الاسم : سعد بن محمد نور بن محمد ولي الرقم الجامعي : 4350167

1. الاسم : سعد بن محمد نور بن محمد ولي الرقم الجامعي : 4350167 التخصص : معيد بكلية الصيدلة قسم الأدوية Pharmacology استخدام الحاسب لتقديم محاضرة في موضوع مختص بالبوربوينت

3. Umm Al-Qura UniversityFaculty Of PharmacyMedicinal Chemistry Department

4. Female Sex Hormones

5. Female sex hormones • After ovulation there are two probabilities • No pregnancy (no fertilization) → decline of hormones & menses • Pregnancy (fertilization) → ovary stop releasing hormones but • corpus luteum & placenta start their hormonal secretion • Sex hormones • Necessary for reproduction & developmentof secondary sex characters • All hormones are biosynthesized in bothsex butin female [estrogen & progesterone produced in large amounts] & in male [testosterone]

6. Estrogen • Female sex hormone produced by: • In female by ovary, adrenal cortex & placenta (pregnancy) • In male (small amounts produced by testes & adrenal cortex) • Physiological role: • Development of ♀ primary sex characters (ovary, uterus & vagina) • Development of ♀ secondary sex characters (breast, soft of skin & voice) • Induction of uterus • Activation of Ca precipitation in bones • Prevention of anginal attack? • ( mobilize circulating fats from blood to fat depot )

7. Synthesis of estrogen:

12. Semi-synthetic estrogen

13. Synthesis • Metabolism of ethinyl estradiol

14. Conjugated estrogen (equine estrogens) • Conjugated water soluble metabolite (exist as ionized salts) They are used as replacement therapyin menopause?? Because they have short duration & weak activity (attenuated), so can be used safely (avoid tumors) used alone or with progesterone • Na equillin (∆7 estrone) sulfate • Sodium 17-oxo-estra-1,3,5(10),7-tetraen-sulfate

15. Pharmcological uses of estrogen: Contraceptive (with progestins) Replacement therapy (menopause) ↓ severity of osteoporosis: (bone thinning) + exercise + nutrition In ttt of endometriosis, androgen dependant prostate cancer, breast cancer in menopause. • Side effects: Can stimulate breast cancer in certain premenopausal women, risk ↑ with long term estrogen therapy Non-cancer side effects: migraine, gallstone & nausea? ? Why its better to use contraceptive containing estrogen + progestins rather than estrogen alone (Progestins prevent or ↓ the risk for cancer formation)

16. Non-steroidal estrogen: DES: have estrogenic activity as estrogen • Uses: • DES & Fosfestrol: used in ttt of prostatic cancer transform has 10 times the activity of cis form?? Because trans isomer resemble more closely estradiol ? No longer used as replacement therapy in menopause Due to high incidence of uterine cancers in women Fosfestrol: Phosphate gp act as targetor for cancer cells

17. Dienestrol: Similar to DES but the two C2H5 gps replaced by two ethylidene gps Uses: Intravaginally for vaginal & urethral atrophy

18. Estrogen antagonist • Uses: (two purpose) As fertility drugs: Estradiol inhibit secretion of gonadotrophic hormone (LH & FSH) by feed back inhibition. Estrogen antagonist allow release of LH & FSH which stimulate ovulation 2. Antitumor: in estrogen dependant breast cancer

19. (why) • Because it has embedded estrogenic activity so it ↑HDL & ↓ LDL→ prophylaxis of angina & ↑ Ca deposition in bone • Assay: Non aqueous titration

20. Aromatase inhibitors • Inhibit Aromatase enzyme so block conversion of androgen → estrogen • They can so affect reproduction functions • Conversion of androgen to estrogen • Uses: Treatment of estrogen dependant cancers (e.g. breast cancer) Second line treatment after Tamoxifen

21. Aminoglutethimide • Not selective, reversible Competitive inhibitor • Aniline N interact with heme iron atom in Aromatase enzyme preventing binding to steroidal substrate

22. Progestins

23. Progestins Secreted by: Corpus luteum (ruptured follicles in ovary) & placenta (in pregnancy) • Physiological role • Inhibit uterus contraction (maintain pregnancy) • Prevent ovulation (during pregnancy) • Produce viscous cervical mucous(estrogen produces liquefiedalkaline mucous) • Excess progesterone → feed back inhibition of LH (contraception)

26. Therapeutic uses of progestins • Contraceptive (with or with out estrogen) • Prophylaxis & treatment of endometrial cancer (postmenopausal) • Habitual abortion & uterine bleeding • Pregnant derivatives Dydrogesterone (Duphastone ®) These changes in chemical structure causes Improved oral activity & chemical stability Lack of estrogenic, androgenic & mineralocorticoids properties • Uses: to maintain pregnancy does not inhibit ovulation (i.e no contraception)

27. Protection of ring D 17α-hydroxyprogesteron hexanoate (caproate) It is more active & longer duration > progesterone ???? Due to 17α-ester which hinder reduction of 20-one gp

28. Protection of ring D with changes in ring B Medroxyprogesterone acetate Highly active orally????? Due to C6 methyl gp → hinders 6- hydroxylation 17α-ester → hinders reduction of 20-one gp Depo-Provera: IM contraceptive for prolonged period (3-6monthes) Mechanism:increase viscosity of vaginal fluid → difficult in movement of sperms to fertile ovum

29. Contraceptive agents Mechanism: • Estrogens: inhibit LH & FSH (negative feed back mechanism) • Progestins: ↑ viscosity of vaginal fluid, hinder sperms movement & fertilization

30. Any Questions

32. Presented by: SaadNoorWali