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Testosterone Deficiency

Testosterone Deficiency is a topic covered in the 5-Minute Clinical Consult.

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  • Testosterone (T) is a critical anabolic hormone involved in various key metabolic pathways.
  • It is the principle circulating androgen in males.
  • Critical in bodily processes of the cardiovascular, reproductive, and central nervous systems
  • Testosterone deficiency (TD), or hypogonadism, is characterized by low levels of T, often in addition with signs and symptoms attributed to low T levels.
  • No universally accepted threshold of T concentration to distinguish eugonadal from hypogonadal men, but the FDA definition is T <300 ng/dL
  • T levels can be affected by disruptions to the hypothalamic–pituitary–testis axis, age, and medical comorbidities.
  • T levels correlate with overall health and may be associated with sexual dysfunction.
  • T levels decline by 1% per year after age 40 years.
  • Special consideration is needed for men with low T who desires future fertility.
  • Synonym(s): hypogonadism, hypoandrogenism, androgen deficiency, and low T


  • Overall incidence increases with age.
  • Symptomatic TD in United States ages 30 to 79 years is 5.6%.
  • 481,000 new cases in United States in men 40 to 69 years

  • Estimates of TD vary widely, but typically 20% of men >60 years, 30% >70 years, and 50% >80 years of age.
  • 2 to 4 million men in United States

Etiology and Pathophysiology

  • Normal hypothalamic–pituitary–testis axis:
    • Hypothalamus produces GnRH, which stimulates pituitary to produce follicle-stimulating hormone (FSH) and luteinizing hormone (LH).
    • LH stimulates Leydig cells to produce T; responsible for 90% of the body’s T
    • T inhibits LH and GnRH through negative feedback at level of hypothalamus and pituitary.
  • Primary hypogonadism: Testes produces insufficient amount of T; FSH/LH levels are elevated.
  • Secondary hypogonadism: low T from inadequate production of LH
  • Congenital syndromes: cryptorchidism, Klinefelter, hypogonadotropic hypogonadism
  • Acquired: cancer, trauma, orchiectomy, steroid use
  • Infectious: mumps orchitis, HIV, tuberculosis
  • Systemic: Cushing, hemochromatosis, autoimmune, severe illness (e.g., renal and liver disease), metabolic syndrome, obesity, obstructive sleep apnea
  • Drugs and medications: LHRH agonists (leuprolide), corticosteroids, ethanol, ketoconazole, spironolactone, marijuana, opioids, cimetidine, SSRIs
  • Elevated prolactin: prolactinoma, dopamine antagonists (neuroleptics and metoclopramide)

  • Usually normal
  • Klinefelter: XXY karyotype
  • Kallmann syndrome: abnormal GnRH secretion due to abnormal hypothalamus development

Risk Factors

  • Obesity, diabetes, COPD, depression, thyroid disorders, malnutrition, alcohol, stress
  • Chronic infections or inflammatory diseases
  • Medications that affect T production or metabolism
  • Undescended testicles
  • Trauma, cancer, testicular radiation, chemotherapy, disorders of the pituitary and/or hypothalamus

General Prevention

  • General health maintenance and treatment of obesity
  • Recent data suggests in men with low T and unexplained anemia; T replacement can significantly increase hemoglobin levels (1).
  • Recent data suggests men with low bone mineral density and low T can increase bone density and bone strength with T replacement.
  • Older men with low T and age-associated memory impairment; T replacement was not seen as beneficial.

Commonly Associated Conditions

  • Infertility, erectile dysfunction, low libido
  • Poorer health outcomes
  • Osteopenia/osteoporosis and fractures
  • Diabetes and insulin resistance, metabolic syndrome
  • Increased body weight, adiposity
  • Depressed mood, poor concentration, irritability

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Stephens, Mark B., et al., editors. "Testosterone Deficiency." 5-Minute Clinical Consult, 27th ed., Wolters Kluwer, 2019. Medicine Central, im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116889/all/Testosterone_Deficiency.
Testosterone Deficiency. In: Stephens MB, Golding J, Baldor RA, et al, eds. 5-Minute Clinical Consult. 27th ed. Wolters Kluwer; 2019. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116889/all/Testosterone_Deficiency. Accessed April 21, 2019.
Testosterone Deficiency. (2019). In Stephens, M. B., Golding, J., Baldor, R. A., & Domino, F. J. (Eds.), 5-Minute Clinical Consult. Available from https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116889/all/Testosterone_Deficiency
Testosterone Deficiency [Internet]. In: Stephens MB, Golding J, Baldor RA, Domino FJ, editors. 5-Minute Clinical Consult. Wolters Kluwer; 2019. [cited 2019 April 21]. Available from: https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116889/all/Testosterone_Deficiency.
* Article titles in AMA citation format should be in sentence-case
TY - ELEC T1 - Testosterone Deficiency ID - 116889 ED - Stephens,Mark B, ED - Golding,Jeremy, ED - Baldor,Robert A, ED - Domino,Frank J, BT - 5-Minute Clinical Consult, Updating UR - https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116889/all/Testosterone_Deficiency PB - Wolters Kluwer ET - 27 DB - Medicine Central DP - Unbound Medicine ER -