MALE SEX HORMONES
Mr.D.Raju M.Pharm., Lecturer MALE SEX HORMONES Androgens Anabolic steroids
´ Synthesis& secretion ´ Differ from androgens?
´ Regulation ´ Preparations
´ Pharmacological actions ´ Therapeutic uses
´ Pharmacokinetics ´ Adverse effects
´ Preparations Anti-androgens
´ Therapeutic uses Danazole
´ Adverse effects Cyproterone acetate Flutamide Finasteride Sildenafil ANDROGENS
- Includes testosterone, DHT & androstenedione
-Testosterone serves as a prohormone for « Dihydrotestosterone (DHT) « Oestradiol Cholesterol
Oestriol Pregnenolone 17-α- Hydroxy Dehydro-epi pregnenolone androsterone
Progesterone 17- Hydroxy Andro- Oestrone progesterone stenedione
TESTOSTERONE OESTRADIOL Regulation of secretion
• Oestrogen – similar to Testosterone • Inhibin inhibits FSH secretion at A.P level cytoplasm Nucleus
R
T- R T- R
10%
90% T DHT DHT- R
R
5-αreductase 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 Dose Testosterone aq. suspension 50-100mg / 2 weeks
Testosterone esters: • Testo. propionate 25-50 mg / 3 times a week • Testo. phenylpropionate 40-60mg / 1 or 2 week • Testo. cypionate 100 – 200mg / 2 weeks • Testo. enanthoate 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 FEMALE SEX HORMONES: PROGESTERONE FEMALE SEX HORMONES Oestrogens Progestrogens
´ Synthesis & secretion ´ Synthesis& secretion
´ Regulation ´ Regulation
´ Pharmacological actions ´ Pharmacological actions
´ Pharmacokinetics ´ Pharmacokinetics
´ Preparations ´ Preparations
´ Therapeutic uses ´ Therapeutic uses
´ Adverse effects ´ Adverse effects Anti-Oestrogens Anti-progestrogens Clomiphene citrate Mifepristone Cyclofenil Tamoxifen citrate Raloxifene Ormeloxifene Cholesterol
Oestriol Pregnenolone 17-α- Hydroxy Dehydro-epi pregnenolone androsterone
Progesterone 17- Hydroxy Andro- Oestrone progesterone stenedione
TESTOSTERONE OESTRADIOL Oestrogen
Progesterone
LH FSH HTTP://ANATOMY.IUPUI.EDU/COURSES/HISTO_D502/D502F04/LECTURE.F04/FEMALE04/CYCLE.JPG Type Hormonal activities Progest Oestrogen Androg Anabolic Progesterone derivatives Progesterone +--- Hydroxyprogesterone Capr. +-slight - Medroxyprogesterone acet +-+- Megesterol acetate +--- Testosterone derivative Dimethisterone slight --- Nor-testosterone derivative Norethynodrel slight +-- Lynestrenol slight +++ Norethindrone + slight ++ Ethynodiol diacetate + slight + Norgesterol +-+- PROGESTROGEN: ACTIONS
Uterus: ¾ secretray changes (with oestrogen) ¾ If ovum is fertilized ¾ prepare endometrium ¾ oxytocin & ergonovine actions ¾ FSH, LH ovulation ¾ cervical secretion – thick and viscid
Vagina: WBC infiltration & cornified epithelium Breast Body temperature Respiration Pituitary Clinical uses of Progesterones
´as OCS ´endometriosis ´DUB ´threatened abortion ´HRT ´ post-partum ´dysmenorrhea lactation ´premenstrual syndrome ´endometrial cancer ´hypoventilation Adverse effects of Progesterone
• breast engorgement, headache, rise in body temp., oedema, acne & mood swings • masculinization of external genitalia in the foetus • Increased incidences of congenital abnormalities • irregular bleeding or amenorrhea • lower HDL (19-nortestosterone derivatives) • hyperglycaemia PHARMACOKINETICS
´Absorption: ´ progesterone undergoes high first pass metabolism. Therefore synthetic preparations are more commonly used. ´ Progesterone esters in oily soln. for i.m. admn.
´Metabolism: « by liver enzymes «excretion by urine after conjugation