Description

• Testosterone (T) is the principal circulating androgen in males. Testosterone deficiency (TD) is characterized by low levels of T in addition to signs and symptoms.
• No universally accepted threshold of T concentration to distinguish eugonadal from hypogonadal men, but the U.S. Food and Drug Administration (FDA) definition is T <300 ng/dL
• T levels correlate with overall health and may be associated with sexual dysfunction.
• Synonym(s): hypogonadism, hypoandrogenism, androgen deficiency, low T

Epidemiology

Incidence
Overall incidence increases with age. T levels decline by 1% per year after the age of 40 years.

Prevalence

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

Etiology and Pathophysiology

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.

• 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 syndrome, 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)

Genetics

• Klinefelter syndrome: 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
• 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
• Osteopenia/osteoporosis
• Diabetes, insulin resistance, metabolic syndrome, adiposity
• Depressed mood, poor concentration, irritability