Primary Androgens
Initiating Factors
Effects
  • Induce spermatogenesis in conjunction with FSH products
  • Anabolic effects, esp. in skeletal muscle and bone
  • Erythropoesis
  • Secondary Male Sex characteristics
  • Masculinzation in the CNS
Side Effects
  • Virilization
  • Feminization due to aromatase conversion to Estrogen
  • Edema due to simulation of Aldosterone receptors
  • Jaundice, Hepatic carcinoma?
Side Effects of Abuse
  • Sexual dysfunction due to inhibition of GnRH

    • impotence
    • Testicular Atrophy
    • Reduced sperm count
  • Breast development in men due to aromatase conversion to Estrogen
  • Enlarged prostate (remember proliferative effects of Estrogen, similar effects of Testosterone on the prostate)
  • Secondary sex characteristics in women
  • Bad Breath
  • Hypertension
  • Reduction in HDL
  • Acne
Detection of Abuse
  • Epitestosterone is a metabolic byproduct of DHEA metabolism via 3 beta HSD and 17 alpha HSD
  • Inbalance of Testosterone and epi-Testosterone

    • Normally 1:1
    • Abnormal 6:1
Regulation of Testosterone 754GonadatropinsMales.GIF
Biosynthesis Pathway of Testosterone
  1. DHEA
  2. Androstenedione
  3. Testosterone

    1. DHT

      • 5 Alpha Reductase catalyzed reaction
      • High potency Androgen (~10x Testosterone)
    2. Estradiol

      • Aromatase Catalyzed reaction

754Estrogen.GIF

Agents used to block DHT synthesis & Testosterone effects
Metabolism of Androgens
Effects of Testosterone on the fetus
  • up until 6 weeks gestation, the Primitive Gonad is undifferentiated
  • Week 6 the Mullerian and Wolffian ducts develop
  • Week 7 sex-determining region Y (SRY) triggers production of Testosterone by Leydig cells & Sertoli cells seret mullerian inhibitiory substance
  • Week 8 male genitalia develop
  • interuption of Testosterone signaling (either with testosterone production of receptor signaling) will cause a phenotypic appearance of female sex characteristics
Changes in Testosterone associated with maturation
  • Negative feedback is less sensitive during the teens, when Testosterone is high
  • Testosterone secretion drops when men are in their third decade :(...
Pathologies

Included from Androgen Insensitivity Syndrome

Indications for Testosterone and Testosterone Analogs
Dosage Forms
  • PO, IM, Transdermal Patch

    • Testoderm requires application directly to the scrotum using adhesive tape, making rotation difficult as the patch is 60 cm2
      60cmpatch.jpg
Agent Structure Details
Testosterone C00535.gif
  • Not orally available
  • Transdermal, IM
  • 17β Ester as depot
  • 17α methyl orally available
Nandrolone C07254.gif
  • 17β-Esters common
  • Indications - Anemia
  • Stimulates Erythropoesis
Fluoxymesterone D00327.gif
  • Highly orally available
  • Note 9αF, 11-OH, and 17α-methyl
Stanozolol C07311.gif

Indication

  • angioedema
  • Ben Johnson must have had angioedema

Metabolism

  • 3' and 16β Hydroxylation
Oxandrolone C07346.gif

Indications

Danazol D00289.gif

MOA

Side Effects

  • Endometrial Atrophy
  • Tx Endometriosis, but pretty crappy due to androgenic effects

Metabolism

2-Hydroxymethyl esthisterone (Hydrolysis of N-O bond)

Other Therapeutic Agents
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