Estradiol benzoate

The medical uses of estradiol benzoate are the same as those of estradiol and other estrogens. Estradiol benzoate is used in hormone therapy for the treatment of menopausal symptoms such as hot flashes and vaginal atrophy and in the treatment of hypoestrogenism and delayed puberty due to hypogonadism or other causes in women. Aside from hormone therapy, estradiol benzoate is used in the treatment of gynecological disorders such as menstrual disorders, dysfunctional uterine bleeding, and breast engorgement. The dosage used in hormone therapy for transgender women is 0.5 to 1.5 mg two to three times per week. Follivirin (and previously Femandren M) is the brand name of a product containing 2.5 mg microcrystalline estradiol benzoate and 25 to 50 mg microcrystalline testosterone isobutyrate in aqueous suspension. A vaginal tablet formulation containing 0.125 mg estradiol benzoate and 10 mg monalazone sodium (a vaginal disinfectant and spermicidal contraceptive) has been marketed under the brand name Malun 25. Estradiol benzoate was also formerly available as 50 and 100 mg pellets for subcutaneous implantation and as a 2 mg/g ointment. ==Contraindications==

Contraindications of estrogens include coagulation problems, cardiovascular diseases, liver disease, and certain hormone-sensitive cancers such as breast cancer and endometrial cancer, among others. ==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. ==Overdose==

Symptoms of estrogen overdosage may include nausea, vomiting, bloating, increased weight, water retention, breast tenderness, vaginal discharge, heavy legs, and leg cramps. These side effects can be diminished by reducing the estrogen dosage. ==Interactions==

Inhibitors and inducers of cytochrome P450 may influence the metabolism of estradiol and by extension circulating estradiol levels. ==Pharmacology==

, the active form of estradiol benzoate. Pharmacodynamics Estradiol benzoate is an estradiol ester, or a prodrug of estradiol. As such, it is an estrogen, or an agonist of the estrogen receptors. As such, estradiol benzoate is regarded as essentially inactive in terms of estrogenic effect itself, acting solely as a prodrug to estradiol. The decidua (pregnancy-type endometrium) induction dosage of estradiol benzoate/progesterone in oil solution is 2 to 5 mg estradiol benzoate and 20 to 100 mg progesterone by intramuscular injection daily for 5 to 7 weeks, whereas the decidua induction dosage of estradiol benzoate/progesterone in microcrystalline aqueous suspension is 10 to 20 mg estradiol benzoate and 200 to 250 mg progesterone in microcrystalline aqueous suspension by intramuscular injection once per week for about 6 weeks. As with other estrogens and forms of estradiol, estradiol benzoate dose-dependently suppresses gonadotropin and testosterone levels in men and transgender women. The elimination half-life of estradiol benzoate in oil solution by intramuscular injection has been reported to be 48 to 120 hours (2 to 5 days). This is in accordance with known production rates of estradiol in women (e.g., 300 μg/day in the luteal phase). Aqueous suspension Microcrystalline estradiol benzoate in aqueous suspension (brand names Agofollin Depot and Ovocyclin M alone and Follivirin in combination with testosterone isobutyrate) Whereas the duration of a single intramuscular injection of estradiol benzoate in oil solution is 6 days, the duration of a single intramuscular injection of microcrystalline estradiol benzoate in aqueous suspension is 16 to 21 days. Other routes The duration of estradiol benzoate is not prolonged if it is administered directly into the circulation via intravenous injection, in contrast to intramuscular injection. Estradiol benzoate is active with oral and sublingual administration, similarly to estradiol valerate and estradiol acetate. This level of oral potency has been described as remarkably high. ==Chemistry==

Estradiol benzoate is a synthetic estrane steroid and the C3 benzoate (benzenecarboxylate) ester of estradiol. ==History==

Estradiol benzoate was one of the first estrogens to be developed and marketed. Schwenk and Hildebrant at Schering discovered estradiol via reduction of estrone in 1933, and they proceeded to synthesize estradiol benzoate from estradiol the same year. Estradiol benzoate was patented by Schering in 1933 and was introduced in an oil solution for use by intramuscular injection under the brand name Progynon B that year as well. By the early 1940s, Ben-Ovocylin had been introduced by Ciba as well. Following their introduction, estradiol benzoate and estradiol dipropionate were the most widely used esters of estradiol for many years. However, estradiol valerate and estradiol cypionate, which are longer-acting esters that require less frequent administration, were developed and introduced in the 1950s, and have since largely superseded estradiol benzoate and estradiol dipropionate. ==Society and culture==

Generic names Estradiol benzoate is the generic name of the drug and its , , and , while oestradiol benzoate was formerly its . Brand names The major brand name of estradiol benzoate is Progynon-B. Availability Estradiol benzoate is available in Europe and in other parts of the world. However, it is approved and marketed in the United States for veterinary use as a subdermal implant both alone and in combination with the androgen/anabolic steroid trenbolone acetate (brand names Celerin and Synovex, respectively). Outside of the United States, estradiol benzoate is also marketed in combination with progesterone for use as an intramuscular injection. Microcrystalline estradiol benzoate in aqueous suspension is available in the Czech Republic and Slovakia alone under the brand name Agofollin Depot and in combination with microcrystalline testosterone isobutyrate under the brand name Folivirin. ==Research==

Estradiol benzoate has been studied in combination with norethisterone enanthate as a once-a-month combined injectable contraceptive, but ultimately did not complete development for this indication. ==References==