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Gonadal hormones. The three sex hormones are estrogen, progesterone and testosterone. Estrogen. Natural estrogens : Estradiol, Estrone and Estriol. Synthetic Steroidal : Ethinyl Estradiol, Mestranol. Synthetic Non-steroidal : Diethylstilbestrol, Dienestrol. Estrogen.

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Gonadal hormones

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Gonadal hormones l.jpg

Gonadal hormones

The three sex hormones are estrogen, progesterone and testosterone


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Estrogen

  • Natural estrogens : Estradiol, Estrone and Estriol.

  • Synthetic Steroidal: Ethinyl Estradiol, Mestranol.

  • Synthetic Non-steroidal : Diethylstilbestrol, Dienestrol.


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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.


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Estrogen

Physiological actions of estrogens :

  • Estrogen sensitizes the myometrium to oxytocin at term and facilitates labor.

  • Estrogen decrease the resorption of bone.


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Estrogen

Indications of Estrogens :

  • Hypogonadism in girls.

  • Hormonal replacement therapy

  • Contraception

  • Osteoporosis

  • Prostate carcinoma

  • Turner's syndrome (Gonadal dysgenesis).


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Estrogen

Adverse Effects :

  • Gall stones and pulmonary embolism.

  • ↑ the risk of endometrial and breast cancer.

  • DES during pregnancy increase vaginal adenocarcinoma in female offspring.


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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.


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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.


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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.


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Aromatase inhibitor

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

  • Used in post menopausal breast cancer resistant to tamoxifen.

Anastrozole


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Progestins

  • First generation: Norethindrone, Ethynodiol diacetate.

  • Second generation: Levonorgestrel,Norgestrel.

  • Third generation: Desogestrel, Norgestimate.

  • Fourth generation: Drospirenone.


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Progestins

Clinical uses :

  • Hormonal replacement therapy

  • Contraception

    Adverse effects :

  • Breakthrough bleeding

  • Hirsutism and acne (androgenic)

  • Abnormal lipid and glucose levels.


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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.


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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.


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Hormonal contraceptives

Contents of oral contraceptives:

  • Estrogen:Ethinly estradiol (EE), Mestranol

  • Progesterone: Norethindrone, Norgestrel, Levonorgestrel, Desogestrel, Drospirenone.


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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.


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Hormonal contraceptives


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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.


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Hormonal contraceptives

Progesterone only: Mini pills :

  • Norethindrone (Nor-QD)orally.

  • Levonorgesterol implanted under the skin.

  • Medroxyprogesterone depot injection.

  • IUD of progesterone.


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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.


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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).


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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.


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Androgens Testosterone


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adipose tissue

5  reductase


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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.


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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).


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Synthetic androgens


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Androgens

Clinical uses :

  • Hypogonadism.

  • Endometriosis.

  • Anemia.

  • Osteoporosis.

  • Aging.


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Androgens

Adverse effects :

  • Hirsutism, acne, deepening of voice.

  • Cholestatic jaundice.

    Contraindications :

  • Pregnancy.

  • Prostate cancer.


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Anti-androgens

There are different types of anti-androgens

  • Androgen receptor antagonist

  • GnRH analogs

  • Androgen synthesis inhibitors Ketoconazole


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Anti-androgens


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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


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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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