1. ESTROGENS AND ANDROGENS

2. Estrogens Natural: Estradiol, estrone & estriol
Conjugated: premarin (estrone and equillin)
Steroidal synthetic: Mestranol & Ethinyl estradiol
Non-steroidal synthetic: Diethylstilbesterol
Rationale for synthetic: to ↑ oral-bioavailability, half-life and ↑ feedback inhibition on FSH & LH

3. Estradiol – Transdermal patch, IM
Oral – Premarin ( Estrone + Equilin) , Estinyl estradiol , Mestranol
Excretion - Renal

4. Estrogens: Clinical Uses
Contraception: ↓ feedback release of gonadotropins
Female Hypogonadism (estrogen + progestin) or ovarian failure
Estrogens for hormone replacement therapy in menopausal women to ↓ bone resorption
Uterine bleeding
Dysmenorrhea
Men with androgen dependent prostate cancer to slow the growth of the cancer cell.

5. Endometrial hyperplasia Increased skin pigmentation
SIDE EFFECT:
Nausea
Breast tenderness
Endometrial hyperplasia
Increased skin pigmentation
Increased blood coagulation at high doses
Increased risk of endometrial cancer unless progestin is added
Breakthrough bleeding
DES clear cell adenocarcinoma of vagina in females exposed to DES in utero.
Estrogen increases melanin
Increase factor 2, 7, 9 & 10 as well as decrease antithrombin III

6. Contraindicated Patients:
With estrogen-dependent neoplasm (e.g. endometrial carcinoma)
At higher risk for or with breast carcinoma that are estrogen dependent
Predisposed to thromboembolic disease

7. SELECTIVE ESTROGEN RECEPTOR MODULATOR (SERMS)
Are non-steroidal compounds that bind to estrogen receptors.
They can act as either agonist, partial agonists and antagonists depending on the tissue

8. Tamoxifene:
Has various actions depending on the tissue
Bone: agonist to prevent bone resorption
Breast: antagonist
Endometrium: a partial agonist with the risk of increasing endometrial cancer
USES: estrogen dependent breast cancer
SE: Hot flushes, nausea and vomiting

9. Raloxifene Bone: agonist Uterus and breast: antagonist
USES: prophylaxis of postmenopausal osteoporosis.
SE: increased risk of DVT, pulmonary embolism

10. Clomiphene MOA: ↓ feedback inhibition→ ↑FSH and LH
USE: for infertility caused by anovulatory cycle such as those seen in patients with PCOS
Side effect: multiple pregnancies, ovarian enlargement

11. ANTI ESTROGENS Anastrozole:
MOA: is an aromatase inhibitor, resulting in decreased estrogen synthesis
USE: estrogen-dependent postmenopausal breast cancer.

12. Progestin's Progestins can be androgenic and antiestrogenic in action
Progesterone: major natural progesterone
Medroxyprogesterone
Norethindrone
17α-Hydroxyprogesterone
Norgestrel
Desogestrel: devoid of androgenic and antiestrogenic actions

13. Clinical Uses: Progestins
Major uses:
hormone contraception : ↑ feedback inhibition esp LH → no ovulation
hormone replacement treatment along with estrogen to decrease endometrial cancer
dysmenorrhea

14. Adverse Effects: Progestins
reduce plasma HDL ↑LDL
Breakthrough bleeding
Acne, weight gain and hirsutism (androgenic effect)

15. ANTIPROGESTIN Mifepristone (RU-486):
Used as an abortifacient, administered with misoprostol (PGE₁)
Also an antiglucocorticoid
SIDE EFFECT: bleeding, GI effects(nausea, vomiting) and abdominal pain

16. Hormonal Contraception
Progestins (Mini pill) only (norethindrone or norgestrel)
Estrogens and progestins (combination pills)
Progestin implants
Post-coital contraception uses estrogen (mestranol or etinyl estradiol)
Mechanism of Action: contraception
ovulation-inhibition by suppressing gonadotropins
change in cervical mucus(progesterone)

17. Drug interaction: p450 inducers ↓ contraceptive effectiveness
Can result in unwanted pregnancies

18. Combined oral contraceptive pill
ADVANTAGE
DISADVANTAGE
Reliable (<1% failure)
Taken daily
↓ risk of endometrial and ovarian cancer
No protection against STDs
↓ pelvic infections
↑ triglycerides
↓ risk of osteoporosis
Depression, weight gain, nausea, hypertension
No dysmenorrhea
Hypercoagulable state

19. SIDE EFFECTS ESTROGENS: Nausea Bloating Headache Mastalgia
Increase skin pigmentation
Weight gain
Breakthrough bleeding
Withdrawal bleeding

20. PROGESTIN:
Weight gain
Hirsutism
Acne
Increase LDL

21. Adverse Effects of combined ocps
Venous Thromboembolic Disease
breakthrough bleeding
Withdrawal bleeding
RISK FACTORS: Smoking, Increased age

22. ANDROGENS Testosterone - Cypionate, Enanthate,Propionate
dihydrotestosterone
Fluoxymesterone
Danazol
androstenedione
Nandrolone

23. USES:
Male hypogonadism
For anabolic actions to increase muscle mass
Illicit use in athletes

24. Replacement therapy in men
Acne
excessive libido & erections,
increased muscle & bone mass,
aggravation of pre existing prostate cancer.
  Reduce plasma HDL and increase LDL

25. Gynecological Disorders: Androgens
Danazol
used in the treatment of endometriosis which is the growth of endometrial tissue outside the uterus, especially in the pelvis.

26. SIDE EFFECTS OF ANDROGENS
SE:
Excessive masculinization
Premature closure of epiphysis
Aggression
Dependence and abuse
Depression of menses and hirsutism in women

28. Contraindications: Androgenic Steroids
Pregnant women: its teratogenic
Children Androgens - Not used in children
Men with prostatic carcinoma

29. Anti-Androgen
Cyproterone acetate
Flutamide
Finasteride

30. Androgen Suppression & Antiandrogens
Symptomatic Management of prostatic carcinoma
Management of BPH

31. Antiandrogens Finasteride: Inhibits 5 alpha reductase
Conversion Inhibitors
Finasteride:
Inhibits 5 alpha reductase
decreases dihydrotestosterone levels in the prostate
Uses – BPH to reduce the size of the prostate and male pattern baldness
Has been replaced by α1 blockers in the symptomatic treatment of BPH
DHT causes hair loss and prostate enlargement

32. Antiandrogens Competitive androgenic Receptor Inhibitors:
Cyproterone & Cyproterone acetate
Clinical use:
Women - hirsutism
Men - reduction of sexual drive

33. Antiandrogens Flutamide Competitive inhibitor of androgens
Used in androgen receptor positive Prostatic Carcinoma
Testosterone causes the cancer cell to grow more rapidly

34. Bicalutamide
Effective orally for the treatment of metastatic prostatic cancer.