Week4: Androgens

Question 1

Testosterone cypionate

Answer 1

• esterified: increases solubility in vehicle (oil). Injected and stays at site of injection, released slowly. 2-3 weeks.
• drawback: fluctuations in mood, sexual function due to variation in plasma levels.
• used for induction and maintenance of secondary sex characteristics, somatic dev., libido, potency

Question 2

Transdermal delivery of native testosterone and gels

Answer 2

PATCHES
-requires larger patch for 5 mg of testosterone/24 hours
-scrotal skin patch: greater absorption
-nonscrotal skin patches: have permeation enhancers, but may cause skin irritation
-able to maintain physiological levels without fluctuations
GEL
-risk of transfer and virilization in close contact with female or children

Question 3

Indications for androgen replacement therapy

Answer 3

-primary hypogonadism
-secondary hypogonadism
-prepuberal hypogonadism: goal to induce and maintain male sex characteristics, behavior, somatic development, induce pubertal growth spurt
-post puberal: goal is to restore and maintain secondary sex characteristics and sex behavior
(17a alkylated androgens not used because they can’t be aromatized to estradiol or converted to DHT)

Question 4

Side effects of androgen replacement therapy

Answer 4

1. acne
2. polycythemia: due to stimulation of secretion of EPO
   and increase of erythropoeisis
3. gynecomastia: high testosterone converted to estrogen in adipose due to saturation of androgen receptors
   CONTRAINDICATIONS
   -prostate carcinoma, benign prostatic hyperplasia, pregnant women, children

Question 5

17a -alkylated androgens (anabolic steroids)

Answer 5

• names: stanozolol, oxandrolone
• alkylation reduces hepatic inactivation, induces “hepatic effect”
• not aromatized. High anabolic and low androgenic activity
• Uses: stimulate appetite, muscle mass in patients with cancer, chronic infection, extensive surgery, severe trauma. Counteract glucocorticoid induced protein catabolism. AIDS patients with hypogonadism
• side effects: infertility (suppression of GnRH, LH, FSH), hepatotoxicity due to hepatic effect, coronary artery disease

Question 6

Danazol (17-a alkylated steroid)

Answer 6

• weak androgen, progestin, antiestrogen.
• clinical use: hereditary angioneurotic edema. It increases the synthesis of C1-esterase inhibitor due to hepatic effect to prevent uninhibited activation of complement system
• prevents acute attacks in hereditary angioneurotic edema

Question 7

Androgen suppression and anti androgens LIST

Answer 7

1. GnRH agonist: Leuprolide and Goserelin
2. Androgen synthesis inhibitor: abiraterone
3. 5a-reductase inhibitor: Finasteride
4. AntiAndrogens
   - spironolactone
   - flutamide
   - bicalutamide

Question 8

Finasteride

Answer 8

• 4-aza-testosterone derivative that selectively inhibits 5a-reductase
• inhibits conversion of testosterone to DHT in prostate and skin
• uses: benign prostatic hyperplasia, to increase hair growth on the scalp (alopecia), reducing chest hair
• well tolerated, impotence only in few, only few have decrease in libido

Question 9

Spironolactone

Answer 9

• aldosterone antagonist with weak anti-androgenic activity
• mechanism: blocks 17a hydroxylase and 17,20 desmolase, inhibiting androgen synthesis. and Blocks testosterone binding to SHBG.
• uses: Hirsutism, alopecia androgenica (women), acne, precocious puberty