Androgens and anabolic steroids

Androgens - The Manly Molecules

• Mechanism: Act as intracellular steroid hormones. Bind to receptors in the cytoplasm, translocate to the nucleus, and modulate gene expression.
• Key Androgens: Testosterone, Dihydrotestosterone (DHT), Dehydroepiandrosterone (DHEA).

• Clinical Use:

  • Hypogonadism (primary or secondary)
  • Delayed puberty in boys
  • Muscle wasting in cachectic states (e.g., AIDS)
  • Anemia (stimulate erythropoietin)

• Adverse Effects:

  • Masculinization in females; gynecomastia in males (via aromatization)
  • ↓ Spermatogenesis (negative feedback on LH/FSH)
  • Premature closure of epiphyseal plates in children
  • ↑ LDL, ↓ HDL
  • Peliosis hepatis, cholestasis, hepatocellular carcinoma

⭐ Finasteride, a 5α-reductase inhibitor, blocks the conversion of testosterone to the more potent DHT. It's used to treat benign prostatic hyperplasia (BPH) and male pattern baldness.

Steroid Arsenal - Clinical Uses

• Hypogonadism (Primary & Secondary):
  • Serves as testosterone replacement therapy (TRT) in cases of testicular, pituitary, or hypothalamic failure.
  • Induces puberty in individuals with constitutional delay.
• Andropause: Addresses symptoms related to age-associated decline in testosterone.
• Wasting Syndromes (Cachexia):
  • Promotes anabolism and counters protein loss in chronic diseases like AIDS or cancer.
  • Aids recovery in severe burn patients by ↑ protein synthesis.
• Anemias:
  • Stimulates erythropoietin, historically used for aplastic anemia.
• Hereditary Angioedema:
  • Danazol is used to ↑ synthesis of C1 esterase inhibitor.

⭐ Exam Favorite: Abuse of anabolic steroids for athletic enhancement paradoxically leads to hypogonadism. Exogenous testosterone suppresses GnRH, LH, and FSH, causing ↓ endogenous testosterone production, testicular atrophy, and azoospermia.

Roid Rage & Risks - The Downsides

• Cardiovascular
  • Dyslipidemia (↑LDL, ↓HDL), hypertension, left ventricular hypertrophy.
  • ↑Risk of thrombosis, myocardial infarction, and stroke.
• Psychiatric & Behavioral
  • "Roid rage": aggression, irritability, hostility.
  • Mood swings, mania, depression, psychosis.
• Endocrine & Reproductive
  • Men: ↓Endogenous testosterone, testicular atrophy, infertility, gynecomastia (aromatization to estrogen), male pattern baldness.
  • Women: Virilization (hirsutism, acne, voice deepening, clitoromegaly), menstrual irregularities.
  • Adolescents: Premature epiphyseal closure → stunted growth.
• Hepatic
  • Cholestasis, peliosis hepatis (blood-filled cysts), hepatic neoplasms.

⭐ High-Yield: Exogenous androgens suppress the hypothalamic-pituitary-gonadal (HPG) axis, leading to ↓LH and FSH secretion. This causes decreased endogenous testosterone production and testicular atrophy.

• Androgens (e.g., testosterone, methyltestosterone) bind to intracellular receptors, acting as transcription factors.
• Clinically used for hypogonadism, muscle wasting (cachexia), and promoting secondary sexual characteristics.
• Anabolic steroid abuse causes testicular atrophy and gynecomastia in males due to negative feedback and peripheral conversion to estrogen.
• Key adverse effects include hepatotoxicity (especially 17-alpha-alkylated orals), virilization in females, altered lipids (↓HDL, ↑LDL), and premature epiphyseal closure in children.