Subscribe for unlimited access to DynaMed content, CME/CE & MOC credit, and email alerts on content you follow.

Already subscribed? Sign in now

Learn more about CME

Hypogonadism in Men

General Information

Description

  • 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

Definitions

  • 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

Types

  • 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)

References

References

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

  • The DynaMed Team systematically monitors clinical evidence to continuously provide a synthesis of the most valid relevant evidence to support clinical decision-making (see 7-Step Evidence-Based Methodology).
  • Guideline recommendations summarized in the body of a DynaMed topic are provided with the recommendation grading system used in the original guideline(s), and allow users to quickly see where guidelines agree and where guidelines differ from each other and from the current evidence.
  • In DynaMed content, we synthesize the current evidence, current guidelines from leading authorities, and clinical expertise to provide recommendations to support clinical decision-making in the Overview & Recommendations section.
  • We use the Grading of Recommendations Assessment, Development and Evaluation (GRADE) to classify synthesized recommendations as Strong or Weak.
    • Strong recommendations are used when, based on the available evidence, clinicians (without conflicts of interest) consistently have a high degree of confidence that the desirable consequences (health benefits, decreased costs and burdens) outweigh the undesirable consequences (harms, costs, burdens).
    • Weak recommendations are used when, based on the available evidence, clinicians believe that desirable and undesirable consequences are finely balanced, or appreciable uncertainty exists about the magnitude of expected consequences (benefits and harms). Weak recommendations are used when clinicians disagree in judgments of relative benefit and harm, or have limited confidence in their judgments. Weak recommendations are also used when the range of patient values and preferences suggests that informed patients are likely to make different choices.
  • DynaMed synthesized recommendations (in the Overview & Recommendations section) are determined with a systematic methodology:
    • Recommendations are initially drafted by clinical editors (including ≥ 1 with methodological expertise and ≥ 1 with content domain expertise) aware of the best current evidence for benefits and harms, and the recommendations from guidelines.
    • Recommendations are phrased to match the strength of recommendation. Strong recommendations use "should do" phrasing, or phrasing implying an expectation to perform the recommended action for most patients. Weak recommendations use "consider" or "suggested" phrasing.
    • Recommendations are explicitly labeled as Strong recommendations or Weak recommendations when a qualified group has explicitly deliberated on making such a recommendation. Group deliberation may occur during guideline development. When group deliberation occurs through DynaMed Team-initiated groups:
      • Clinical questions will be formulated using the PICO (Population, Intervention, Comparison, Outcome) framework for all outcomes of interest specific to the recommendation to be developed.
      • Systematic searches will be conducted for any clinical questions where systematic searches were not already completed through DynaMed content development.
      • Evidence will be summarized for recommendation panel review including for each outcome, the relative importance of the outcome, the estimated effects comparing intervention and comparison, the sample size, and the overall quality rating for the body of evidence.
      • Recommendation panel members will be selected to include at least 3 members that together have sufficient clinical expertise for the subject(s) pertinent to the recommendation, methodological expertise for the evidence being considered, and experience with guideline development.
      • All recommendation panel members must disclose any potential conflicts of interest (professional, intellectual, and financial), and will not be included for the specific panel if a significant conflict exists for the recommendation in question.
      • Panel members will make Strong recommendations if and only if there is consistent agreement in a high confidence in the likelihood that desirable consequences outweigh undesirable consequences across the majority of expected patient values and preferences. Panel members will make Weak recommendations if there is limited confidence (or inconsistent assessment or dissenting opinions) that desirable consequences outweigh undesirable consequences across the majority of expected patient values and preferences. No recommendation will be made if there is insufficient confidence to make a recommendation.
      • All steps in this process (including evidence summaries which were shared with the panel, and identification of panel members) will be transparent and accessible in support of the recommendation.
    • Recommendations are verified by ≥ 1 editor with methodological expertise, not involved in recommendation drafting or development, with explicit confirmation that Strong recommendations are adequately supported.
    • Recommendations are published only after consensus is established with agreement in phrasing and strength of recommendation by all editors.
    • If consensus cannot be reached then the recommendation can be published with a notation of "dissenting commentary" and the dissenting commentary is included in the topic details.
    • If recommendations are questioned during peer review or post publication by a qualified individual, or reevaluation is warranted based on new information detected through systematic literature surveillance, the recommendation is subject to additional internal review.

DynaMed Editorial Process

  • DynaMed topics are created and maintained by the DynaMed Editorial Team and Process.
  • All editorial team members and reviewers have declared that they have no financial or other competing interests related to this topic, unless otherwise indicated.
  • DynaMed content includes Practice-Changing Updates, with support from our partners, McMaster University and F1000.

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.
  • DynaMed topics are written and edited through the collaborative efforts of the above individuals. Deputy Editors, Section Editors, and Topic Editors are active in clinical or academic medical practice. Recommendations Editors are actively involved in development and/or evaluation of guidelines.
  • Editorial Team role definitions
    Topic Editors define the scope and focus of each topic by formulating a set of clinical questions and suggesting important guidelines, clinical trials, and other data to be addressed within each topic. Topic Editors also serve as consultants for the internal DynaMed Editorial Team during the writing and editing process, and review the final topic drafts prior to publication.
    Section Editors have similar responsibilities to Topic Editors but have a broader role that includes the review of multiple topics, oversight of Topic Editors, and systematic surveillance of the medical literature.
    Recommendations Editors provide explicit review of Overview and Recommendations sections to ensure that all recommendations are sound, supported, and evidence-based. This process is described in "Synthesized Recommendation Grading."
    Deputy Editors oversee DynaMed internal publishing groups. Each is responsible for all content published within that group, including supervising topic development at all stages of the writing and editing process, final review of all topics prior to publication, and direction of an internal team.

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 https://www.dynamed.com/topics/dmp~AN~T916436. Registration and login required.

top

Subscribe for unlimited access to DynaMed content.
Already subscribed? Sign in