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)
Estriol is a far less potent estrogen than is estradiol, and is a relatively weak and atypical estrogen. Given by subcutaneous injection in mice, estradiol is about 10-fold more potent than estrone and about 100-fold more potent than estriol. In most tissues, such as the liver and endometrium, estriol is weakly estrogenic, but in the vaginal epithelium, it produces pronounced and full estrogenic responses. The medication has been found to reduce hot flashes, improve vaginal atrophy, reverse the postmenopausal decline in skin thickness and collagen content, suppress gonadotropin secretion, and produce proliferation of breast epithelium. Conversely, estriol does not consistently affect bone resorption or fracture risk, does not increase breast density or the risk of breast cancer, and, at oral dosages of 2 to 4 mg/day, does not affect liver proteins, lipid metabolism, or hemostatic parameters. Additionally, vaginal estriol does not appear to produce endometrial proliferation or increase the risk of endometrial hyperplasia, and some studies have found this to be the case for oral estriol as well. On the other hand, it appears that estriol may be able to stimulate the growth of active breast cancer. Via the oral route, estriol has approximately 30% of the potency of estradiol on hot flashes relief and suppression of follicle-stimulating hormone secretion and about 20% of the potency of estradiol on stimulation of liver production of high-density lipoprotein (HDL) cholesterol. In relation to its differing effects, estriol can be considered a safer estrogen than estradiol.