The major oestrogens are oestrogens are oestrodial, oestrone, and oestriol. They are produced by Graafian follicle, placenta, and to small extent by testes and adrenal cortex. The primary source of oestradial is ovaries. In the liver oestradiol is biotransformed into oestrone and oestriol. Since they are subjected to extensive first pass hepatic metabolism, they are not effective by oral route. However, synthetic oestrogens as well as nonsteroidal compounds with oestrogenic activity exhibit less first-pass metabolism and are available by oral route. Bounding with specific protein synthesis. These receptors are present in female reproductive organs and breasts, as well as in the hypothalamus and pituitary. Progestins decrease the number of these receptors. Whereas prolactin increases their number in mammary glands but not in the uterus. Oestrogens can induce the synthesis of progesterone receptors in the female reproductive organs, hypothalamus and anterior pituitary.

ACTION
Oestrogens play an important role in the development and maturation of female reproductive organs, breast and secondary female sex characters at the times of puberty in girls. They are required for the proliferative phase of the endometrium and for maintenance of pregnancy and concomitant growth of breast. They are responsible for the rapid growth of the long bones during puberty and also influence psychological and emotional behaviour. In the non-pregnant premenopausal woman, the rate of oestrogen synthesis in the corpus luteum is modulated by both follicle stimulating hormone (FSH) AND luteinsing hormone (LH). LH stimulates formation of androgens by the theca cells while FSH facilitates the conversion of androgen to oestrogens in the granulose cells. During pregnancy oestrogen is mainly formed in the corpus luteum for the first 9-10 weeks and there after by placenta. All clinically used oestrogens with globulin and albumin. They are metabolized in liver and are excreted in urine as glucuronide and sulphate conjugates.

CLINICAL USES
Oestrigens are used to treat woman who have abnormally low oestrogen such as in primary ovarian failure and female hypogonadism. Vasomotor instability, headache and emotional lability are seen in a few per cent of woman during and after menopause if these symptoms are severe, Oestrogen therapy many be used and the dose should be individually adjusted, overdose may cause troublesome toxic effects. Oestrogen progestogen combination is useful in the treatment of pelvic endometriosis, habitual abortion. High doses of oestrogens have been employed in the treatment of primary and metastatic forms of the carcinoma of prostate. They have also been used in the treatment of female, hirsutism, acne in females, senile vaginitis, epistaxis, atrophic rhinitis and male hypersexuality. For oral contraception they may be employed in combination with progesterone of given alone.

ADVERSE EFFECTS
These include feminization in males; sodium retention, oedema, aggravation of hypertension and congestive cardiac failure, increase in migraine, nausea, vomiting, diarrhea, cholestasis and gallbladder, disease, thromboembolism; endometrial carcinoma on long term use during menopause. They are contraindicated in premenopausal breast cancer and in patients with history of thromboembolism. They should be cautiously used in presence of hypertension, hepatic dysfunction, diabetes mellitus, migraine and uterine fibroid because all of them may be aggravated by them.