Estradiol, estra-1,3,5(10)-triene-3,17β-diol, is the most activeof the natural steroid estrogens.
Although its 17β-OHgroup is vulnerable to bacterial and enzymatic oxidation toestrone, it can be temporarily protected as anester at C3 or C17, or permanently protected by adding a17α-alkyl group (e.g., 17α-ethinyl estradiol, the most commonlyused estrogen in oral contraceptives).
The increasedoil solubility of the 17β-esters (relative to estradiol) permitsthe esters to remain in oil at the IM injection site for extendedperiods.
These derivatives illustrate the principles of steroidmodification.
Transdermal estradiolproducts avoid first-pass metabolism, allowing estradiol tobe as effective as oral estrogens for treating menopausalsymptoms.
A new transdermal spray, Evamist, was approvedin 2007.
Estradiol itself is typically not very effective orallybecause of rapid metabolism, but an oral formulation of micronizedestradiol that allows more rapid absorption of thedrug is available (Estrace).
In addition to the oral and transdermalproducts, estradiol is also available in gel, cream, andvaginal ring formulations.
The commercially available estradiolesters are the following:
Estradiol 3-acetate, USP (oral; vaginal ring)
Estradiol 17-valerate, USP (IM injection)
Estradiol 17-cypionate, USP (IM injection).