Update on clinical trials of growth factors and anabolic steroids in cachexia and wasting

Abstract

This article and others that focused on the clinical features, mechanisms, and epidemiology of skeletal muscle loss and wasting in chronic diseases, which include chronic kidney disease, cancer, and AIDS, were presented at a symposium entitled "Cachexia and Wasting: Recent Breakthroughs in Understanding and Opportunities for Intervention," held at Experimental Biology 2009. The clinical and anabolic efficacy of specific growth factors and anabolic steroids (eg, growth hormone, testosterone, megestrol acetate) in malnutrition and other catabolic states has been the subject of considerable research during the past several decades. Research on the effects of these agents in cachexia or wasting conditions, characterized by progressive loss of skeletal muscle and adipose tissue, focused on patients with AIDS in the early 1990s, when the devastating effects of the loss of body weight, lean body mass, and adipose tissue were recognized as contributors to these patients' mortality. These same agents have also been studied as methods to attenuate the catabolic responses observed in cancer-induced cachexia and in wasting induced by chronic obstructive pulmonary disease, congestive heart failure, renal failure, and other conditions. This article provides an updated review of recent clinical trials that specifically examined the potential therapeutic roles of growth hormone, testosterone, oxandrolone, and megestrol acetate and emerging data on the orexigenic peptide ghrelin, in human cachexia and wasting.Am J Clin Nutr 2010;91(suppl):1143S-7S.

Synergistic stimulation of myogenesis by glucocorticoid and IGF-I signaling

“…GC are frequently administered to COPD patients and are known to induce muscle atrophy (14,20,34), but little is known regarding their influence on muscle regrowth. Yet recovery of muscle mass is an important and main goal of pulmonary rehabilitation programs for muscle-wasted COPD patients.…”

“…These pulmonary rehabilitation programs are often multimodal and typically include a personalized exercise program combined with nutritional support upon indication. The last two decades, several studies addressed complementation of this approach with muscle growth-stimulating pharmaceuticals, including anabolic steroids (20,22). Many of the effects of anabolic steroids are a consequence of increased androgen receptor-mediated expression of IGF-I in skeletal muscle, which, in an auto/paracrine fashion, induces local IGF signaling and subsequent muscle growth (18,23,41,44,50).…”

An Official American Thoracic Society/European Respiratory Society Statement: Update on Limb Muscle Dysfunction in Chronic Obstructive Pulmonary Disease

“…In this regard, GH has demonstrated clear anabolic effects in such patients and is currently approved for use in HIV/AIDS-associated wasting syndrome as well as in other conditions, such as chronic renal failure and some cases of short bowel syndrome. GH has also been used in patients with COPD and malnutrition, inducing substantial weight improvement and lean body mass gain (594,595). Nonetheless, results on respiratory and limb muscle strength and exercise capacity are still controversial (587,594,596,597).…”

Hypogonadism in DM1 and its relationship to erectile dysfunction

“…Experimental trials, in which sexual function was not however tested, have shown that weekly T administration in DM1 increases the muscle protein synthesis rate in DM1 [25] as well as the basal metabolic rate and lean body mass in healthy men and in men with muscular dystrophy (DM1, facioscapulohumeral and limb girdle dystrophy) [26], but has no effect on muscle strength in DM1 [27]. Moreover, the use of T to enhance strength and muscle mass has been considered not only in hypogonadal [28] and aging men [29] but also in glucocorticoid induced myopathy [30,31] and in HIV and cancer-related skeletal muscle loss and wasting [32,33]. Lastly, the effect of oxandrolone, a synthetic dehydroepiandrosterone derivative, has been investigated in dystrophynopathies and inclusion body myositis [34,35].…”