Oestrogens
These drugs can be classified into three groups.
- Natural – estradiol, esterone, estriol
- Semisynthetic – Ethnylestradiol
- Synthetic: Diethylstibosterol
Natural
Estradiol: Estradiol is most potent, major secretory product of ovary.It is oxidized into esterone
by liver; estrone is hydrated to estriol and synthesized by ovarian follicle, adrenal cortex,
fetoplacental unit, and testis. Androgen and testestrone are precursor for estrogen. Certain
tissue can make estrone from androgen.
Semisynthetic
Ethylestadiol: Highly potent, effective orally
Absorption and Fate: It is absorbed from GI and skin and rapidly metabolized in the liver
Physiologic actions:
Genital system
Ovary: estrogen affects the ovary through indirectly influencing the secretion of gonadotrophin
Uterus: it affects the ‘proliferative phase’ of the endometrium and also increases the growth and
sensitivity of myometrium for oxytocin.
Cervix: it makes cervical mucus thin and alkaline
Vagina: Stratification, cornification and glycogen deposit is affected by estrogen.
Breast
Estrogen causes the growth of gland and duct system
Anterior pitutary
Estrogen inhibit release of gonadotrophins (FSH, LH)
Metabolic action:
a) Retention of salt and water
b) Plasma lipid level: it increases the level of high density lipoprotein and
triglycerides while decreases the level of low density lipoprotein and cholesterol.
c) Increases Catt bone deposition
d) It has a mild anabolic action
Blood coagulation
Enhance level of factor II, VII, IX, X so, increase the coagulability of blood and may predispose
to thromboembolic condition
Therapeutic use: contraceptive in combination with progestogens, Functional uterine bleeding,
Dysmenorrhea, Alleviation of menopausal disorder, Osteoporosis, Replacement therapy in
ovarian failure, Prevents senile and atrophic vaginitis
Side effects: Thromboembolism, Sodium and water retention, Withdrawal bleeding, nausea,
endometrial carcinoma
Contraindication: History of thromboembolism condition, Undiagnosed uterine bleeding,
endometrial Carcinoma, liver disease
PROGESTOGENS
Progestrone is natural occuring progestational hormone.it is synthesized by corpus luteum,
placenta, adrenal cortex, testis. It is less effective orally due to complete metabolism by liver so
it’s given through intramuscular route.
136
Actions on genital organs:
Ovary – Inhibition of ovulation
Uterus – converts the endometrum for secretory phase and makes the myometrium less
sensitive to oxytocin. It also causes relaxation of the uterus in late pregnancy.
Metabolic actions:
(a) Thermogenic action
(b) Competes with aldosterone at renal tubule so inhibits sodium reabsorption.
Synthetic /Senisynthetic progestogens:
Derivative of progestrone: Hydroxyprogesterone capriot/medroxyprogestrone
Derivative of testestrone: Dimethisterone
Nortestrone: Norethisterone
Therapeutic use: Hormonal contraception, functional uterine bleeding, dymennorrhea
Ammenorrhea, Endometrial Carcinoma, Premenustral tension
ORAL CONTRACEPTIVEs
These are drugs taken orally to prevent conception. They are available in the following forms: - Combined regimen type
- sequential regimen type
- triphasic pill regimen
Combined regimen: involves the administration of pills containing combination of Estrogen and
Progestogen. They are administered starting 5th day of menustral cycle for 21 days.
They can also be classified as fixed dose combination (monophasic), biphasic and triphasic
pills. Fixed dose combination: the commonest procedure is to administer one pill containing both
an estrogen and progestin daily at bed time for 21 days. In biphasic and triphasic pills: these are
combined oral contraceptive pills containing varying proportion of an estrogen and a
progesterone designed to stimulate the normal pattern of menustral cycle.
Formulation:
a) low estrogen, low progesterone(0.03mg ethinylestradiol+0.15 mg norgestril
b) Low esterogen, high progestogen
(0.03 mg ethinylestradiol + 1.5 mg norethindrone)
137
c) High estrogen, high progestrone
(0.05 mg ethinylestradiol + 0.5 mg norgestril)
Mechanism: includes inhibition of release of FSH and LH, increase viscosity of cervical mucus
endometrial changes, interfere with contraction of cervix, uterus and fallopian tube
Single Entity preparation
A. Continuous progestrone
i) Oral progestrone
Norethindone (Norgestril)
ii) Depot
IM injection of long acting progestogen.
e.g. Medroxyprogestrone acetate (Depoprovera®)
iii) Subcutanous implant
L – norgestril (Norplant®)
Mechanism: It makes cervical mucus thick, though & hostile and also alter endometrial wall
B. Post coital “morning after” pill
Oestrogen like Diethyl stilbosterol used within 72 hrs
Combined oral contraceptive pills can also be used.
Side effects of oral contraceptive: Thromboembolic complication, Weight gain & fluid retention,
Menstrual disorder, Breast tenderness & fullness, Skin changes, Nausea & vomiting, Depressed
mood, Reduced lactation
Beneficial effects of estrogen /progesterone oral contraceptive
1) Reduced risk of endometrial Carcinoma, ovarian cyst
2) regular Menses, No excessive blood loss
3) Less premenustrual tension and dysmennorrhea
4) Relief of endometriosis
Contraindication: In patients withcardiovascular diseases (hypertension, coronary heart
disease)
Thromboemolic disease, breast Cancer, diabetes mellitus, liver disease, women > 35 years
(esp. smokers and hypertensives)
Drug interaction: - Effect reduced when taken with enzyme inducers like Rifampicin, Phenytoin,
Phenobarbitone etc. It may result in unexpected pregnancy and spotting. - Oral contraceptive antagonize the effect of Coumarin anticoagulant and some
antihypertensives
Ovulation inducing drug
These are drugs used in the treatment of infertility due to ovulatory failure.
Clomiphen
It is antiestrogenic drug. It interferes with estrogen feedback inhibition at hypothalamus and
anterior pitutary so enhance secretion of FSH, LH causing ovarian stimulation which finally
leads to ovulation.
Leave a Reply