Emerging medication for the treatment of male hypogonadism

References

• Plymate SR. Hypogonadism in men: an overview. In: Bagatell CJ, Bremner WJ, editors. Androgens in health and disease. Totowa (NJ): Humana Press; 2003. p. 23–44.
   Google Scholar
• Bhasin S, Cunningham GR, Hayes FJ, et al.; Task Force, Endocrine Society. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010;95:2536–2559.
   PubMed Web of Science ®Google Scholar
• Araujo AB, Esche GR, Kupelian V, et al. Prevalence of symptomatic androgen deficiency in men. J Clin Endocrinol Metab. 2007;92:4241–4247.
   PubMed Web of Science ®Google Scholar
• Snyder PJ, Bhasin S, Cunningham GR, et al. Effects of testosterone treatment in older men. N Engl J Med. 2016;374:611–624.
   PubMed Web of Science ®Google Scholar
• Bhattacharya RK, Khera M, Blick G, et al. Effect of 12 months of testosterone replacement therapy on metabolic syndrome components in hypogonadal men: data from the Testim Registry in the US (TRiUS). BMC Endocr Disord. 2011;1:11–18.
   Google Scholar
• Stellato RK, Feldman HA, Hamdy O, et al. Testosterone, sex hormone-binding globulin, and the development of type 2 diabetes in middle-aged men: prospective results from the Massachusetts male aging study. Diabetes Care. 2000;23:490–494.
   PubMed Web of Science ®Google Scholar
• Laaksonen DE, Niskanen L, Punnonen K, et al. Testosterone and sex hormone-binding globulin predict the metabolic syndrome and diabetes in middle-aged men. Diabetes Care. 2004;27:1036–1041.
   PubMed Web of Science ®Google Scholar
• Ding EL, Song Y, Malik VS, et al. Sex differences of endogenous sex hormones and risk of type 2 diabetes: a systematic review and meta-analysis. JAMA. 2006;295:1288–1299.
   PubMed Web of Science ®Google Scholar
• Chahla EJ, Hayek ME, Morley JE. Testosterone replacement therapy and cardiovascular risk factors modification. Aging Male. 2011;14:83–90.
   PubMed Web of Science ®Google Scholar
• Edelstein D, Basaria S. Testosterone undecanoate in the treatment of male hypogonadism. Expert Opin Pharmacother. 2010;11:2095–2106.
   PubMed Web of Science ®Google Scholar
• Swerdloff RS, Wang C. Three-year follow-up of androgen treatment in hypogonadal men: preliminary report with testosterone gel. Aging Male. 2003;6:207–211.
   PubMedGoogle Scholar
• Parkes AS. Biological aspects of the control of human fertility. Practitioner. 1965;194:455–462.
   Google Scholar
• Carnegie C. Diagnosis of hypogonadism: clinical assessments and laboratory tests. Rev Urol. 2004;6 Suppl 6(Suppl 6):S3–8.
   PubMedGoogle Scholar
• Basaria S, Coviello AD, Travison TG, et al. Adverse events associated with testosterone administration. N Engl J Med. 2010;363:109–122.
   PubMed Web of Science ®Google Scholar
• Wu FCW, Farley TMM, Peregoudov A, et al. Effects of testosterone enanthate in normal men: experience from a multicenter contraceptive efficacy study. World Health Organization Task Force on Methods for the Regulation of Male Fertility. Fertil Steril. 1996;65:626–636.
   PubMed Web of Science ®Google Scholar
• Anderson RA, Wallace AM, Sattar N, et al. Evidence for tissue selectivity of the synthetic androgen 7 alpha-methyl-19-nortestosterone in hypogonadal men. J Clin Endocrinol Metab. 2003;88:2784–2793.
   PubMed Web of Science ®Google Scholar
• Anderson RA, Martin CW, Kung AW, et al. 7 alpha-methyl-19-nortestosterone maintains sexual behavior and mood in hypogonadal men. J Clin Endocrinol Metab. 1999;84:3556–3562.
   PubMed Web of Science ®Google Scholar
• Ruzicka L, Goldberg MW, Rosenberg HR. Sexual hormone X. herstellung des 17-methyltestosteron und anderer androstenund androstanderivate. Helv Chim Acta. 1935;18:1487–1498.
   Google Scholar
• Raynaud JP, Legros JJ, Rollet J, et al. Efficacy and safety of a new testosterone-in-adhesive matrix patch applied every 2 days for 1 year to hypogonadal men. J Steroid Biochem Mol Biol. 2008;109:168–176.
   PubMed Web of Science ®Google Scholar
• Abadilla KA, Dobs AS. Topical testosterone supplementation for the treatment of male hypogonadism. Drugs. 2012;72:1591–1603.
   PubMed Web of Science ®Google Scholar
• Mazer N, Fisher D, Fischer J, et al. Transfer of transdermally applied testosterone to clothing: a comparison of a testosterone patch versus a testosterone gel. J Sex Med. 2005;2:227–234.
   PubMed Web of Science ®Google Scholar
• Leung KMYB, Alrabeeah K, Carrier S. Update on testosterone replacement therapy in hypogonadal men. Curr Urol Rep. 2015;16:57.
   PubMed Web of Science ®Google Scholar
• Wang C, Festin MPR, Swerdloff RS, et al. Male hormonal contraception: where are we now? Curr Obstet Gynecol Rep. 2016;5:38–47.
   PubMed Web of Science ®Google Scholar
• Bassil N, Alkaade S, Morley JE. The benefits and risks of testosterone replacement therapy: a review. Ther Clin Risk Manag. 2009;5:427–448.
   PubMedGoogle Scholar
• Nguyen CP, Hirsch MS, Moeny D, et al. Testosterone and “age-related hypogonadism”—FDA concerns. N Engl J Med. 2015;373:689–691.
   PubMed Web of Science ®Google Scholar
• Kumar P, Kumar N, Thakur DS, et al. Male hypogonadism: symptoms and treatment. J Adv Pharm Technol Res. 2010;1:297–301.
   PubMedGoogle Scholar
• The State of Aging and Health in America. 2004. Available from: www.agingsociety.org/agingsociety/pdf/SAHA_2004.pdf
   Google Scholar
• Seftel A. Male hypogonadism. Part II: etiology, pathophysiology, and diagnosis. Int J Impot Res. 2006;18:223–228.
   PubMed Web of Science ®Google Scholar
• Institute of Medicine (US) Committee on Assessing the Need for Clinical Trials of Testosterone Replacement Therapy, Liverman CT, Blazer DG, editors. Testosterone and aging. Washington (DC): National Academies Press (US); 2004.
   Google Scholar
• Carruthers M. Time for international action on treating testosterone deficiency syndrome. Aging Male. 2009;12:21–28.
   PubMed Web of Science ®Google Scholar
• Annual testosterone drug revenue in the U.S. in 2013 and 2018 (in billion U.S. dollars). Available from: http://www.statista.com/statistics/320301/predicted-annual-Testosterone-drug-revenues-in-the-us/
   Google Scholar
• Testosterone replacement therapy (TRT)-A global strategic business report. Available from: http://www.strategyr.com/Testosterone_Replacement_Therapy_TRT_Market_Report.asp
   Google Scholar
• Data Trends Report - Encuity research testosterone replacement therapy. Available from: http://answergenerator.encuity.com/docs/Encuity%20-%20Data%20Trends%20Report%20-%20TRT%20-%20May%202014.pdf
   Google Scholar
• Nankin HR, Spark RF, Swerdloff RS, et al. AACE Hypogonadism Task Force. Endocr Pract. 2002;8:439–456.
   Google Scholar
• Basaria S, Dobs AS. Hypogonadism and androgen replacement therapy in elderly men. Am J Med. 2001;110:563–572.
   PubMed Web of Science ®Google Scholar
• Oral testosterone for the treatment of hypogonadism in males. Available from: https://clinicaltrials.gov/ct2/show/NCT02222558
   Google Scholar
• Nieschlag E, Kumar N, Sitruk-Ware R. 7α-methyl-19-norT (MENTR): the population council’s contribution to research on male contraception and treatment of hypogonadism. Contraception. 2013;87:288–295.
   PubMed Web of Science ®Google Scholar
• Kovac JR. Reproductive endocrinology: oral enclomiphene citrate in obese men with hypogonadism. Nat Rev Urol. 2016;13:133–134.
   PubMed Web of Science ®Google Scholar
• Narayanan R, Mohler ML, Bohl CE, et al. Selective androgen receptor modulators in preclinical and clinical development. Nucl Recept Signal. 2008;6:e010.
   PubMedGoogle Scholar
• Acute Hip Fracture Study in patients 65 years or greater. Available from: https://clinicaltrials.gov/ct2/show/NCT02578095
   Google Scholar
• Piu F, Gardell LR, Son T, et al. Pharmacological characterization of AC-262536, a novel selective androgen receptor modulator. J Steroid Biochem Molec Biol. 2008;109:129–137.
   Google Scholar
• Jones A, Hwang DJ, Duke CB 3rd, et al. Nonsteroidal selective androgen receptor modulators enhance female sexual motivation. J Pharmacol Exp Ther. 2010;334:439–448.
   PubMed Web of Science ®Google Scholar
• Allan GF, Tannenbaum P, Sbriscia T, et al. A selective androgen receptor modulator with minimal prostate hypertrophic activity enhances lean body mass in male rats and stimulates sexual behavior in female rats. Endocrine. 2007;32:41–51.
   PubMed Web of Science ®Google Scholar
• Phase 1 Study of Dimethandrolone Undecanoate in healthy men (DMAUPhase1). Available from: https://clinicaltrials.gov/ct2/show/NCT01382069
   Google Scholar
• Single dose, Dose-Ranging Study of 11-β methyl nortestosterone dodecylcarbonate (11β-MNTDC) in healthy men (CCN014). Available from: https://clinicaltrials.gov/ct2/show/NCT02754687
   Google Scholar
• Kaufman JM, Miller MG, Garwin JL, et al. Efficacy and safety study of 1.62% testosterone gel for the treatment of hypogonadal men. J Sex Med. 2011;8:2079–2089.
   PubMed Web of Science ®Google Scholar
• Dobs AS, McGettigan J, Norwood P, et al. A novel testosterone 2% gel for the treatment of hypogonadal males. J Androl. 2012;33:601–607.
   PubMedGoogle Scholar
• Stahlman J, Britto M, Fitzpatrick S, et al. Effects of skin washing on systemic absorption of T in hypogonadal males after administration of 1.62% testosterone gel. Curr Med Res Opin. 2012;28:271–279.
   PubMed Web of Science ®Google Scholar
• Kühnert B, Byrne M, Simoni M, et al. Testosterone substitution with a new transdermal, hydroalcoholic gel applied to scrotal or non-scrotal skin: a multicentre trial. Eur J Endocrinol. 2005;153:317–326.
   PubMed Web of Science ®Google Scholar
• Wittert GA, Harrison RW, Buckley MJ, et al. An open-label, phase 2, single centre, randomized, crossover design bioequivalence study of AndroForte 5 testosterone cream and Testogel 1% testosterone gel in hypogonadal men: study LP101. Andrology. 2016;4:41–45.
   PubMed Web of Science ®Google Scholar
• Danner C, Frick J. Androgen substitution with testosterone containing nasal drops. Int J Androl. 1980;3:429–435.
   PubMedGoogle Scholar
• Rogol AD, Tkachenko N, Bryson N. Natesto(™), a novel Testosterone nasal gel, normalizes androgen levels in hypogonadal men. Andrology. 2016;4:46–54.
   PubMed Web of Science ®Google Scholar
• Nieschlag E, Mauss J, Coert A, et al. Plasma androgen levels in men after oral administration of testosterone or testosterone undecanoate. Acta Endocrinol (Copenh). 1975;79:366–374.
   PubMedGoogle Scholar
• Von Eckardstein S, Nieschlag E. Treatment of male hypogonadism with testosterone undecanoate injected at extended intervals of 12 weeks: phase II study. J Androl. 2002;23:419–425.
   PubMedGoogle Scholar
• Zitzmann M, Nieschlag E. Androgen receptor gene CAG repeat length and body mass index modulate the safety of long-term intramuscular testosterone undecanoate therapy in hypogonadal men. J Clin Endocrinol Metab. 2007;92:3844–3853.
   PubMed Web of Science ®Google Scholar
• Zitzmann M, Mattern A, Hanisch J, et al. IPASS: a study on the tolerability and effectiveness of injectable testosterone undecanoate for the treatment of male hypogonadism in a worldwide sample of 1,438 men. J Sex Med. 2013;10:579–588.
   PubMed Web of Science ®Google Scholar
• Jacobeit JW, Schulte HM. Long-acting intramuscular testosterone undecanoate (TU, Nebido) in treatment of aging males with hypogonadism. 8th European Congress of Endocrinology; 2006 Apr 1–5; Glasgow; Poster No. P184.
   Google Scholar
• Minnemann T, Schubert M, Hubler D, et al. A four-year efficacy and safety study of the long-acting parenteral testosterone undecanoate. Aging Male. 2007;10:155–158.
   PubMed Web of Science ®Google Scholar
• Nieschlag E, Buchter D, von Eckardstein S, et al. Repeated intramuscular injections of testosterone undecanoate for substitution therapy in hypogonadal men. Clin Endocrinol (Oxf). 1999;51:757–763.
   PubMed Web of Science ®Google Scholar
• Wang C, Harnett M, Dobs AS, et al. Pharmacokinetics and safety of long-acting testosterone undecanoate injections in hypogonadal men: an 84-week phase III clinical trial. J Androl. 2010;31:457–465.
   PubMedGoogle Scholar
• AVEED™ REMS (Risk Evaluation and Mitigation Strategy) Program. Available from: https://www.aveedrems.com/AveedUI/rems/preHome.action
   Google Scholar
• AVEED® Risk Evaluation and Mitigation Strategy (REMS) Program. Available from: http://aveedusa.com/hypogonadism-provider-enrollment.aspx
   Google Scholar
• Wang C, Swerdloff RS. Should the nonaromatizable androgen dihydrotestosterone be considered as an alternative to testosterone in the treatment of the andropause? J Clin Endocrinol Metab. 2002;87:1462–1466.
   PubMed Web of Science ®Google Scholar
• De Lignieres B, Morville R. Treatment of male hypogonadism by topical administration of androgens. In: Mauvais-Jarvis P, Vickers CFH, Wepierre J, eds. Percutaneous absorption of steroids. London: Academic Press; 1980. p. 273–283.
   Google Scholar
• De Lignieres B. Transdermal dihydrotestosterone treatment of ‘andropause.’. Ann Med. 1993;25:235–241.
   PubMed Web of Science ®Google Scholar
• Dougan GC, Uli N, Shulman DI. Progressive central puberty in a toddler with partial androgen insensitivity. J Pediatr. 2014;164:655–657.
   PubMed Web of Science ®Google Scholar
• Ly LP, Jimenez M, Zhuang TN, et al. A double-blind, placebo-controlled, randomized clinical trial of transdermal dihydrotestosterone gel on muscular strength, mobility, and quality of life in older men with partial androgen deficiency. J Clin Endocrinol Metab. 2001;86:4078–4088.
   PubMed Web of Science ®Google Scholar
• Santen RJ, Leonard JM, Sherins RJ, et al. Short‑ and long‑term effects of clomiphene citrate on the pituitary‑testicular axis. J Clin Endocrinol Metab. 1971;33:970–979.
   PubMed Web of Science ®Google Scholar
• Practice Committee of American Society for Reproductive Medicine, Birmingham, Alabama. Gonadotropin preparations: past, present, and future perspectives. Fertil Steril. 2008;90:13–20.
   PubMedGoogle Scholar
• Liu PY, Baker HW, Jayadev V, et al. Induction of spermatogenesis and fertility during gonadotropin treatment of gonadotropin-deficient infertile men: predictors of fertility outcome. J Clin Endocrinol Metab. 2009;94:801–808.
   PubMed Web of Science ®Google Scholar
• Liu PY, Wishart SM, Celermajer DS, et al. Do reproductive hormones modify insulin sensitivity and metabolism in older men? A randomized, placebo-controlled clinical trial of recombinant human chorionic gonadotropin. Eur J Endocrinol. 2003;148:55–66.
   PubMed Web of Science ®Google Scholar
• Cailleux-Bounacer A, Reznik Y, Cauliez B, et al. Evaluation of endocrine testing of Leydig cell function using extractive and recombinant human chorionic gonadotropin and different doses of recombinant human LH in normal men. Eur J Endocrinol. 2008;159:171–178.
   PubMed Web of Science ®Google Scholar
• George B, Bantwal G. Endocrine management of male subfertility. Indian J Endocrinol Metab. 2013;17:32–34.
   Google Scholar
• Han TS, Bouloux PM. What is the optimal therapy for young males with hypogonadotropic hypogonadism? Clin Endocrinol. 2009;72:731–737.
   PubMed Web of Science ®Google Scholar
• Rohayem J, Sinthofen N, Nieschlag E, et al. Causes of hypogonadotropic hypogonadism predict response to gonadotropin substitution in adults. Andrology. 2016;4:87–94.
   PubMed Web of Science ®Google Scholar
• Burris AS, Rodbard HW, Winters SJ, et al. Gonadotropin therapy in men with isolated hypogonadotropic hypogonadism: the response to human chorionic gonadotropin is predicted by initial testicular size. J Clin Endocrinol Metab. 1988;66:1144–1151.
   PubMed Web of Science ®Google Scholar
• Liu PY, Wishart SM, Handelsman DJ. A double-blind, placebo-controlled, RCT of recombinant human chorionic gonadotropin on muscle strength and physical function and activity in older men with partial age-related androgen deficiency. J Clin Endocrinol Metab. 2002;87:3125–3135.
   PubMed Web of Science ®Google Scholar
• Meier C, Liu PY, Ly LP, et al. Recombinant human chorionic gonadotropin but not dihydrotestosterone alone stimulates osteoblastic collagen synthesis in older men with partial age-related androgen deficiency. J Clin Endocrinol Metab. 2004;89:3033–3041.
   PubMed Web of Science ®Google Scholar
• Young J, Couzinet B, Chanson P, et al. Effects of human recombinant luteinizing hormone and follicle-stimulating hormone in patients with acquired hypogonadotropic hypogonadism: study of Sertoli and Leydig cell secretions and interactions. J Clin Endocrinol Metab. 2000;85:3239–3244.
   PubMed Web of Science ®Google Scholar
• La Vignera S, Condorelli RA, Cimino L, et al. Late-onset hypogonadism: the advantages of treatment with human chorionic gonadotropin rather than testosterone. Aging Male. 2016;19:34–39.
   PubMed Web of Science ®Google Scholar
• Morishima A, Grumbach MM, Simpson ER, et al. Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens. J Clin Endocrinol Metab. 1995;80:3689–3698.
   PubMed Web of Science ®Google Scholar
• Corona G, Rastrelli G, Vignozzi L, et al. Emerging medication for the treatment of male hypogonadism. Expert Opin Emerg Drugs. 2012;17:239–259.
   PubMed Web of Science ®Google Scholar
• Whitten SJ, Nangia AK, Kolettis PN. Select patients with hypogonadotropic hypogonadism may respond to treatment with clomiphene citrate. Fertil Steril. 2006;86:1664–1668.
   PubMed Web of Science ®Google Scholar
• Maggi M, Buvat J, Corona G, et al. Hormonal Causes of Male sexual dysfunctions and their management (Hyperprolactinemia, Thyroid Disorders, GH Disorders, DHEA). J Sex Med. 2012;10:661–677.
   PubMed Web of Science ®Google Scholar
• Yuan J, Wang PQ, Ge SR, et al. Pharmacokinetics of anastrozole in Chinese male volunteers. Acta Pharmacol Sin. 2001;22:573–576.
   PubMed Web of Science ®Google Scholar
• Loves S, Ruinemans-Koerts J, De Boer H. Letrozole once a week normalizes serum testosterone in obesity-related male hypogonadism. Eur J Endocrinol. 2008;158:741–747.
   PubMed Web of Science ®Google Scholar
• Richardson D, Goldmeier D, Frize G, et al. Letrozole versus testosterone. a single-center pilot study of HIV-infected men who have sex with men on highly active anti-retroviral therapy (HAART) with hypoactive sexual desire disorder and raised estradiol levels. J Sex Med. 2007;4:502–508.
   PubMed Web of Science ®Google Scholar
• Leder BZ, Finkelstein JS. Effect of aromatase inhibition on bone metabolism in elderly hypogonadal men. Osteoporos Int. 2005;16:1487–1494.
   PubMed Web of Science ®Google Scholar
• McCullough A. Alternatives to testosterone replacement: testosterone restoration. Asian J Androl. 2015;17:201–205.
   PubMed Web of Science ®Google Scholar
• Veldhuis JD, Iranmanesh A. Short‑term aromatase‑enzyme blockade unmasks impaired feedback adaptations in luteinizing hormone and T secretion in older men. J Clin Endocrinol Metab. 2005;90:211–218.
   PubMed Web of Science ®Google Scholar
• Gao W, Dalton JT. Expanding the therapeutic use of androgens via selective androgen receptor modulators (SARMs). Drug Discov Today. 2007;12:241–248.
   PubMed Web of Science ®Google Scholar
• de Ronde W. Therapeutic uses of aromatase inhibitors in men. Curr Opin Endocrinol Diabetes Obes. 2007;14:235–240.
   PubMedGoogle Scholar
• Eastell R, Adams JE, Coleman RE, et al. Effect of anastrozole on bone mineral density: 5‑year results from the anastrozole, tamoxifen, alone or in combination trial 18233230. J Clin Oncol. 2008;26:1051–1057.
   PubMed Web of Science ®Google Scholar
• Burnett-Bowie S-AM, McKay EA, Lee H, et al. Effects of aromatase inhibition on bone mineral density and bone turnover in older men with low testosterone levels. J Clin Endocrinol Metabol. 2009;94:4785–4792.
   PubMed Web of Science ®Google Scholar
• Hero M, Toiviainen-Salo S, Wickman S, et al. Vertebral morphology in aromatase inhibitor-treated males with idiopathic short stature or constitutional delay of puberty. J Bone Mineral Res. 2010;25:1536–1543.
   PubMed Web of Science ®Google Scholar
• Glasier AF, Irvine DS, Wickings EJ, et al. A comparison of the effects on follicular development between clomiphene citrate, its two separate isomers and spontaneous cycles. Hum Reprod. 1989;4:252–256.
   PubMed Web of Science ®Google Scholar
• Cargille CM, Ross GT, Bardin CW. Clomiphene and gonadotrophin in men. Lancet. 1968;292:1298.
   Google Scholar
• Shabsigh A, Kang Y, Shabsigh R, et al. Clomiphene citrate effects on testosterone/estrogen ratio in male hypogonadism. J Sex Med. 2005;2:716–721.
   PubMed Web of Science ®Google Scholar
• Taylor F, Levine L. Clomiphene citrate and testosterone gel replacement therapy for male hypogonadism: efficacy and treatment cost. J Sex Med. 2010;7:269–276.
   PubMed Web of Science ®Google Scholar
• Moskovic DJ, Katz DJ, Akhavan A, et al. Clomiphene citrate is safe and effective for long‑term management of hypogonadism. BJU Int. 2012;110:1524–1528.
   PubMed Web of Science ®Google Scholar
• Kulin HE, Grumbach MM, Kaplan SL. Gonadal-hypothalamic interaction in prepubertal and pubertal man: effect of clomiphene citrate on urinary follicle-stimulating hormone and luteinizing hormone and plasma testosterone. Pediatr Res. 1972;6:162–171.
   PubMed Web of Science ®Google Scholar
• Vandekerckhove P, Lilford R, Vail A, et al. Clomiphene or tamoxifen for idiopathic oligo/asthenospermia. Cochrane Database Syst Rev. 2000;CD000151. doi:10.1002/14651858.
   Google Scholar
• Samaras N, Samaras D, Frangos E, et al. A review of age-related dehydroepiandrosterone decline and its association with well-known geriatric syndromes: is treatment beneficial? Rejuvenation Res. 2013;16:285–294.
   PubMed Web of Science ®Google Scholar
• Kushnir MM, Blamires T, Rockwood AL, et al. Liquid chromatographytandem mass spectrometry assay for androstenedione, dehydroepiandrosterone, and testosterone with pediatric and adult reference intervals. Clin Chem. 2010;56:1138–1147.
   PubMed Web of Science ®Google Scholar
• Genazzani AD, Lanzoni C, Genazzani AR. Might DHEA be considered a beneficial replacement therapy in the elderly? Drugs Aging. 2007;24:173–185.
   PubMed Web of Science ®Google Scholar
• Hyde Z, Flicker L, Hankey GJ, et al. Prevalence and predictors of sexual problems in men aged 75–95 years: A population-based study. J Sex Med. 2012;9:442–453.
   PubMed Web of Science ®Google Scholar
• Basar MM, Aydin G, Mert HC, et al. Relationship between serum sex steroids and Aging Male Symptoms score and International Index of Erectile Function. Urology. 2005;66:597–601.
   PubMed Web of Science ®Google Scholar
• Hayashi T, Esaki T, Muto E, et al. Dehydroepiandrosterone retards atherosclerosis formation through its conversion to estrogen: the possible role of nitric oxide. Arterioscler Thromb Vasc Biol. 2000;20:782–792.
   PubMed Web of Science ®Google Scholar
• Hansen PA, Han DH, Nolte LA, et al. DHEA protects against visceral obesity and muscle insulin resistance in rats fed a high-fat diet. Am J Physiol. 1997;273:1704–1708.
   PubMed Web of Science ®Google Scholar
• Feldman HA, Johannes CB, Araujo AB, et al. Low dehydroepiandrosterone and ischemic heart disease in middle-aged men: prospective results from the Massachusetts Male Aging Study. Am J Epidemiol. 2001;153:79–89.
   PubMed Web of Science ®Google Scholar
• Valenti G, Denti L, Maggio M, et al. Effect of DHEAS on skeletal muscle over the life span: the In CHIANTI study. J Gerontol Ser A, Biol Sci Med Sci. 2004;59:466–472.
   PubMed Web of Science ®Google Scholar
• Wang L, Wang YD, Wang WJ, et al. Dehydroepiandrosterone improves murine osteoblast growth and bone tissue morphometry via mitogen-activated protein kinase signaling pathway independent of either androgen receptor or estrogen receptor. J Mol Endocrinol. 2007;38:467–479.
   PubMed Web of Science ®Google Scholar
• Clarke BL, Ebeling PR, Jones JD, et al. Predictors of bone mineral density in aging healthy men varies by skeletal site. Calcified Tiss Int. 2002;70:137–145.
   PubMed Web of Science ®Google Scholar
• Schmidt PJ, Daly RC, Bloch M, et al. Dehydroepiandrosterone monotherapy in midlife-onset major and minor depression. Arch Gen Psychiatry. 2005;62:154–162.
   PubMed Web of Science ®Google Scholar
• Nair KS, Rizza RA, O’Brien P, et al. DHEA in elderly women and DHEA or testosterone in elderly men. N Engl J Med. 2006;355:1647–1659.
   PubMed Web of Science ®Google Scholar
• Ward HW. Anti-oestrogen therapy for breast cancer: a trial of tamoxifen at two dose levels. Br Med J. 1973;1:13–14.
   PubMed Web of Science ®Google Scholar
• Zhang X, Sui Z. Deciphering the selective androgen receptor modulators paradigm. Expert Opin Drug Discov. 2013;8:191–218.
   PubMed Web of Science ®Google Scholar
• Kacker R, Traish AM, Morgentaler A. Estrogens in men: clinical implications for sexual function and the treatment of testosterone deficiency. J Sex Med. 2012;9:1681–1696.
   PubMed Web of Science ®Google Scholar
• Finkelstein JS, Lee H, Burnett-Bowie S-AM, et al. Gonadal steroids and body composition, strength, and sexual function in men. N Engl J Med. 2013;369:1011–1022.
   PubMed Web of Science ®Google Scholar
• Miner JN, Chang W, Chapman MS, et al. An orally active selective androgen receptor modulator is efficacious on bone, muscle, and sex function with reduced impact on prostate. Endocrinology. 2007;148:363–373.
   PubMed Web of Science ®Google Scholar
• DART Therapeutics Inc. DART therapeutics develops drug candidate for Duchenne muscular dystrophy. 2013. Available from: www.reuters.com/article/2013/03/20/ma-dart-theraputicsidUSnPnNE79920+160+PRN20130320
   Google Scholar
• Srinath R, Dobs A. Enobosarm (GTx- 024, S-22): a potential treatment for cachexia. Future Oncol. 2014;10:187–194.
   PubMed Web of Science ®Google Scholar
• Basaria S, Collins L, Dillon EL, et al. The safety, pharmacokinetics, and effects of LGD-4033, a novel nonsteroidal oral, selective androgen receptor modulator, in healthy young men. J Gerontol A Biol Sci Med Sci. 2013;68:87–95.
   PubMed Web of Science ®Google Scholar
• Dalton JT, Barnette KG, Bohl CE, et al. The selective androgen receptor modulator GTx‑024 (enobosarm) improves lean body mass and physical function in healthy elderly men and postmenopausal women: results of a double‑blind, placebo‑controlled phase II trial. J Cachexia Sarcopenia Muscle. 2011;2:153–161.
   PubMed Web of Science ®Google Scholar
• Araujo AB, O’Donnell AB, Brambilla DJ, et al. Prevalence and incidence of androgen deficiency in middle-aged and older men: estimates from the Massachusetts Male Aging Study. J Clin Endocrinol Metab. 2004;89:5920–5926.
   PubMed Web of Science ®Google Scholar
• Ashby J, Goldmeier D, Sadeghi-Nejad H. Hypogonadism in human immunodeficiency virus-positive men. Korean J Urol. 2014;55:9–16.
   PubMedGoogle Scholar
• Moreno-Perez O, Escoin C, Serna-Candel C, et al. The determination of total testosterone and free testosterone (RIA) are not applicable to the evaluation of gonadal function in HIV-infected males. J Sex Med. 2010;7:2873–2883.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Bhasin S, Parker RA, Sattler F, et al. Effects of testosterone supplementation on whole body and regional fat mass and distribution in human immunodeficiency virus-infected men with abdominal obesity. J Clin Endocrinol Metab. 2007;92:1049–1057.
   PubMed Web of Science ®Google Scholar
• Traish AM, Haider A, Doros G, et al. Long-term testosterone therapy in hypogonadal men ameliorates elements of the metabolic syndrome: an observational, long-term registry study. Int J Clin Pract. 2014;68:314–329.
   PubMed Web of Science ®Google Scholar
• Jones TH, Arver S, Behre HM, et al. Testosterone replacement in hypogonadal men with type 2diabetes and/or metabolic syndrome (the TIMES2 study). Diabetes Care. 2011;34:828–837.
   PubMed Web of Science ®Google Scholar
• Finkle WD, Greenland S, Ridgeway GK, et al. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS One. 2014;9;e85805.
   PubMed Web of Science ®Google Scholar