Testosterone Deficiency

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  • Testosterone (T) is a critical anabolic hormone.
  • It is the principle circulating androgen in males.
  • Critical in cardiovascular, reproductive, and metabolic systems
  • Testosterone deficiency (TD) is characterized by low levels of T in addition with signs and symptoms.
  • 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.
  • 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.
  • 481,000 new cases in United States ages 40 to 69 years

  • Estimates of TD vary, typically 20% of men >60 years, 30% >70 years, and 50% >80 years of age.
  • Symptomatic TD in United States ages 40 to 69 years is 6–12.3%.
  • 2.4 million men in United States ages 40 to 69 years

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.
    • T inhibits LH/GnRH through negative feedback.
  • 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 (Kallmann)
  • Acquired: cancer, trauma, orchiectomy, steroids
  • Infectious: mumps orchitis, HIV, tuberculosis
  • Systemic: Cushing, hemochromatosis, autoimmune, severe illness (e.g., renal and liver disease), metabolic syndrome, obesity, obstructive sleep apnea
  • Medications and drugs: LHRH agonists, corticosteroids, ethanol, marijuana, opioids, SSRIs
  • Elevated prolactin: prolactinoma, dopamine antagonists (neuroleptics and metoclopramide)

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

Risk Factors

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

General Prevention

General health maintenance and treatment of obesity

Commonly Associated Conditions

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

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