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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
- 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 health maintenance and treatment of obesity
Commonly Associated Conditions
- Infertility, erectile dysfunction, low libido
- Poorer health outcomes
- Diabetes, insulin resistance, metabolic syndrome
- Increased body weight, adiposity
- Depressed mood, poor concentration, irritability
- Chronic narcotic and corticosteroids use