Female Sex HormonesFemale Sex Hormones(Estrogens and (Estrogens and

Progestins)Progestins)

Control:Control: Follicle –Stimulating Hormone (FSH) Follicle –Stimulating Hormone (FSH) stimulate the production of Estrogens.stimulate the production of Estrogens.

Luteinizing Hormone (LH) stimulate the Luteinizing Hormone (LH) stimulate the production of Progestins.production of Progestins.

EstrogensEstrogens

Natural Estrogens:Natural Estrogens:

HO

OH

OH

HO

O

HO

OH

17-estradiol Estrone Estriol

HO

O

HO

OH

17-estradiol

Estrone

O

OH

Testosterone

O

O

AndrostenedioneO

Progesterone

O

HO

O

17-Hydroxypregnenolone

OH

HO

O

Pregnenolone

HO

Cholestrol

Biosynthesis of Female and Male sex Hormones

aromatase

Physiological EffectsPhysiological Effects Development of the female sexual organs.Development of the female sexual organs. Development of the female secondary sex characters.Development of the female secondary sex characters. Control of the menstrual cycle.Control of the menstrual cycle.

UsesUses Birth control pills.Birth control pills. Failure of ovarian development.Failure of ovarian development. Menstrual disturbances.Menstrual disturbances. Suppress lactation after birth.Suppress lactation after birth. Postmenopausal osteoporosis.Postmenopausal osteoporosis. Prostate cancer.Prostate cancer.

Side EffectsSide Effects Nausea, vomiting and diarrhea.Nausea, vomiting and diarrhea. Sodium and water retention.Sodium and water retention. Inhibition of ovulation in large doses.Inhibition of ovulation in large doses. Accelerate epiphyseal closure.Accelerate epiphyseal closure.

Structure Activity Structure Activity Relation Ships:Relation Ships:

Aromatic ring with C-3-OH is essential for Aromatic ring with C-3-OH is essential for activity.activity.

Steroidal structures is not essential for Steroidal structures is not essential for activity.activity.

Alkylation of the aromatic ring decrease the Alkylation of the aromatic ring decrease the activity.activity.

The 17The 17-hydroxyl with constant distance from -hydroxyl with constant distance from 3-OH is essential for activity.3-OH is essential for activity.

The group between the two hydroxyl must be The group between the two hydroxyl must be hydrophobic.hydrophobic.

Unsaturation of ring B decreases the activity.Unsaturation of ring B decreases the activity. 1717- and 16 position when modified enhance - and 16 position when modified enhance

the activity.the activity.

Steroidal Estrogenic Drugs:Steroidal Estrogenic Drugs: Estradiol:Estradiol:

Most active natural estrogen.Most active natural estrogen. Very short duration of action due to first pass metabolism.Very short duration of action due to first pass metabolism. Mainly used for local effect on the uterus.Mainly used for local effect on the uterus.

Ethinyl estradiol:Ethinyl estradiol: 15- 20 more potent than estradiol orally.15- 20 more potent than estradiol orally.

HO

OHC CH

HO

OH

17-estradiol Ethinyl estradiol(Stertoidal Semisynthetic estrogen)

Nonsteroidal EstrogensNonsteroidal Estrogens Diethylstilbesterol:Diethylstilbesterol:

The The transtrans form is the active one. form is the active one. Advantages:Advantages:

As active as Estradiol.As active as Estradiol. Longer duration of action.Longer duration of action. Orally activeOrally active Cheap.Cheap.

Disadvantages:Disadvantages: Increase the risk of uterine cancer.Increase the risk of uterine cancer.

Uses:Uses: Treatment of prostate cancer.Treatment of prostate cancer.

OH

HO

Xenoestrogens Xenoestrogens (Enviromental Estrogens)(Enviromental Estrogens)

Estrogenic compounds with weak activity Estrogenic compounds with weak activity present in food and drinks.present in food and drinks.

Isoflavones and comesterol derivatives present Isoflavones and comesterol derivatives present in family Leguminosae are examples of in family Leguminosae are examples of xenoestrogens.xenoestrogens.

O

OH

OH

HO

O

Genisten

O

OHO

O

Coumesterol

Estrogen AntagonistsEstrogen Antagonists Impeded Estrogens:Impeded Estrogens:

Steroids weakly bind to receptors.Steroids weakly bind to receptors. Can compete with estrogens when reach Can compete with estrogens when reach

receptors in high Concentration.receptors in high Concentration.

Triphenylethylene antagonists:Triphenylethylene antagonists: They are related to stilbene in structure.They are related to stilbene in structure. Antagonist bind strongly to the receptors.Antagonist bind strongly to the receptors.

Aromatase inhibitors:Aromatase inhibitors: Steroidal or nonsteroidal.Steroidal or nonsteroidal. Block conversion of androgens to estrogens.Block conversion of androgens to estrogens.

Uses:Uses: Treatment of estrogen Treatment of estrogen dependent cancers.dependent cancers.

ProgestinsProgestins Progesterone in the major natural Progesterone in the major natural

progestin.progestin. Secretion:Secretion: By the ovary mainly the corpus By the ovary mainly the corpus

luteum during the second half of the menstrual cycle.luteum during the second half of the menstrual cycle. Physiological Effects:Physiological Effects:

Development of the endometrium.Development of the endometrium. Development of the mammary gland during Development of the mammary gland during

pregnancy.pregnancy. Milk secretion stats when its level decrease Milk secretion stats when its level decrease

with birth.with birth. Thermogenic action.Thermogenic action.

O

O

Structure Activity Structure Activity Relation-ships:Relation-ships:

Steroidal nucleus essential for activity.Steroidal nucleus essential for activity. Have some androgenic activity.Have some androgenic activity. Removal of the 19 CHRemoval of the 19 CH33 increase activity. increase activity. Unsaturation of ring B or C increase the Unsaturation of ring B or C increase the

activity.activity. Removal of the keto function remove Removal of the keto function remove

androgenic activity.androgenic activity.

Progestrogenic DrugsProgestrogenic Drugs Lynestrenol:Lynestrenol:

Semisynthetic progestin with pure Semisynthetic progestin with pure progestrogenic activity.progestrogenic activity.

O

O

Progesterone(Natural)

OH

Lynesrenol(Synthetic)

C CH

Uses:Uses: Contraceptive pills.Contraceptive pills. Uterine bleeding.Uterine bleeding. Prevention of abortion.Prevention of abortion. Amenorrhea, dysmenorrhea, endometriosis.Amenorrhea, dysmenorrhea, endometriosis. Suppression of lactation.Suppression of lactation. Endometrial, renal and breast carcinoma.Endometrial, renal and breast carcinoma. Enhance respiration (for Hypoventilation).Enhance respiration (for Hypoventilation).

Side Effects:Side Effects:Nausea, vomiting, irregular bleeding, Nausea, vomiting, irregular bleeding,

edema, weight gain, breakthrough edema, weight gain, breakthrough bleeding, beast disconfort.bleeding, beast disconfort.

Progestin Progestin Antagonists:Antagonists:

Mifepristone:Mifepristone: Compete with the progestin receptors.Compete with the progestin receptors. Uses:Uses:

Contraceptive.Contraceptive. Abortifacient.Abortifacient.

Female Oral ContraceptiveFemale Oral Contraceptive Sequential Preparations:Sequential Preparations:

Estrogens for 16 days then Estrogen and Progesterone for Estrogens for 16 days then Estrogen and Progesterone for 5- 6 days.5- 6 days.

98- 99% successful.98- 99% successful.

Combination Preparation:Combination Preparation: Estrogens and Progesterone from the beginning to the end Estrogens and Progesterone from the beginning to the end

in small doses.in small doses. 99- 100% successful.99- 100% successful.

Mechanism: Mechanism: The above two types inhibit both FSH and The above two types inhibit both FSH and LH so prevent ovulation.LH so prevent ovulation.

Minipills:Minipills: Small doses of Progesterone from the beginning to the end.Small doses of Progesterone from the beginning to the end. 97- 98% successful.97- 98% successful.

Mechanism:Mechanism: Alter the structure of the Endometrium.Alter the structure of the Endometrium. Increase consistency of the cervical mucus.Increase consistency of the cervical mucus.

Side Effects (Due to Estrogens):Side Effects (Due to Estrogens):

Increase risk of breast, vaginal and uterine Increase risk of breast, vaginal and uterine cancers.cancers.

Increase risk of thromboembolic and Increase risk of thromboembolic and vascular problems.vascular problems.

Nausea, vomiting, headache, menstrual Nausea, vomiting, headache, menstrual disturbances and weight gain.disturbances and weight gain.

Male Sex HormonesMale Sex Hormones(Androgens)(Androgens)

Control:Control: Luteinizing Hormone (LH) or Interstatial Cell-Luteinizing Hormone (LH) or Interstatial Cell-

Stimulating Hormones (ICSH) stimulate the Stimulating Hormones (ICSH) stimulate the production of Androgens.production of Androgens.

Natural Androgens:Natural Androgens:

O

OH

Testosterone(Natural)

O

OH

Dihydrotestosterone(Natural)

H

Physiological EffectsPhysiological Effects Development of the male Phenotype during Development of the male Phenotype during

embryonic life.embryonic life. Development of the male sexual organs and male Development of the male sexual organs and male

secondary sex characters.secondary sex characters. Anabolic effect.Anabolic effect. Enhance growth and secretion of subaceous Enhance growth and secretion of subaceous

glands.glands.

Uses:Uses: Replacement therapy in cases of hypogonadism.Replacement therapy in cases of hypogonadism. Anabolic effect.Anabolic effect.

Side Effects:Side Effects: Sodium and water retention leads to edema.Sodium and water retention leads to edema. Masculinization of women.Masculinization of women. Hepatic dysfunction.Hepatic dysfunction.

Structure Activity Structure Activity Relation-ships:Relation-ships:

Steroidal nucleus essential for activity.Steroidal nucleus essential for activity. The C-3 and C-17 oxygenation is not essential The C-3 and C-17 oxygenation is not essential

but they increase the activity.but they increase the activity. Oxidation of C-17 to carbonyl eliminates Oxidation of C-17 to carbonyl eliminates

activity.activity. C-17 esters prolonged the activity.C-17 esters prolonged the activity. Trans A/B ring junction is essential for Trans A/B ring junction is essential for

activity.activity. 17 17 -substitutions render compounds orally -substitutions render compounds orally

active.active.

O

OH

Androgenic DrugsAndrogenic Drugs 17 17 -methyltestosterone:-methyltestosterone:

Orally active.Orally active. Prolonged action.Prolonged action. Androgenic and anabolic effects.Androgenic and anabolic effects.

Synthetic Anabolic Steroids:Synthetic Anabolic Steroids: NorethandroloneNorethandrolone

Orally active.Orally active. Anabolic effects.Anabolic effects. C-10 CHC-10 CH33 group removed to group removed to

eliminate androgenic effect.eliminate androgenic effect.

O

OH

17-Methyltestosterone(Semisythetic)

CH3

O

OH

Norethandrolone(Sythetic-Pure anabolic)

C2H5

Androgen AntagonistsAndrogen Antagonists Androgen Receptor Antagonists:Androgen Receptor Antagonists:

Cyproterone acetate:Cyproterone acetate: Has antiandrogenic and progestrogenic activity.Has antiandrogenic and progestrogenic activity. Used for treatment of acne, hirsutism, prostate Used for treatment of acne, hirsutism, prostate

hypertrophy, prostate cancer and precocious hypertrophy, prostate cancer and precocious puberty.puberty.

Flutamide:Flutamide: Non steroidal antiandrogen.Non steroidal antiandrogen. Used for treatment of hirsutism and prostate cancer Used for treatment of hirsutism and prostate cancer

55-Reductase inhibitors:-Reductase inhibitors: They prevent conversion of testosterone into They prevent conversion of testosterone into

dihydrotestosterone.dihydrotestosterone. Used for treatment of Benign Prostatic Hyperplasia Used for treatment of Benign Prostatic Hyperplasia

(BPH).(BPH).

Male ContraceptivesMale Contraceptives

Gossypol:Gossypol: Is a phenolic compound present in cotton Is a phenolic compound present in cotton

seed oil. seed oil. Decrease number of sperms and impairs Decrease number of sperms and impairs

their motility.their motility. It effect is reversible.It effect is reversible. Side Effects:Side Effects:

Hypokalemia, weakness, diarrhea and Hypokalemia, weakness, diarrhea and edema.edema.