Estradiol sulfate
As the sodium salt, sodium estradiol sulfate, E2S is present as a minor constituent (0.9%) of conjugated equine estrogens (CEEs), or Premarin. It effectively functions as a prodrug to estradiol in this preparation, similarly to E1S. E2S is also formed as a metabolite of estradiol, as well as of estrone and E1S. Aside from its presence in CEEs, E2S is not available as a commercial pharmaceutical drug.
Pharmacokinetics of estradiol
In contrast to estradiol, estrone has very low activity as an estrogen. The affinities of estrone for the human ERs and its estrogenic activity have been reported to be approximately 3 to 4% of those of estradiol. In addition, unlike estradiol and estriol, estrone is not accumulated in target tissues. Because estrone can be transformed into estradiol, most of its activity "in vivo" is actually due to conversion into estradiol. In accordance, dosages of oral and transdermal estradiol that achieve similar levels of estradiol have been found, in spite of markedly elevated levels of estrone with oral estradiol but not with transdermal estradiol, to possess equivalent and non-significantly different potency in terms of clinical measures including suppression of LH and FSH levels, inhibition of bone resorption, and relief of menopausal symptoms such as hot flashes. In addition, estradiol levels were found to correlate with these effects, while estrone levels did not. These findings suggest that estrone contributes very little or not at all to the estrogenic potency of estradiol, while also not antagonizing the estrogenic activity of estradiol. This contradicts some "in vitro" research suggesting that estrone might be able to partially antagonize the actions of estradiol.