1. Female sex hormones

2. Gonadotropin releasing hormone (GnRH)
Released in “pulsalite manner” from the hypothalamus and acts on Pituitary to stimulate the secretion of gonadotropins-
FSH & LH

3. 1. GnRH analogs A. Short-acting analogs Gonadorelin (t 1/2 = 4 min.)
It can be used in “Pulsatile” manner to stimulate pituitary to secrete FSH and LH.
Uses:
Diagnostic purpose
In infertility: Hypothalamic amenorrhea

4. B. Long-acting analogs
Goserelin, Nafarelin, Leuprolide
After initial stimulation, they will cause suppression of gonadotropin (FSH, LH) secretion. (down-regulation)
Therapeutic Uses:
For Medical castration:
In precocious puberty
Breast Ca
Prostate Ca
Leiomyoma
Endometriosis
Adverse effects:
Gonadal steroidal inhibition in females can cause: Hot flashes, Vaginal atrophy, Decreased bone density

5. 2. GnRH antagonist Ganirelix Cetrorelix
These are pure GnRH antagonists and do not cause initial increase in gonadotropin secretion.

6. 3. Gonadotropins: FSH & LH
Gonadotropin preparations:
Menotropins (LH + FSH)
Recombinant FSH and LH
hCG (Human chorionic gonadotropin)

7. Follicle-Stimulating Hormone (FSH)
Therapeutic uses:
Treatment of infertility caused by hypogonadism in both sexes.
To stimulate ovulation as a part of in-vitro fertilization (IVF) programs.
Side effects:
Hyperstimulation syndrome (enlarged ovaries, ascites, fever, embolism, etc.).
Multiple births.
Gynecomastia in men.

8. Human chorionic gonadotropin (hCG)
It is glycoprotein produced by the placenta
hCG can be used as LH substitute.
Therapeutic uses:
Treatment of infertility both sexes.
In females hCG is used as a part of invitro fertilization (IVF) programs to induce ovulation when mature follicles are present (ovulation occurs 36-40hrs from injection).
HCG injections are used to stimulate the Leydig cells to synthesize testosterone.
Treatment hypogonadism
Treatment of undescended testes (cryptorchidism)

9. 4. Estrogens Physiological Role:
Development of genital tract and breast.
Secondary sex characters. Menstrual cycle
During follicular phase it cause endometrium to grow
Metabolic effects:
Increase bone mass and prevent bone resorption.
Increase blood glucose.
Increase serum TGs and decrease cholesterol.
Salt and water retention.
Increase blood coagulation and platelet adhesiveness.

10. Types of estrogen Natural estrogens Estradiol Estriol Estrone
Synthetic estrogens
Ethinyl estradiol
Routes of adminstration
Oral IM
Transdermal

11. Uses of Estrogens:
Hormone Replacement therapy:
Primary hypogonadism
Premature ovarian failure; surgical removal of ovaries
Menopause
Oral contraception
Osteoporosis
Atrophic vaginitis

12. Adverse effects
Nausea, vomiting
Thromboembolic problems
Myocardial infarction
Breast Ca
Endometrial Ca
Postmenopausal uterine bleeding
Diethylstilbestrol: Clear cell Ca (cervical & vagina)

13. Prolonged administrations of estrogen  abnormal endometrial hyperplasia, abnormal bleeding patterns, associated with high incidence of endometrial cancer.
This can be prevented by administration of progesterone accompanies the estrogen.
Thus, women taking HRT must also take a progesterone unless they have had a hysterectomy.

14. 5. Selective estrogen receptor modulators (SERMs)
Tamoxifen, Raloxifene
These are drugs that interact with estrogen receptors but have different effects on different tissues.
They can show agonism or antagonism depending upon the tissue type.

15. A. Tamoxifen Antiestrogenic effect: on Breast
Effective in the treatment of breast Ca in patients with tumor cells that are estrogen receptor- positive.
can be given after surgery to eradicate micrometastases
Estrogenic effect: on Endometrium
Can cause endometrial Ca
Not prescribed to treat breast Ca for longer than 3-5 years in non-hysterectomized women

16. Adverse effects:
Nausea/Vomiting
Hot flashes
Vaginal bleeding
Risk of Endometrial Ca
Thromboembolic disorders

17. B. Raloxifene Antiestrogenic effect: Breast, Endometrium
Estrogenic effect: Bones, lipid metabolism
Unlike Tamoxifen, it does not increase the risk of endometrial Ca.
Approved to be used for the prevention of osteoporosis in postmenopausal women

18. 6. Estrogen antagonists Clomiphene (Ovulation inducer):
It blocks estrogen receptors in the hypothalamus and anterior pituitary so reduces negative feedback
↑ FSH and LH secretion leads to ovarian follicle development and ovulation
Side effects include; Multiple pregnancies, Enlarged cystic ovaries.
Used for Inadequate ovulation or low sperm count in males

19. 7. Aromatase inhibitors
Anastrozole : non-steroidal agents; competitive inhibitors
Exemestane : steroidal agent; irreversible inhibitor
Estriol
Estrone
Estradiol

20. Mechanism of action:
Aromatase inhibitors block the synthesis of estrogens from androgen precursors by inhibiting aromatase enzyme.
Uses:
it can be used to inhibit the growth of estrogen-dependent tumors e.g., breast cancer.
Used in postmenopausal women with advanced breast cancer. Unlike tamoxifen, they DO NOT increase the risk of endometrial carcinoma or venous thromboembolism.
Endometriosis

21. 8. Progestins
The physiological role of progesterone is maintenance of pregnancy
Progestins are often combined with estrogen in various formulations to counteract the harmful effects of estrogens (Estrogen can cause endometrial carcinoma)

22. Types Progestins:
Natural progestins:
Progesterone, 17-alpha hydroxyprogesterone
Synthetic progestins:
Medroxyprogesterone (Oral-daily, IM every 1-3 month)
Norgestrel, Levonorgestrel
Norgestimate (less androgenic)
Desogestrel (less androgenic)

23. Uses:
As contraceptive and menopausal hormone therapy
Combined with estrogen (in COCPs & menopausal hormonal therapy)
Progestin only contraceptive preparations
As post coital contraception
Dysmenorrhea
Dysfunctional uterine bleeding
Endometriosis

24. Adverse effects:
Edema
Depression
Breakthrough bleeding
ADRs of progestins having Androgen-like activity:
Increase the ratio of LDL to HDL cholesterol
Thrombophlebitis
Pulmonary embolism
Acne
Hirsutism
Weight gain
Liver dysfunction

25. 9. Progesterone antagonist
Mifepristone:
Progesterone receptor antagonist
Glucocorticoid receptor antagonist
Therapeutic uses:
Medical termination of pregnancy
(Mifepristone followed 48 hrs later by Misoprostol)

26. Infertility Clomifene Safest & cheapest , Antiestrogens Gonadotropins
Used in women with hypopituitarism or do not respond to clomifene therapy.
Treatment starts with daily injection of menotrophin (LH = FSH ) or (FSH), followed by 1-2 large doses of chorionic gonadotropin (mostly LH) to induce ovulation.
Adverse Effects: Multiple births, Ovarian hyperstimulation syndrome (OHSS), Bleeding, Low birth weight, Birth defects
In men with hypogonadism, both LH and FSH are given to stimulate spermatogenesis and androgen release.

27. Bromocriptine
Dopamine agonist that inhibits prolactin release
GnRH releasing hormone (Gn-RH) analogs
Aromatase inhibitors
Metformin (Polycystic ovary syndrome)

28. Drugs affecting uterine smooth muscle
1.Stimulatants of uterus
Include Oxytocin, Ergot alkaloid, Prostaglandins
A. Oxytocin
Enhances uterine contraction
Adverse Effects: Uterine rupture, fetal hypoxia or trauma, hypertension, CVA.
Uses: Post-partum hemorrhage, induce and maintain labor.

29. B. Ergot alkaloid :
Ergometrine, Methylergometrine
Effects:
Contract uterus
Vasoconstriction: Damage vascular endothelial cells at high dose can lead to dry gangrene of the extremities after long term use.
Uses:
Postpartum hemorrhage
To enhance the delivery of the placenta.
Migraine

30. Adverse effects
GI disturbances: diarrhea, nausea, and vomiting prolonged vasospasm
Contraindications
Cerebrovascular diseases; pregnancy

31. C. Prostaglandins
Dinoprostone，(PGE2）
Dinoprost and carboprost (PGF2）
Used in
Medical abortion: combined with mifepristone
Induction of labor
Adverse effects
GI disturbances: nausea, vomiting and abdominal pain
Contraindications
Bronchial asthma; glaucoma

32. 2. Relaxants of uterus (tocolytics):
Ritodrine, Terbutaline, Salbuterol, Magnesium sulfate, nifedipine
Used to delay Premature birth or preterm labor
Ritodrine
Selective β2 adrenergic receptor agonist that relaxes uterus
Used in preterm labor
Adverse Effects: palpitations, tachycardia

33. Good luck