CAS Number: 4956-37-0
Molecular Weight: 384.556
Molecular Formula: C25H36O3
Appearance: Crystalline powder
Physical State: Solid
Solubility: Soluble in water (slightly).
Storage: Store at room temperature
Melting Point: 94-96 ° C
Boiling Point: ~509.5 ° C at 760 mmHg (Predicted)
Density: ~1.1 g/cm3 (Predicted)
Estradiol enantate (EEn or E2-EN), also spelled estradiol enanthate and sold under the brand names Perlutal and Topasel among others, is an estrogen medication which is used in hormonal birth control for women.It is formulated in combination with dihydroxyprogesterone acetophenide (DHPA; algestone acetophenide), a progestin, and is used specifically as a combined injectable contraceptive. Estradiol enantate is not available for medical use alone.The medication, in combination with DHPA, is given by injection into muscle once a month.
Side effects of estradiol enantate include breast tenderness, breast enlargement, nausea, headache, and fluid retention. Estradiol enantate is an estrogen and hence is an agonist of the estrogen receptor, the biological target of estrogens like estradiol.It is an estrogen ester and a long-lasting prodrug of estradiol in the body. Because of this, it is considered to be a natural and bioidentical form of estrogen.
Estradiol enantate was first described by 1954,and was first studied in combination with DHPA as a combined injectable contraceptive in 1964.The combination was introduced for clinical use by the mid-1970s.Estradiol enantate is not available as a standalone medication (i.e., by itself without DHPA).The combination is available in Latin America and Hong Kong, and was also previously marketed in Spain and Portugal
Estradiol enantate is used in combination with the progestin DHPA as a once-monthly combined injectable contraceptive for women in Latin America and Hong Kong. Estradiol enantate has been studied in feminizing hormone therapy for transgender women as well. The combination of estradiol enantate and DHPA has likewise been used by transgender women for such purposes
Estradiol enantate is an estradiol ester, or a prodrug of estradiol. As such, it is an estrogen, or an agonist of the estrogen receptors. Estradiol enantate is of about 41% higher molecular weight than estradiol due to the presence of its C17β enantate ester.Because estradiol enantate is a prodrug of estradiol, it is considered to be a natural and bioidentical form of estrogen.
The combination of 10 mg estradiol enantate and 150 mg DHPA as a once-monthly combined injectable contraceptive (which achieves levels of estradiol of around 350 pg/mL)has been found to have little to no effect on many markers of estrogen-modulated liver protein synthesis, including circulating levels of HDL and LDL cholesterol, copper, ceruloplasmin, total and free cortisol, corticosteroid-binding globulin, and sex hormone-binding globulin. However, it was found to significantly increase levels of triglycerides and to significantly decrease levels of total and free testosterone.In contrast to the estradiol enantate-containing combined injectable contraceptive, low-dose ethinylestradiol-containing birth control pills produce highly significant changes in all of the preceding parameters.
Studies in women and female capuchin monkeys have found that injections of estradiol enantate and DHPA significantly alter levels of coagulation factors.
The clinical estrogenic effects of estradiol enantate and ethinylestradiol have been compared in other studies as well
When estradiol enantate is administered in an oil solution by intramuscular injection, a depot effect occurs, and this results in it having a long duration of action. The duration of action of estradiol enantate is considerably longer than that of various other estradiol esters, such as estradiol benzoate, estradiol valerate, and estradiol cypionate, whereas its duration is shorter than that of estradiol undecylate. In general, the longer the fatty acid ester chain, the more lipophilic the estradiol ester, the more slowly it is released from the depot and absorbed into the circulation, and the longer its duration of action.
The pharmacokinetics of estradiol enantate have been assessed in a number of studies. It has usually been studied in combination with DHPA. Following an intramuscular injection of estradiol enantate, levels of estradiol have been found to peak after 3 to 8 days. Maximal levels of estradiol after a 5 mg injection of estradiol enantate have been found to be about 163 to 209 pg/mL and after a 10 mg injection of estradiol enantate have been found to be about 283 to 445 pg/mL. However, one outlying study reported peak estradiol levels of 850 pg/mL after an intramuscular injection of 10 mg estradiol enantate in three postmenopausal women. It used radioimmunoassay for the determinations, with no mention of chromatographic separation. Estradiol levels following an intramuscular injection of 10 mg estradiol enantate have been found to return to baseline levels of around 50 pg/mL after about 20 to 30 days. However, a metabolic study found that traces of radiolabeled estradiol enantate remained detectable in blood for at least 30 to 40 days and for as long as 60 days.Studies have reported that the elimination half-life of estradiol enantate after a single 10 mg intramuscular injection was 5.6 to 7.5 days.The volume of distribution of estradiol enantate has been reported to be 5.087 L.Estradiol enantate is excreted preferentially in urine.
There were concerns about possible accumulation of estradiol enantate and consequent estrogenic overexposure with once-monthly combined injectable contraceptives containing the medication due its long duration, and this may have limited the use of such combined injectable contraceptives. Subsequent clinical studies have found that there is very limited or no accumulation of estradiol enantate when it is used in once-a-month injectable contraceptives