Male sex hormones By Akrum Hamdy

Male sex hormones 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

Androgens -Includes testosterone, DHT & androstenedione - T estosterone serves as a prohormone for –Dihydrotestosterone (DHT) –Oestradiol

Cholesterol Pregnenolone Progesterone 17-α- Hydroxy pregnenolone 17- Hydroxy progesterone Dehydro-epi androsterone Andro- stenedione Oestrone Oestriol TESTOSTERONEOESTRADIOL

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

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

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 PreparationsDose Testosterone aq. suspension50-100mg / 2 weeks Testosterone esters: Testo. propionate Testo. phenylpropionate Testo. cypionate Testo. enanthoate mg / 3 times a week 40-60mg / 1 or 2 week 100 – 200mg / 2 weeks 250 mg / 2 weeks Orally active preparations: Methyl testosterone tab. Fluoxymesterone Mesterolone Transdermal patches 2 patches /day (back,abdomen,thigh) Implants 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 DrugAnabolic Androgenic ratio Preparation & Dose Methandienone 3:1 5 – 15 mg/day, p.o. Nandrolone phenylpropionate 3:1 10 – 50 mg/wk, i.m. Nandrolone decanoate 3:1 25 – 50 mg/3 wk, i.m. Stanozolol 3: mg/day, p.o. Ethyloestrenol 3: 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 Uses: Endometriosis Menorrhagia Fibrocystic breast disease Hereditary angioneurotic oedema Gynecomastia Infertility Side effects: Dose related Amenorrhea (High doses) Androgenic side effects FSH & LH release in both sexes Binding of steroids to receptors Enzymes needed for steroid synthesis Weak androgenic, anabolic, progestational & glucocorticoid action

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 GnRH agonist Female hirusitism Dose: 250 mg tds.

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

SILDENAFIL

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

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

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 headache, flushing, dyspepsia, myalgia