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Male sex hormones

Male sex hormones. By Akrum Hamdy. Androgens Synthesis& secretion Regulation Pharmacological actions Pharmacokinetics Preparations Therapeutic uses Adverse effects. Anabolic steroids Differ from androgens? Preparations Therapeutic uses Adverse effects Anti-androgens Danazole

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Male sex hormones

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  1. Male sex hormones By Akrum Hamdy

  2. Androgens Synthesis& secretion Regulation Pharmacological actions Pharmacokinetics Preparations Therapeutic uses Adverse effects Anabolic steroids Differ from androgens? Preparations Therapeutic uses Adverse effects Anti-androgens Danazole Cyproterone acetate Flutamide Finasteride Sildenafil Male sex hormones

  3. Androgens • Includes testosterone, DHT & androstenedione - Testosterone serves as a prohormone for • Dihydrotestosterone (DHT) • Oestradiol

  4. Cholesterol Oestriol 17-α- Hydroxy pregnenolone Dehydro-epi androsterone Pregnenolone Progesterone 17- Hydroxy progesterone Andro-stenedione Oestrone TESTOSTERONE OESTRADIOL

  5. Regulation of secretion • Oestrogen – similar to Testosterone • Inhibin inhibits FSH secretion at A.P level

  6. cytoplasm Nucleus R T- R T- R 10% 90% T DHT DHT- R R 5-reductase

  7. Testosterone & DHT

  8. Pharmacokinetics • Absorption:undergoes high first pass metabolism. Therefore i.m. injections or synthetic preparations are used. • Transport:highly protein bound (98%, SHBG,albumin) • Metabolism: • by liver enzymes : androsterone & etiocholanolone • excretion by urine after conjugation • small quantity of oestrogen also produced from testosterone

  9. Clinical uses of testosterone • Testicular failure: Primary & Secondary • Chronic illness • Burns • Osteoporosis • Long term corticosteroid therapy • Pituitary dwarfism • Carcinoma of breast • Hereditary angioneurotic oedema • Anaemia (refractory) • Menopausal syndrome

  10. Adverse effects of testosterone • Virilization (female) • Feminizing side effects (male) • Precocious puberty & stunted growth • Cholestatic jaundice • Enlargement of prostate • Atherosclerosis • Hepatic carcinoma • Oedema

  11. Anabolic steroids

  12. Uses of anabolic steroids • Osteoporosis • Catabolic states • Short stature • Anaemia (refractory) • Athletic performance

  13. Anti-androgens • Danazol • Cyproterone acetate • Flutamide • Finasteride

  14. Danazol • FSH & LH release in both sexes • Binding of steroids to receptors • Enzymes needed for steroid synthesis • Weak androgenic, anabolic, progestational & glucocorticoid action

  15. Cyproterone acetate • Block androgen receptors • secretion of gonadotropins Uses: • Acne • Male pattern of baldness • hirusitism • Ca. of prostate • Virilizing syndrome • Precocious puberty • Inappropriate behaviour

  16. Flutamide • Non-steroidal anti-inflammatory • Antagonise androgens: • Accessory sex organs • Pituitary Uses: • Cancer of prostate along with GnRH agonist • Female hirusitism Dose: 250 mg tds.

  17. 5  reductase inhibitors Finasteride • Prostate volume • Symptom score • Peak urine flow rate • DHT level in prostate • Orally active • DHT levels • Benign prostatic hyperplasia Dose: 5mg/day Also used for prevention of hair loss Side effects:Loss of libido & impotence in 5 % pts.

  18. SILDENAFIL

  19. Hypothalamus ANS Parasympathetic Sympathetic Noradrenaline Acetyl choline vasoconstriction Muscarinic Receptors Penile flaccidity Penile erection

  20. Muscarinic Receptors ↑ VP ↑ NO ATP AC GC GTP cGMP cAMP PDE V  Ca ++ 5’ GMP Vasodilatation Penile Erection

  21. Sildenafil • Inhibits PDE5 in the corpus cavernosa of the penis • 50mg, p.o. 1 h before sexual activity • potentiate nitrate’s hypotension activity • ketoconazole & erythromycin increases its level • renal & hepatic disease increases its level • Side effects: headache, flushing, dyspepsia, myalgia

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