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Updated: Dec 2 2021


  • Snapshot
    • A 31-year-old man presents to his primary care physician for the evaluation of infertility. He and his wife have been trying to become pregnant for over a year. His wife was extensively evaluated, which showed no reason on her end for their inability to conceive. Upon further questioning, the patient reports decreased spontaneous erections, breast discomfort, and a reduced need to shave. On physical examination, the patient has a eunuchoid body habitus, gynecomastia, and small testes. On laboratory testing, there is a elevated follicle-stimulating hormone (FSH) and luteinizing hormone (LH) with a low testosterone level. The patient is prescribed testosterone replacement therapy after testing his hematocrit and prostate-specific antigen (PSA) level. (Klinefelter syndrome)
  • Introduction
    • Mechanism of action
      • testosterone has 3 modes of action (based on its structure or its derivatives)
        • directly on androgen receptors as testosterone
        • as dihydrotestosterone (DHT) after being converted by 5-α-reductase
          • DHT has a higher avidity for androgen receptors than testosterone
          • leads to development of external genitalia (e.g., hair and prostate)
        • as estrogen after being converted by aromatase, acting on estrogen receptors
    • Clinical use
      • testosterone should only be administered in a man who is hypogonadal
      • primary hypogonadism
        • can be congenital (e.g., Klinefelter syndrome)
        • can be acquired (e.g., orchitis caused by mumps and radiation)
      • secondary hypogonadism
        • can be congenital (e.g., congenital GnRH deficiency)
        • can be acquired (e.g., hyperprolactinemia)
        • low testosterone, low GnRH, low FSH/LH ratio
          • initial diagnostic testing should also include TSH and prolactin levels
          • further testing may include brain imaging and karotyping
      • anabolic steroid abuse
        • anabolic steroids are structural analogs of testosterone and have anabolic and androgenic effects
        • anabolic effects
          • increased protein synthesis
          • increased muscle mass
          • increased RBC production (i.e., elevated hematocrit)
        • androgenic effects
          • increased libido
          • acne
          • male pattern hair loss
          • gynecomastia
          • dyslipidemia
          • irritability
          • aggressive behavior
        • chronic use leads to suppression of the hypothalamic-pituitary-gonadal axis, causing hypogonadotropic hypogonadism
        • treatment involves cessation of the anabolic steroid
          • may take several months for the hypothalamic-pituitary-gonadal axis to recover
    • Adverse effects
      • masculinization in females
      • prostate disorders (e.g., benign prostatic hyperplasia)
      • worsening of sleep apnea
      • erythrocytosis
      • testicular atrophy in males
      • premature closure of epiphyseal plates in adolescents
      • worsening of lipid profile
        • ↑ LDL and ↓ HDL
      • hepatic adenoma
        • benign mass that can rupture
        • cause of sudden hypotension in a weightlifter (presumably abusing steroids)
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