ANDROGEN

Question 1

Hypothalamic-pituitary-gonadal axis

Answer 1

• GnRH is secreted in Pulsatile fashion
• Testosterone released from LEYDIG cells diffuses into the blood stream
  
  • Androgen binding protein (ABP) helps concentrate testosterone
• Negatie feedback at anterior pituitary and hypothalamus

Question 2

anabolic effects of androgens

Answer 2

• IInhibits lipid accumulation in adipocytes, stimulate lipolysis, inhibits differentiation of adipocyte precursors
• Lowers blood glucuse –> increase glucose transporter
• SKELETON
  
  • reduces bone reabsorption and enhances bone formation
  • at puberty, estradiol facilitates closure of epiphysial growth plate
• RBCs = increases production of erythropoietin
• Muscles = increases protein synthesis and inhibits protein breakdown

Question 3

Therapeutic uses of androgens

Answer 3

• Stimulate sexual development and increase height of teenagers with delayed puberty
  
  • low doses
  • high doses = premature closure of epiphyseal plates and virilization occur
• Rreplacement therapy in Hypogonadal men
• Aging
  
  • Low T syndrome = vitality, vigor, reduce bone loss, body comp.
  • Sexual dysfunction = males, females
• Anabolic effects
  
  • debilitated states
    
    • AIDS-associated wasting
    • prolonged immobilization

Question 4

Primary Hypogonadism

Answer 4

• Testicular dysfunction leads to a decrease in testosterone production
• loss of negative feedback causes an increase in circulating gonadotrophins (HYPERGONADOTROPIC HYPOGONADISM)
• Symtpoms
  
  • child = short stature, anemia, underdeveloped muscles, underdeveloped sex organs with delyaed or absent spermatogenesis
  • Adult = decrease in bone mass, anemia, muscle atrophy, decreased sexual function, and spermatogenesis, mood changes

Question 5

secondary hypogonadism

Answer 5

• caused by Hypothalamus/pituitary
• morbid obesity
• decrease in circualting gonadotrophins (HYPOgonadotropic hypoganadism)
  
  • low testosterone in the setting of low LH and FSH
• Symtpoms
  • child = short stature, anemia, underdeveloped muscles, underdeveloped sex organs with delyaed or absent spermatogenesis
  • Adult = decrease in bone mass, anemia, muscle atrophy, decreased sexual function, and spermatogenesis, mood changes

Question 6

Methyltestosterone

Testosterone enanthate

testosterone

Answer 6

• methyltestosterone = oral, sublingual (buccal)
  
  • Significantly Slower liver catabolism
  • LIVER TOXCITY and HEPATIC cancer can occur
• testosterone enanthate = intramuscular
  
  • Increases lipophilicity of molecules
• dissolved in oil and given intramuscularly
• SLOW RELEASE –> LONGER DURATION
• testosterone = transdermal or topical gel

Question 7

Benefits of androgen replacement therapy

Answer 7

• increased:
  
  • libido and improved sexual function
  • bone density
  • muscle mass
• decreased
  
  • body mass index
  • body fat
• improved
  
  • mood, quality of life, glycemic control, insulin resistance and cholesterol with type 2 diabetes

memory and cognition

Question 8

Adverse effects of androgen therapy

Answer 8

• increase muscle and tendon injuries
• Hepatic dysfunction (cholestatic jaundice, peliosis, carcinoma)
• Lipid metabolsim
  
  • decrease HDL and increase LDL –> risk of atherosclerosis
• Renal dysfunction
  
  • edema, fluid retention (Hypertension)
• Polycythemia
• mental disturbances (mood swings, aggression, depression, psychosis)

Question 9

Therapeutic uses for antiandrogens

Answer 9

• female
  
  • hirsutism
• males
  
  • precocious puberty
  • benign prostatic hyperplasia (BPH)
  • prostate cancer
  • alopecia