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Review

The safety of available treatments of male hypogonadism in organic and functional hypogonadism

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Pages 277-292 | Received 01 Nov 2017, Accepted 03 Jan 2018, Published online: 15 Jan 2018

References

  • Corona G, Rastrelli G, Vignozzi L, et al. Emerging medication for the treatment of male hypogonadism. Expert Opin Emerg Drugs. 2012;17:239–259.
  • Corona G, Rastrelli G, Maggi M. The pharmacotherapy of male hypogonadism besides androgens. Expert Opin Pharmacother. 2015;16:369–387.
  • Corona G, Mannucci E, Petrone L, et al. A comparison of NCEP-ATPIII and IDF metabolic syndrome definitions with relation to metabolic syndrome-associated sexual dysfunction. J Sex Med. 2007;4:789–796.
  • Kelly DM, Jones TH. Testosterone and obesity. Obes Rev. 2015;16:581–606.
  • Corona G, Maseroli E, Rastrelli G, et al. Is late-onset hypogonadotropic hypogonadism a specific age-dependent disease, or merely an epiphenomenon caused by accumulating disease-burden? Minerva Endocrinol. 2016;41:196–210.
  • 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.
  • Layton JB, Kim Y, Alexander GC, et al. Association between direct-to-consumer advertising and testosterone testing and initiation in the United States, 2009-2013. JAMA. 2017;317:1159–1166.
  • Ahern T, Swiecicka A, Eendebak RJ, et al. Natural history, risk factors and clinical features of primary hypogonadism in ageing men: longitudinal data from the European male ageing study. Clin Endocrinol (Oxf). 2016;85:891–901.
  • 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.
  • Tajar A, Forti G, O’Neill TW, et al. Characteristics of secondary, primary, and compensated hypogonadism in aging men: evidence from the European male ageing study. J Clin Endocrinol Metab. 2010;95:1810–1818.
  • Morelli A, Sarchielli E, Comeglio P, et al. Metabolic syndrome induces inflammation and impairs gonadotropin-releasing hormone neurons in the preoptic area of the hypothalamus in rabbits. Mol Cell Endocrinol. 2014;382:107–119.
  • Yeap BB, Grossmann M, McLachlan RI, et al. Endocrine Society of Australia position statement on male hypogonadism (part 1): assessment and indications for testosterone therapy. Med J Aust. 2016;205:173–178.
  • Corona G, Maggi M. Perspective: regulatory agencies’ changes to testosterone product labeling. J Sex Med. 2015;12:1690–1693.
  • Corona G, Giagulli VA, Maseroli E, et al. Therapy of endocrine disease: testosterone supplementation and body composition: results from a meta-analysis study. Eur J Endocrinol. 2016;174:R99–R116.
  • Corona G, Isidori AM, Buvat J, et al. Testosterone supplementation and sexual function: a meta-analysis study. J Sex Med. 2014;11:1577–1592.
  • Corona G, Rastrelli G, Morgentaler A, et al. Meta-analysis of results of testosterone therapy on sexual function based on international index of erectile function scores. Eur Urol. 2017 Dec;72(6):1000–1011.
  • Nieschlag E, Nieschlag S. Testosterone deficiency: a historical perspective. Asian J Androl. 2014;16:161–168.
  • Corona G, Rastrelli G, Monami M, et al. Body weight loss reverts obesity-associated hypogonadotropic hypogonadism: a systematic review and meta-analysis. Eur J Endocrinol. 2013;168:829–843.
  • Corona G, Giagulli VA, Maseroli E, et al. Testosterone supplementation and body composition: results from a meta-analysis of observational studies. J Endocrinol Invest. 2016;39:967–981.
  • Corona G1, Maseroli E, Maggi M. Injectable testosterone undecanoate for the treatment of hypogonadism. Expert Opin Pharmacother. 2014;15:1903–1926.
  • Saad F, Yassin A, Doros G, et al. Effects of long-term treatment with testosterone on weight and waist size in 411 hypogonadal men with obesity classes I-III: observational data from two registry studies. Int J Obes (Lond). 2016;40:162–170.
  • Corona G, Vignozzi L, Sforza A, et al. Obesity and late-onsethypogonadism. Mol Cell Endocrinol. 2015;418(Pt 2):120–133.
  • Rastrelli G, Corona G, Mannucci E, et al. Factors affecting spermatogenesis upon gonadotropin-replacement therapy: a meta-analytic study. Andrology. 2014;2:794–808.
  • Nieschlag E. Current topics in testosterone replacement of hypogonadal men. Best Pract Res Clin Endocrinol Metab. 2015;29:77–90.
  • Ohlander SJ, Varghese B, Pastuszak AW. Erythrocytosis Following Testosterone Therapy. Sex Med Rev. 2018 Jan;6(1):77–85.
  • Liu PY, Wishart SM, Handelsman DJ. A double-blind, placebo-controlled, randomized clinical trial 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.
  • Tsujimura A, Matsumiya K, Takao T, et al. Treatment with human chorionic gonadotropin for PADAM: a preliminary report. Aging Male. 2005;8:175–179.
  • 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.
  • Rastrelli G, Vignozzi L, Maggi M. Different medications for hypogonadotropic hypogonadism. Endocr Dev. 2016;30:60–78.
  • Ley SB, Leonard JM. Male hypogonadotropic hypogonadism: factors influencing response to human chorionic gonadotropin and human menopausal gonadotropin, including prior exogenous androgens. J Clin Endocrinol Metab. 1985;61:746–752.
  • Schopohl J, Mehltretter G, Von Zumbusch R, et al. Comparison of gonadotropin-releasing hormone and gonadotropin therapy in male patients with idiopathic hypothalamic hypogonadism. Fertil Steril. 1991;56:1143–1150.
  • Kliesch S, Behre HM, Nieschlag E. High efficacy of gonadotropin or pulsatile gonadotropin-releasing hormone treatment in hypogonadotropic hypogonadal men. Eur J Endocrinol. 1994;131:347–354.
  • Burgues S, Calderon MD. Subcutaneous self-administration of highly-purified follicle stimulating hormone and human chorionic gonadotrophin for the treatment of male hypogonadotrophic hypogonadism. Spanish collaborative group on male hypogonadotropic hypogonadism. Hum Reprod. 1997;12:980–986.
  • European Metrodin HP Study Group. Efficacy and safety of highly-purified urinary follicle-stimulating hormone with human chorionic gonadotropin for treating men with isolated hypogonadotropic hypogonadism. Fertil Steril. 1998;70:256–262.
  • Liu PY, Turner L, Rushford D, et al. Efficacy and safety of recombinant human follicle stimulating hormone (Gonal-F) with urinary human chorionic gonadotrophin for induction of spermatogenesis and fertility in gonadotrophin-deficient men. Hum Reprod. 1999;14:1540–1545.
  • Bouloux P, Warne DW, Loumaye E, et al. Efficacy and safety of recombinant human follicle-stimulating hormone in men with isolated hypogonadotropichypogonadism. Fertil Steril. 2002;77:270–273.
  • Bouloux PM, Nieschlag E, Burger HG, et al. Induction of spermatogenesis by recombinant follicle-stimulating hormone (puregon) in hypogonadotropic azoospermic men who failed to respond to human chorionic gonadotropin alone. J Androl. 2003;24:604–611.
  • Matsumoto AM, Snyder PJ, Bhasin S, et al. Stimulation of spermatogenesis with recombinant human follicle-stimulating hormone (follitropinalfa; GONAL-f): long-term treatment in azoospermic men with hypogonadotropic hypogonadism. Fertil Steril. 2009;92:979–990.
  • Warne DW, Decosterd G, Okada H, et al. A combined analysis of data to identify predictive factors for spermatogenesis in men with hypogonadotropic hypogonadism treated with recombinant human follicle-stimulating hormone and human chorionic gonadotropin. Fertil Steril. 2009;92:594–604.
  • Sinisi AA, Esposito D, Bellastella G, et al. Efficacy of recombinant human follicle stimulating hormone at low doses in inducing spermatogenesis and fertility in hypogonadotropic hypogonadism. J Endocrinol Invest. 2010;33:618–623.
  • Milsom S, Duggan K, O’sullivan S, et al. Treatment of infertility with hypogonadotropichypogonadism: 10-year experience in Auckland, New Zealand. Aust N Z J Obstet Gynaecol. 2012;52:293–298.
  • Calof OM, Singh AB, Lee ML, et al. Adverse events associated with testosterone replacement in middle-aged and older men: a meta-analysis of randomized, placebo-controlled trials. J Gerontol A BiolSci Med Sci. 2005;60:1451–1457.
  • Haddad RM, Kennedy CC, Caples SM, et al. Testosterone and cardiovascular risk in men: a systematic review and meta-analysis of randomized placebo-controlled trials. Mayo Clin Proc. 2007;82:29–39.
  • Fernández-Balsells MM, Murad MH, Lane M, et al. Clinical review 1: adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2010;95:2560–2575.
  • Xu L, Freeman G, Cowling BJ, et al. Testosterone therapy and cardiovascular events among men: a systematic review and meta-analysis of placebo-controlled randomized trials. BMC Med. 2013;11:108.
  • Corona G, Maseroli E, Rastrelli G, et al. Cardiovascular risk associated with testosterone boosting medications: a systematic review and meta-analysis. Expert Opin Drug Saf. 2014;13:1327–1351.
  • Borst SE, Shuster JJ, Zou B, et al. Cardiovascular risks and elevation of serum DHT vary by route of testosterone administration: a systematic review and meta-analysis. BMC Med. 2014;12:211.
  • Albert SG, Morley JE. Testosterone therapy, association with age, initiation and mode of therapy with cardiovascular events: a systematic review. Clin Endocrinol (Oxf). 2016;85:436–443.
  • Alexander GC, Iyer G, Lucas E, et al. Cardiovascular risks of exogenous testosterone use among men: a systematic review and meta-analysis. Am J Med. 2017;130:293–305.
  • Cui Y, Zhang Y. The effect of androgen-replacement therapy on prostate growth: a systematic review and meta-analysis. Eur Urol. 2013;64:811–822.
  • Cui Y, Zong H, Yan H, et al. The effect of testosterone replacement therapy on prostate cancer: a systematic review and meta-analysis. Prostate Cancer Prostatic Dis. 2014;17:132–143.
  • Guo C, Gu W, Liu M, et al. Efficacy and safety of testosterone replacement therapy in men with hypogonadism: A meta-analysis study of placebo-controlled trials. Exp Ther Med. 2016;11:853–863.
  • Kang DY, Li HJ. The effect of testosterone replacement therapy on prostate-specific antigen (PSA) levels in men being treated for hypogonadism: a systematic review and meta-analysis. Medicine (Baltimore). 2015;94:e410.
  • Boyle P, Koechlin A, Bota M, et al. Endogenous and exogenous testosterone and the risk of prostate cancer and increased prostate-specific antigen (PSA) level: a meta-analysis. BJU Int. 2016;118:731–741.
  • Corona G, Rastrelli G, Maseroli E, et al. Testosterone replacement therapy and cardiovascular risk: a review. World J Mens Health. 2015;33:130–142.
  • Xu L, Schooling CM. Differential risks in men and women for first and recurrent venous thrombosis: the role of genes and environment: comment. J Thromb Haemost. 2015;13:884.
  • Carlson HE, Kane P, Lei ZM, et al. Presence of luteinizing hormone/human chorionic gonadotropin receptors in male breast tissues. J Clin Endocrinol Metab. 2004;89:4119–4123.
  • Maseroli E, Rastrelli G, Corona G, et al. Gynecomastia in subjects with sexual dysfunction. J Endocrinol Invest. 2014;37:525–532.
  • Ebling FJ. Hormonal control and methods of measuring sebaceous gland activity. J Invest Dermatol. 1974;62:161–171.
  • Katsambas AD, Dessinioti C. Hormonal therapy for acne: why not as first line therapy? Facts and controversies. Clin Dermatol. 2010;28:17–23.
  • Aydogdu A, Bolu E, Sonmez A, et al. Effects of three different medications on metabolic parameters and testicular volume in patients with hypogonadotropic hypogonadism: 3-year experience. Clin Endocrinol (Oxf). 2013;79:243–251.
  • Basaria S, Coviello AD, Travison TG, et al. Adverse events associated with testosterone administration. N Engl J Med. 2010;363:109–122.
  • Vigen R, O’Donnell CI, Barón AE, et al. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA. 2013;310:1829–1836.
  • 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.
  • Isidori AM, Balercia G, Calogero AE, et al. Outcomes of androgen replacement therapy in adult male hypogonadism: recommendations from the Italian society of endocrinology. J Endocrinol Invest. 2015;38:103–112.
  • Corona G, Sforza A, Maggi M. Testosterone replacement therapy: long-term safety and efficacy. World J Mens Health. 2017;35:65–76.
  • Elkhoury FF, Rambhatla A, Mills JN, et al. Cardiovascular health, erectile dysfunction, and testosterone replacement: controversies and correlations. Urology. 2017 Jul 31. pii: S0090-4295(17)30777-X. [Epub ahead of print].
  • Sharma R, Oa O, Gupta K, et al. Normalization of testosterone level is associated with reduced incidence of myocardial infarction and mortality in men. Eur Heart J. 2015;36:2706–2715.
  • Hedges LV, Vevea JL. Fixed - and random-effects models in meta-analysis. Psychol Methods. 1998;3:486–504.
  • Testosterone treatment of men with alcoholic cirrhosis: a double-blind study. The copenhagen study group for liver diseases. Hepatology. 1986;6:807–813.
  • Corona G, Dicuio M, Rastrelli G, et al. Testosterone treatment and cardiovascular and venous thromboembolism risk: what is ‘new’? J Investig Med. 2017;65:964–973.
  • Corona G, Baldi E, Maggi M. Androgen regulation of prostate cancer: where are we now? J Endocrinol Invest. 2011;34:232–243.
  • Vignozzi L, Gacci M, Cellai I, et al. Fat boosts, while androgen receptor activation counteracts, BPH-associated prostate inflammation. Prostate. 2013;73:789–800.
  • Vignozzi L, Rastrelli G, Corona G, et al. Benign prostatic hyperplasia: a new metabolic disease? J Endocrinol Invest. 2014;37:313–322.
  • Lopez DS, Advani S, Tsilidis KK, et al. Endogenous and exogenous testosterone and prostate cancer: decreased-, increased- or null-risk? Transl Androl Urol. 2017;6:566–579.
  • Pastuszak AW, Rodriguez KM, Nguyen TM, et al. Testosterone therapy and prostate cancer. Transl Androl Urol. 2016;5:909–920.
  • Morgentaler A, Traish AM. Shifting the paradigm of testosterone and prostate cancer: the saturation model and the limits of androgen-dependent growth. Eur Urol. 2009;55:310–320.
  • Rastrelli G, Corona G, Vignozzi L, et al. Serum PSA as a predictor of testosterone deficiency. J Sex Med. 2013;10:2518–2528.
  • Corona G, Boddi V, Lotti F, et al. The relationship of testosterone to prostate-specific antigen in men with sexual dysfunction. J Sex Med. 2010;7(1 Pt 1):284–292.
  • Gacci M, Corona G, Apolone G, et al. Influence of serum testosterone on urinary continence and sexual activity in patients undergoing radical prostatectomy for clinically localized prostate cancer. Prostate Cancer Prostatic Dis. 2010;13:168–172.
  • Takizawa I, Nishiyama T, Hara N, et al. Serum prostate-specific antigen levels reflect the androgen milieu in patients with localized prostate cancer receiving androgen deprivation therapy: tumor malignant potential and androgen milieu. Prostate. 2010;70:1395–1401.
  • Melmed S, Casanueva FF, Hoffman AR, et al. Diagnosis and treatment of hyperprolactinemia: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2011;96:273–288.
  • Snyder PJ, Bhasin S, Cunningham GR, et al. Effects of testosterone treatment in older men. N Engl J Med. 2016;374:611–624.
  • Onasanya O, Iyer G, Lucas E, et al. Association between exogenous testosterone and cardiovascular events: an overview of systematic reviews. Lancet Diabetes Endocrinol. 2016;4:943–956.

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