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Pharmacology of sex hormons
- 1. Slide ( 1/ 48 ) Dalia K. Zaafar Lecturer of Pharmacology
- 2. Slide ( 2/ 48 ) Female sex hormones • In females, the ovaries and adrenal glands are the main producers of sex hormones. • Female sex hormones include estrogen, progesterone, and small quantities of testosterone. Sex hormones
- 3. Slide ( 3/ 48 ) Regulation of menstrual cycle Sex hormones
- 4. Slide ( 4/ 48 ) Pharmacological action of Estrogens • Required for normal sexual maturation & growth of female • Stimulate development of vagina, uterus & uterine tubes as well as secondary sex characteristics • Stimulate stromal development & ductal growth in breast • Responsible for accelerated growth phase Estrogens
- 5. Slide ( 5/ 48 ) Pharmacological action of Estrogens • Epiphysial closure of long bones at puberty • Distribution of body fat alteration to produce typical female body shape • ↓ rate of resorption of bone by antagonizing effects of parathyroid hormone • stimulate adipose tissue production Estrogens
- 6. Slide ( 6/ 48 ) Pharmacological action of Estrogens • ↑ in high density lipoproteins (HDL) ↓ in low-density lipoproteins (LDL) • ↓ in total plasma cholesterol levels • Plasma triglyceride levels are ↑ • ↓ Platelet adhesiveness Estrogens
- 7. Slide ( 7/ 48 ) Types of Estrogens Estrogens Estrogens Natural Synthetic Estradiol Estrone Estriol Steroidal Non- steroidal Ethinyl estradiol Diethylstilb esterol
- 8. Slide ( 8/ 48 ) Estrogen Receptors • There are two types of Estrogen receptors which are tissue specific ERα and ERβ • ERα is found endometrium, breast, hypothalamus and blood vessels • ERβ is found in prostate gland in, ovaries, brain and heart cells Estrogens
- 9. Slide ( 9/ 48 ) I-Selective Estrogen Receptor Modulators (SERMs) • They are drugs with tissue selective actions • Estrogenic action in some tissue and non estrogenic action in some other tissue • mixed agonists/antagonists • Examples: Clomiphene, Tamoxifen and Raloxifene Anti-estrogens
- 10. Slide ( 10/ 48 ) Selective Estrogen Receptor Modulators (SERMs) Anti-estrogens
- 11. Slide ( 11/ 48 ) Clomiphene • Binds to both ERα & ERß & acts as a pure estrogen antagonist in all human tissues • Induces Gn secretion in women by blocking estrogenic feedback inhibition of pituitary gland • Consequently, ovaries enlarge & ovulation occurs • Used in ttt of infertility due to ovulation failure Anti-estrogens
- 12. Slide ( 12/ 48 ) Tamoxifen • Binds to both ERα & ERβ • acts as an estrogen agonist on bone and lipid metabolism • Act as a partial agonist on endometrium • Act as an antagonist on breast cells and so can be used in treatment of advanced breast cancer in postmenopausal patients Anti-estrogens
- 13. Slide ( 13/ 48 ) Tamoxifen Anti-estrogens
- 14. Slide ( 14/ 48 ) Raloxifene • Binds to both ERα & ERβ • acts as a estrogen agonist in bone and lipid metabolism • Antagonist on endometrium and breast • Used in post menopausal osteoporosis Anti-estrogens
- 15. Slide ( 15/ 48 ) II- Aromatase Inhibitors • Anastrozole • Selective inhibitor of aromatase enzyme • Decrease estrogen synthesis • Used in treatment of breast cancer in post menopausal patients resistant to tamoxifen Anti-estrogens
- 16. Slide ( 16/ 48 ) Progesterone • A natural steroidal hormone • Precursor to estrogens, androgens & adrenocortical steroids • Secreted by the corpus luteum and the placenta Progesterone
- 17. Slide ( 17/ 48 ) Progesterone • Rapidly absorbed following administration by any route • Half-life in plasma 5 minutes • Completely metabolized by liver ineffective when administered orally • High-dose oral micronized progesterone preparations have been developed that provide adequate effect Progesterone
- 18. Slide ( 18/ 48 ) Synthetic progestin • A number of synthetic progestin with high oral activity has been produced. norethisterone, levonorgestrel, norgestrel, desogestrel Progesterone
- 19. Slide ( 19/ 48 ) Uses of Progesterone • Hormone replacement therapy & hormonal contraception • Dysmenorrhea endometriosis & bleeding disorders Progesterone
- 20. Slide ( 20/ 48 ) Anti-progestin (Mifepristone) • binds strongly to progesterone receptor & inhibits activity of progesterone • Major use terminate early pregnancies • used in treatment of endometriosis, breast cancer & other neoplasms that contain glucocorticoid or progesterone receptors Progesterone
- 21. Slide ( 21/ 48 ) Hormonal Contraceptives • Hormonal preparations used for reversible suppression of fertility receptor & inhibits activity of estrogen and progesterone • They can be used in improvement of menstrual cycle regularity, decrease risk of endometriosis and management of perimenopause Contraceptives
- 22. Slide ( 22/ 48 ) Oral contraceptive pills (Combined pills) • Monophasic pills Each tablet contain a fixed concentration of both estrogen and progestin • Biphasic pills Each tablet contain a fixed amount of estrogen and but the amount of progestin increases in the second half of the cycle Contraceptives
- 23. Slide ( 23/ 48 ) Oral contraceptive pills (Combined pills) • Triphasic pills Introduced to permit reduction in total steroid dose without compromising efficacy • mimic normal hormonal pattern in a menstrual cycle • Estrogen dose is constant (or varied slightly) while amount of progestin is low in first phase & is progressively higher in second & third phases Contraceptives
- 24. Slide ( 24/ 48 ) Oral contraceptive pills (Combined pills) • Combined pills are taken for 21 consecutive days followed by 7 pill free days causing a withdrawal bleed Contraceptives
- 25. Slide ( 25/ 48 ) Oral contraceptive pills (Combined pills) • MOA: Estrogen inhibits secretion of FSH by -ve feedback……. Suppress the development of ovarian follicle • Progestin inhibits secretion of LH…… Prevent ovulation • Both estrogen and progestin alter the endometrium in a way to discourage implantation Contraceptives
- 26. Slide ( 26/ 48 ) Oral contraceptive pills (Combined pills) • Common adverse effects • Weight gain (due to fluid retention or anabolic effect) • Nausea, depression, dizziness and irritability • Acne or increased pigmentation • Thromboembolism and hypertension Contraceptives
- 27. Slide ( 27/ 48 ) Oral contraceptive pills (Combined pills) • Contraindications • Thromboembolic& cerebrovascular disease • Moderate-to-severe hypertension and hyperlipidemia • Active liver disease • Suspected malignancy of genitals/ breast • Impending major surgery—to avoid excess risk of postoperative thromboembolism Contraceptives
- 28. Slide ( 28/ 48 ) Oral contraceptive pills (progestin only pills) • Progestins used: levonorgestrel, norethisterone. • Taken daily without interruption • Less reliable than combined pills • Used when estrogen is contraindicated Contraceptives
- 29. Slide ( 29/ 48 ) Pharmacokinetics • Ora contraceptives are metabolized by hepatic cytochrome p450 system • So any concomitant use of enzyme inducers may lead to contraceptive failure • Examples of these drugs: Carbamazepine, phenytoin, Griseofulvin and rifampicin Contraceptives
- 30. Slide ( 30/ 48 ) Injectable contraceptives • Depot medroxyprogesterone acetate (DMPA) 150 mg at 3-month intervals • Norethindrone (Norethisterone) enanthate (NEE) 200 mg at 2-month intervals • Highly effective • Given i.m as oily solution Contraceptives
- 31. Slide ( 31/ 48 ) Injectable contraceptives • Major limitations • Menstrual irregularities, excessive bleeding or amenorrhea are very common • Return of fertility may take 6–30 months after discontinuation • May cause permanent sterility Contraceptives
- 32. Slide ( 32/ 48 ) Testosterone • It is the male sex hormone which is responsible of the normal development in males at puberty and to maintain fertility and libido • Produced by testes, adrenal gland and ovary Androgens
- 33. Slide ( 33/ 48 ) Testosterone • Pharmacological action • Skeletal muscle growth stimulation • Acceleration of bone epiphysis closure • Stimulation of renal erythropoietin Androgens
- 34. Slide ( 34/ 48 ) Testosterone • Uses • Hypogonadism • Anemia • Osteoporosis Androgens
- 35. Slide ( 35/ 48 ) Testosterone • Pharmacokinetics • Due to extensive hepatic metabolism it is taken transdermally or i.m. • Methyltestosterone is resistant to hepatic metabolism so can be taken orally Androgens
- 36. Slide ( 36/ 48 ) Danazol • A synthetic steroid with antigonadotrophic and anti- estrogenic activities and some androgenic properties • used in the treatment of endometriosis and some benign breast disorders • Voice changes, hirsutism and acne are the main side effects Androgens
- 37. Slide ( 37/ 48 ) Types of anti-androgens • 1- Androgen receptor antagonist • Cyproterone acetate: active orally, with increased risk of liver toxicity and thromboembolic disease Anti-androgens
- 38. Slide ( 38/ 48 ) Types of anti-androgens • 2- GnRH agonist • GnRH agonists initially increase FSh and LH secretion “Flare effect”. After 2 weeks of administration a profound hypogonadal effect is achieved through receptor down regulation Anti-androgens
- 39. Slide ( 39/ 48 ) Types of anti-androgens • 2- GnRH agonist A- Goserelin: used for breast cancer B- Leuprolide: used for breast and prostate cancer C- Buserelin: used for prostate cancer and male baldness Anti-androgens
- 40. Slide ( 40/ 48 ) Types of anti-androgens • 3- Androgen synthesis inhibitor A- Finasteride • Used for hirsutism, male pattern baldness and benign prostatic hyperplasia • Taken orally • Inhibit the 5-α reductase II enzyme So inhibit the conversion of testosterone into DHT Anti-androgens
- 41. Slide ( 41/ 48 ) Types of anti-androgens • 3- Androgen synthesis inhibitor B- Ketoconazole • At high dosages it inhibits the conversion of cholesterol to testosterone and glucocorticoids • it can be used as a second-line treatment for advanced prostate cancer and in the treatment of Cushing’s syndrome Anti-androgens
- 42. Slide ( 42/ 48 )