Description

• 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 Federal Drug Administration (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 desire future fertility.
• Synonym(s): hypogonadism; hypoandrogenism; androgen deficiency; low T

Epidemiology

• Overall incidence increases with age. T levels decline by 1% per year after age 40.
• 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. Leydig cells are responsible for 90% of the body’s T.
  • T inhibits LH/GnRH through negative feedback. Hence, exogenous testosterone can impair spermatogenesis.
• Primary hypogonadism: Testes produce 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