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Estrogen. Natural estrogens : Estradiol, Estrone and Estriol.Synthetic Steroidal : Ethinyl Estradiol, Mestranol.Synthetic Non-steroidal : Diethylstilbestrol, Dienestrol.. Estrogen. Physiological actions of estrogen :Estrogens ? the synthesis of II, VII, IX, X, fibrinogen and ? anti-thrombin.Estr

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gonadal hormones
Gonadal hormones

The three sex hormones are estrogen, progesterone and testosterone

estrogen
Estrogen
  • Natural estrogens : Estradiol, Estrone and Estriol.
  • Synthetic Steroidal: Ethinyl Estradiol, Mestranol.
  • Synthetic Non-steroidal : Diethylstilbestrol, Dienestrol.
estrogen3
Estrogen

Physiological actions of estrogen :

  • Estrogens ↑the synthesis of II, VII, IX, X, fibrinogen and ↓ anti-thrombin.
  • Estrogen – continuous exposure leads to hyperplasia of endometrium.
  • It decrease the LDL and increase HDL.
estrogen4
Estrogen

Physiological actions of estrogens :

  • Estrogen sensitizes the myometrium to oxytocin at term and facilitates labor.
  • Estrogen decrease the resorption of bone.
estrogen5
Estrogen

Indications of Estrogens :

  • Hypogonadism in girls.
  • Hormonal replacement therapy
  • Contraception
  • Osteoporosis
  • Prostate carcinoma
  • Turner's syndrome (Gonadal dysgenesis).
estrogen6
Estrogen

Adverse Effects :

  • Gall stones and pulmonary embolism.
  • ↑ the risk of endometrial and breast cancer.
  • DES during pregnancy increase vaginal adenocarcinoma in female offspring.
selective estrogen receptor modulator serm
Selective Estrogen Receptor Modulator(SERM)

Clomiphene:

  • It acts by inhibiting the action of estrogen on the hypothalamus / pituitary gland.
  • It ↓ the negative feedback of estrogen on hypothalamus / pituitary and ↑FSH / LH secretion.
  • Used as ovulation inducing drug.
  • Adverse effects – multiple pregnancy.
selective estrogen receptor modulator serm8
Selective Estrogen Receptor Modulator(SERM)

Tamoxifen : It is a partial agonist at estrogen receptor.

  • Agonist on bone and lipid metabolism.
  • Antagonist on breast.
  • Used in advanced breast cancer in postmenopausal women.
  • Partial agonist on endometrium can cause endometrial cancer.
selective estrogen receptor modulator serm9
Selective Estrogen Receptor Modulator (SERM)

Raloxifene:

  • Agonist on bone and lipid metabolism.
  • Antagonist on endometrium and breast.
  • Does not cause endometrial cancer.
  • It is used for the prevention of post menopausal osteoporosis.
aromatase inhibitor
Aromatase inhibitor

Anastrozole is a selective inhibitor of aromatase and thus ↓estrogen synthesis.

  • Used in post menopausal breast cancer resistant to tamoxifen.

Anastrozole

progestins
Progestins
  • First generation: Norethindrone, Ethynodiol diacetate.
  • Second generation: Levonorgestrel,Norgestrel.
  • Third generation: Desogestrel, Norgestimate.
  • Fourth generation: Drospirenone.
progestins12
Progestins

Clinical uses :

  • Hormonal replacement therapy
  • Contraception

Adverse effects :

  • Breakthrough bleeding
  • Hirsutism and acne (androgenic)
  • Abnormal lipid and glucose levels.
antiprogestins
Antiprogestins

Mifepristone:

  • It is a progesterone receptor antagonist. It is also a glucocorticoid receptor antagonist.
  • If mifepristone is taken shortly after intercourse, it prevents pregnancy.
  • Mifepristone is widely used to terminate early pregnancy.
hormonal contraceptives
Hormonal contraceptives

They are of two types :

  • Estrogen and Progestin
  • Progestin Only

These exert the contraceptive effect mainly

through selective inhibition of gonadotropin

release from the pituitary, especially

midcycle LH surge.

hormonal contraceptives15
Hormonal contraceptives

Contents of oral contraceptives:

  • Estrogen:Ethinly estradiol (EE), Mestranol
  • Progesterone: Norethindrone, Norgestrel, Levonorgestrel, Desogestrel, Drospirenone.
hormonal contraceptives16
Hormonal contraceptives

Oral contraceptives are classified as

monophasic, biphasic and triphasic depending

upon the estrogen and progestin content.

  • Monophasic

They contain same amount of estrogen and

progestin throughout the cycle.

  • Biphasic and Triphasic

These contain variable amount of estrogen

and progesterone in phases.

hormonal contraceptives18
Hormonal contraceptives

Benefits of oral contraceptives :

  • Decrease risk of endometrial and ovarian cancer.
  • Decrease risk of endometriosis.
  • Reduced incidence of pelvic inflammatory disease.
  • Decrease osteoporosis.
hormonal contraceptives19
Hormonal contraceptives

Progesterone only: Mini pills :

  • Norethindrone (Nor-QD)orally.
  • Levonorgesterol implanted under the skin.
  • Medroxyprogesterone depot injection.
  • IUD of progesterone.
hormonal contraceptives20
Hormonal contraceptives

Progesterone Only:

  • MDPA (Depo-Provera) depot injection will provide effective contraception for upto 3 months.
  • Levonorgestrel subcutaneous implant are effective for ~ 5 yrs.
  • They are suited for women who smoke and estrogen contraindicated.
  • Failure rates are high.
hormonal contraceptives21
Hormonal contraceptives

Postcoital contraception :"morning-after pill"

  • Oral levonorgestrel: within 120 hours for best results.
  • Estrogens and Progestins : It is started within 72 hrs for best results.
  • Mifepristone is effective as postcoital contraception along with misopristol (PGE1).
androgens testosterone
Androgens Testosterone
  • Testosterone is responsible for normal development of male fetus, changes in male at puberty and also to maintain fertility and libido.
  • Testosterone and related androgens are produced by the testes, adrenal gland and ovary.
slide24
adipose tissue

5  reductase

androgens testosterone25
Androgens Testosterone
  • It is given i.m or transdermally to avoid extensive hepatic metabolism.
  • Testosterone cypionate is available for intramuscular administration.
  • Methyltestosterone is active orally and resistant to hepatic metabolism, but can result in hepatoxicity.
synthetic androgens
Synthetic Androgens

Danazol : It is a weak androgen, derivative of testosterone which has anti-estrogenic activity.

  • Primarily used in endometriosis and fibrocystic breast disease.
  • It is also used in the treatment of hereditary angioedema (↑C-1 esterase inhibitor).
androgens
Androgens

Clinical uses :

  • Hypogonadism.
  • Endometriosis.
  • Anemia.
  • Osteoporosis.
  • Aging.
androgens29
Androgens

Adverse effects :

  • Hirsutism, acne, deepening of voice.
  • Cholestatic jaundice.

Contraindications :

  • Pregnancy.
  • Prostate cancer.
anti androgens
Anti-androgens

There are different types of anti-androgens

  • Androgen receptor antagonist
  • GnRH analogs
  • Androgen synthesis inhibitors Ketoconazole
anti androgens32
Anti-Androgens

GnRH agonist

  • GnRH agonists initially ↑ FSH and LH secretion "flare effect". However, after about two weeks, a profound hypogonadal effect is achieved through receptor down regulation.
  • Goserelin Zoladex, Buserelin
  • Used for prostate cancer and male baldness
anti androgens33
Anti-androgens

Finasteride :

  • Orally active and inhibits 5-α-reductase -IIenzyme producing a reduction of dihydrotestosterone in prostate and skin.
  • Dihydrotestosterone is an important androgen in the prostate.
  • It is approved for treatment of benign hypertrophy of prostate.
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