Hypogonadism, Male

  • Diagnosis
  • Algorithms
  • Background
  • Lab Tests
  • References
  • Related Topics

Indications for Testing

  • Signs and symptoms of hypogonadism

Laboratory Testing

  • Screen using serum testosterone concentration – preferably in the early morning with repeat measurement to confirm
    • Children – mass spectrometry assay
    • Adult males – electrochemiluminescent assay (mass spectrometry not necessary); total testosterone measurement is adequate for most patients as initial test (with or without sex hormone binding globulin)
      • <200 ng/dL – repeat testing
      • 200-400 ng/dL – repeat using free or bioavailable testosterone measurements
      • >400 ng/dL – normal testosterone
    • Biochemical evidence of deficiency is necessary to prescribe treatment (ASCP's Pathology-Related Choosing Wisely Recommendations, 2015; American Urological Society, The Endocrine Society, American Association of Clinical Endocrinologists)
  • FSH/LH – use to differentiate between primary and secondary etiologies after low testosterone established by two measurements
    • Elevated LH and FSH, low testosterone – primary hypogonadism
    • Normal or low LH and FSH, low testosterone – secondary or tertiary hypogonadism
      • Consider prolactin measures in secondary hypogonadism – prolactin often normal but may be elevated
    • Normal LH, elevated FSH, normal testosterone – seminiferous tubule disease
    • Normal LH, FSH, and testosterone – consider other etiologies

Imaging Studies

  • Secondary hypogonadism – consider MRI for pituitary imaging

Differential Diagnosis (also see Etiologies in Clinical Background section)

Hypogonadism is one of the most common endocrine disorders in men and is characterized by low serum testosterone levels and/or low sperm counts with clinical signs and symptoms of androgen loss.

Epidemiology

  • Prevalence
    • ~4-5 million men in U.S.
    • 20% of men ≥60 years
    • Frequency increases with obesity, aging, and diabetes mellitus type II

Etiologies

Pathophysiology

  • Gonadotropin-releasing hormone (GnRH) is secreted from the hypothalamus
  • GnRH stimulates the release of leuteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary
    • LH promotes secretion of testosterone from Leydig cells
    • FSH stimulates spermatogenesis
      • Inhibin B production from Sertoli cells inhibits FSH
  • 1-3% of circulating testosterone is free – responsible for biologic activity of testosterone
  • 91-98% of circulating testosterone is bound
    • 60% bound to albumin
    • 40% bound to sex hormone binding globulin (SHBG)
      • Substantial alterations in SHBG affect total testosterone level
        • Free testosterone and bioavailable testosterone levels more accurately reflect bioactive testosterone under these circumstances
        • Bioavailable testosterone = free testosterone plus albumin-bound testosterone
      • Alterations in SHBG
        • Increased by aging, hyperthyroidism, liver disease, HIV anticonvulsant drugs
        • Decreased by obesity, diabetes mellitus, hypothyroidism, glucocorticoids, androgens, progestins, nephrotic syndrome

Clinical Presentation

  • Manifestations depend on the following
    • Age of onset
    • Duration of deficiency
    • Profoundness of deficiency
  • Prepubertal/pubertal hypogonadism
    • Eunuchoidal body habitus
    • Gynecomastia
    • Small testes – volume typically <5 cm3
    • Lack of secondary sexual characteristics
    • Most common cause is Klinefelter syndrome
      • Hypogonadism signs and symptoms listed above plus
        • Small testes – 5ml
        • Long length of legs
        • Psychosocial abnormality unrelated to hypogonadism
        • Impaired higher level linguistic competence
        • Inability to sustain attention without impulsivity
        • Predisposition to develop morbidities later in life unrelated to hypogonadism
  • Postpubertal hypogonadism
    • Sexual – decreased libido, impotence, decrease in testicular volume
    • Psychological – depression
    • Constitutional – weakness, fatigue
    • Low bone mineral density
    • Gynecomastia
    • Muscle loss
    • Abdominal adiposity
    • Other signs and symptoms dependent on etiology
      • Pituitary tumor – visual field cuts
      • Prolactinoma and galactorrhea

Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Testosterone, Adult Male 0070130
Method: Quantitative Electrochemiluminescent Immunoassay

Limitations

Not recommended for females or children

Luteinizing Hormone and Follicle Stimulating Hormone 0070193
Method: Quantitative Electrochemiluminescent Immunoassay

Testosterone, Bioavailable and Sex Hormone Binding Globulin (Includes Total Testosterone), Adult Male 0070102
Method: Quantitative Electrochemiluminescent Immunoassay
The concentrations of free and bioavailable testosterone are derived from mathematical expressions based on constants for the binding of testosterone to albumin and/or sex hormone binding globulin.

Limitations

Not recommended for females or children

Testosterone Free, Adult Male 0070111
Method: Quantitative Electrochemiluminescent Immunoassay
Total Testosterone and SHBG are measured and free testosterone is estimated from these measurements.

Limitations

Not recommended for females or children

Testosterone Free, Females or Children 0081059
Method: Quantitative High Performance Liquid Chromatography-Tandem Mass Spectrometry/Electrochemiluminescent Immunoassay
Total Testosterone and SHBG are measured and free testosterone is estimated from these measurements.

Luteinizing Hormone (LH), Pediatric 2007567
Method: Quantitative Electrochemiluminescent Immunoassay

Limitations

For patients ≥7 years, order luteinizing hormone, serum

Related Tests

Guidelines

American Society for Clinical Pathology. Choosing Wisely - Pathology-Related Choosing Wisely Recommendations. An initiative of the ABIM Foundation. [Initial posting Feb 2015; Accessed: Nov 2015]

Bhasin S, Basaria S. Diagnosis and treatment of hypogonadism in men. Best Pract Res Clin Endocrinol Metab. 2011; 25(2): 251-70. PubMed

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(6): 2536-59. PubMed

Kushnir MM, Blamires T, Rockwood AL, Roberts WL, Yue B, Erdogan E, Bunker AM, Meikle W. Liquid chromatography-tandem mass spectrometry assay for androstenedione, dehydroepiandrosterone, and testosterone with pediatric and adult reference intervals. Clin Chem. 2010; 56(7): 1138-47. PubMed

Paduch DA, Brannigan RE, Fuchs EF, Kim ED, Marmar JL, Sandlow JI. The laboratory diagnosis of testosterone deficiency. Urology. 2014; 83(5): 980-8. PubMed

General References

Arver S, Lehtihet M. Current guidelines for the diagnosis of testosterone deficiency. Front Horm Res. 2009; 37: 5-20. PubMed

Basaria S. Male hypogonadism. Lancet. 2014; 383(9924): 1250-63. PubMed

Ho CK M, Beckett GJ. Late-onset male hypogonadism: clinical and laboratory evaluation. J Clin Pathol. 2011; 64(6): 459-65. PubMed

Morales A, Collier CP, Clark AF. A critical appraisal of accuracy and cost of laboratory methodologies for the diagnosis of hypogonadism: the role of free testosterone assays. Can J Urol. 2012; 19(3): 6314-8. PubMed

Palmert MR, Dunkel L. Clinical practice. Delayed puberty. N Engl J Med. 2012; 366(5): 443-53. PubMed

Pantalone KM, Faiman C. Male hypogonadism: more than just a low testosterone. Cleve Clin J Med. 2012; 79(10): 717-25. PubMed

Traish AM, Miner MM, Morgentaler A, Zitzmann M. Testosterone deficiency. Am J Med. 2011; 124(7): 578-87. PubMed

Viswanathan V, Eugster EA. Etiology and treatment of hypogonadism in adolescents. Pediatr Clin North Am. 2011; 58(5): 1181-200, x. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

Hammoud AO, Meikle W, Peterson M, Stanford J, Gibson M, Carrell DT. Association of 25-hydroxy-vitamin D levels with semen and hormonal parameters. Asian J Androl. 2012; 14(6): 855-9. PubMed

Kushnir MM, Rockwood AL, Roberts WL, Pattison EG, Bunker AM, Fitzgerald RL, Meikle W. Performance characteristics of a novel tandem mass spectrometry assay for serum testosterone. Clin Chem. 2006; 52(1): 120-8. PubMed

Medical Reviewers

Last Update: April 2016