Androgens (Testosterone, Methyltestosterone)

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Summary

Testosterone, methyltestosterone, androstenedione, and dihydrotestosterone or DHT are drugs related to the hormone testosterone. These drugs all work by activating androgen receptors. This increases androgen signaling, which may be useful in treatment of hypogonadism or low testosterone. This agonist activity is also responsible for muscular growth and masculinization. Major adverse effects of taking external sources of testosterone include acne and gonadal atrophy.

Key Points

  • Testosterone
    • Medications
      • Testosterone
      • Methyltestosterone
        • Mainly used as as illicit steroid
      • Dihydrotestosterone (DHT)
        • More potent form
        • Produced from testosterone by 5-alpha-reductase
      • Androstenedione
        • Weak androgen and precursor to testosterone and estrogen
    • Mechanism
      • Agonist at androgen receptors
        • Testosterone develops male internal genitalia in utero
          • promotes differentiation of the epididymis, vas deferens, seminal vesicles (internal genitalia except prostate)
        • DHT: mediates the development of external male genitalia in utero
        • Testosterone: develops secondary sex characteristics in puberty
          • Deepening of the voice, development of male external genitalia, increased facial hair
        • Growth spurt
          • Testosterone prompts the growth of the penis, seminal vesicles, sperm, muscle, and RBCs.
    • Indications
      • Hypogonadism
        • May be used to treat or replace endogenous testosterone in hypogonadism (e.g. Klinefelter syndrome, etc.)
      • Muscle/Tissue Growth (anabolism)
        • Stimulates anabolism to promote recovery after a burn or injury
        • Used illicitly as anabolic steroids
          • E.g. by athletes, bodybuilders, etc.
      • ER-positive breast cancer
        • ↑ testosterone stimulates negative feedback → decreased LH/FSH →  ↓ estrogen release
          • Exemestane (aromatase inhibitor) is given rather than providing testosterone directly
      • Decreased libido
    • Adverse Effects
      • Masculinization
        • Due to agonist activity at androgen receptors
        • Includes deepening of the voice, excessive facial hair (hirsutism), female virilization and breast atrophy, and baldness
      • Gonadal/testicular atrophy
        • Exogenous testosterone suppresses hypothalamic-pituitary axis → decreases luteinizing hormone  → decreases intratesticular testosterone → decreased testicular size (gonadal atrophy)
      • Acne (e.g. cystic nodular acne)
        • Androgens stimulate proliferation of skin around hair follicles and increased sebum production, leading to increased risk of acne
      • Premature closure of epiphyseal/growth plates
        • Testosterone is converted to estrogen via aromatase and estrogen promotes early closure of growth plates
        • Reduced height potential
      • Aggressive behavior
      • Worsening of lipid profile
        •  Increased LDL and decreased HDL
      • Hepatic Adenoma
        • Benign mass can rupture upon exposure to testosterone
        • Can cause sudden hypotension in a weightlifter who may be abusing steroids