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.
Cyclodiol
Cyclodiol (developmental code name ZK-115194; also known as 14α,17α-ethano-17β-estradiol) is a synthetic estrogen which was studied in the 1990s and was never marketed. It is a derivative of estradiol with a bridge between the C14α and C17α positions. Cyclodiol has 100% of the relative binding affinity of estradiol for the human ERα and similar transactivational capacity as estradiol at the receptor. It has comparable potency to estradiol when administered by subcutaneous injection. The drug shows genotoxicity similarly to estradiol. Cyclodiol showed an absolute bioavailability of 33 ± 19% and a terminal half-life of 28.7 hours in pharmacokinetic studies in women.