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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
- 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 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