A., Jordan, B. D. & Price, R. W. (1986). The AIDS dementia complex. I. Clinical features. Annals of Neurology 19, 517–524.CrossRefGoogle ScholarPubMed
Oster, M. H., Enders, S. R., Samuels, S. J., Cone, L. A., Hooton, T. M., Browder, H. P. & Flvnn, N. M. (1994). Megestrol acetate in patients with AIDS and cachexia. Annals of Internal Medkine 121, 400–408.Google Scholar
Patton, J. S., Shepard, H. M., Wilking, H., Lewis, G., Agganval, B. B., Eessalu, T. E., Gavin, L. A. & Grunfeld, C. (1986). Interferons and tumor necrosis factors have similar catabolic effects on 3T3 L1 cells. Proceedings of the National Academy of Sciences, USA 83, 8313–8317.CrossRefGoogle ScholarPubMed
Probert, L., Keffer, J., Corbella, P., Cazlaris, H., Patsavoudi, E., Stephens, S. & Kaslaris, E. (1993). Wasting, ischemia, and lymphoid abnormalities in mice expressing T-cell targeted human tumor necrosis factor transgenes. Journal of Immunology 151, 1894–1906.Google Scholar
Reddy, M. M., Sorrell, S. J., Lange, M. & Grieco, M. H. (1988). Tumor necrosis factor and HIV p24 antigen levels in serum of HIV-infected populations. Journal of the Acquired Immune Deficiency Syndrome 1, 436–440.Google Scholar
Schedel, I., Ballmaier, M., Rohde, F., Suttmann, U. & Deicher, H. (1994). Ketotifen inhibits tumor necrosis factor alpha production in the peripheral blood mononuclear cells of patients infected with human immunodeficiency virus. Journal of Interferon Research 14, 291–292.Google Scholar
Shibuya, A., Ninomiya, N., Nakazawa, M., Nagasawa, t, Yoda, Y. & Abe, T. (1988). Oxymetholone therapy with familial antithrombin I11 deficiency. Thrombosis and Haemostasis 60, 495–497.Google Scholar
Spitzer, W. O., Dobson, A. J., Hall, J., Chesterman, E., Levi, J., Shepherd, R. & Battista, R. N. (1981). Measuring the quality of life of cancer patients: a concise QL-index for use by physicians. Journal of Chronic Diseases 34, 585–597.Google Scholar
Turani, H., Levi, J., Zevin, D. & Kessler, E. (1983). Hepatic lesions in patients on anabolic androgenic therapy. Israel Journal of Medical Sciences 19, 332–337.Google Scholar
Ullrich, R., Zeitz, M., Heise, W., L'age, M., Hofien, G. & Riecken, E. O. (1989). Small intestine function in patients infected with human immunodeficiency virus (HIV): evidence for HIV-induced enteropathy. Annals of Internal Medicine 111, 15–21.CrossRefGoogle ScholarPubMed
von Roenn, J. H., Armstrong, D., Kotler, D. P., Cohn, D. L., Klimas, N. G., Tchekmedyian, N. S., Cone, L., Brennan, P. J., & Weitzman, S. A. (1994). Megestrol acetate in patients with AIDS-related cachexia. Annals of Internal Medicine 121, 393–399.Google Scholar
Welle, S., Jozefowicz, R., Forbes, G. & Griggs, R. C., (1992). Effect of testosterone on metabolic rate and body composition in normal men and men with muscular dystrophy. Journal of Clinical Endocrinology and Metabolism 74, 332–335.Google ScholarPubMed
Williams-Ashman, H. G. (1971). Metabolic effects of testicular androgens. In Handbook of Physiology, section 3, vol. 5 [Green, R. O. and Astwood, E. G., editors]. Washington D. C.: American Physiological Society.Google Scholar
Williams, G., Ghatei, M., Burrin, J. & Bloom, S. (1986). Severe hyperglucagonaemia during treatment with oxymetholone. British Medical Journal 292, 1637–1638.Google Scholar