Hormone treatment and muscle anabolism during aging: androgens.

Aging is associated with a gradual decline in circulating testosterone concentrations and decreased musculature in men. While testosterone administration is often considered when symptoms of hypogonadism are presented, the long-term effects of androgen use on muscle physiology are not yet fully understood. The definition of hypogonadism in men remains obscure but is generally indicated by total testosterone concentrations less than a threshold value of 300-500 ng/dL. Androgen replacement therapy is generally safe in men and women with low endogenous testosterone concentrations. The development of selective androgen receptor modulators (SARMs) may provide additional options in treatment of hypogonadism while lowering the potential of side effects often associated with long-term androgen use. Androgen administration, either alone or in combination with other treatments, can be successful in improving muscle mass by increasing protein anabolism and reducing protein catabolism in men and women. Further research is necessary to optimize the anabolic and anticatabolic properties of androgens for treatment and prevention of muscle loss in men and women.

[1]  L. Woodhouse,et al.  Changes in Muscle Mass, Muscle Strength, and Power but Not Physical Function Are Related to Testosterone Dose in Healthy Older Men , 2008, Journal of the American Geriatrics Society.

[2]  A. Morales,et al.  Androgen deficiency in the aging male. , 2003, International journal of impotence research.

[3]  P. Snyder.  Hypogonadism in elderly men--what to do until the evidence comes. , 2004, The New England journal of medicine.

[4]  G. Dinant,et al.  Measures of bioavailable serum testosterone and estradiol and their relationships with muscle mass, muscle strength and bone mineral density in postmenopausal women: a cross-sectional study. , 2009, European journal of endocrinology.

[5]  G. Braunstein,et al.  Safety of testosterone use in women. , 2009, Maturitas.

[6]  D. Herndon,et al.  The Effect of Oxandrolone on the Endocrinologic, Inflammatory, and Hypermetabolic Responses During the Acute Phase Postburn , 2007, Annals of surgery.

[7]  Marybeth Brown,et al.  Skeletal muscle and bone: effect of sex steroids and aging. , 2008, Advances in physiology education.

[8]  G. Ostir,et al.  Assessing Functional Status Measures In Older Adults: A Guide For Healthcare Professionals , 2002 .

[9]  H. Burger,et al.  Female androgen insufficiency: the Princeton consensus statement on definition, classification, and assessment. , 2002, Fertility and sterility.

[10]  A. Kenny,et al.  Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels. , 2001, The journals of gerontology. Series A, Biological sciences and medical sciences.

[11]  V. Montori,et al.  Testosterone therapy in adult men with androgen deficiency syndromes: an endocrine society clinical practice guideline. , 2006, The Journal of clinical endocrinology and metabolism.

[12]  L. Fried,et al.  Multiple hormonal deficiencies in anabolic hormones are found in frail older women: the Women's Health and Aging studies. , 2009, The journals of gerontology. Series A, Biological sciences and medical sciences.

[13]  K. Nair,et al.  The effects of growth hormone and/or testosterone on whole body protein kinetics and skeletal muscle gene expression in healthy elderly men: a randomized controlled trial. , 2008, The Journal of clinical endocrinology and metabolism.

[14]  E. Wilson.  Muscle-bound? A tissue-selective nonsteroidal androgen receptor modulator. , 2007, Endocrinology.

[15]  S. Ratcliffe,et al.  Determinants of serum total and free testosterone levels in women over the age of 65 years. , 2007, The Journal of clinical endocrinology and metabolism.

[16]  Shalender Bhasin,et al.  Drug Insight: testosterone and selective androgen receptor modulators as anabolic therapies for chronic illness and aging , 2006, Nature Clinical Practice Endocrinology &Metabolism.

[17]  R. Wolfe,et al.  Testosterone administration to older men improves muscle function: molecular and physiological mechanisms. , 2002, American journal of physiology. Endocrinology and metabolism.

[18]  K. Channer,et al.  The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men. , 2004, The Journal of clinical endocrinology and metabolism.

[19]  G. Butler-Browne,et al.  Androgen replacement therapy improves function in male rat muscles independently of hypertrophy and activation of the Akt/mTOR pathway , 2009, Acta physiologica.

[20]  A. Dorner,et al.  Measurement of myostatin concentrations in human serum: Circulating concentrations in young and older men and effects of testosterone administration , 2009, Molecular and Cellular Endocrinology.

[21]  H. Burger,et al.  Testosterone enhances estradiol's effects on postmenopausal bone density and sexuality. , 1995, Maturitas.

[22]  J. Berlin,et al.  Effects of testosterone replacement in hypogonadal men. , 2000, The Journal of clinical endocrinology and metabolism.

[23]  R. Tompkins,et al.  Regulation of signaling pathways downstream of IGF-I/insulin by androgen in skeletal muscle of glucocorticoid-treated rats. , 2009, The Journal of trauma.

[24]  R. Casaburi,et al.  The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men. , 1996, The New England journal of medicine.

[25]  Matthew T. Haren,et al.  Oral testosterone supplementation increases muscle and decreases fat mass in healthy elderly males with low-normal gonadal status. , 2003, The journals of gerontology. Series A, Biological sciences and medical sciences.

[26]  L. Woodhouse,et al.  Proof of the effect of testosterone on skeletal muscle. , 2001, The Journal of endocrinology.

[27]  M. Sowers,et al.  Testosterone, sex hormone-binding globulin and free androgen index among adult women: chronological and ovarian aging. , 2009, Human reproduction.

[28]  E. Metter,et al.  Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. , 2001, The Journal of clinical endocrinology and metabolism.

[29]  W. Mbagaya.  Higher serum testosterone concentration in older women is associated with insulin resistance, metabolic syndrome, and cardiovascular disease , 2010 .

[30]  W. Bauman,et al.  Expression of the muscle atrophy factor muscle atrophy F-box is suppressed by testosterone. , 2008, Endocrinology.

[31]  A. Meikle.  Testosterone and Growth Hormone Improve Body Composition and Muscle Performance in Older Men , 2010 .

[32]  K. Miller,et al.  Androgen deficiency: effects on body composition , 2008, Pituitary.

[33]  Z. Baka,et al.  Androgens negatively regulate myostatin expression in an androgen-dependent skeletal muscle. , 2007, Biochemical and biophysical research communications.

[34]  K. Nair,et al.  Higher muscle protein synthesis in women than men across the lifespan, and failure of androgen administration to amend age‐related decrements , 2009, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[35]  J. Rosenblatt,et al.  Androgen therapy induces muscle protein anabolism in older women. , 2006, The Journal of clinical endocrinology and metabolism.

[36]  G. Kleiverda,et al.  The influence of testosterone combined with a PDE5-inhibitor on cognitive, affective, and physiological sexual functioning in women suffering from sexual dysfunction. , 2009, The journal of sexual medicine.

[37]  R. Wolfe,et al.  Testosterone administration to elderly men increases skeletal muscle strength and protein synthesis. , 1995, The American journal of physiology.

[38]  F. Martin,et al.  The effects of growth hormone and/or testosterone in healthy elderly men: a randomized controlled trial. , 2006, The Journal of clinical endocrinology and metabolism.

[39]  S. Khosla,et al.  Androgen therapy in women: an Endocrine Society Clinical Practice guideline. , 2006, The Journal of clinical endocrinology and metabolism.

[40]  A. Matsumoto,et al.  Tissue selectivity of the anabolic steroid, 19-nor-4-androstenediol-3beta,17beta-diol in male Sprague Dawley rats: selective stimulation of muscle mass and bone mineral density relative to prostate mass. , 2008, Endocrinology.

[41]  M. Horowitz,et al.  Effect of testosterone and a nutritional supplement, alone and in combination, on hospital admissions in undernourished older men and women. , 2009, The American journal of clinical nutrition.

[42]  Russell Turner,et al.  An orally active selective androgen receptor modulator is efficacious on bone, muscle, and sex function with reduced impact on prostate. , 2007, Endocrinology.

[43]  M. Mazzocco,et al.  Effects of treatment with oxandrolone for 4 years on the frequency of severe arithmetic learning disability in girls with Turner syndrome. , 2009, The Journal of pediatrics.

[44]  Z. Yeşilova,et al.  The effects of gonadotropin treatment on the immunological features of male patients with idiopathic hypogonadotropic hypogonadism. , 2000, The Journal of clinical endocrinology and metabolism.

[45]  H. Burger,et al.  Testosterone enhances estradiol's effects on postmenopausal bone density and sexuality. , 2008, Maturitas.

[46]  A. Vandenbark,et al.  Androgens alter the cytokine profile and reduce encephalitogenicity of myelin-reactive T cells. , 1999, Journal of immunology.

[47]  T. V. Staaa,et al.  Study of adverse outcomes in women using testosterone therapy , 2009 .

[48]  S. Bhasin,et al.  0021-972X/06/$15.00/0 The Journal of Clinical Endocrinology & Metabolism 91(8):3024–3033 Printed in U.S.A. Copyright © 2006 by The Endocrine Society doi: 10.1210/jc.2006-0357 Effects of Testosterone Supplementation on Skeletal Muscle Fiber Hypertrophy and , 2022 .

[49]  S. Bhasin.  Testosterone supplementation for aging-associated sarcopenia. , 2003, The journals of gerontology. Series A, Biological sciences and medical sciences.

[50]  C. Leeuwenburgh,et al.  Skeletal muscle apoptosis, sarcopenia and frailty at old age , 2006, Experimental Gerontology.

[51]  J. Davis,et al.  Modulation of overload-induced inflammation by aging and anabolic steroid administration , 2006, Experimental Gerontology.

[52]  P. Snyder.  Effects of age on testicular function and consequences of testosterone treatment. , 2001, The Journal of clinical endocrinology and metabolism.

[53]  H. E. Maclean,et al.  Continuous testosterone administration prevents skeletal muscle atrophy and enhances resistance to fatigue in orchidectomized male mice. , 2006, American journal of physiology. Endocrinology and metabolism.

[54]  S. Boonen,et al.  Impact of Androgens, Growth Hormone, and IGF‐I on Bone and Muscle in Male Mice During Puberty , 2006, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[55]  N. Ancy,et al.  The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men. , 1996 .

[56]  W. Bauman,et al.  Testosterone protects against dexamethasone-induced muscle atrophy, protein degradation and MAFbx upregulation , 2008, The Journal of Steroid Biochemistry and Molecular Biology.

[57]  E. Szeszycki.  Testosterone replacement increases fat-free mass and muscle size in hypogonadal men. , 1997, JPEN. Journal of parenteral and enteral nutrition.

[58]  W. O'Fallon,et al.  Effect of estrogen versus testosterone on circulating osteoprotegerin and other cytokine levels in normal elderly men. , 2002, The Journal of clinical endocrinology and metabolism.

[59]  A. Morgentaler,et al.  Wide variability in laboratory reference values for serum testosterone. , 2006, The journal of sexual medicine.

[60]  A. Rockwood,et al.  Pharmacokinetics of a testosterone gel in healthy postmenopausal women. , 2006, The Journal of clinical endocrinology and metabolism.

[61]  R. Voskuhl,et al.  Testosterone Acts Directly on CD4+ T Lymphocytes to Increase IL-10 Production1 , 2001, The Journal of Immunology.

[62]  L. Gooren,et al.  Safety aspects of 36 months of administration of long-acting intramuscular testosterone undecanoate for treatment of female-to-male transgender individuals. , 2009, European journal of endocrinology.

[63]  T. Dorff,et al.  Testosterone replacement in prostate cancer survivors with hypogonadal symptoms , 2009, BJU international.

[64]  J. S. Tenover,et al.  Effects of testosterone supplementation in the aging male. , 1992, The Journal of clinical endocrinology and metabolism.

[65]  Ramesh Narayanan,et al.  Selective androgen receptor modulators in preclinical and clinical development , 2008, Nuclear receptor signaling.

[66]  R. Meir,et al.  THE EFFECT OF SHORT‐TERM USE OF TESTOSTERONE ENANTHATE ON MUSCULAR STRENGTH AND POWER IN HEALTHY YOUNG MEN , 2007, Journal of strength and conditioning research.