ATC code G03CA03 (WHO) Molar mass 376.488 g/mol | Bioavailability Intramuscular: 100% Route Intramuscular injection | |
 | ||
Pronunciation ESS-tra-DYE-ole benz-oh-ate Trade names Agofollin, Benovocyclin, Benzofoline, Dimenformon, Progynon-B, many others Routes ofadministration Intramuscular injection Legal status In general: ℞ (Prescription only) | ||
Estradiol benzoate (EB, E2B) (INN) (brand name Progynon-B, many others), or oestradiol benzoate (BAN), is a synthetic, steroidal estrogen and an estrogen ester – specifically, the 3-benzoate ester of estradiol – which is marketed in Europe and elsewhere throughout the world. It acts as a prodrug of estradiol, and hence, is considered to be a natural, bioidentical form of estrogen. Estradiol benzoate was introduced in 1936 and was one of the first forms of estrogen to be marketed. Along with estradiol dipropionate, it was one of the most widely used estradiol esters prior to the 1950s. However, estradiol benzoate is now little used, having largely been superseded by longer-acting esters of estradiol like estradiol valerate and estradiol cypionate that require less frequent administration.
Contents
- Medical uses
- Side effects
- Pharmacology
- Pharmacokinetics
- Intramuscular administration
- Chemistry
- History
- Avaiability
- References
Medical uses
The medical uses of estradiol benzoate are the same as those of estradiol and other estrogens. An example of an indication for the drug is hormone replacement therapy for menopausal symptoms or hypoestrogenism.
Side effects
The side effects of estradiol benzoate are the same as those of estradiol. Examples of such side effects include breast tenderness and enlargement, nausea, bloating, edema, headache, and melasma.
Pharmacology
Esters of estradiol like estradiol benzoate are readily hydrolyzed prodrugs of estradiol, but have an extended duration when administered in oil via intramuscular injection due to a depot effect afforded by their fatty acid ester moiety. As prodrugs of estradiol, estradiol benzoate and other estradiol esters are estrogens.
Pharmacokinetics
Upon ingestion, regardless of the route of administration, estradiol benzoate behaves as a prodrug via cleavage by esterases into estradiol and the natural fatty acid benzoic acid. This cleavage occurs not only in the liver, but also in the blood and in tissues.
Intramuscular administration
A single dose of 2.5 mg estradiol benzoate by intramuscular injection was found to produce plasma estradiol levels of >400 pg/mL, measured 24 hours post-injection, in a group of patients with minimal baseline levels of estradiol (due to GnRH analogue therapy with triptorelin).
A single intramuscular injection of 5 mg estradiol benzoate has been found to result in peak circulating concentrations of 940 pg/mL estradiol and 343 pg/mL estrone, which occurred at about 2 days post-injection (see table). Compared to two other commonly used estradiol esters (which were also assessed in the study), estradiol benzoate had the shortest duration, at approximately 4 to 5 days, whereas estradiol valerate and estradiol cypionate were found to last for 7–8 days and 11 days, respectively. This is because estradiol benzoate has a shorter and less bulky fatty acid chain and in relation to this is comparatively less lipophilic. For a given estradiol ester, the shorter or less extensive the fatty acid chain is, the less lipophilic, shorter-lasting, and less uniform/plateau-like the resultant levels of estradiol are as well as the higher the peak/maximal levels are (and hence more spike-like).
Chemistry
Estradiol benzoate is an estrane (C18) steroid and the C3 benzoate (or phenylcarboxylate) fatty acid ester of estradiol. It is also known as estra-1,3,5(10)-triene-3,17β-diol 3-benzoate. Two related estradiol esters are estradiol dipropionate, the 3,17β-dipropionate ester of estradiol, and estradiol acetate, the 3-acetate ester of estradiol.
History
Estradiol benzoate was one of the first forms of estrogen to be developed and marketed. It was synthesized in 1933. The drug was patented by Schering-Kahlbaum in 1936 in an oil preparation for injectable use and introduced later that year as Progynon-B. It has been mostly superseded by newer forms of estradiol with improved pharmacokinetics that require less frequent administration such as estradiol valerate and estradiol cypionate. Prior to the introduction of the two aforementioned esters in the 1950s, estradiol benzoate and estradiol dipropionate were the most widely used esters of estradiol.
Avaiability
Estradiol benzoate is not approved by the FDA for use in humans in the United States. However, it is approved and marketed in this country for veterinary use as a subdermal implant both alone and in combination with the androgenic-anabolic steroid trenbolone acetate (brand names Celerin and Synovex, respectively).