Cairo University Faculty of Pharmacy Department of Pharmacology & Toxicology

1. Sex Hormones Cairo University Faculty of Pharmacy Department of Pharmacology & Toxicology Pharmacology III Practical Sessions

2. Regulation of secretion Hypothalamus Gn RH Anterior Pituitary FSH & LH - Gonads Sex Hormones

3. Hormones Pharma-III Practical I- Female sex hormones 1. Oestrogens

4. Hormones Pharma-III Practical Physiological actions of estrogen • Oestrogens are largely responsible for the normal maturation of the female changes that take place at puberty in girls and include: • Development of female sexual organs • Development of female secondary sexual characters • They are responsible for the accelerated growth phase and closing of the epiphses at puberty. • Estrogen also ↓ the rate of resorption of bones. • Psychological and emotional effects. Oestrogens play an important role in the femine behavior.

5. Hormones Pharma-III Practical • 2. Metabolic Effects: • Slight sodium and water retention. • ↓LDL and ↑HDL. 3. Effect on blood: Oestrogens enhance coagulation of blood. Exogenous estrogen On short term → enhance coagulation of blood On long term → liver dysfunction → decrease coagulation of blood 4. Effect on the pituitary gland: Relatively high doses of oestrogens inhibit the secretion of FSH & GnRF.

6. Hormones Pharma-III Practical 1. Replacement therapy in hypogonadism. 2. Hormone Replacement Therapy (HRT) after menopause to treat or prevent postmenopaual symptoms. 3. As component of oral contraceptives. 4. Prophylaxis from postcoital pregnancy. 5. Treatment of certain of prostatic carcinoma. 7. Acne.

7. Hormones Pharma-III Practical • These include nausea, vomiting, anorexia, thromboembolism, carbohydrate intolerance, & retention of salts & edema. • 2. When given to males, they cause feminization.

8. Hormones Pharma-III Practical 2. Anti-Oestrogens A- Clomiphene It competes with oestrogen for binding sites at the hypothalamic level. Indications: 1. Treatment of female infertility due to ovulatory failure. 2. Treatment of infertility in males with oligospermia.

9. Hormones Pharma-III Practical B- Tamoxifen It blocks estrogen receptors mainly peripherally e.g. in breast. Indications: Treatment of advanced oestrogen-dependent breast cancer.

10. Hormones Pharma-III Practical 3. Progesterone Physiological actions of progesterone • Preparation of the uterus for implantation of the fertilized ovum. • 2. It is essential for maintenance of the endometrium.

11. Hormones Pharma-III Practical 3. Progesterone causes relaxation of the myometrium. 4. Progesterone (relatively high dose) inhibits LH. 5. Progesterone has a thermogenic effect through the hypothalamus. 6. Progesterone causes the cervix to secrete thick, viscous cervical secretion. 7. It ↓ the rate of oocyst transport in the oviduct.

12. Hormones Pharma-III Practical • Treatment of amenorrhoea and functional uterine bleeding. • 2. Treatment of endometriosis. • 3 As a component of oral contraceptives. • 4. To postpone menstruation.

13. Hormones Pharma-III Practical 4. Antiprogesterone Mifepristone Progesterone antagonist [Abortifacient]

14. Hormones Pharma-III Practical II- Male sex hormones 1. Testosterone

15. Hormones Pharma-III Practical Physiological actions of progesterone • Effect during Embryonic life: • Androgens virilize the urogenital tract of the male embryo. • ii. Testosterone causes the testes to descend from the abdominal cavity into the scrotum in newly born infants

16. Hormones Pharma-III Practical 2. Effect at puberty: A- Androgens act to transform the body at puberty into a man. i. The sex organs increase in size. ii. Development of skeletal muscles and increase in physical vigor. iii. Development of male secondary sex characters: B- Effect on bones: Testosterone increases the rate of growth of bones at puberty and promotes epiphyseal closure. C- Effect on sebacious glands: D- Together with FSH, it stimulates spermatogenesis. E- Suppresses the secretion of LH. F- Testosterone promotes erythropoiesis. G- Anabolic effects.

17. Hormones Pharma-III Practical • Treatment of androgen deficiency as replacement therapy. • 2. Treatment of refractory anaemias. • 3. As anabolic, e g. nandrolone. • 4. In postmenopausal breast cancer.

18. Hormones Pharma-III Practical Adverse effects: • Liver damage. • 2. In children leads to short stature, and in females, acne and musculinization [Hirsutism]. • 4. In older males, prostatic hyperplasia.

19. Hormones Pharma-III Practical 2. Anabolic Steroids Nandrolone & Stanozol • Clinical Uses: • Debilitating & wasting conditions. • 2. Used by some athletes to ↑ strength & athletic performance.

20. Hormones Pharma-III Practical 3. Anti-Androgens Cyproterone • Clinical Uses: • Prostate carcinoma. • 2. Musculinization in females [Acne & hirsutism].

21. Hormones Pharma-III Practical 4. Drugs that inhibit 5α-Reductase Finasteride Clinical Uses: Used in benign prostatic hyperplasia

22. Contraceptives Steroid contraceptives Intrauterine device Spermicides Oral contraceptives Injectable steroids Subcutaneous implants Vaginal rings Hormones Pharma-III Practical

23. Hyperprolactinemia Causes 1-Prolactinoma -Macro-adenoma (Secreting, functioning tumors) >than 10 mm in diameter, prolactin > 200 ng/ml. -Micro-adenoma (may be Secreting or non functional tumors) <than 10 mm in diameter, prolactin < 200 ng/ml. Block the flow of dopamine from the brain. 2- Other pituitary tumors: Other tumors may block the flow of dopamine from the brain, which normally inhibits its prolactin-secreting cells. Such so-called "mixed" tumors, (acromegaly) or (Cushing's disease). These can also cause the pituitary to secrete more prolactin.

24. 3- 1ryhypothyrodism Hyperplasia of both thyrotrophs and lactotrophs as a response to TRH hypersecretion. The hyperplasia can result in significant enlargement of the pituitary. 4- Physiological (i.e., non-pathological) causes include: pregnancy, breastfeeding, and mental stress. 5- Medications SSRIs and MAOIs

25. Symptoms In male • - Erectile dysfunction • - Infertility • - Gynaecomastia In female - Anovulatory infertility. -A decrease in menstruation. or amenorrhoea - Galactorrhoea • -Headaches and eye problems (as double vision) caused by the enlarged pituitary pressing against the adjacent optic chiasm. • -Osteoprosis ??

26. Thank You