Week4: Androgens Flashcards
Testosterone cypionate
- 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
Transdermal delivery of native testosterone and gels
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
Indications for androgen replacement therapy
-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)
Side effects of androgen replacement therapy
- acne
- polycythemia: due to stimulation of secretion of EPO
and increase of erythropoeisis - gynecomastia: high testosterone converted to estrogen in adipose due to saturation of androgen receptors
CONTRAINDICATIONS
-prostate carcinoma, benign prostatic hyperplasia, pregnant women, children
17a -alkylated androgens (anabolic steroids)
- 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
Danazol (17-a alkylated steroid)
- 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
Androgen suppression and anti androgens LIST
- GnRH agonist: Leuprolide and Goserelin
- Androgen synthesis inhibitor: abiraterone
- 5a-reductase inhibitor: Finasteride
- AntiAndrogens
- spironolactone
- flutamide
- bicalutamide
Finasteride
- 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
Spironolactone
- 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