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Hypogonadism in Men

General Information


  • clinical syndrome due to disrupted activity of ≥ 1 hormone levels of the hypothalamic-pituitary-testicular axis resulting in low serum testosterone and/or reduced spermatozoa levels1,2,3
  • hypogonadism common with advancing age and associated with impaired function of multiple organ systems and decrease in quality of life (4, 28318076Int J Clin Pract 2017 Mar;71:3)

Also called

  • androgen deficiency syndrome
  • testosterone deficiency syndrome
  • androgen deficiency in the ageing male
  • andropause
  • late-onset hypogonadism


  • normal testosterone level1,4
    • definition for normal ranges for serum total and free testosterone may vary according to laboratory and type of assay performed
    • lower limit of normal total testosterone level harmonized to Centers for Disease Control and Prevention (CDC) standard for healthy young men who are not obese is 264 ng/dL (9.2 nmol/L)
    • no harmonized normal free testosterone range determined; free testosterone level as low as 65 pg/mL (225 pmol/L) or 70 pg/mL (243 pmol/L) and as high as 100 pg/mL (347 pmol/L) have been considered as lower limit of normal
  • testosterone deficiency - biochemical and clinical syndrome characterized by low levels of testosterone, testosterone action, and presence of signs and symptoms of testosterone deficiency2
  • frequently used terms to describe timing of hypogonadism diagnosis2,3
    • adult-onset hypogonadism - signs and symptoms of testosterone in men who had normal pubertal development and have normal male secondary sex characteristics
    • late-onset hypogonadism - also known as age-associated testosterone deficiency syndrome; associated with older age and characterized by low serum testosterone levels (below reference range of young healthy adult male) and symptoms associated with testosterone deficiency


  • hypogonadism in males is typically classified according to level of dysfunction along hypothalamic-pituitary-testicular axis1,2,3
    • primary hypogonadism or hypergonadotropic hypogonadism
      • primary testicular failure due to impaired Leydig cell function
      • results in low testosterone levels, impairment of spermatogenesis, and elevated gonadotropin levels
    • secondary hypogonadism or hypogonadotropic hypogonadism
      • central defects of hypothalamus or pituitary gland
      • results in low testosterone levels, impairment of spermatogenesis, and low or inappropriately normal gonadotropin levels (inadequate gonadotropic stimulation of Leydig cells)
    • combined primary and secondary hypogonadism
      • combined primary and secondary testicular failure
      • results in low testosterone levels, impaired spermatogenesis and variable gonadotropin levels (depending on whether primary or secondary testicular failure is predominant)
  • hypogonadism in males also classified as1
    • organic hypogonadism (also called classical hypogonadism) - permanent hypothalamic, pituitary, or testicular dysfunction (primary or secondary hypogonadism) due to congenital, structural, or destructive disorder
    • functional hypogonadism - hypogonadism that is potentially reversible with treatment of the underlying etiology (conditions that suppress gonadotropin and testosterone concentrations)



General references used

  1. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018 May 1;103(5):1715-1744
  2. Dean JD, McMahon CG, Guay AT, et al. The International Society for Sexual Medicine's Process of Care for the Assessment and Management of Testosterone Deficiency in Adult Men. J Sex Med. 2015 Aug;12(8):1660-86
  3. Dohle GR, Arver S, Bettocchi C, Jones T, Kliesch S. European Association of Urology (EAU) guideline on male hypogonadism. EAU 2019
  4. Lunenfeld B, Mskhalaya G, Zitzmann M, et al. Recommendations on the diagnosis, treatment and monitoring of hypogonadism in men. Aging Male. 2015 Mar;18(1):5-15full-text

Recommendation grading systems used

  • Endocrine Society recommendations based on GRADE system
    • strength of recommendation
      • Strong - 'recommend', action will provide, on average, more good than harm
      • Conditional - 'suggest', action depends on person's circumstances, values, and preferences
      • Ungraded good practice statement - evidence either not available or not systematically appraised; emphasizes benefits vs. risks, shared decision making, and basic principles of screening, diagnosis, and treatment
    • quality of evidence
      • High-quality - consistent evidence from well-performed randomized controlled trials, or exceptionally strong evidence from unbiased observational studies
      • Moderate-quality - randomized controlled trials with important limitations (inconsistent results, methodological flaws, indirect or imprecise evidence), or unusually strong evidence from unbiased observational studies
      • Low-quality - ≥ 1 critical outcome from observational studies, randomized controlled trials with serious flaws, or indirect evidence
      • Very low-quality - ≥ 1 of the critical outcomes from unsystematic clinical observations or very indirect evidence
    • Reference - Endocrine Society guideline on testosterone therapy in men with hypogonadism (29562364J Clin Endocrinol Metab 2018 May 1;103(5):1715)
  • The International Society for Sexual Medicine (ISSM) uses Oxford Center of Evidence-Based Medicine (OCEBM) levels of evidence and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) levels of recommendation
    • levels of evidence
      • Level 1 - systematic review of randomized trials, systematic review of nested case-control studies
      • Level 2 - individual randomized trial or (exceptionally) observational study with dramatic effect
      • Level 3 - nonrandomized controlled cohort/follow-up study (postmarketing surveillance)
      • Level 4 - case-series, case-control, or historically controlled studies
      • Level 5 - mechanism-based reasoning
    • level of recommendation
      • Grade A - high
      • Grade B - moderate
      • Grade C - low
      • Grade D - very low
    • Reference - ISSM process of care for the assessment and management of testosterone deficiency in adult men (26081680J Sex Med 2015 Aug;12(8):1660)
  • International Society of Andrology/International Society for the Study of the Aging Male/European Association of Urology/European Academy of Andrology/American Society of Andrology (ISA/ISSAM/EAU/EAA/ASA) grading system for recommendations
    • grades of recommendation (which may be changed if panel consensus)
      • Grade A - based on clinical studies of good quality and consistency addressing the specific recommendations and includes ≥ 1 randomized trial
      • Grade B - based on well-conducted clinical studies, but without randomized clinical trials
      • Grade C - made despite the absence of directly applicable clinical studies of good quality
    • levels of evidence
      • Level 1a - meta-analysis of randomized trials
      • Level 1b - ≥ 1 randomized trial
      • Level 2a - ≥ 1 well-designed controlled study without randomization
      • Level 2b - ≥ 1 other type of well-designed quasi-experimental study
      • Level 3 - well-designed nonexperimental studies; such as comparative studies, correlation studies, and case reports
      • Level 4 - expert committee reports or opinions or clinical experience of respected authorities
  • European Association of Urology (EAU) uses Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system
    • strength of recommendation
      • Strong or Weak based on:
        • overall quality of existing evidence
        • magnitude of effect (individual or combined effects)
        • certainty of results (including precision, consistency, heterogeneity, and other statistical or study-related factors)
        • balance between desirable and undesirable outcomes
        • patient values and preferences
        • certainty of patient values and preferences
    • levels of evidence
      • Level 1a - meta-analysis of randomized trials
      • Level 1b - ≥ 1 randomized trial
      • Level 2a - ≥ 1 well-designed controlled study without randomization
      • Level 2b - ≥ 1 other type of well-designed quasi-experimental study
      • Level 3 - well-designed nonexperimental studies; such as comparative studies, correlation studies, and case reports
      • Level 4 - expert committee reports or opinions or clinical experience of respected authorities
    • Reference - EAU guideline on male hypogonadism (EAU 2019)

Synthesized Recommendation Grading System for DynaMed Content

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Special acknowledgements

On behalf of the American College of Physicians
  • Barbara Turner, MD, MSEd, MACP, ACP Deputy Editor, Clinical Decision Resource, as part of the ACP-EBSCO Health collaboration, managed the ACP peer review of the Overview and Recommendations section and related clinical content in this topic.
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How to cite

National Library of Medicine, or "Vancouver style" (International Committee of Medical Journal Editors):

  • DynaMed [Internet]. Ipswich (MA): EBSCO Information Services. 1995 - . Record No. T916436, Hypogonadism in Men; [updated 2018 Nov 30, cited place cited date here]. Available from Registration and login required.


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