Skip to main content
SpringerLink
Log in

Senescence and Late-Onset Hypogonadism

  • Chapter
  • First Online:
Andrology

  • 550 Accesses

Abstract

Thanks to increasing life expectancy with its concomitant number of aging men, medicine is forced to focus more strongly on the endocrine situation of this age group. In men, although there is no climacteric, there is a gradual decline in testosterone, and levels may well remain within the normal range of younger men. In some men, however, levels fall below normal. When this occurs in conjunction with characteristic symptoms, it may be genuine late-onset hypogonadism (LOH) or functional hypogonadism. In these cases, testosterone substitution may be considered and must be closely monitored.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 219.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 279.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abrams P, Cardozo L, Fall M, Griffiths D, Rosier P, Ulmsten U, Van Kerrebroeck P, Victor A, Wein A (2003) The standardisation of terminology in lower urinary tract function: report from the standardisation sub-committee of the International Continence Society. Urology 61:37–49

    PubMed  Google Scholar 

  • Aguiar-Oliveira MH, Bartke A (2019) Growth hormone deficiency: health and longevity. Endocr Rev 40:575–601

    PubMed  Google Scholar 

  • Allan CA, Strauss BJ, Burger HG, Forbes EA, McLachlan RI (2008) Testosterone therapy prevents gain in visceral adipose tissue and loss of skeletal muscle in nonobese aging men. J Clin Endocrinol Metab 93:139–146

    CAS  PubMed  Google Scholar 

  • Amin S, Zhang Y, Felson DT, Sawin CT, Hannan MT, Wilson PW, Kiel DP (2006) Estradiol, testosterone, and the risk for hip fractures in elderly men from the Framingham Study. Am J Med 119:426–433

    CAS  PubMed  Google Scholar 

  • Andriole GL, Bostwick DG, Brawley OW, Gomella LG, Marberger M, Montorsi F, Pettaway CA, Tammela TL, Teloken C, Tindall DJ, Somerville MC, Wilson TH, Fowler IL, Rittmaster RS, REDUCE Study Group (2010) Effect of dutasteride on the risk of prostate cancer. N Engl J Med 362:1192–1202

    CAS  PubMed  Google Scholar 

  • Araujo AB, Esche GR, Kupelian V, O’Donnell AB, Travison TG, Williams RE, Clark RV, McKinlay JB (2007) Prevalence of symptomatic androgen deficiency in men. J Clin Endocrinol Metab 92:4241–4247

    CAS  PubMed  Google Scholar 

  • Azoulay L, Eberg M, Benayoun S, Pollak M (2015) 5α-reductase inhibitors and the risk of cancer-related mortality in men with prostate cancer. JAMA Oncol 1:314–320

    PubMed  Google Scholar 

  • Bachmann R, Happle R, Held KR, Holzgreve W, Kunze J, Rauskolb R, Rehder H, Sewig K-Fr. Schmidtke J, Wolff G, Wollersheim U. Wissenschaftlicher Beirat der Bundesärztekammer (2007) Richtlinien zur pränatalen Diagnostik von Krankheiten und Krankheitsdispositionen. http://www.bundesärztekammer.de

    Google Scholar 

  • Baillargeon J, Urban RJ, Kuo YF, Ottenbacher KJ, Raji MA, Du F, Lin YL, Goodwin JS (2014) Risk of myocardial infarction in older men receiving testosterone therapy. Ann Pharmacother 48:1138–1144

    CAS  PubMed  PubMed Central  Google Scholar 

  • Baillargeon J, Al Snih S, Raji MA, Urban RJ, Sharma G, Sheffield-Moore M, Lopez DS, Baillargeon G, Kuo YF (2016) Hypogonadism and the risk of rheumatic autoimmune disease. Clin Rheumatol 35:2983–2987

    PubMed  PubMed Central  Google Scholar 

  • Baillargeon J, Kuo YF, Westra JR, Urban RJ, Goodwin JS (2018) Testosterone prescribing in the United States, 2002-2016. JAMA 320:200–202

    PubMed  PubMed Central  Google Scholar 

  • Baran C, Hellstrom WJ, Sikka SC (2015) A comparative evaluation of semen parameters in pre- and post-Hurricane Katrina human population. Asian J Androl 17:17676–17680

    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 (2010) Adverse events associated with testosterone administration. N Engl J Med 363:109–122

    CAS  PubMed  PubMed Central  Google Scholar 

  • Behre HM, Bohmeyer J, Nieschlag E (1994) Prostate volume in testosterone-treated and untreated hypogonadal men in comparison to age-matched normal controls. Clin Endocrinol 40:341–349

    CAS  Google Scholar 

  • Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, Montori VM (2006) Testosterone therapy in adult men with androgen deficiency syndromes: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 91:1995–2010

    CAS  PubMed  Google Scholar 

  • Bhasin S, Valderrábano RJ, Gagliano-Jucá T (2022) Age-related changes in the male reproductive system. In: Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dhatariya K, Dungan K, Hershman JM, Hofland J, Kalra S, Kaltsas G, Koch C, Kopp P, Korbonits M, Kovacs CS, Kuohung W, Laferrère B, Levy M, McGee EA, McLachlan R, Morley JE, New M, Purnell J, Sahay R, Singer F, Sperling MA, Stratakis CA, Trence DL, Wilson DP, editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000–. PMID: 25905229

  • Bordson BL, Leonardo VS (1991) The appropriate upper age limit for semen donors: a review of the genetic effects of paternal age. Fertil Steril 56:397–401

    CAS  PubMed  Google Scholar 

  • Bryant J, Loveman E, Cave C, Chase D, Milne R (2002) Endocrinology trial design: adverse event reporting in randomised controlled trials of recombinant human GH in GH-deficient adults. J Endocrinol 175:545–552

    CAS  PubMed  Google Scholar 

  • Calof OM, Singh AB, Lee ML, Kenny AM, Urban RJ, Tenover JL, Bhasin S (2005) Adverse events associated with testosterone replacement in middle-aged and older men: a meta-analysis of randomized, placebo-controlled trials. J Gerontol A Biol Sci Med Sci 60:1451–1457. https://doi.org/10.1093/gerona/60.11.1451

    Article  PubMed  Google Scholar 

  • Corona G, Rastrelli G, Di Pasquale G, Sforza A, Mannucci E, Maggi M (2018) Endogenous testosterone levels and cardiovascular risk: meta-analysis of observational studies. J Sex Med 15:1260–1271

    PubMed  Google Scholar 

  • Corona G, Goulis DG, Huhtaniemi I, Zitzmann M, Toppari J, Forti G, Vanderschueren D, Wu FC (2020) European Academy of Andrology (EAA) guidelines on investigation, treatment and monitoring of functional hypogonadism in males: Endorsing organization: European Society of Endocrinology. Andrology 8:970–987

    PubMed  Google Scholar 

  • Crow JF (1997) The high spontaneous mutation rate: is it a health risk? Proc Natl Acad Sci U S A 94:8380–8386

    CAS  PubMed  PubMed Central  Google Scholar 

  • Dakouane M, Bicchieray L, Bergere M, Albert M, Vialard F, Selva J (2005) A histomorphometric and cytogenetic study of testis from men 29-102 years old. Fertil Steril 83:923–928

    PubMed  Google Scholar 

  • de la Rochebrochard E, Thonneau P (2002) Paternal age and maternal age are risk factors for miscarriage results of a multicentre European study. Hum Reprod 17:1649–1656

    PubMed  Google Scholar 

  • de Spiegeleer A, Beckwée D, Bautmans I, Petrovic M (2018) Sarcopenia Guidelines Development group of the Belgian Society of Gerontology and Geriatrics (BSGG). Pharmacological interventions to improve muscle mass, muscle strength and physical performance in older people: an umbrella review of systematic reviews and meta-analyses. Drugs Aging 35:719–734

    PubMed  Google Scholar 

  • Debruyne FM, Behre HM, Roehrborn CG, Maggi M, Wu FC, Schröder FH, Jones TH, Porst H, Hackett G, Wheaton OA, Martin-Morales A, Meuleman E, Cunningham GR, Divan HA, Rosen RC, Investigators RHYME (2017) Testosterone treatment is not associated with increased risk of prostate cancer or worsening of lower urinary tract symptoms: prostate health outcomes in the Registry of Hypogonadism in Men. BJU Int 119:216–224

    CAS  PubMed  Google Scholar 

  • Delhez M, Hansenne M, Legros JJ (2003) Andropause and psychopathology: minor symptoms rather than pathological ones. Psychoneuroendocrinology 28:863–874

    CAS  PubMed  Google Scholar 

  • Dhindsa S, Champion C, Deol E, Lui M, Campbell R, Newman J, Yeggalam A, Nadella S, Ahir V, Shrestha E, Kannampallil T, Diwan A (2022) Association of male hypogonadism with risk of hospitalization for COVID-19. JAMA Netw Open. 5:e2229747. https://doi.org/10.1001/jamanetworkopen.2022.29747

    Article  PubMed  PubMed Central  Google Scholar 

  • Diver MJ, Imtiaz KE, Ahmad AM, Vora JP, Fraser WD (2003) Diurnal rhythms of serum total, free and bioavailable testosterone and of SHBG in middle-aged men compared with those in young men. Clin Endocrinol 58:710–717

    CAS  Google Scholar 

  • du Fossé NA, van der Hoorn MP, van Lith JMM, le Cessie S, Lashley EELO (2020) Advanced paternal age is associated with an increased risk of spontaneous miscarriage: a systematic review and meta-analysis. Hum Reprod Update 26:650–669

    PubMed  PubMed Central  Google Scholar 

  • Elliot ML (1990) Psychological aspects of sexual dysfunction in the elderly. In: Armbrecht HJ, Coe RM, Wongsurawat N (eds) Endocrine function and age. Springer, Heidelberg, pp 136–146

    Google Scholar 

  • Ergun-Longmire B, Mertens AC, Mitby P, Qin J, Heller G, Shi W, Yasui Y, Robison LL, Sklar CA (2006) Growth hormone treatment and risk of second neoplasms in the childhood cancer survivor. J Clin Endocrinol Metab 91:3494–3498

    CAS  PubMed  Google Scholar 

  • FDA Drug Safety Communication: FDA cautions about using testosterone products for low testosterone due to aging; requires labeling change to inform of possible increased risk of heart attack and stroke with use (3.3.2015)

    Google Scholar 

  • Finkle WD, Greenland S, Ridgeway GK, Adams JL, Frasco MA, Cook MB, Fraumeni JF Jr, Hoover RN (2014) Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS One 9:e85805. https://doi.org/10.1371/journal.pone.0085805

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Flynn MA, Weaver-Osterholtz D, Sharpe-Timms KL, Allen S, Krause G (1999) Dehydroepiandrosterone replacement in aging humans. J Clin Endocrinol Metab 84:1527–1533

    CAS  PubMed  Google Scholar 

  • Francis RM (1999) The effects of testosterone on osteoporosis in men. Clin Endocrinol 50:411–414

    CAS  Google Scholar 

  • Frattarelli JL, Miller KA, Miller BT, Elkind-Hirsch K, Scott RT Jr (2008) Male age negatively impacts embryo development and reproductive outcome in donor oocyte assisted reproductive technology cycles. Fertil Steril 90:97–103

    PubMed  Google Scholar 

  • Gallardo E, Simon C, Levy M, Guanes PP, Remohi J, Pellicer A (1996) Effect of age on sperm fertility potential: oocyte donation as a model. Fertil Steril 66:260–264

    CAS  PubMed  Google Scholar 

  • Gann PH, Hennekens CH, Longcope C, Verhoek-Oftedahl W, Grodstein F, Stampfer MJ (1995) A prospective study of plasma hormone levels, nonhormonal factors, and development of benign prostatic hyperplasia. Prostate 26:40–49

    CAS  PubMed  Google Scholar 

  • Garfinkel D, Berner YN (1998) Antioxidants and aging: is melatonin a possible, practical new hope? Nutrition 14:712–713

    CAS  PubMed  Google Scholar 

  • Garfinkel D, Laudon M, Nof D, Zisapel N (1995) Improvement of sleep quality in elderly people by controlled-release melatonin. Lancet 346:541–544

    CAS  PubMed  Google Scholar 

  • Giovannucci E, Platz EA, Stampfer MJ, Chan A, Krithivas K, Kawachi I, Willett WC, Kantoff PW (1999) The CAG repeat within the androgen receptor gene and benign prostatic hyperplasia. Urology 53:121–125

    CAS  PubMed  Google Scholar 

  • Gratten J, Wray NR, Peyrot WJ, McGrath JJ, Visscher PM, Goddard ME (2016) Risk of psychiatric illness from advanced paternal age is not predominantly from de novo mutations. Nat Genet 48:718–724

    CAS  PubMed  Google Scholar 

  • Gray A, Feldman HA, McKinlay JB, Longcope C (1991) Age, and changing sex hormone levels in middle-aged men: results of the Massachusetts male aging study. J Clin Endocrinol Metab 73:1016–1025

    CAS  PubMed  Google Scholar 

  • Greendale GA, Unger JB, Rowe JW, Seeman TE (1999) The relation between cortisol excretion and fractures in healthy older people: results from the MacArthur studies. J Am Geriat Soc 47:799–803

    CAS  PubMed  Google Scholar 

  • Grimley Evans J, Malouf R, Huppert F, van Niekerk JK (2006) Dehydroepiandrosterone (DHEA) supplementation for cognitive function in healthy elderly people. Cochrane Database Syst 18:BCD006221

    Google Scholar 

  • Halvaei I, Litzky J, Esfandiari N (2020) Advanced paternal age: effects on sperm parameters, assisted reproduction outcomes and offspring health. Reprod Biol Endocrinol 18:110

    PubMed  PubMed Central  Google Scholar 

  • Handelsman DJ, Staraj S (1985) Testicular size: the effects of aging, malnutrition, and illness. J Androl 6:144–151

    CAS  PubMed  Google Scholar 

  • Harkonen K, Huhtaniemi I, Makinen J, Hubler D, Irjala K, Koskenvuo M, Oettel M, Raitakari O, Saad F, Pollanen P (2003) The polymorphic androgen receptor gene CAG repeat, pituitary-testicular function and andropausal symptoms in ageing men. Int J Androl 26:187–194

    CAS  PubMed  Google Scholar 

  • Harzmann R, Weckermann D, Wawroschek F (1998) Treatment of benign prostate hyperplasia. Z Arztl Fortbild Qualitatssich 92:319–324

    CAS  PubMed  Google Scholar 

  • Hassan MA, Killick SR (2003) Effect of male age on fertility: evidence for the decline in male fertility with increasing age. Fertil Steril 79:1520–1527

    PubMed  Google Scholar 

  • Heidenreich A, Bastian PJ, Bellmunt J, Bolla M, Joniau S, van der Kwast T, Mason M, Matveev V, Wiegel T, Zattoni F, Mottet N, European Association of Urology (2014) EAU guidelines on prostate cancer. Part 1: screening, diagnosis, and local treatment with curative intent-update. Eur Urol 65:124–137

    PubMed  Google Scholar 

  • Hellstrom WJ, Overstreet JW, Sikka SC, Denne J, Ahuja S, Hoover AM, Sides GD, Cordell WH, Harrison LM, Whitaker JS (2006) Semen and sperm reference ranges for men 45 years of age and older. J Androl 27:421–428

    PubMed  Google Scholar 

  • Herbert J (1995) The age of dehydroepiandrosterone. Lancet 345:1193–1194

    CAS  PubMed  Google Scholar 

  • Holstein AF (1989) Morphological evidence for the involution of spermatogenesis during senescence. In: Holstein AF, Voigt KD, Grässlin D (eds) Reproductive biology and medicine. Diesbach Verlag, Berlin, pp 66–77

    Google Scholar 

  • Iwen KA, Brabant G (2020) Therapie mit Schilddrüsenhormonen im Alter [Thyroid hormone therapy in old age]. Internist 61:541–548

    CAS  PubMed  Google Scholar 

  • Jenkins PJ, Mukherjee A, Shalet SM (2006) Does growth hormone cause cancer? Clin Endocrinol 64:115–121

    CAS  Google Scholar 

  • Johnson L, Grumbles JS, Bagheri A, Petty CS (1990) Increased germ cell degeneration during postprophase of meiosis is related to increased serum follicle-stimulating hormone concentrations and reduced daily sperm production in aged men. Biol Reprod 42:281–287

    CAS  PubMed  Google Scholar 

  • Kapoor D, Malkin CJ, Channer KS, Jones TH (2005) Androgens, insulin resistance and vascular disease in men. Clin Endocrinol 63:239–250

    CAS  Google Scholar 

  • Kapoor D, Goodwin E, Channer KS, Jones TH (2006) Testosterone replacement therapy improves insulin resistance, glycaemic control, visceral adiposity and hypercholesterolaemia in hypogonadal men with type 2 diabetes. Eur J Endocrinol 154:899–906

    CAS  PubMed  Google Scholar 

  • Kaufman JM, Vermeulen A (2005) The decline of androgen levels in elderly men and its clinical and therapeutic implication. Endocr Rev 26:833–876

    CAS  PubMed  Google Scholar 

  • Kelleher S, Conway AJ, Handelsman DJ (2004) Blood testosterone threshold for androgen deficiency symptoms. J Clin Endocrinol Metab 89:3813–3817

    CAS  PubMed  Google Scholar 

  • Khaw KT, Dowsett M, Folkerd E, Bingham S, Wareham N, Luben R, Welch A, Day N (2007) Endogenous testosterone and mortality due to all causes, cardiovascular disease, and cancer in men: European prospective investigation into cancer in Norfolk (EPIC-Norfolk) Prospective Population Study. Circulation 116:2694–2697

    CAS  PubMed  Google Scholar 

  • Kidd SA, Eskenazi B, Wyrobek A (2001) Effects of male age on semen quality and fertility: a review of the literature. Fertil Steril 75:237–248

    CAS  PubMed  Google Scholar 

  • Kirkwood TB (2008) Understanding ageing from an evolutionary perspective. J Intern Med 263:117–127

    CAS  PubMed  Google Scholar 

  • Krassas GE, Perros P (2003) Thyroid disease and male reproductive function. J Endocrinol Investig 26:372–380

    CAS  Google Scholar 

  • Kristal AR, Price DK, Till C, Schenk JM, Neuhouser ML, Ockers S, Lin DW, Thompson IM, Figg WD (2010) Androgen receptor CAG repeat length is not associated with the risk of incident symptomatic benign prostatic hyperplasia: results from the Prostate Cancer Prevention Trial. Prostate 70:584–590

    CAS  PubMed  PubMed Central  Google Scholar 

  • Krzastek SC, Smith RP (2020) Non-testosterone management of male hypogonadism: an examination of the existing literature. Transl Androl Urol 9(Suppl 2):160–170

    Google Scholar 

  • Kühnert B, Nieschlag E (2004) Reproductive functions of the ageing male. Hum Reprod Update 10:327–339

    PubMed  Google Scholar 

  • Kupelian V, Page ST, Araujo AB, Travison TG, Bremner WJ, McKinlay JB (2006) Low sex hormone-binding globulin, total testosterone, and symptomatic androgen deficiency are associated with development of the metabolic syndrome in non-obese men. J Clin Endocrinol Metab 91:843–850

    CAS  PubMed  Google Scholar 

  • Laaksonen DE, Niskanen L, Punnonen K, Nyyssonen K, Tuomainen TP, Valkonen VP, Salonen R, Salonen JT (2004) Testosterone and sex hormone-binding globulin predict the metabolic syndrome and diabetes in middle-aged men. Diabetes Care 27:1036–1041

    CAS  PubMed  Google Scholar 

  • Laughlin GA, Barrett-Connor E, Bergstrom J (2008) Low serum testosterone and mortality in older men. J Clin Endocrinol Metab 93:68–75

    CAS  PubMed  Google Scholar 

  • Lepor H (2004) Pathophysiology, epidemiology, and natural history of benign prostatic hyperplasia. Rev Urol 6:3–10

    Google Scholar 

  • Levitas E, Lunenfeld E, Weisz N, Friger M, Potashnik G (2007) Relationship between age and semen parameters in men with normal sperm concentration: analysis of 6022 semen samples. Andrologia 39:45–50

    CAS  PubMed  Google Scholar 

  • Li Z, Zhou Q, Li Y, Fu J, Huang X, Shen L (2016) Growth hormone replacement therapy reduces risk of cancer in adult with growth hormone deficiency: a meta-analysis. Oncotarget 7:81862–81869

    PubMed  PubMed Central  Google Scholar 

  • Li L, Ju H, Jin H, Chen H, Sun M, Zhou Z (2022) Low testosterone level and risk of adverse clinical events among male patients with chronic kidney disease: a systematic review and meta-analysis of cohort studies. J Healthc Eng 2022:3630429. https://doi.org/10.1155/2022/3630429

    Google Scholar 

  • Liu PY, Iranmesh A, Nehra AX, Keenan DM, Veldhuis JD (2005) Mechanisms of hypoandrogenemia in healthy aging men. Endocrinol Metab Clin N Am 34:935–955

    CAS  Google Scholar 

  • Lombardi G, Di Somma C, Rota F, Colao A (2005) Associated hormonal decline in aging: is there a role for GH therapy in aging men? J Endocrinol Investig 28:99–108

    CAS  Google Scholar 

  • Lucia MS, Epstein JI, Goodman PJ, Darke AK, Reuter VE, Civantos F, Tangen CM, Parnes HL, Lippman SM, La Rosa FG, Kattan MW, Crawford ED, Ford LG, Coltman CA Jr, Thompson IM (2007) Finasteride and high-grade prostate cancer in the Prostate Cancer Prevention Trial. J Natl Cancer Inst 99:1375–1383

    CAS  PubMed  Google Scholar 

  • Luetjens CM, Rolf C, Gassner P, Werny JE, Nieschlag E (2002) Sperm aneuploidy rates in younger and older men. Hum Reprod 17:1826–1832

    CAS  PubMed  Google Scholar 

  • Madersbacher S, Alivizatos G, Nordling J, Sanz CR, Emberton M, de la Rosette JJ (2004) EAU 2004 guidelines on assessment, therapy and follow-up of men with lower urinary tract symptoms suggestive of benign prostatic obstruction (BPH guidelines). Eur Urol 46:547–554

    PubMed  Google Scholar 

  • Madersbacher S, Berger I, Ponholzer A, Marszalek M (2008) Plant extracts: sense or nonsense? Curr Opin Urol 18:16–20

    PubMed  Google Scholar 

  • Magnani JW, Moser CB, Murabito JM, Sullivan LM, Wang N, Ellinor PT, Vasan RS, Benjamin EJ, Coviello AD (2014) Association of sex hormones, aging, and atrial fibrillation in men: the Framingham Heart Study. Circ Arrhythm Electrophysiol 7:307–312

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mahmoud AM, Goemaere S, El-Garem Y, Van Pottelberg Y, Comhaire FH, Kaufman JM (2003) Testicular volume in relation to hormonal indices of gonadal function in community-dwelling elderly men. J Clin Endocrinol Metab 88:179–184

    CAS  PubMed  Google Scholar 

  • Maslej MM, Bolker BM, Russell MJ, Eaton K, Durisko Z, Hollon SD, Swanson GM, Thomson JA Jr, Mulsant BH, Andrews PW (2017) The mortality and myocardial effects of antidepressants are moderated by preexisting cardiovascular disease: a meta-analysis. Psychother Psychosom 86:268–282

    PubMed  Google Scholar 

  • McVary KT (2006) BPH: epidemiology and comorbidities. Am J Manag Care 12:122–128

    Google Scholar 

  • Meier C, Nguyen TV, Handelsman DJ, Schindler C, Kushnir MM, Rockwood AL, Meikle AW, Center JR, Eisman JA, Seibel MJ (2008) Endogenous sex hormones and incident fracture risk in older men: the Dubbo Osteoporosis Epidemiology Study. Arch Intern Med 14:47–54

    Google Scholar 

  • Morganti S, Ceda GP, Saccani M, Milli B, Ugolotti D, Prampolini R, Maggio M, Valenti G, Ceresini G (2007) Thyroid disease in the elderly: sex-related differences in clinical expression. J Endocrinol Investig 28:101–104

    Google Scholar 

  • Morley JE, Kaiser FE, Johnson LE (1990) Male sexual function. In: Cassel CK, Riesenberg DE, Sorensen LB, Walsh JR (eds) Geriatric medicine, 2nd edn. Springer, Berlin, pp 256–270

    Google Scholar 

  • Muller M, Grobbee DE, den Tonkelaar I, Lamberts SW, van der Schouw YT (2005) Endogenous sex hormones and metabolic syndrome in aging men. J Clin Endocrinol Metab 90:2618–2623

    CAS  PubMed  Google Scholar 

  • Mulligan T, Frick MF, Zuraw QC, Stemhagen A, McWhirter C (2006) Prevalence of hypogonadism in males aged at least 45 years: the HIM study. Int J Clin Pract 60:762–769

    CAS  PubMed  Google Scholar 

  • Muraleedharan V, Marsh H, Kapoor D, Channer KS, Jones TH (2013) Testosterone deficiency is associated with increased risk of mortality and testosterone replacement improves survival in men with type 2 diabetes. Eur J Endocrinol 169:725–733

    CAS  PubMed  Google Scholar 

  • Neaves WB, Johnson L, Porter JC, Parker CR, Petty CS (1985) Leydig cell numbers, daily sperm production, and serum gonadotropin-levels in aging men. J Clin Endocrinol Metab 59:756–763

    Google Scholar 

  • Neuhouser ML, Schenk J, Song YJ, Tangen CM, Goodman PJ, Pollak M, Penson DF, Thompson IM, Kristal AR (2008) Insulin-like growth factor-1, insulin-like growth factor binding protein-3 and risk of benign prostate hyperplasia in the prostate cancer prevention trial. Prostate 68:1477–1486

    PubMed  PubMed Central  Google Scholar 

  • Nieschlag E (2019) Late-onset hypogonadism: a concept comes of age. Andrology 8:1506–1511

    PubMed  Google Scholar 

  • Nieschlag E, Michel E (1986) Reproductive functions in grandfathers. In: Mastroianni L, Paulsen CA (eds) Aging, reproduction, and the climacteric. Plenum Publishing Corporation, New York, pp 59–71

    Google Scholar 

  • Nieschlag E, Lammers U, Freischem CW, Langer K, Wickings EJ (1982) Reproductive functions in young fathers and grandfathers. J Clin Endocrinol Metab 55:676–681

    CAS  PubMed  Google Scholar 

  • Nieschlag E, Brinkworth M, Rolf C, Lerchl A (2000) Fertility and fertility related problems in the ageing male. Proceedings of the 9th International Menopause Society, World Congress of the Menopause, Parthenon, London

    Google Scholar 

  • Nieschlag E, Swerdloff R, Behre HM, Gooren LJ, Kaufman JM, Legros JJ, Lunenfeld B, Morley JE, Schulman C, Wang C, Weidner W, Wu FC (2005) Investigation, treatment and monitoring of late-onset hypogonadism in males: ISA, ISSAM, and EAU recommendations. Int J Androl 28:125–127

    CAS  PubMed  Google Scholar 

  • Nybo Andersen AM, Hansen KD, Andersen PK, Davey Smith G (2004) Advanced paternal age and risk of fetal death: a cohort study. Am J Epidemiol 160:1214–1222

    PubMed  Google Scholar 

  • Pergialiotis V, Prodromidou A, Frountzas M, Korou LM, Vlachos GD, Perrea D (2016) Diabetes mellitus and functional sperm characteristics: A meta-analysis of observational studies. J Diabetes Complicat 30:1167–1176

    Google Scholar 

  • Quinn M, Babb P (2002) Patterns and trends in prostate cancer incidence, survival, prevalence and mortality. Part I: international comparisons. BJU Int 90:162–173

    CAS  PubMed  Google Scholar 

  • Reid IR, Wattie DJ, Evans MC, Stapleton JP (1996) Testosterone therapy in glucocorticoid-treated men. Arch Intern Med 156:1173–1177

    CAS  PubMed  Google Scholar 

  • Reynolds RM, Dennison EM, Walker BR, Syddall HE, Wood PJ, Andrew R, Phillips DI, Cooper C (2005) Cortisol secretion and rate of bone loss in a population-based cohort of elderly men and women. Calcif Tissue Int 77:134–138

    CAS  PubMed  Google Scholar 

  • Roelfsema F, van Heemst D, Iranmanesh A, Takahashi P, Yang R, Veldhuis JD (2017) Impact of age, sex and body mass index on cortisol secretion in 143 healthy adults. Endocr Connect 6:500–509

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rolf C, Nieschlag E (1998) Potential adverse effects of long-term testosterone therapy. Baillières Clin Endocrinol Metab 12:521–534

    CAS  PubMed  Google Scholar 

  • Rolf C, Behre HM, Nieschlag E (1996) Reproductive parameters of older compared to younger men of infertile couples. Int J Androl 19:5–142

    Google Scholar 

  • Rolf C, Kenkel S, Nieschlag E (2002a) Age-related disease pattern in infertile men: increasing incidence of infections in older patients. Andrologia 34:209–217

    CAS  PubMed  Google Scholar 

  • Rolf C, von Eckardstein S, Koken U, Nieschlag E (2002b) Testosterone substitution of hypogonadal men prevents the age-dependent increases in body mass index, body fat and leptin seen in healthy ageing men: results of a cross-sectional study. Eur J Endocrinol 146:505–511

    CAS  PubMed  Google Scholar 

  • Rossiello F, Jurk D, Passos JF, d’Adda di Fagagna F (2022) Telomere dysfunction in ageing and age-related diseases. Nat Cell Biol 24:135–114

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rudman D, Feller AG, Nagraj HS, Nagraj HS, Gergans GA, Lalitha PY, Goldberg AF, Schlenker RA, Cohn L, Rudman IW, Mattson DE (1990) Effects of human growth hormone in men over 60 years old. N Engl J Med 323:1–6

    CAS  PubMed  Google Scholar 

  • Salvio G, Martino M, Balercia G, Arnaldi G (2022) Acromegaly and male sexual health. Rev Endocr Metab Disord 23:671–678

    CAS  PubMed  PubMed Central  Google Scholar 

  • Schlüter D (1978) Die endokrinen Organe der Über-Neunzigjährigen. Dissertation Universität Hamburg

    Google Scholar 

  • Seidman SN, Araujo AB, Roose SP, McKinlay JB (2001) Testosterone level, androgen receptor polymorphism, and depressive symptoms in middle-aged men. Biol Psychiatry 50:371–376

    CAS  PubMed  Google Scholar 

  • Sermondade N, Faure C, Fezeu L, Shayeb AG, Bonde JP, Jensen TK, Van Wely M, Cao J, Martini AC, Eskandar M, Chavarro JE, Koloszar S, Twigt JM, Ramlau-Hansen CH, Borges E Jr, Lotti F, Steegers-Theunissen RP, Zorn B, Polotsky AJ, La Vignera S, Eskenazi B, Tremellen K, Magnusdottir EV, Fejes I, Hercberg S, Lévy R, Czernichow S (2013) BMI in relation to sperm count: an updated systematic review and collaborative meta-analysis. Hum Reprod Update 19:221–231

    CAS  PubMed  Google Scholar 

  • Sharma P, Sampath H (2019) Mitochondrial DNA integrity: role in health and disease. Cells 29:100. https://doi.org/10.3390/cells8020100

    Article  CAS  Google Scholar 

  • Sharma R, Oni OA, Gupta K, Sharma M, Sharma R, Singh V, Parashara D, Kamalakar S, Dawn B, Chen G, Ambrose JA, Barua RS (2017) Normalization of testosterone levels after testosterone replacement therapy is associated with decreased incidence of atrial fibrillation. J Am Heart Assoc 6:e004880. https://doi.org/10.1161/JAHA.116.004880

    Article  PubMed  PubMed Central  Google Scholar 

  • Shores MM, Matsumoto AM, Sloan KL, Kivlahan DR (2006) Low serum testosterone and mortality in male veterans. Arch Intern Med 166:1660–1665

    CAS  PubMed  Google Scholar 

  • Shores MM, Smith NL, Forsberg CW, Anawalt BD, Matsumoto AM (2012) Testosterone treatment and mortality in men with low testosterone levels. J Clin Endocrinol Metab 97:2050–2058

    CAS  PubMed  Google Scholar 

  • Sih R, Morley JE, Kaiser FE, Perry HM 3rd, Patrick P, Ross C (1997) Testosterone replacement in older hypogonadal men: a 12-month randomized controlled trial. J Clin Endocrinol Metab 82:1661–1667

    CAS  PubMed  Google Scholar 

  • Smith GD, Ben-Shlomo Y, Beswick A (2005) Cortisol, testosterone, and coronary heart disease: prospective evidence from the Caerphilly study. Circulation 112:332–340

    CAS  PubMed  Google Scholar 

  • Snyder PJ, Peachey H, Hannoush P, Berlin JA, Loh L, Holmes JH, Dlewati A, Staley J, Santanna J, Kapoor SC, Attie MF, Haddad JG Jr, Strom BL (1999a) Effect of testosterone treatment on bone mineral density in men over 65 years of age. J Clin Endocrinol Metab 84:1966–1972

    CAS  PubMed  Google Scholar 

  • Snyder PJ, Peachey H, Hannoush P, Berlin JA, Loh L, Lenrow DA, Holmes JH, Dlewati A, Santanna J, Rosen CJ, Strom BL (1999b) Effect of testosterone treatment on body composition and muscle strength in men over 65 years of age. J Clin Endocrinol Metab 84:2647–2653

    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 ER 3rd, Parsons JK, Wenger NK, Zeldow B, Landis JR, Ellenberg SS (2016) Testosterone trials I. Effects of testosterone treatment in older men. N Engl J Med 374:611–624

    CAS  PubMed  PubMed Central  Google Scholar 

  • Soliman T, Shaher H, Mohey A, El-Shaer W, Sebaey A (2022) Gonadotoxic effect of tramadol administration: a prospective controlled study. Arab J Urol 20:54–60

    PubMed  Google Scholar 

  • Suzuki K, Ito K, Ichinose Y, Kurokawa K, Suzuki T, Imai K, Yamanaka H, Honma S (1995) Endocrine environment of benign prostatic hyperplasia: prostate size and volume are correlated with serum estrogen concentration. Scand J Urol Nephrol 29:65–68

    CAS  PubMed  Google Scholar 

  • Swerdlow AJ (2006) Does growth hormone therapy increase the risk of cancer? Nat Clin Pract Endocrinol Metab 2:530–531

    PubMed  Google Scholar 

  • Tarin JJ, Brines J, Cano A (1998) Long-term effects of delayed parenthood. Hum Reprod 13:2371–2376

    CAS  PubMed  Google Scholar 

  • Thompson IM, Goodman PJ, Tangen CM, Lucia MS, Miller GJ, Ford LG, Lieber MM, Cespedes RD, Atkins JN, Lippman SM, Carlin SM, Ryan A, Szczepanek CM, Crowley JJ, Coltman CA Jr (2003) The influence of finasteride on the development of prostate cancer. N Engl J Med 349:215–224

    CAS  PubMed  Google Scholar 

  • Tivesten A, Mellström D, Jutberger H, Fagerberg B, Lernfelt B, Orwoll E, Karlsson MK, Ljunggren O, Ohlsson C (2007) Low serum testosterone and high serum estradiol associate with lower extremity peripheral arterial disease in elderly men. The MrOS Study in Sweden. J Am Coll Cardiol 50:1070–1076

    CAS  PubMed  Google Scholar 

  • Umbreit K (1993) Ist eine Substitution mit Estradiol auch bei Männern angezeigt? Gynecologie 14:56–60

    Google Scholar 

  • Valtonen M, Niskanen L, Kangas AP, Koskinen T (2005) Effect of melatonin-rich night-time milk on sleep and activity in elderly institutionalized subjects. Nord J Psychiatry 59:217–221

    PubMed  Google Scholar 

  • Vance ML (2003) Can growth hormone prevent aging? N Engl J Med 348:779–780

    PubMed  Google Scholar 

  • Vance ML, Mauras N (1999) Growth hormone therapy in adults and children. N Engl J Med 341:1206–1216

    Google Scholar 

  • Vermeulen A, Kaufman JM (1995) Ageing of the hypothalamo-pituitary-testicular axis in men. Horm Res 43:2528

    Google Scholar 

  • Vermeulen A, Kaufman JM, Goemaere S, van Pottelberg I (2002) Estradiol in elderly men. Aging Male 5:98–102

    CAS  PubMed  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 (2013) Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels. JAMA 310:1829–1836

    CAS  PubMed  Google Scholar 

  • von Mühlen D, Laughlin GA, Kritz-Silverstein D, Bergstrom J, Bettencourt R (2008) Effect of dehydroepiandrosterone supplementation on bone mineral density, bone markers, and body composition in older adults: the DAWN trial. Osteoporos Int 19:699–670

    Google Scholar 

  • Walther A, Breidenstein J, Miller R (2019) Association of testosterone treatment with alleviation of depressive symptoms in men: a systematic review and meta-analysis. JAMA Psychiatry 76:31–40

    PubMed  Google Scholar 

  • Wang C, Alexander G, Berman N, Salehian B, Davidson T, McDonald V, Steiner B, Hull L, Callegari C, Swerdloff RS (1996) Testosterone replacement therapy improves mood in hypogonadal men – a clinical research center study. J Clin Endocrinol Metab 81:3578–3583

    CAS  PubMed  Google Scholar 

  • Wang C, Nieschlag E, Swerdloff RS, Behre H, Hellstrom WJ, Gooren LJ, Kaufman JM, Legros JJ, Lunenfeld B, Morales A, Morley JE, Schulman C, Thompson IM, Weidner W, Wu FC (2008) ISA, ISSAM, EAU, EAA and ASA recommendations: investigation, treatment and monitoring of late-onset hypogonadism in males. Aging Male 1:1–8

    Google Scholar 

  • Woodhouse LJ, Gupta N, Bhasin M, Singh AB, Ross R, Phillips J, Bhasin S (2004) Dose-dependent effects of testosterone on regional adipose tissue distribution in healthy young men. J Clin Endocrinol Metab 89:718–726

    CAS  PubMed  Google Scholar 

  • Wu FC, Tajar A, Pye SR, Silman AJ, Finn JD, O’Neill TW, Bartfai G, Casanueva F, Forti G, Giwercman A, Huhtaniemi IT, Kula K, Punab M, Boonen S, Vaderschueren D, European Male Aging Study Group (2008) Hypothalamic-pituitary-testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: the European Male Aging Study. J Clin Endocrinol Metab 93:2737–2745

    CAS  PubMed  Google Scholar 

  • Zizmann M (2006) Testosterone and the brain. Aging Male 9:195–199

    Google Scholar 

  • Zitzmann M (2020) Testosterone, mood, behaviour and quality of life. Andrology 8:1598–1605

    CAS  PubMed  Google Scholar 

  • Zitzmann M, Nieschlag E (2003) Der Altershypogonadismus des Mannes, rationale Diagnostik und Therapie. Internist 10:1313–1321

    Google Scholar 

  • Zitzmann M, Nieschlag E (2007) 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 92:3844–3853

    CAS  PubMed  Google Scholar 

  • Zitzmann M, Depenbusch M, Gromoll J, Nieschlag E (2003) Prostate volume and growth in testosterone-substituted hypogonadal men are dependent on the CAG repeat polymorphism of the androgen receptor gene: a longitudinal pharmacogenetic study. J Clin Endocrinol Metab 88:2049–2054

    CAS  PubMed  Google Scholar 

  • Zitzmann M, Faber S, Nieschlag E (2006) Association of specific symptoms and metabolic risks with serum testosterone in older men. J Clin Endocrinol Metab 91:4335–4343

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. St. Mary’s Hospital, Friesoythe, Germany

    Claus Rolf

  2. University Center for Reproductive Medicine and Andrology, Münster, Germany

    Michael Zitzmann

  3. Center of Reproductive Medicine and Andrology, University Hospital Münster, Münster, Germany

    Eberhard Nieschlag

Authors
  1. Claus Rolf
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael Zitzmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eberhard Nieschlag
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael Zitzmann .

Editor information

Editors and Affiliations

  1. Center for Reproductive Medicine and Andrology, University Hospital Münster, Münster, Germany

    Eberhard Nieschlag

  2. Center for Reproductive Medicine and Andrology, University Hospital Halle (Saale), Martin Luther University Halle-Wittenberg, Halle (Saale), Germany

    Hermann M. Behre

  3. Center for Reproductive Medicine and Andrology, University Hospital Münster, Münster, Germany

    Sabine Kliesch

  4. Center for Reproductive Medicine and Andrology, University Hospital Münster, Münster, Germany

    Susan Nieschlag

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Rolf, C., Zitzmann, M., Nieschlag, E. (2023). Senescence and Late-Onset Hypogonadism. In: Nieschlag, E., Behre, H.M., Kliesch, S., Nieschlag, S. (eds) Andrology. Springer, Cham. https://doi.org/10.1007/978-3-031-31574-9_25

Download citation

  • DOI: https://doi.org/10.1007/978-3-031-31574-9_25

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-031-31573-2

  • Online ISBN: 978-3-031-31574-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation