Dr. Areej M. Al-Taweel Pharmacognosy Department Pharmacognosy Department

Estrogens Natural Estrogens: Natural Estrogens: Female Sex Hormones (Estrogens and Progestins) Sex Hormones

Structure Activity Relation Ships  Aromatic ring with C-3-OH is essential for activity.  Steroidal structures is not essential for activity.  Alkylation of the aromatic ring decrease the activity.  Unsaturation of ring B decreases the activity.  17α- and 16 position when modified enhance the activity.

Physiological 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.Uses Birth control pills. Birth control pills. Failure of ovarian development. Failure of ovarian development. Menstrual disturbances. Menstrual disturbances. Postmenopausal osteoporosis. Postmenopausal osteoporosis. Prostate cancer. Prostate cancer. Side 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.

Steroidal Estrogenic Drugs Estradiol: Most active natural estrogen. Most active natural estrogen. Very short duration of action. Very short duration of action. Mainly used for local effect on the uterus. Mainly used for local effect on the uterus. Ethinyl estradiol: more potent than estradiol orally more potent than estradiol orally.

Nonsteroidal Estrogens Diethylstilbestrol: The trans form is the active one. The trans form is the active one.Advantages: As active as Estradiol. As active as Estradiol. Longer duration of action. Longer duration of action. Orally active Orally active Cheap. Cheap.Disadvantages: Increase the risk of uterine cancer. Increase the risk of uterine cancer.Uses: Treatment of prostate cancer. Treatment of prostate cancer.

Estrogen Antagonists  Impeded Estrogens: Steroids weakly bind to receptors. Steroids weakly bind to receptors. Can compete with estrogens when reach receptors in high Concentration. Can compete with estrogens when reach receptors in high Concentration.  Triphenylethylene antagonists: They are related to stilbene in structure (non steroid). They are related to stilbene in structure (non steroid). Antagonist bind strongly to the receptors. Antagonist bind strongly to the receptors.  Aromatase inhibitors: Steroidal or nonsteroidal. Steroidal or nonsteroidal. Block conversion of androgens to estrogens. Block conversion of androgens to estrogens. Uses: Treatment of estrogen dependent cancers. Uses: Treatment of estrogen dependent cancers.

Side Effects (Due to Estrogens): Increase risk of breast, vaginal and uterine cancers. Increase risk of breast, vaginal and uterine cancers. Increase risk of thromboembolic and vascular problems. Increase risk of thromboembolic and vascular problems. Nausea, vomiting, headache, menstrual disturbances and weight gain. Nausea, vomiting, headache, menstrual disturbances and weight gain.

Progestins Progesterone in the major natural progestin. Progesterone in the major natural progestin. Secretion: By the ovary mainly the corpus luteum during the second half of the menstrual cycle. Physiological Effects: Development of the endometrium. Development of the endometrium. Development of the mammary gland during pregnancy. Development of the mammary gland during pregnancy.

Structure Activity Relation-ships: Steroidal nucleus essential for activity. Steroidal nucleus essential for activity. Removal of the 19 CH 3 increase activity. Removal of the 19 CH 3 increase activity. Unsaturation of ring B or C increase the activity. Unsaturation of ring B or C increase the activity. Have some androgenic activity. Have some androgenic activity. Removal of the keto function remove androgenic activity. Removal of the keto function remove androgenic activity.

Progestrogenic Drugs Lynestrenol: Semisynthetic progestin with pure progestrogenic activity. Semisynthetic progestin with pure progestrogenic activity.

Uses: Contraceptive pills. Contraceptive pills. Uterine bleeding. Uterine bleeding. Prevention of abortion. Prevention of abortion. Amenorrhea, dysmenorrhea, endometriosis. Amenorrhea, dysmenorrhea, endometriosis. Endometrial, renal and breast carcinoma. Endometrial, renal and breast carcinoma. Side Effects: Nausea, vomiting, irregular bleeding, edema, weight gain. Nausea, vomiting, irregular bleeding, edema, weight gain.

Progestin Antagonists: Mifepristone:  Compete with the progestin receptors. Uses: Abortifacient. Abortifacient.

Female Oral Contraceptive Sequential Preparations: Estrogens for 16 days then Estrogen and Progesterone for 5- 6 days. Estrogens for 16 days then Estrogen and Progesterone for 5- 6 days % successful % successful. Combination Preparation: Estrogens and Progesterone from the beginning to the end in small doses. Estrogens and Progesterone from the beginning to the end in small doses % successful % successful.Mechanism: The above two types inhibit both FSH and LH so prevent ovulation. The above two types inhibit both FSH and LH so prevent ovulation.

Female Oral Contraceptive (Cont.) Minipills: Small doses of Progesterone from the beginning to the end. Small doses of Progesterone from the beginning to the end % successful % successful.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.