Skip to main content

Treatment of Hypogonadism

  • Reference work entry
  • First Online:
Endocrinology of the Testis and Male Reproduction

Part of the book series: Endocrinology ((ENDOCR))

  • 2229 Accesses

Abstract

Hypogonadism is a frequent condition, in particular during adult age. Whereas no doubts exist on the opportunity of treating patients with hypogonadism deriving from definite conditions affecting the hypothalamic-pituitary-testicular axis, more concerns are present for treatment of men with age-related testosterone (T) decline, the so-called late-onset hypogonadism (LOH). Several options are available for treating hypogonadism, and the choice should be done according to rationale, indications, and expected outcomes, taking also into account the advantages and disadvantages associated with each molecule and preparation. Although GnRH and gonadotropins are the cornerstone of therapy in secondary hypogonadism (sHG) men requiring fertility, few data are present on their use in LOH. Testosterone replacement therapy (TRT) is the most studied therapy in this particular and controversial condition. Randomized clinical trials (RCTs) on TRT are few and short lasting. However, there is substantial consistence on the efficacy of TRT in improving sexual function, increasing lean mass, and decreasing fat mass. The results are more controversial on the effectiveness of TRT in improving glycolipid profile and mood. Concerning bone mineral density, the evidence is scarce and those concerning fractures are nonexisting. An intense debate is ongoing on the putative risk of cardiovascular (CV) events associated with TRT. Pending results from RCTs specifically designed for assessing this outcome, available evidence reassures on CV safety of TRT, but caution should be used in older and frail men.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Institutional subscriptions

References

  • 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(3):436–43.

    Article  CAS  PubMed  Google Scholar 

  • Amsterdam JD, Winokur A, Caroff S, Snyder P. Gonadotropin release after administration of GnRH in depressed patients and healthy volunteers. J Affect Disord. 1981;3:367–80.

    Article  CAS  PubMed  Google Scholar 

  • Anawalt BD. Approach to male infertility and induction of spermatogenesis. J Clin Endocrinol Metab. 2013;98:3532–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Araujo AB, Dixon JM, Suarez EA, Murad MH, Guey LT, Wittert GA. Clinical review: Endogenous testosterone and mortality in men: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2011;96:3007–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Baischer W, Koinig G, Hartmann B, Huber J, Langer G. Hypothalamicpituitary-gonadal axis in depressed premenopausal women: Elevated blood testosterone concentrations compared to normal controls. Psychoneuroendocrinology. 1995;20:553–9.

    Article  CAS  PubMed  Google Scholar 

  • Basaria S, Coviello AD, Travison TG, Storer TW, Farwell WR, Jette AM, Eder R, Tennstedt S, Ulloor J, Zhang A, Choong K, Lakshman KM, Mazer NA, Miciek R, Krasnoff J, Elmi A, Knapp PE, Brooks B, Appleman E, Aggarwal S, Bhasin G, Hede-Brierley L, Bhatia A, Collins L, LeBrasseur N, Fiore LD, Bhasin S. Adverse events associated with testosterone administration. N Engl J Med. 2010;363:109–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bedognetti D, Rubagotti A, Conti G, Francesca F, De Cobelli O, Canclini L, Gallucci M, Aragona F, Di Tonno P, Cortellini P, Martorana G, Lapini A, Boccardo F. An open, randomised, multicentre, phase 3 trial comparing the efficacy of two tamoxifen schedules in preventing gynaecomastia induced by bicalutamide monotherapy in prostate cancer patients. Eur Urol. 2010;57:238–45.

    Article  CAS  PubMed  Google Scholar 

  • Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, Montori VM, Task Force, Endocrine Society. Testosterone therapy in men with androgen deficiency syndromes: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2010;95:2536–59.

    Article  CAS  PubMed  Google Scholar 

  • Bianco SD, Kaiser UB. The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism. Nat Rev Endocrinol. 2009;5:569–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brambilla F, Maggioni M, Ferrari E, Scarone S, Catalano M. Tonic and dynamic gonadotropin secretion in depressive and normothymic phases of affective disorders. Psychiatry Res. 1990;32:229–39.

    Article  CAS  PubMed  Google Scholar 

  • Brock G, Heiselman D, Maggi M, Kim SW, Rodríguez Vallejo JM, Behre HM, McGettigan J, Dowsett SA, Hayes RP, Knorr J, Ni X, Kinchen K. Effect of Testosterone Solution 2% on Testosterone Concentration, Sex Drive and Energy in Hypogonadal Men: Results of a Placebo Controlled Study. J Urol. 2016;195:699–705.

    Article  CAS  PubMed  Google Scholar 

  • Buchter D, Behre HM, Kliesch S, Nieschlag E. Pulsatile GnRH or human chorionic gonadotropin/human menopausal gonadotropin as effective treatment for men with hypogonadotropic hypogonadism: a review of 42 cases. Eur J Endocrinol. 1998;139:298–303.

    Article  CAS  PubMed  Google Scholar 

  • Burris AS, Banks SM, Carter CS, Davidson JM, Sherins RJ. A long-term, prospective study of the physiology and behavioral effects of hormone replacement in untreated hypogonadal men. J Androl. 1992;13:297–304.

    CAS  PubMed  Google Scholar 

  • Chandrapal JC, Nielson S, Patel DP, Zhang C, Presson AP, Brant WO, Myers JB, Hotaling JM. Characterising the safety of clomiphene citrate in male patients through prostate-specific antigen, haematocrit, and testosterone levels. BJU Int. 2016;118(6):994–1000.

    Article  CAS  PubMed  Google Scholar 

  • Chua ME, Escusa KG, Luna S, Tapia LC, Dofitas B, Morales M. Revisiting oestrogen antagonists (clomiphene or tamoxifen) as medical empiric therapy for idiopathic male infertility: a meta-analysis. Andrology. 2013;1:749–57.

    Article  CAS  PubMed  Google Scholar 

  • Comeglio P, Morelli A, Cellai I, Vignozzi L, Sarchielli E, Filippi S, Maneschi E, Corcetto F, Corno C, Gacci M, Vannelli GB, Maggi M. Opposite effects of tamoxifen on metabolic syndrome-induced bladder and prostate alterations: a role for GPR30/GPER? Prostate. 2014;74:10–28.

    Article  CAS  PubMed  Google Scholar 

  • Corona G, Maggi M. Perspective: regulatory agencies’ changes to testosterone product labeling. J Sex Med. 2015;12:1690–3.

    Article  PubMed  Google Scholar 

  • Corona G, Rastrelli G, Vignozzi L, Mannucci E, Maggi M. Testosterone, cardiovascular disease and the metabolic syndrome. Best Pract Res Clin Endocrinol Metab. 2011a;2:337–53.

    Article  CAS  Google Scholar 

  • Corona G, Rastrelli G, Monami M, Guay A, Buvat J, Sforza A, Forti G, Mannucci E, Maggi M. Hypogonadism as a risk factor for cardiovascular mortality in men: a meta-analytic study. Eur J Endocrinol. 2011b;165:687–701.

    Article  CAS  PubMed  Google Scholar 

  • Corona G, Rastrelli G, Monami M, Melani C, Balzi D, Sforza A, Forti G, Mannucci E, Maggi M. Body mass index regulates hypogonadism-associated CV risk: results from a cohort of subjects with erectile dysfunction. J Sex Med. 2011c;8:2098–105.

    Article  PubMed  Google Scholar 

  • Corona G, Jannini EA, Vignozzi L, Rastrelli G, Maggi M. The hormonal control of ejaculation. Nat Rev Urol. 2012;9:508–19.

    Article  CAS  PubMed  Google Scholar 

  • Corona G, Rastrelli G, Monami M, Saad F, Luconi M, Lucchese M, Facchiano E, Sforza A, Forti G, Mannucci E, Maggi M. Body weight loss reverts obesity-associated hypogonadotropic hypogonadism: a systematic review and meta-analysis. Eur J Endocrinol. 2013;168:829–43.

    Article  CAS  PubMed  Google Scholar 

  • Corona G, Isidori AM, Buvat J, Aversa A, Rastrelli G, Hackett G, Rochira V, Sforza A, Lenzi A, Mannucci E, Maggi M. Testosterone supplementation and sexual function: a meta-analysis study. J Sex Med. 2014a;11:1577–92.

    Article  CAS  PubMed  Google Scholar 

  • Corona G, Rastrelli G, Maseroli E, Fralassi N, Sforza A, Forti G, Mannucci E, Maggi M. Low testosterone syndrome protects subjects with high cardiovascular risk burden from major adverse cardiovascular events. Andrology. 2014b;2:741–7.

    Article  CAS  PubMed  Google Scholar 

  • Corona G, Maseroli E, Rastrelli G, Isidori AM, Sforza A, Mannucci E, Maggi M. Cardiovascular risk associated with testosterone-boosting medications: a systematic review and meta-analysis. Expert Opin Drug Saf. 2014c;13:1327–51.

    Article  CAS  PubMed  Google Scholar 

  • Corona G, Rastrelli G, Maggi M. The pharmacotherapy of male hypogonadism besides androgens. Expert Opin Pharmacother. 2015;16:369–87.

    CAS  PubMed  Google Scholar 

  • Corona G, Giagulli VA, Maseroli E, Vignozzi L, Aversa A, Zitzmann M, Saad F, Mannucci E, Maggi M. Testosterone supplementation and body composition: results from a meta-analysis study. Eur J Endocrinol. 2016;174:R99–116.

    Article  CAS  PubMed  Google Scholar 

  • Delhez M, Hansenne M, Legros JJ. Andropause and psychopathology: Minor symptoms rather than pathological ones. Psychoneuroendocrinology. 2003;28:863–74.

    Article  CAS  PubMed  Google Scholar 

  • Dobs AS, Matsumoto AM, Wang C, Kipnes MS. Short-term pharmacokinetic comparison of a novel testosterone buccal system and a testosterone gel in testosterone deficient men. Curr Med Res Opin. 2004;20:729–38.

    Article  CAS  PubMed  Google Scholar 

  • Dohle GR, Arver S, Bettocchi C, Jones TH, Kliesch S, Punab M. Guidelines on male hypogonadism. Arnhem: European Association of Urology; 2015. Available: http://uroweb.org/wp-content/uploads/EAU-Guidelines-Male-Hypogonadism-2015.pdf.

    Google Scholar 

  • Drake MT, Murad MH, Mauck KF, Lane MA, Undavalli C, Elraiyah T, Stuart LM, Prasad C, Shahrour A, Mullan RJ, Hazem A, Erwin PJ, Montori VM. Clinical review. Risk factors for low bone mass-related fractures in men: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2012;97:1861–70.

    Article  CAS  PubMed  Google Scholar 

  • Dwyer AA, Sykiotis GP, Hayes FJ, Boepple PA, Lee H, Loughlin KR, Dym M, Sluss PM, Crowley Jr WF, Pitteloud N. Trial of recombinant follicle-stimulating hormone pretreatment for GnRH-induced fertility in patients with congenital hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 2013;98:E1790–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dwyer AA, Raivio T, Pitteloud N. Gonadotrophin replacement for induction of fertility in hypogonadal men. Best Pract Res Clin Endocrinol Metab. 2015;29:91–103.

    Article  CAS  PubMed  Google Scholar 

  • Fernandez-Balsells MM, Murad MH, Lane M, Lampropulos JF, Albuquerque F, Mullan RJ, Agrwal N, Elamin MB, Gallegos-Orozco JF, Wang AT, Erwin PJ, Bhasin S, Montori VM. Clinical review 1: adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2010;95:2560–75.

    Article  CAS  PubMed  Google Scholar 

  • Finkelstein JS, Yu EW, Burnett-Bowie SA. Gonadal steroids and body composition, strength, and sexual function in men. N Engl J Med. 2013;369:2457.

    Article  CAS  PubMed  Google Scholar 

  • Finkle WD, Greenland S, Ridgeway GK, Adams JL, Frasco MA, Cook MB, Fraumeni Jr JF, Hoover RN. Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS ONE. 2014;9:e85805.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Grossmann M, Hoermann R, Wittert G, Yeap BB. Effects of testosterone treatment on glucose metabolism and symptoms in men with type 2 diabetes and the metabolic syndrome: a systematic review and meta-analysis of randomized controlled clinical trials. Clin Endocrinol (Oxf). 2015;83:344–51.

    Article  CAS  PubMed  Google Scholar 

  • Guay AT, Bansal S, Heatley GJ. Effect of raising endogenous testosterone levels in impotent men with secondary hypogonadism: double blind placebo controlled trial with clomiphene citrate. J Clin Endocrinol Metab. 1995;80:3546–52.

    CAS  PubMed  Google Scholar 

  • Gupta BP, Murad MH, Clifton MM, Prokop L, Nehra A, Kopecky SL. The effect of lifestyle modification and cardiovascular risk factor reduction on erectile dysfunction: a systematic review and meta-analysis. Arch Intern Med. 2011;171:1797–803.

    Article  PubMed  Google Scholar 

  • Hadgraft J, Lane ME. Transdermal delivery of testosterone. Eur J Pharm Biopharm. 2015;92:42–8.

    Article  CAS  PubMed  Google Scholar 

  • Helo S, Mahon J, Ellen J, Wiehle R, Fontenot G, Hsu K, Feustel P, Welliver C, McCullough A. Serum levels of enclomiphene and zuclomiphene in men with hypogonadism on long-term clomiphene citrate treatment. BJU Int. 2016. doi:10.1111/bju.13625. [Epub ahead of print].

    PubMed  Google Scholar 

  • Hildreth K, Barry DW, Moreau KL, Vande Griend J, Meacham RB, Nakamura T, Wolfe P, Kohrt WM, Ruscin JM, Kittelson J, Cress ME, Ballard R, Schwartz RS. Effects of testosterone and progressive resistance exercise in healthy, highly functioning older men with low-normal testosterone levels. J Clin Endocrinol Metab. 2013;98:1891–900.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huo S, Scialli AR, McGarvey S, Hill E, Tügertimur B, Hogenmiller A, Hirsch AI, Fugh-Berman A. Treatment of men for “low testosterone”: a systematic review.

    Google Scholar 

  • Isidori AM, Giannetta E, Greco EA, Gianfrilli D, Bonifacio V, Isidori A, Lenzi A, Fabbri A. Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle-aged men: a meta-analysis. Clin Endocrinol (Oxf). 2005;63:280–93.

    Article  CAS  PubMed  Google Scholar 

  • Isidori AM, Buvat J, Corona G, Goldstein I, Jannini EA, Lenzi A, Porst H, Salonia A, Traish AM, Maggi M. A critical analysis of the role of testosterone in erectile function: from pathophysiology to treatment-a systematic review. Eur Urol. 2014;65:99–112.

    Article  CAS  PubMed  Google Scholar 

  • Kacker R, Conners W, Zade J, Morgentaler A. Bone mineral density and response to treatment in men younger than 50 years with testosterone deficiency and sexual dysfunction or infertility. J Urol. 2014;191:1072–6.

    Article  CAS  PubMed  Google Scholar 

  • Kaminetsky J, Werner M, Fontenot G, Wiehle RD. Oral enclomiphene citrate stimulates the endogenous production of testosterone and sperm counts in men with low testosterone: comparison with testosterone gel. J Sex Med. 2013;10:1628–35.

    Article  CAS  PubMed  Google Scholar 

  • Kamischke A, Nieschlag E. Analysis of medical treatment of male infertility. Hum Reprod. 1999;14(Suppl 1):1–23.

    Article  PubMed  Google Scholar 

  • Kaufman JM, Miller MG, Garwin JL, Fitzpatrick S, McWhirter C, Brennan JJ. Efficacy and safety study of 1.62% testosterone gel for the treatment of hypogonadal men. J Sex Med. 2011;8:2079–89.

    Article  CAS  PubMed  Google Scholar 

  • Kaufman JM, Miller MG, Fitzpatrick S, McWhirter C, Brennan JJ. One-year efficacy and safety study of a 1.62% testosterone gel in hypogonadal men: results of a 182-day open-label extension of a 6-month double-blind study. J Sex Med. 2012;9:1149–61.

    Article  CAS  PubMed  Google Scholar 

  • Kenny AM, Kleppinger A, Annis K, Rathier M, Browner B, Judge JO, McGee D. Effects of transdermal testosterone on bone and muscle in older men with low bioavailable testosterone levels, low bone mass, and physical frailty. J Am Geriatr Soc. 2010;58:1134–43.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kim ED, McCullough A, Kaminetsky J. Oral enclomiphene citrate raises testosterone and preserves sperm counts in obese hypogonadal men, unlike topical testosterone: restoration instead of replacement. BJU Int. 2016;117:677–85.

    Article  CAS  PubMed  Google Scholar 

  • La Vignera S, Condorelli RA, Cimino L, Russo GI, Morgia G, Calogero AE. Late-onset hypogonadism: the advantages of treatment with human chorionic gonadotropin rather than testosterone. Aging Male. 2016;19:34–9.

    Article  CAS  PubMed  Google Scholar 

  • LeBlanc ES, Nielson CM, Marshall LM, Lapidus JA, Barrett-Connor E, Ensrud KE, Hoffman AR, Laughlin G, Ohlsson C, Orwoll ES. The effects of serum testosterone, estradiol, and sex hormone binding globulin levels on fracture risk in older men. J Clin Endocrinol Metab. 2009;94:3337–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu L, Banks SM, Barnes KM, Sherins RJ. Two-year comparison of testicular responses to pulsatile gonadotropin-releasing hormone and exogenous gonadotropins from the inception of therapy in men with isolated hypogonadotropic hypogonadism. J Clin Endocrinol Metab. 1988a;67:1140–5.

    Article  CAS  PubMed  Google Scholar 

  • Liu L, Chaudhari N, Corle D, Sherins RJ. Comparison of pulsatile subcutaneous gonadotropin-releasing hormone and exogenous gonadotropins in the treatment of men with isolated hypogonadotropic hypogonadism. Fertil Steril. 1988b;49:302–8.

    Article  CAS  PubMed  Google Scholar 

  • 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;87:3125–35.

    Article  CAS  PubMed  Google Scholar 

  • Liu PY, Wishart SM, Celermajer DS, Jimenez M, Pierro ID, Conway AJ, Handelsman DJ. 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.

    Article  CAS  PubMed  Google Scholar 

  • Liu PY, Baker HW, Jayadev V, Zacharin M, Conway AJ, Handelsman DJ. Induction of spermatogenesis and fertility during gonadotropin treatment of gonadotropin-deficient infertile men: predictors of fertility outcome. J Clin Endocrinol Metab. 2009;94:801–8.

    Article  CAS  PubMed  Google Scholar 

  • Liu Z, Mao J, Wu X, Xu H, Wang X, Huang B, Zheng J, Nie M, Zhang H. Efficacy and outcome predictors of gonadotropin treatment for male congenital hypogonadotropic hypogonadism: a retrospective study of 223 patients. Medicine (Baltimore). 2016;95:e2867.

    Article  CAS  Google Scholar 

  • MacLean C, Newberry S, Maglione M, McMahon M, Ranganath V, Suttorp M, Mojica W, Timmer M, Alexander A, McNamara M, Desai SB, Zhou A, Chen S, Carter J, Tringale C, Valentine D, Johnsen B, Grossman J. Systematic review: comparative effectiveness of treatments to prevent fractures in men and women with low bone density or osteoporosis. Ann Intern Med. 2008;148:197–213.

    Article  PubMed  Google Scholar 

  • Maggi M, Buvat J. Standard operating procedures: pubertas tarda/delayed puberty–male. J Sex Med. 2013;10:285–93.

    Article  PubMed  Google Scholar 

  • Maneschi E, Morelli A, Filippi S, Cellai I, Comeglio P, Mazzanti B, Mello T, Calcagno A, Sarchielli E, Vignozzi L, Saad F, Vettor R, Vannelli GB, Maggi M. Testosterone treatment improve metabolic syndrome-induced adipose tissue derangements. J Endocrinol. 2012;215:347–62.

    Article  CAS  PubMed  Google Scholar 

  • Maneschi E, Vignozzi L, Morelli A, Mello T, Filippi S, Cellai I, Comeglio P, Sarchielli E, Calcagno A, Mazzanti B, Vettor R, Vannelli GB, Adorini L, Maggi M. FXR activation normalizes insulin sensitivity in visceral preadipocytes of a rabbit model of MetS. J Endocrinol. 2013;218:215–31.

    Article  CAS  PubMed  Google Scholar 

  • Mao J, Xu H, Wang X, Huang B, Liu Z, Zhen J, Nie M, Min L, Wu X. Congenital combined pituitary hormone deficiency patients have better responses to gonadotrophin-induced spermatogenesis than idiopathic hypogonadotropic hypogonadism patients. Hum Reprod. 2015;30:2031–7.

    Article  CAS  PubMed  Google Scholar 

  • Meier C, Nguyen TV, Handelsman DJ, Schindler C, Kushnir MM, Rockwood AL, Meikle AW, Center JR, Eisman JA, Seibel MJ. Endogenous sex hormones and incident fracture risk in older men. Arch Intern Med. 2008;168:47–54.

    Article  CAS  PubMed  Google Scholar 

  • Meikle AW, Arver S, Dobs AS, Sanders SW, Rajaram L, Mazer NA. Pharmacokinetics and metabolism of a permeation-enhanced testosterone transdermal system in hypogonadal men: influence of application site – a clinical research center study. J Clin. Endocrinol. Metab. 1996;81:1832–40.

    CAS  PubMed  Google Scholar 

  • Miller J, Britto M, Fitzpatrick S, McWhirter C, Testino SA, Brennan JJ, Zumbrunnen TL. Pharmacokinetics and relative bioavailability of absorbed testosterone after administration of a 1.62% testosterone gel to different application sites in men with hypogonadism. Endocr Pract. 2011;17:574–83.

    Article  PubMed  Google Scholar 

  • Moskovic DJ, Katz DJ, Akhavan A, Park K, Mulhall JP. Clomiphene citrate is safe and effective for long-term management of hypogonadism. BJU Int. 2012;110:1524–8.

    Article  CAS  PubMed  Google Scholar 

  • Muram D, Ni X. Utility of a single serum testosterone measurement to determine response to topical testosterone replacement in hypogonadal men. Curr Med Res Opin. 2016;32:263–9.

    Article  CAS  PubMed  Google Scholar 

  • Oppermann D, Happ J, Mayr WR. Stimulation of spermatogenesis and biological paternity by intranasal (low dose) gonadotropin-releasing hormone (GnRH) in a male with Kallmann’s syndrome: intraindividual comparison of GnRH and gonadotropins for stimulation of spermatogenesis. J Clin Endocrinol Metab. 1987;65:1060–6.

    Article  CAS  PubMed  Google Scholar 

  • Osran H, Reist C, Chen CC, Lifrak ET, Chicz-DeMet A, Parker LN. Adrenal androgens and cortisol in major depression. Am J Psychiatry. 1993;150:806–9.

    Article  CAS  PubMed  Google Scholar 

  • Perdonà S, Autorino R, De Placido S, D'Armiento M, Gallo A, Damiano R, Pingitore D, Gallo L, De Sio M, Bianco AR, Di Lorenzo G. Efficacy of tamoxifen and radiotherapy for prevention and treatment of gynaecomastia and breast pain caused by bicalutamide in prostate cancer: a randomised controlled trial. Lancet Oncol. 2005;6:295–300.

    Article  PubMed  CAS  Google Scholar 

  • Pesonen E, Pussinen P, Huhtaniemi I. Adaptation to acute coronary syndrome-induced stress with lowering of testosterone: a possible survival factor. Eur J Endocrinol. 2016;174:481–9.

    Article  CAS  PubMed  Google Scholar 

  • Pope Jr HG, Amiaz R, Brennan BP, Orr G, Weiser M, Kelly JF, Kanayama G, Siegel A, Hudson JI, Seidman SN. Parallel-group placebo-controlled trial of testosterone gel in men with major depressive disorder displaying an incomplete response to standard antidepressant treatment. J Clin Psychopharmacol. 2010;30:126–34.

    Article  CAS  PubMed  Google Scholar 

  • Raivio T, Wikström AM, Dunkel L. Treatment of gonadotropin-deficient boys with recombinant human FSH: long-term observation and outcome. Eur J Endocrinol. 2007;156:105–11.

    Article  CAS  PubMed  Google Scholar 

  • Rastrelli G, Corona G, Vignozzi L, Maseroli E, Silverii A, Monami M, Mannucci E, Forti G, Maggi M. Serum PSA as a predictor of testosterone deficiency. J Sex Med. 2013;10:2518–28.

    Article  CAS  PubMed  Google Scholar 

  • Rastrelli G, Corona G, Mannucci E, Maggi M. Factors affecting spermatogenesis upon gonadotropin-replacement therapy: a meta-analytic study. Andrology. 2014;2:794–808.

    Article  CAS  PubMed  Google Scholar 

  • Rastrelli G, Carter EL, Ahern T, Finn JD, Antonio L, O'Neill TW, Bartfai G, Casanueva FF, Forti G, Keevil B, Maggi M, Giwercman A, Han TS, Huhtaniemi IT, Kula K, Lean ME, Pendleton N, Punab M, Vanderschueren D, Wu FC, EMAS Study Group. Development of and recovery from secondary hypogonadism in aging men: prospective results from the EMAS. J Clin Endocrinol Metab. 2015;100:3172–82.

    Article  CAS  PubMed  Google Scholar 

  • Rastrelli G, Vignozzi L, Maggi M. Different medications for hypogonadotropic hypogonadism. Endocr Dev. 2016a;30:60–78.

    Article  PubMed  Google Scholar 

  • Rastrelli G, Giovannini L, Calogero AE, Gianfrilli D, Serra E, Pizzocaro A, Giagulli VA, Motta G, Vancieri G, Sperandio A, Andò S, Selice R, Luca G, Cocchiara F, Canale D, Maggi M. Predictors and clinical consequences of starting androgen therapy in men with low testosterone: results from the SIAMO-NOI registry. J Endocrinol Invest. 2016b;39:695–708.

    Article  CAS  PubMed  Google Scholar 

  • Riggs BL, Hartmann LC. Selective estrogen-receptor modulators – mechanisms of action and application to clinical practice. N Engl J Med. 2003;348:618–29.

    Article  CAS  PubMed  Google Scholar 

  • Rochira V, Zirilli L, Madeo B, Balestrieri A, Granata AR, Carani C. Sex steroids and sexual desire mechanism. J Endocrinol Invest. 2003;26:29–36.

    Article  CAS  PubMed  Google Scholar 

  • Sachar EJ, Halpern F, Rosenfeld RS, Galligher TF, Hellman L. Plasma and urinary testosterone levels in depressed men. Arch Gen Psychiatry. 1973;28:15–8.

    Article  CAS  PubMed  Google Scholar 

  • Saltzstein D, Sieber P, Morris T, Gallo J. Prevention and management of bicalutamide-induced gynecomastia and breast pain: randomized endocrinologic and clinical studies with tamoxifen and anastrozole. Prostate Cancer Prostatic Dis. 2005;8:75–83.

    Article  CAS  PubMed  Google Scholar 

  • Seidman SN, Walsh BT. Testosterone and depression in aging men. Am J Geriatr Psychiatry. 1999;7:18–33.

    Article  CAS  PubMed  Google Scholar 

  • Sheffield-Moore M, Dillon EL, Casperson SL, Gilkison CR, Paddon-Jones D, Durham WJ, Grady JJ, Urban RJ. A randomized pilot study of monthly cycled testosterone replacement or continuous testosterone replacement versus placebo in older men. J Clin Endocrinol Metab. 2011;96:E1831–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smith MR, Fallon MA, Lee H, Finkelstein JS. Raloxifene to prevent gonadotropin-releasing hormone agonist-induced bone loss in men with prostate cancer: a randomized controlled trial. J Clin Endocrinol Metab. 2004;89:3841–6.

    Article  CAS  PubMed  Google Scholar 

  • Smith MR, Morton RA, Barnette KG, Sieber PR, Malkowicz SB, Rodriguez D, Hancock ML, Steiner MS. Toremifene to reduce fracture risk in men receiving androgen deprivation therapy for prostate cancer. J Urol. 2010;184:1316–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smith MR, Malkowicz SB, Brawer MK, Hancock ML, Morton RA, Steiner MS. Toremifene decreases vertebral fractures in men younger than 80 years receiving androgen deprivation therapyfor prostate cancer. J Urol. 2011;186:2239–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smith MR, Morton RA, Barnette KG, Sieber PR, Malkowicz SB, Rodriguez D, Hancock ML, Steiner MS. Toremifene to reduce fracture risk in men receiving androgen deprivation therapy for prostate cancer. J Urol. 2013;189(1 Suppl):S45–50.

    Article  CAS  PubMed  Google Scholar 

  • Snyder PJ, Bhasin S, Cunningham GR, Matsumoto AM, Stephens-Shields AJ, Cauley JA, Gill TM, Barrett-Connor E, Swerdloff RS, Wang C, Ensrud KE, Lewis CE, Farrar JT, Cella D, Rosen RC, Pahor M, Crandall JP, Molitch ME, Cifelli D, Dougar D, Fluharty L, Resnick SM, Storer TW, Anton S, Basaria S, Diem SJ, Hou X, Mohler 3rd ER, Parsons JK, Wenger NK, Zeldow B, Landis JR, Ellenberg SS, Testosterone Trials Investigators, Snyder PJ, Barrett-Connor E, Bhasin S, Cauley JA, Cella D, Crandall JP, Cunningham G, Ellenberg SS, Ensrud KE, Farrar JT, Gill TM, Lewis CE, Matsumoto AM, Molitch ME, Pahor M, Resnick S, Rosen RC, Swerdloff RS, Ellenberg SS, Hou X, Stephens-Shields A, Landis JR, Zeldow B, Cen L, Moore RH, Cifelli D, Dougar D, Fluharty L, Gallagher L, Ballard S, Chai T, Dattilo J, Brown T, Smith S, Chicchi F, Kasner SE, Lewis CE, Messe SR, Mohler 3rd ER, Crandall JP, Tabatabaie V, Epstein E, Barzel U, Trandafirescu G, Cunningham GR, Cordero E, Marino P, Bhasin S, Basaria S, Eder R, Appleman E, Halley KA, Molitch M, Toft D, Wallia A, Larsen D, Massaro E, Adelman D, Lewis CE, Shikany J, Kolettis P, Johnson P, Pike MN, Joffrion IJ, Swerdloff R, Wang C, Han X, Ashai J, Barrett-Connor E, Herbst K, Hofflich H, Parsons J, Kamantigue N, Carrion-Peterson ML, Reno G, Claravall L, Smith J, Pahor M, Nayfield S, Anton SD, Manini T, Dahm P, Marsiske M, Sandesara B, Lewis M, Black ML, Knaggs J, Marena W, Lu JC, Ensrud KE, Diem SJ, Fink H, Warlick C, Potter S, Welch L, Van Covering P, Jacobson KL, Miller L, Cauley J, Horwitz MJ, Greenspan SL, Jaffe TM, Prebehalla L, Bonk JT, Rush JL, Matsumoto AM, Gilchriest J, Winter K, Wojtowicz M, Gill TM, deRekeneire N, Kashaf S, Katz L, Mojibian H, McGloin J, Wu K, Martinez D, Shepard D. Effects of testosterone treatment in older men. N Engl J Med. 2016;374:611–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stahlman J, Britto M, Fitzpatrick S, McWhirter C, Testino SA, Brennan JJ, Zumbrunnen TL. Serum testosterone levels in non-dosed females after secondary exposure to 1.62% testosterone gel: effects of clothing barrier on testosterone absorption. Curr Med Res Opin. 2012a;28:291–301.

    Article  CAS  PubMed  Google Scholar 

  • Stahlman J, Britto M, Fitzpatrick S, McWhirter C, Testino SA, Brennan JJ, Zumbrunnen TL. Effect of application site, clothing barrier, and application site washing on testosterone transfer with a 1.62% testosterone gel. Curr Med Res Opin. 2012b;28:281–90.

    Article  CAS  PubMed  Google Scholar 

  • Stahlman J, Britto M, Fitzpatrick S, McWhirter C, Testino SA, Brennan JJ, Zumbrunnen TL. Effects of skin washing on systemic absorption of testosterone in hypogonadal males after administration of 1.62% testosterone gel. Curr Med Res Opin. 2012c;28:271–9.

    Article  CAS  PubMed  Google Scholar 

  • Tajar A, Huhtaniemi IT, O'Neill TW, Finn JD, Pye SR, Lee DM, Bartfai G, Boonen S, Casanueva FF, Forti G, Giwercman A, Han TS, Kula K, Labrie F, Lean ME, Pendleton N, Punab M, Vanderschueren D, Wu FC. EMAS Group. Characteristics of androgen deficiency in late-onset hypogonadism: results from the European Male Aging Study (EMAS). J Clin Endocrinol Metab. 2012;97:1508–16.

    Article  CAS  PubMed  Google Scholar 

  • Tracz MJ, Sideras K, Boloña ER, Haddad RM, Kennedy CC, Uraga MV, Caples SM, Erwin PJ, Montori VM. Testosterone use in men and its effects on bone health. A systematic review and meta-analysis of randomized placebo-controlled trials. J Clin Endocrinol Metab. 2006;91:2011–6.

    Article  CAS  PubMed  Google Scholar 

  • Tran TS, Center JR, Seibel MJ, Eisman JA, Kushnir MM, Rockwood AL, Nguyen TV. Relationship between Serum Testosterone and Fracture Risk in Men: A Comparison of RIA and LC-MS/MS. Clin Chem. 2015;61:1182–90.

    Article  CAS  PubMed  Google Scholar 

  • Travison TG, Basaria S, Storer TW, Jette AM, Miciek R, Farwell WR, Choong K, Lakshman K, Mazer NA, Coviello AD, Knapp PE, Ulloor J, Zhang A, Brooks B, Nguyen AH, Eder R, LeBrasseur N, Elmi A, Appleman E, Hede-Brierley L, Bhasin G, Bhatia A, Lazzari A, Davis S, Ni P, Collins L, Bhasin S. Clinical meaningfulness of the changes in muscle performance and physical function associated with testosterone administration in older men with mobility limitation. J Gerontol A Biol Sci Med Sci. 2011;66:1090–9.

    Article  PubMed  CAS  Google Scholar 

  • Tsujimura A, Matsumiya K, Takao T, Miyagawa Y, Takada S, Koga M, Iwasa A, Takeyama M, Okuyama A. Treatment with human chorionic gonadotropin for PADAM: a preliminary report. Aging Male. 2005;8:175–9.

    Article  CAS  PubMed  Google Scholar 

  • Tuomilehto J, Lindström J, Eriksson JG, Valle TT, Hämäläinen H, Ilanne-Parikka P, Keinänen-Kiukaanniemi S, Laakso M, Louheranta A, Rastas M, Salminen V, Uusitupa M, Finnish Diabetes Prevention Study Group. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. 2001;344:1343–50.

    Article  CAS  PubMed  Google Scholar 

  • Unden F, Ljunggren JG, Beck-Friis J, Kjellman BF, Wetterberg L. Hypothalamic pituitary-gonadal axis in major depressive disorders. Acta Psychiatr Scand. 1988;78:138–46.

    Article  CAS  PubMed  Google Scholar 

  • Vandekerckhove P, Lilford R, Vail A, Hughes E. Clomiphene or tamoxifen for idiopathic oligo/asthenospermia. Cochrane Database Syst Rev. 2000;2:CD000151.

    Google Scholar 

  • Vigen R, O’Donnell CI, Barón AE, Grunwald GK, Maddox TM, Bradley SM, Barqawi A, Woning G, Wierman ME, Plomondon ME, Rumsfeld JS, Ho PM. Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA. 2013;310:1829–36.

    Article  CAS  PubMed  Google Scholar 

  • Wallis CJ, Lo K, Lee Y, Krakowsky Y, Garbens A, Satkunasivam R, Herschorn S, Kodama RT, Cheung P, Narod SA, Nam RK. Survival and cardiovascular events in men treated with testosterone replacement therapy: an intention-to-treat observational cohort study. Lancet Diabetes Endocrinol. 2016;4:498–506.

    Article  CAS  PubMed  Google Scholar 

  • Wang C, Swerdloff R, Kipnes M, Matsumoto AM, Dobs AS, Cunningham G, Katznelson L, Weber TJ, Friedman TC, Snyder P, Levine HL. New testosterone buccal system (Striant) delivers physiological testosterone levels: pharmacokinetics study in hypogonadal men. J Clin Endocrinol Metab. 2004;89:3821–9.

    Article  CAS  PubMed  Google Scholar 

  • Wang C, Nieschlag E, Swerdloff R, Behre HM, Hellstrom WJ, Gooren LJ, Kaufman JM, Legros JJ, Lunenfeld B, Morales A, Morley JE, Schulman C, Thompson IM, Weidner W, Wu FC, International Society of Andrology (ISA), International Society for the Study of Aging Male (ISSAM), European Association of Urology (EAU), European Academy of Andrology (EAA), American Society of Andrology (ASA). Investigation, treatment, and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA, and ASA recommendations. J Androl. 2009;30:1–9.

    Article  PubMed  Google Scholar 

  • Wang C, Ilani N, Arver S, McLachlan RI, Soulis T, Watkinson A. Efficacy and safety of the 2% formulation of testosterone topical solution applied to the axillae in androgen-deficient men. Clin Endocrinol (Oxf). 2011;75:836–43.

    Article  CAS  PubMed  Google Scholar 

  • Wu FC, Tajar A, Beynon JM, Pye SR, Silman AJ, Finn JD, O’Neill TW, Bartfai G, Casanueva FF, Forti G, Giwercman A, Han TS, Kula K, Lean ME, Pendleton N, Punab M, Boonen S, Vanderschueren D, Labrie F. EMAS Group. Identification of late-onset hypogonadism in middle-aged and elderly men. N Engl J Med. 2010;363:123–35.

    CAS  PubMed  Google Scholar 

  • Xu L, Freeman G, Cowling BJ, Schooling CM. Testosterone therapy and cardiovascular events among men: a systematic review and meta-analysis of placebo-controlled randomized trials. BMC Med. 2013;11:108.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yanase T, Fan W, Kyoya K, Min L, Takayanagi R, Kato S, Nawata H. Androgens and metabolic syndrome: lessons from androgen receptor knock out (ARKO) mice. J Steroid Biochem Mol Biol. 2008;109:254–7.

    Article  CAS  PubMed  Google Scholar 

  • Yeh S, Tsai MY, Xu Q, Mu XM, Lardy H, Huang KE, Lin H, Yeh SD, Altuwaijri S, Zhou X, Xing L, Boyce BF, Hung MC, Zhang S, Gan L, Chang C. Generation and characterization of androgen receptor knockout (ARKO) mice: an in vivo model for the study of androgen functions in selective tissues. Proc Natl Acad Sci U S A. 2002;99:13498–503.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yesavage JA, Davidson J, Widrow L, Berger PA. Plasma testosterone levels, depression, sexuality and age. Biol Psychiatry. 1985;20:199–228.

    Article  Google Scholar 

  • Young J, Couzinet B, Chanson P, Brailly S, Loumaye E, Schaison G. 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;85:3239–44.

    Article  CAS  PubMed  Google Scholar 

  • Zarrouf FA, Artz S, Griffith J, Sirbu C, Kommor M. Testosterone and depression: Systematic review and meta-analysis. J Psychiatr Pract. 2009;15:289–305.

    Article  PubMed  Google Scholar 

  • Zhao J, Schooling CM. Promotion of "Low T" and citation bias in testosterone studies. Int J Cardiol. 2015;184:510–1.

    Article  PubMed  Google Scholar 

  • Zitzmann M, Mattern A, Hanisch J, Gooren L, Jones H, Maggi M. 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;10:579–88.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mario Maggi .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this entry

Cite this entry

Rastrelli, G., Maggi, M. (2017). Treatment of Hypogonadism. In: Simoni, M., Huhtaniemi, I. (eds) Endocrinology of the Testis and Male Reproduction. Endocrinology. Springer, Cham. https://doi.org/10.1007/978-3-319-44441-3_32

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-44441-3_32

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-44440-6

  • Online ISBN: 978-3-319-44441-3

  • eBook Packages: MedicineReference Module Medicine

Publish with us

Policies and ethics