SEX HORMONES ผศ . พญ . มาลียา

มโนรถ

Sex Hormones

21 carbon : progestin 19 carbon : androgen 18 carbon : estrogen

Hypothalamus

Anterior pituitary

FSH LH

Follicle Corpus luteum

Estrogen Progesterone

Testis

Testosterone

EstrogenEstrogenEstrogenic 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 E2 : SHBG (sex hormone binding glo

bulin) Free fraction : physiologic active Metabolism : liver + other tissues (e

nterohepatic circulatin) Breast milk : small amount

Physiologic Effects

Maturation of genital organ Secondary sex characteristics Breast stromal development Menstrual cycle Coagulability of blood factors II, VII, IX, X Plasma lipids : ญHDL, slight ญLDL

Contraindication

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

Clinical Uses

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

Adverse Reactions

Post menopausal bleeding Nausea & breast tenderness Hyperpigmentation ญ frequency : migraine headache Cholestasis & gall bladder disease, hyperten

sion

ProgesteroneProgesterone Synthesized : ovary, placenta–follicular phase : 0.03 g/dL

–Luteal phase : 0.5 - >2 g/dL

–[Synthetic & natural progestational agents are called progestins]

Metabolized : liver

Physiological Effects

Marked : carbohydrate metabolismEndometrium : maturation & secreto

ry changesEndocervical gland : scant viscid mat

erial

Adverse Reaction

ญ HDLญ incidence of atherosclerosis

Clinical Uses Hormonal contraception Dysmenorrhea Precocious puberty Diagnostic use

AndrogenAndrogen Testosterone 20 sex characteristic Inactivated : liver

Clinical Uses

Androgen replacement therapy (man)

Gynecologic disorders Anemia Use as protein anabolic agents Osteoporosis

Anabolic SteroidsAnabolic SteroidsTestosterone derivatives relatively more anabolic

(building) effects Action : ญ synthesis of anabolic

proteins

Adverse Reactions

Musculinizing actions (woman, prepubertal children)

Sodium retention & edema Hepatic dysfunction Cholestatic jaundice Prostatic hyperplasia

AntiandrogensAntiandrogensSpironolactone–Competitive inhibitor of aldosterone–Rx. Hirsutism in woman

Flutamide– Potent antiandrogen–Rx. Prostatic carcinoma– SE : mild gynecomastia

AntiestrogenAntiestrogen

Tamoxifen–Competitive inhibitor at estradiol receptor–Nonsteroidal agent–Rx. Advanced breast cancer– SE : hot flushes, nausea, vomiting

Ketoconazole– Inhibitor : glucocorticoid & androgen synth

esis (adrenal)

AntiprogestinAntiprogestin

Mifepristone (RU 486)– Potent competitive inhibitors : progesterone receptors– Terminate early pregnancy–Major adverse effect : prolong bleeding

Clomiphene–Weak estrogenic–Competitive inhibitor : endogenous estrogen–Ovulation-inducing agent

AntiprogestinAntiprogestin

Danazol–Weak progestational, androgenic activities

–Rx. Endometriosis

–Major adverse effects : weight gain, hot flushes