Androgens and Anabolic Steroids

Androgens and Anabolic Steroids - Hormone Hotshots

• Key Androgens: Testosterone (T), Dihydrotestosterone (DHT - more potent).
• Regulation: Hypothalamus (GnRH) → Pituitary (LH) → Leydig cells (T synthesis). T exerts negative feedback.
• Mechanism: Bind intracellular androgen receptors (AR) → modulate gene expression.
• Anabolic Steroids: Synthetic T analogs (e.g., Nandrolone, Stanozolol). Aim: ↑anabolic / ↓androgenic effects.
• Uses: Hypogonadism, Aplastic anemia, Osteoporosis, Catabolic states, Angioedema (Danazol).
• Adverse Effects: Virilization, Gynecomastia (aromatization), ↓Spermatogenesis, Dyslipidemia (↑LDL, ↓HDL), Hepatotoxicity (esp. 17α-alkylated), Acne, Premature epiphyseal closure, Aggression.

⭐ Anabolic steroid abuse can lead to peliosis hepatis (blood-filled cysts in liver), especially with 17α-alkylated oral steroids.

Androgens and Anabolic Steroids - Steroid Signals

• Type: Lipid-soluble; act via intracellular Androgen Receptors (AR), part of nuclear receptor superfamily.
• AR Location: Cytoplasm (complexed with Heat Shock Proteins - HSPs) or nucleus.
• Mechanism:
  • Steroid diffuses into cell.
  • Binds to AR; HSPs dissociate.
  • Hormone-AR complex dimerizes, translocates to nucleus.
  • Binds to Androgen Response Elements (AREs) on DNA.
  • Modulates gene transcription → alters mRNA & protein synthesis → physiological effects.
• Kinetics: Slow onset of action, prolonged duration.
• Transport: Circulate bound to Sex Hormone-Binding Globulin (SHBG) with high affinity, and albumin with low affinity.
  • Only free fraction (~2%) is biologically active.

⭐ Dihydrotestosterone (DHT) exhibits a higher binding affinity for the Androgen Receptor (approximately 2-3 times greater) compared to testosterone.

Androgens and Anabolic Steroids - Healing Hormones

• Therapeutic Applications:
  • Testosterone Replacement Therapy (TRT):
    • Male hypogonadism (Klinefelter's, pituitary failure).
    • Delayed puberty in boys (select cases, cautious).
  • Anabolic Support:
    • Catabolic states: burns, chronic illness, post-surgery (Nandrolone).
    • Osteoporosis (adjunctive, limited).
  • Hematological Disorders:
    • Aplastic anemia, anemia of renal disease (Oxymetholone, Nandrolone) via erythropoiesis stimulation.
  • Hereditary Angioedema (HAE):
    • Danazol, Stanozolol: Long-term prophylaxis by ↑ hepatic C1-INH synthesis.
  • Other Uses:
    • Endometriosis (Danazol; ovarian suppression).
    • Palliative in some advanced breast cancers.

⭐ Danazol is key for hereditary angioedema (HAE) long-term prophylaxis, increasing hepatic C1 esterase inhibitor (C1-INH) synthesis.

Androgens and Anabolic Steroids - Risky Business

• Adverse Effects (Dose-dependent & Prolonged Use):
  • Hepatic: Cholestatic jaundice, peliosis hepatis, hepatocellular carcinoma.
  • Cardiovascular: ↑LDL, ↓HDL, hypertension, LVH, thrombosis, cardiomyopathy.
  • Endocrine/Reproductive:
    • Males: Testicular atrophy, ↓spermatogenesis, gynecomastia (aromatization), priapism.
    • Females: Virilization (hirsutism, clitoromegaly, deep voice), menstrual irregularities.
    • Children: Premature epiphyseal closure, precocious puberty.
  • Behavioral: Aggression ("roid rage"), mood swings, dependence.
  • Skin: Acne, striae, alopecia.
  • Musculoskeletal: Tendon rupture.
  • Other: Fluid retention, polycythemia.

• Contraindications: Prostate/breast cancer (male), pregnancy, lactation, severe cardiac/hepatic/renal disease.

⭐ High-Yield Fact: Anabolic steroid-induced hypogonadism can persist for months after cessation, requiring careful management and patient education regarding recovery timelines. This is due to suppression of the HPG axis (Hypothalamic-Pituitary-Gonadal axis).

High‑Yield Points - ⚡ Biggest Takeaways

• Testosterone is converted to potent DHT by 5α-reductase; Finasteride/Dutasteride are inhibitors.
• Anabolic steroids (e.g., Nandrolone) have ↑ anabolic activity; risks include hepatotoxicity, cardiac events, virilization.
• Danazol, a weak androgen, is used for endometriosis and hereditary angioedema.
• Antiandrogens (e.g., Flutamide, Bicalutamide) are key in prostate cancer management.
• Spironolactone acts as an androgen receptor antagonist and inhibits androgen synthesis.
• Ketoconazole is a non-selective inhibitor of gonadal and adrenal steroid synthesis.