Male sex hormones By Akrum Hamdy Male sex
Male sex hormones By Akrum Hamdy
Male sex hormones Androgens Anabolic steroids • Synthesis& secretion • Differ from androgens? • Regulation • Preparations • Pharmacological actions • Therapeutic uses • Pharmacokinetics • Adverse effects Anti-androgens • Preparations Danazole • Therapeutic uses Cyproterone acetate • Adverse effects Flutamide Finasteride Sildenafil
Androgens - Includes testosterone, DHT & androstenedione - Testosterone serves as a prohormone for – Dihydrotestosterone (DHT) – Oestradiol
Cholesterol Pregnenolone 17 -α- Hydroxy pregnenolone Dehydro-epi androsterone Progesterone 17 - Hydroxy progesterone Androstenedione TESTOSTERONE Oestriol Oestrone OESTRADIOL
Regulation of secretion • Oestrogen – similar to Testosterone • Inhibin inhibits FSH secretion at A. P level
cytoplasm Nucleus R T- R 10% 90% T DHT R 5 - reductase DHT- R
Testosterone & DHT • growth of genitals in a boy • production of sperm • growth of facial, pubic & axillary hairs • muscular development • growth of larynx & voice deepens • inhibition of bone growth • thickening of skin, loss of s. c. fat • behavioral changes in men • nitrogen retaining effect • erythropoietin secretion increased • Increased LDL & decreased HDL
Testosterone Preparations Testosterone aq. suspension Dose 50 -100 mg / 2 weeks Testosterone esters: • Testo. propionate • Testo. phenylpropionate • Testo. cypionate • Testo. enanthoate 25 -50 mg / 3 times a week 40 -60 mg / 1 or 2 week 100 – 200 mg / 2 weeks 250 mg / 2 weeks Orally active preparations: • Methyl testosterone tab. • Fluoxymesterone • Mesterolone Transdermal patches Implants 2 patches /day (back, abdomen, thigh) wall of abdomen/thigh
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
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
Adverse effects of testosterone • Virilization (female) • Feminizing side effects (male) • Precocious puberty & stunted growth • Cholestatic jaundice • Enlargement of prostate • Atherosclerosis • Hepatic carcinoma • Oedema
Anabolic steroids
Anabolic Steroids Drug Methandienone Anabolic Preparation & Dose Androgenic ratio 5 – 15 mg/day, p. o. 3: 1 Nandrolone phenylpropionate Nandrolone decanoate Stanozolol 3: 1 10 – 50 mg/wk, i. m. 3: 1 25 – 50 mg/3 wk, i. m. 3: 1 2 - 6 mg/day, p. o. Ethyloestrenol 3: 1 8 - 16 mg/day, p. o. Oxandrolone 3: 1 5 – 10 mg/day, p. o. Fluoxymesterone 3: 1 5 – 10 mg/day, p. o.
Uses of anabolic steroids – Osteoporosis – Catabolic states – Short stature – Anaemia (refractory) – Athletic performance
Anti-androgens • Danazol • Cyproterone acetate • Flutamide • Finasteride
Danazol • FSH & LH release in both sexes • Binding of steroids to receptors • Enzymes needed for steroid synthesis • Weak androgenic, anabolic, progestational & glucocorticoid action Uses: Side effects: • Endometriosis Dose related • Menorrhagia Amenorrhea (High doses) • Fibrocystic breast disease Androgenic side effects • Hereditary angioneurotic oedema • Gynecomastia • Infertility
Cyproterone acetate • Block androgen receptors • secretion of gonadotropins Uses: • • Acne Male pattern of baldness hirusitism Ca. of prostate Virilizing syndrome Precocious puberty Inappropriate behaviour
Flutamide • Non-steroidal anti-inflammatory • Antagonise androgens: – Accessory sex organs – Pituitary Uses: • Cancer of prostate along with Gn. RH agonist • Female hirusitism Dose: 250 mg tds.
5 reductase inhibitors Finasteride • Orally active • DHT levels • Benign prostatic hyperplasia Dose: 5 mg/day Prostate volume Symptom score Peak urine flow rate DHT level in prostate Also used for prevention of hair loss Side effects: Loss of libido & impotence in 5 % pts.
SILDENAFIL
Hypothalamus ANS Parasympathetic Sympathetic Noradrenaline Acetyl choline vasoconstriction Muscarinic Receptors Penile erection Penile flaccidity
Muscarinic Receptors ↑ VP ↑ NO AC GC GTP c. GMP ATP c. AMP PDE V Ca ++ 5’ GMP Vasodilatation Penile Erection
Sildenafil ► Inhibits PDE 5 in the corpus cavernosa of the penis ► 50 mg, 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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