Actions of Estrogens

ACTIONS

1. Sex Organs

The estrogens bring about pubertal changes in the female including growth of uterus, fallopian tubes and vagina. Vaginal epithelium gets thickened, stratified and cornified. They are responsible for the proliferation of endometrium in the preovulatory phase and it is only in concert with estrogens that progesterone brings about secretory changes.

In the absence of progesterone (anovulatory cycles) withdrawal of estrogens alone produces menstruation. If modest doses of estrogen are given continuously without added progesterone —menstruation is delayed but breakthrough bleeding occurs at irregular intervals. However, the normal event which triggers menstruation is progesterone withdrawal—such bleeding cannot be suppressed even by high doses of estrogens.

Estrogens increase rhythmic contractions of the fallopian tubes and uterus, and induce a watery alkaline secretion from the cervix—favourable to sperm penetration. They also sensitize the uterus to oxytocin. Deficiency of estrogens is responsible for atrophic changes in the female reproductive tract that occur after menopause.

2. Secondary Sex Characters

Estrogens produced at puberty cause growth of breasts—proliferation of ducts and stroma, accumulation of fat. The pubic and axillary hair appear, feminine body contours and behaviour are influenced.

Acne is common in girls at puberty as it is in boys—probably due to small amount of androgens produced simultaneously; administration of estrogens to suppress pituitary gonadal axis causes regression of acne.

3. Metabolic Effects

Estrogens are anabolic, similar to but weaker than testosterone. Therefore, small amount of androgen may be contributing to the pubertal growth spurt even in females. Continued action of estrogen promotes fusion of epiphyses.

Estrogen is important in maintaining bone mass primarily by retarding bone resorption. Osteoclast pit formation is inhibited and there is increased expression of bone matrix proteins such as osteonectin, osteocalcin, collagen and alkaline phosphatase. It promotes positive calcium balance, partly by inducing renal hydroxylase enzyme which generates active form of Vit D₃.

Both osteoblasts and osteoclasts express estrogen receptors (ERs). The major action of estrogens is to reduce maturation and activity of osteoclasts by modifying regulatory cytokine signals from osteoblasts. The direct action on osteoclasts is to accelerate their apoptosis.

Pharmacological doses of estrogens can cause mild salt and water retention—edema occurs in predisposed patients, but it can be treated with diuretics. BP may rise after prolonged use. Combination contraceptives containing higher doses of estrogens and progestins impair glucose tolerance: normal blood sugar is not affected but diabetes may be precipitated or its control vitiated. However, amounts used for HRT and low dose contraception do not affect carbohydrate metabolism.

Estrogens decrease plasma LDL cholesterol while HDL and triglyceride levels are raised. The raised HDL : LDL ratio is probably responsible for rarity of atherosclerosis in premenopausal women. However, blood coagulability is increased due to induction of synthesis of clotting factors (factors II, VII, IX and X). Fibrinolytic activity in plasma also tends to increase. Estrogens have been shown to induce nitric oxide synthase in vascular endothelium. The increased availability of nitric oxide could promote vasodilatation. They increase lithogenicity of bile by increasing cholesterol secretion and reducing bile salt secretion. Plasma levels of sex hormone binding globulin (SHBG), thyroxine binding globulin (TBG) and cortisol binding globulin (CBG) are elevated—but without any change in hormonal status.