Estrogen (medication)
Estradiol, estrone, and estriol have all been approved as pharmaceutical drugs and are used medically. Estetrol is currently under development for medical indications, but has not yet been approved in any country. A variety of synthetic estrogen esters, such as estradiol valerate, estradiol cypionate, estradiol acetate, estradiol benzoate, estradiol undecylate, and polyestradiol phosphate, are used clinically. The aforementioned compounds behave as prodrugs to estradiol, and are much longer-lasting in comparison when administered by intramuscular or subcutaneous injection. Esters of estrone and estriol also exist and are or have been used in clinical medicine, for example estrone sulfate (e.g., as estropipate), estriol succinate, and estriol glucuronide (as Emmenin and Progynon).
Estriol (medication)
The bioavailability of estriol is markedly increased with vaginal administration compared to oral administration. The relative bioavailability of oral estriol was found to be about 10% of that of vaginal estriol. In accordance, a single dose of 8 mg oral estriol and of 0.5 mg vaginal estriol have been found to produce similar circulating concentrations of estriol. It has been said that 0.5 to 1 mg vaginal estriol may be equivalent in clinical effect to 8 to 12 mg oral estriol. The high bioavailability of vaginal estriol is due to rapid absorption and low metabolism in atrophic vaginal mucosa. Vaginal estriol at typical clinical dosages results both in high local concentrations of estriol in the vagina and in systemic action. Vaginal administration of low doses of 30 µg estriol and of higher doses of 0.5 and 1 mg estriol have been found to produce equivalent local effects in the vagina and improvement of vaginal symptoms, suggesting that a saturation of estrogenic effect of vaginal estriol has been reached in the vagina by a dose of only 30 µg estriol. In contrast to higher doses of vaginal estriol however, 30 µg/day estriol is not associated with systemic effects. Similarly, the use of 0.5 mg vaginal estriol twice a week instead of daily has been said to largely attenutate the systemic effects of estriol. Whereas oral estriol results in high levels of estriol conjugates which greatly exceed those of unconjugated estriol, vaginal estriol has been found to produce levels of unconjugated estriol and estriol conjugates that are similar.