SEX HORMONES ผศ. พญ. มาลียา มโนรถ

Sex Hormones F 21 carbon : progestin F 19 carbon : androgen F 18 carbon : estrogen

Hypothalamus Anterior pituitary FSH LH FollicleCorpus luteum EstrogenProgesterone Testis Testosterone

Estrogen F Estrogenic Activity 1. Natural : Most potent 17-estradiol, estrone, estriol (E2>E1>E3) 2. Steroidal synthetic : Ethinyl estradiol (EE), Mestranol (ME) 3. Nonsteroidal synthetic : Flavone, isoflavone, diethylstilbestrol (DES)

Pharmacokinetics F E2 : SHBG (sex hormone binding globulin) F Free fraction : physiologic active F Metabolism : liver + other tissues (enterohepatic circulatin) F Breast milk : small amount

Physiologic Effects F Maturation of genital organ F Secondary sex characteristics F Breast stromal development F Menstrual cycle F Coagulability of blood factors II, VII, IX, X  Plasma lipids : ญ  HDL, slight ฏ  LDL

Contraindication F Estrogen-dependent neoplasm F Undiagnosed genital bleeding F Liver disease F Hx. thromboembolic disorder

Clinical Uses F Primary hypogonadism F Postmenopausal hormonal therapy F High risk of osteoporosis F Other uses : dysmenorrhea, OC

Adverse Reactions F Post menopausal bleeding F Nausea & breast tenderness F Hyperpigmentation  ญ frequency : migraine headache F Cholestasis & gall bladder disease, hypertension

Progesterone F Synthesized : ovary, placenta –follicular phase : 0.03 g/dL –Luteal phase : >2 g/dL –[Synthetic & natural progestational agents are called progestins] F Metabolized : liver

Physiological Effects F Marked : carbohydrate metabolism F Endometrium : maturation & secretory changes F Endocervical gland : scant viscid material

Adverse Reaction  ฏ HDL  ญ incidence of atherosclerosis

Clinical Uses F Hormonal contraception F Dysmenorrhea F Precocious puberty F Diagnostic use

Androgen F Testosterone F 2 0 sex characteristic F Inactivated : liver

Clinical Uses F Androgen replacement therapy (man) F Gynecologic disorders F Anemia F Use as protein anabolic agents F Osteoporosis

Anabolic Steroids F Testosterone derivatives F relatively more anabolic (building) effects  Action : ญ synthesis of anabolic proteins

Adverse Reactions F Musculinizing actions (woman, prepubertal children) F Sodium retention & edema F Hepatic dysfunction F Cholestatic jaundice F Prostatic hyperplasia

Antiandrogens F Spironolactone –Competitive inhibitor of aldosterone –Rx. Hirsutism in woman F Flutamide –Potent antiandrogen –Rx. Prostatic carcinoma –SE : mild gynecomastia

Antiestrogen F Tamoxifen –Competitive inhibitor at estradiol receptor –Nonsteroidal agent –Rx. Advanced breast cancer –SE : hot flushes, nausea, vomiting F Ketoconazole –Inhibitor : glucocorticoid & androgen synthesis (adrenal)

Antiprogestin F Mifepristone (RU 486) –Potent competitive inhibitors : progesterone receptors –Terminate early pregnancy –Major adverse effect : prolong bleeding F Clomiphene –Weak estrogenic –Competitive inhibitor : endogenous estrogen –Ovulation-inducing agent

Antiprogestin F Danazol –Weak progestational, androgenic activities –Rx. Endometriosis –Major adverse effects : weight gain, hot flushes