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hypogonadism

Classification: - primary hypogonadism: testicular insufficiency - secondary hypogonadism: hypothalamic/pituitary insufficiency Etiology: - primary hypogonadism - secondary hypogonadism - andropause Epidemiology: - testosterone changes in men with aging (andropause) do not result in symptomatic hypogonadism in most men Pathology: - both androgen & estrogen deficiency may play a role in male hypogonadism or sexual function - sperm production may be diminished Genetics: - implicated genes: LHB Clinical manifestations: 1) infertility 2) pseudohermaphroditism 3) male a) decreasing libido b) erectile dysfunction c) small testes d) signs of feminization if prolonged e) poor sleep, poor concentration f) decreased muscle strength, stamina, energy, less facial hair g) signs/symptoms more subtle when reproductive failure occurs after pubertal development Laboratory: 1) serum testosterone < 100 ng/mL (200 mg/dL [1]) (8 AM) a) two 8 AM serum testosterone measurements [1] b) free testosterone* in obese patients - total serum testosterone may be affected by a decrease in plasma sex hormone-binding globulin (SHBG) [1] c) serum testosterone > 350-400 mg/dL excludes hypogonadism [1] - repeat 8 AM serum testosterone reasonable if serum testosterone < 400 mg/dL [1] 2) if testosterone low, measure serum luteinizing hormone (LH) & serum follicle-stimulating hormone (FSH) a) increased levels with primary gonadal failure b) diminished levels with secondary gonadal failure 3) see ARUP consult [2] * also measure free testosterone in patients with - diabetes, nephrotic syndrome, hypothyroidism, acromegaly, & in patients taking steroids or progestins (decreased serum SHBG) - older age, HIV1 infection, cirrhosis & hepatitis, hyperthyroidism, & in patients taking certain anticonvulsants or those taking estrogen (increased serum SHBG) [9] Complications: - increased risk of mortality in elderly men [7] - low serum testosterone, high serum LH (> 10 IU/L), or very low serum estradiol (< 5.1 pmol/L) associated with increased all-cause mortality [11] - low serum SHBG associated with diminished risk of mortality [11] - U-shaped relationship of serum dihydrotesterone & mortality [11] Management: - determine cause before treatment [1] - testosterone replacement therapy - goal of mid-normal serum testosterone [1] - avoid in men planning for fertility (impairs spermatogenesis) - screening men with non-specific symptoms not recommended [1]

Related

androgen insufficiency (hypoandrogenism, testosterone deficiency) erectile dysfunction (ED) impotence infertility

Specific

andropause primary hypogonadism secondary hypogonadism

General

sexual dysfunction

Database Correlations

OMIM 152780 MORBIDMAP 152780

References

  1. Medical Knowledge Self Assessment Program (MKSAP) 11, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2012, 2015, 2018, 2022.
  2. ARUP Consult: Male Hypogonadism The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/hypogonadism-male - Hypogonadism Testing Algorithm https://arupconsult.com/algorithm/hypogonadism-testing-algorithm
  3. Traish AM, Miner MM, Morgentaler A, Zitzmann M. Testosterone deficiency. Am J Med. 2011 Jul;124(7):578-87. PMID: 21683825
  4. Finkelstein JS et al Gonadal Steroids and Body Composition, Strength, and Sexual Function in Men. N Engl J Med 2013; 369:1011-1022. September 12, 2013 PMID: 24024838 http://www.nejm.org/doi/full/10.1056/NEJMoa1206168 - Handelsman DJ Mechanisms of Action of Testosterone - Unraveling a Gordian Knot. N Engl J Med 2013; 369:1058-1059. September 12, 2013 PMID: 24024843 http://www.nejm.org/doi/full/10.1056/NEJMe1305307
  5. Wu FCW et al. Identification of late-onset hypogonadism in middle-aged and elderly men. N Engl J Med 2010 Jul 8; 363:123 PMID: 20554979
  6. Traish AM. Adverse health effects of testosterone deficiency (TD) in men. Steroids. 2014 Oct;88:106-16. Review. PMID: 24942084
  7. Pye SR, Huhtaniemi IT, Finn JD et al Late-onset hypogonadism and mortality in aging men. J Clin Endocrinol Metab. 2014 Apr;99(4):1357-66. PMID: 24423283
  8. Basaria S. Male hypogonadism. Lancet. 2014 Apr 5;383(9924):1250-63. Review. PMID: 24119423
  9. Sargis RM, Davis AM Evaluation and Treatment of Male Hypogonadism. Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline. JAMA. Published online March 17, 2018. PMID: 29550857 https://jamanetwork.com/journals/jama/fullarticle/2675569
  10. Karavolos S, Reynolds M, Panagiotopoulou N et al Male central hypogonadism secondary to exogenous androgens: a review of the drugs and protocols highlighted by the online community of users for prevention and/or mitigation of adverse effects. Clin Endocrinol (Oxf). 2015 May;82(5):624-32. Review. PMID: 25333666
  11. Yeap BB, Marriot RJ, Dwivedi G et al Associations of Testosterone and Related Hormones With All-Cause and Cardiovascular Mortality and Incident Cardiovascular Disease in Men: Individual Participant Data Meta-analyses. Ann Intern Med 2024. May 14. PMID: 38739921 Review. https://www.acpjournals.org/doi/10.7326/M23-2781