Estradiol hemihydrateProduct ingredient for Estradiol

Estradiol hemihydrate
Drug Entry

Estradiol (also known as E2 or 17β-estradiol) is a naturally occurring hormone that circulates endogenously within the human body. It is the most potent form of mammalian estrogenic steroids and acts as the major female sex hormone. As such, estradiol plays an essential role in the regulation of the menstrual cycle, in the development of puberty and secondary female sex characteristics, as well as in ageing and several hormonally-mediated disease states. Estrogen mediates its effects across the body through potent agonism of the Estrogen Receptor (ER), which is located in various tissues including in the breasts, uterus, ovaries, skin, prostate, bone, fat, and brain. Estradiol binds to both subtypes of the Estrogen Receptor: Estrogen Receptor Alpha (ERα) and Estrogen Receptor Beta (ERβ). Estradiol also acts as a potent agonist of G Protein-coupled Estrogen Receptor (GPER), which has recently been recognized as a major mediator of estradiol's rapid cellular effects 9.

Estradiol is commercially available in several hormone therapy products for managing conditions associated with reduced estrogen production such as menopausal and peri-menopausal symptoms as well as hypoestrogenism. It is also used in transgender hormone therapy, as a component of oral contraceptive pills for preventing pregnancy (most commonly as Ethinylestradiol, a synthetic form of estradiol), and is sometimes used for the palliative treatment of some hormone-sensitive cancers like breast and prostate cancer. Estradiol is available in a number of formulations including oral, transdermal, and injectable.

The primary source of estrogen in normally cycling adult women is the ovarian follicle, which secretes 70 to 500 mcg of estradiol daily, depending on the phase of the menstrual cycle. However, after menopause, most endogenous estrogen is produced by conversion of androstenedione, secreted by the adrenal cortex, to estrone by peripheral tissues. Thus, estrone and the sulphate conjugated form, estrone sulphate, are the most abundant circulating estrogens in postmenopausal women Label. Although circulating estrogens exist in a dynamic equilibrium of metabolic interconversions, estradiol is the principal intracellular human estrogen and is substantially more potent than its metabolites, estrone and estriol at the receptor level. Because of the difference in potency between estradiol and estrone, menopause (and a change in primary hormone from estradiol to estrone) is associated with a number of symptoms associated with this reduction in potency and in estrogenic effects. These include hot flashes, vaginal dryness, mood changes, irregular menses, chills, and sleeping problems.

When used for oral or IM administration, estradiol is commonly synthesized as a pro-drug ester (such as Estradiol acetate, Estradiol benzoate, Estradiol cypionate, Estradiol dienanthate, and Estradiol valerate). It is commonly produced with an ester side-chain as endogenous estradiol has very low oral bioavailability on its own (2-10%). First-pass metabolism by the gut and the liver quickly degrades the estradiol molecule before it gets a chance to enter the systemic circulation and exert its estrogenic effects 10. Esterification of estradiol aims to improve absorption after oral administration (such as with Estradiol valerate) or to sustain release from intramuscular depot injections (such as with Estradiol Cypionate) through improved lipophilicity 14. Following absorption, the esters are cleaved, resulting in the release of endogenous estradiol, or 17β-estradiol.

Recommendations for treatment of menopausal symptoms changed drastically following the release of results and early termination of the Women's Health Initiative (WHI) studies in 2002 as a number of concerns were raised regarding the use of estrogen 11. Specifically, the combined estrogen–progestin arm was discontinued after approximately five years of follow up due to a statistically significant increase in invasive breast cancer and in cardiovascular events 12. Following extensive critique of the WHI results in the years following its release, Hormone Replacement Therapy (HRT) is now recommended to be used only for a short period (for 3-5 years post-menopause) in low doses, and in women without a history of breast cancer or at increased risk of cardiovascular or thromboembolic disease 13. Notably, use of estrogen for menopausal symptoms should always be accompanied by a progestin component due to estrogen's effects on the endometrium; in women with an intact uterus, unopposed estrogen has been shown to promote the growth of the endometrium which can lead to endometrial hyperplasia and possibly cancer in the long-term.

Ethinylestradiol (EE) is a synthetic form of estradiol commonly used as the estrogenic component of most combination Oral Contraceptive Pills (OCPs). Ethinyl Estradiol differs from Estradiol in that it has improved biovailability and greater resistance to metabolism, making it more suitable for oral administration.

Accession Number
Not Available
CAS Number
Average: 562.791
Monoisotopic: 562.36582471
Chemical Formula
InChI Key
bis((1S,10R,11S,14S,15S)-15-methyltetracyclo[^{2,7}.0^{11,15}]heptadeca-2,4,6-triene-5,14-diol) hydrate
External Links
Predicted Properties
Water Solubility0.0213 mg/mLALOGPS
pKa (Strongest Acidic)10.33ChemAxon
pKa (Strongest Basic)-0.88ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area40.46 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity79.9 m3·mol-1ChemAxon
Polarizability31.99 Å3ChemAxon
Number of Rings8ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon