Important lessons about testosterone therapy- weight loss vs. testosterone therapy for symptom resolution, classical vs. functional hypogonadism, and shortterm vs. lifelong testosterone therapy

References

• Ng Tang Fui M, Prendergast LA, Dupuis P, et al. Effects of testosterone treatment on body fat and lean mass in obese men on a hypocaloric diet: a randomised controlled trial. BMC Med. 2016;14:153.
   PubMed Web of Science ®Google Scholar
• Sigal RJ, Kenny GP, Boulé NG, et al. Effects of aerobic training, resistance training, or both on glycemic control in type 2 diabetes: a randomized trial. Ann Intern Med. 2007;147:357–369.
   PubMed Web of Science ®Google Scholar
• McTiernan A, Sorensen B, Irwin ML, et al. Exercise effect on weight and body fat in men and women. Obesity (Silver Spring). 2007;15:1496–1512.
   PubMed Web of Science ®Google Scholar
• Boyanov MA, Boneva Z, Christov VG. Testosterone supplementation in men with type 2 diabetes, visceral obesity and partial androgen deficiency. Dagm. 2003;6:1–7.
   Google Scholar
• Rodriguez-Tolrà J, Torremadé Barreda J, del Rio L, et al. Effects of testosterone treatment on body composition in males with testosterone deficiency syndrome. Aging Male. 2013;16:184–190.
   PubMed Web of Science ®Google Scholar
• Khripun I, Vorobyev S, Belousov I, et al. Influence of testosterone substitution on glycemic control and endothelial markers in men with newly diagnosed functional hypogonadism and type 2 diabetes mellitus: a randomized controlled trial. Aging Male. 2018;1–9. DOI:10.1080/13685538.2018.1506918
   PubMed Web of Science ®Google Scholar
• Allan CA, Strauss BJG, Burger HG, et al. Testosterone therapy prevents gain in visceral adipose tissue and loss of skeletal muscle in nonobese aging men. J Clin Endocrinol Metab. 2008;93:139–146.
   PubMed Web of Science ®Google Scholar
• Garvey WT, Mechanick JI, Brett EM, et al. American association of clinical endocrinologists and american college of endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity. Endocr Pract. 2016;22:1–203.
   PubMed Web of Science ®Google Scholar
• Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. Circulation. 2014;129:S102–S138.
   PubMed Web of Science ®Google Scholar
• Khera R, Murad MH, Chandar AK, et al. Association of pharmacological treatments for obesity with weight loss and adverse events: a systematic review and meta-analysis. JAMA. 2016;315:2424–2434.
   PubMed Web of Science ®Google Scholar
• Gadde KM, Allison DB, Ryan DH, et al. Effects of low-dose, controlled-release, phentermine plus topiramate combination on weight and associated comorbidities in overweight and obese adults (CONQUER): a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377:1341–1352.
   PubMed Web of Science ®Google Scholar
• Pi-Sunyer X, Astrup A, Fujioka K, et al. A randomized, controlled trial of 3.0 mg of liraglutide in weight management. N Engl J Med. 2015;373:11–22.
   PubMed Web of Science ®Google Scholar
• Smith SR, Weissman NJ, Anderson CM, et al. Multicenter, placebo-controlled trial of lorcaserin for weight management. N Engl J Med. 2010;363:245–256.
   PubMed Web of Science ®Google Scholar
• Greenway FL, Fujioka K, Plodkowski RA, et al. Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2010;376:595–605.
   PubMed Web of Science ®Google Scholar
• Stubbs RJ, Morris L, Pallister C, et al. Weight outcomes audit in 1.3 million adults during their first 3 months' attendance in a commercial weight management programme. BMC Public Health. 2015;15:882.
   PubMed Web of Science ®Google Scholar
• Frankenfield D, Roth-Yousey L, Compher C. Comparison of predictive equations for resting metabolic rate in healthy nonobese and obese adults: a systematic review. J Am Diet Assoc. 2005;105:775–789.
   PubMed Web of Science ®Google Scholar
• Storer TW, Woodhouse L, Magliano L, et al. Changes in muscle mass, muscle strength, and power but not physical function are related to testosterone dose in healthy older men. J Am Geriatr Soc. 2008;56:1991–1999.
   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
• 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. 2005;90:678–688.
   PubMed Web of Science ®Google Scholar
• Thirumalai A, Rubinow KB, Cooper LA, et al. Dose-response effects of sex hormone concentrations on body composition and adipokines in medically castrated healthy men administered graded doses of testosterone gel. Clin Endocrinol (Oxf). 2017;87:59–67.
   PubMed Web of Science ®Google Scholar
• Cruz-Jentoft AJ, Baeyens JP, Bauer JM, et al. Sarcopenia: European consensus on definition and diagnosis: report of the European working group on sarcopenia in older people. Age Ageing. 2010;39:412–423.
   PubMed Web of Science ®Google Scholar
• Mankowski RT, Anton SD, Aubertin-Leheudre M. The role of muscle mass, muscle quality, and body composition in risk for the metabolic syndrome and functional decline in older adults. Curr Geri Rep. 2015;4:221–228.
   Web of Science ®Google Scholar
• Wolfe RR. The underappreciated role of muscle in health and disease. Am J Clin Nutr. 2006;84:475–482.
   PubMed Web of Science ®Google Scholar
• Baskin KK, Winders BR, Olson EN. Muscle as a “mediator” of systemic metabolism. Cell Metab. 2015;21:237–248.
   PubMed Web of Science ®Google Scholar
• Frederiksen L, Højlund K, Hougaard DM, et al. Testosterone therapy increased muscle mass and lipid oxidation in aging men. Age (Dordr). 2012;34:145–156.
   PubMed Web of Science ®Google Scholar
• Dhindsa S, Ghanim H, Batra M, et al. Insulin resistance and inflammation in hypogonadotropic hypogonadism and their reduction after testosterone replacement in men with type 2 diabetes. Diabetes Care. 2016;39:82–91.
   PubMed Web of Science ®Google Scholar
• Bhasin S, Travison TG, Storer TW, et al. Effect of testosterone supplementation with and without a dual 5α-reductase inhibitor on fat-free mass in men with suppressed testosterone production: a randomized controlled trial. JAMA. 2012;307:931–939.
   PubMed Web of Science ®Google Scholar
• Basaria S, Harman SM, Travison TG, et al. Effects of testosterone administration for 3 years on subclinical atherosclerosis progression in older men with low or low-normal testosterone levels: a randomized clinical trial. JAMA. 2015;314:570–581.
   PubMed Web of Science ®Google Scholar
• Ng Tang Fui M, Hoermann R, Prendergast LA, et al. Symptomatic response to testosterone treatment in dieting obese men with low testosterone levels in a randomized, placebo-controlled clinical trial. Int J Obes. 2017;41:420–426.
   Web of Science ®Google Scholar
• Kim C, Barrett-Connor E, Aroda VR, et al. Testosterone and depressive symptoms among men in the Diabetes Prevention Program. Psychoneuroendocrinology. 2016;72:63–71.
   PubMed Web of Science ®Google Scholar
• Rastrelli G, Carter EL, Ahern T, et al. Development of and recovery from secondary hypogonadism in aging men: prospective results from the EMAS. J Clin Endocrinol Metab. 2015;100:3172–3182.
   PubMed Web of Science ®Google Scholar
• Corona G, Isidori AM, Buvat J, et al. Testosterone supplementation and sexual function: a meta-analysis study. J Sex Med. 2014;11:1577–1592.
   PubMed Web of Science ®Google Scholar
• Isidori AM, Giannetta E, Greco EA, et al. Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle-aged men: a meta-analysis. Clin Endocrinol (Oxf). 2005;63:280–293.
   PubMed Web of Science ®Google Scholar
• Zarrouf FA, Artz S, Griffith J, et al. Testosterone and depression: systematic review and meta-analysis. J Psychiatr Pract. 2009;15:289–305.
   PubMed Web of Science ®Google Scholar
• Hackett G, Kirby M, Edwards D, et al. British society for sexual medicine guidelines on adult testosterone deficiency, with statements for UK practice. J Sex Med. 2017;14:1504–1523.
   PubMed Web of Science ®Google Scholar
• Corona G, Giagulli VA, Maseroli E, et al. Testosterone supplementation and body composition: results from a meta-analysis study. Eur J Endocrinol. 2016;174:R99–116.
   PubMed Web of Science ®Google Scholar
• Grossmann M, Matsumoto AM. A perspective on middle-aged and older men with functional hypogonadism: focus on holistic management. J Clin Endocrinol Metab. 2017;102:1067–1075.
   PubMed Web of Science ®Google Scholar
• Snyder PJ, Bhasin S, Cunningham GR, et al. Lessons from the testosterone trials. Endocr Rev. 2018;39:369–386.
   PubMed Web of Science ®Google 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
• Morgentaler A, Zitzmann M, Traish AM, et al. Fundamental concepts regarding testosterone deficiency and treatment: international expert consensus resolutions. Mayo Clin Proc. 2016;91:881–896.
   PubMed Web of Science ®Google Scholar
• Ng Tang Fui M, Hoermann R, Zajac JD, et al. The effects of testosterone on body composition in obese men are not sustained after cessation of testosterone treatment. Clin Endocrinol. 2017;87:336–343.
   PubMed Web of Science ®Google Scholar
• Yassin A, Almehmadi Y, Saad F, et al. Effects of intermission and resumption of long-term testosterone replacement therapy on body weight and metabolic parameters in hypogonadal in middle-aged and elderly men. Clin Endocrinol. 2016;84:107–114.
   PubMed Web of Science ®Google Scholar
• Hackett G, Cole N, Mulay A, et al. Long-term testosterone therapy in type 2 diabetes is associated with decreasing waist circumference and improving erectile function. World J Mens Health. 2018. DOI:10.5534/wjmh.180052M
   Google Scholar
• O'Connell MD, Roberts SA, Srinivas-Shankar U, et al. Do the effects of testosterone on muscle strength, physical function, body composition, and quality of life persist six months after treatment in intermediate-frail and frail elderly men? J Clin Endocrinol Metab. 2011;96:454–458.
   PubMed Web of Science ®Google Scholar
• Morgunov LY, Denisova IA, Rozhkova TI, et al. Hypogonadism and its treatment following ischaemic stroke in men with type 2 diabetes mellitus. Aging Male. 2018;1–10. DOI:10.1080/13685538.2018.1487932
   PubMed Web of Science ®Google Scholar
• Francomano D, Bruzziches R, Barbaro G, et al. Effects of testosterone undecanoate replacement and withdrawal on cardio-metabolic, hormonal and body composition outcomes in severely obese hypogonadal men: a pilot study. J Endocrinol Invest. 2014;37:401–411.
   PubMed Web of Science ®Google Scholar
• Yassin A, Nettleship JE, Talib RA, et al. Effects of testosterone replacement therapy withdrawal and re-treatment in hypogonadal elderly men upon obesity, voiding function and prostate safety parameters. Aging Male. 2016;19:64–69.
   PubMed Web of Science ®Google Scholar