Irregular vaginal bleeding usually occurs for the first 3 months but usually stops. In particular, they have a long half-life, in part as a result of their storage in and slow release from adipose tissue. These doses are generally effective in relieving menopausal symptoms and preventing osteoporosis. The lowest dose may be used for women who experience adverse effects. However, whether lower doses confer maximal therapeutic benefit is unknown.
Enterohepatic circulation contributes to the prolonged effect of oral estrogens.
Because the concentration of oral estrogen is 4 to 5 times higher in the portal than in the general circulation, more estrogen is presented to hepatocytes than to cells of other organs. Thus, the liver is more affected by estrogens given orally than by those given parenterally. Vaginally applied estrogens are absorbed and enter the systemic circulation, achieving about one fourth the circulatory level of an equal oral dose. Continued use of vaginal estrogen increases blood estrogen levels because of enhanced transfer across a healthier, better vascularized epithelium. Synthetic estrogens have not been routinely used postmenopausally.