ATC code G03CA03 (WHO) Molar mass 440.658 g/mol | Synonyms RS-1047, SQ-9993 Route Intramuscular injection | |
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Pronunciation ESS-tra-DYE-ole un-deh-sil-ate Trade names Progynon Depot 100, Delestrec, Depogin, Primogyn Depot, Progynon Depot, Oestradiol-Retard Theramex Routes of
administration Intramuscular injection Legal status In general: ℞ (Prescription only) | ||
Estradiol undecylate (INN, USAN) (brand name Progynon Depot 100, others), or estradiol undecanoate, is a synthetic, steroidal estrogen and an estrogen ester – specifically, the 17β-undecanoate ester of estradiol – which is or has been marketed in Europe, including in Germany, the Netherlands, Switzerland, and Monaco. It acts as a prodrug of estradiol, and hence, is considered to be a natural, bioidentical form of estrogen.
Contents
Medical uses
Estradiol undecylate was formerly often used in very high doses (100 mg intramuscular injection every 3 weeks or once per month) to treat prostate cancer, but has since largely been superseded for this indication by newer agents with fewer adverse effects (e.g., gynecomastia and cardiovascular complications) like GnRH analogues and non-steroidal antiandrogens. Along with estradiol valerate, estradiol cypionate, and estradiol benzoate, estradiol undecylate is or has been used as an intramuscular estrogen in hormone replacement therapy for transgender women.
Estradiol undecylate, in combination with norethisterone acetate (at doses of 5 mg and 50 mg, respectively), was studied as a combined injectable contraceptive, but ultimately was not marketed for this purpose.
Side effects
Estradiol undecylate has been used at very high dosages in the treatment of prostate cancer. At these high dosages, it has been associated with a considerable incidence of cardiovascular complications. In a 6-month study of 25 patients administered 100 mg/month intramuscular estradiol undecylate for the treatment of prostate cancer, it was reported that 8 cases of severe cardiovascular complications, including 2 deaths, occurred.
Pharmacology
Esters of estradiol like estradiol undecylate 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 undecylate and other estradiol esters are estrogens.
Antigonadotropic activity
A phase III clinical trial comparing high-dose intramuscular cyproterone acetate (300 mg/week) and high-dose intramuscular estradiol undecylate (100 mg/month) in the treatment of prostate cancer found that estradiol undecylate suppressed testosterone levels into the castrate range (<50 ng/dL) within at least 3 months whereas testosterone levels with cyproterone acetate were significantly higher and above the castrate range even after 6 months of treatment. With estradiol undecylate, testosterone levels fell from 416 ng/dL to 38 ng/mL after 3 months and to 29.6 ng/dL after 6 months, whereas with cyproterone acetate, testosterone levels fell from 434 ng/dL to 107 ng/mL at 3 months and to 102 ng/mL at 6 months. In accordance, whereas estrogens are well-established as able to suppress testosterone levels into the castrate range at sufficiently high dosages, progestogens like cyproterone acetate are able to decrease testosterone levels only up to an apparent maximum of around 70 to 80%.
Pharmacokinetics
The pharmacokinetics of estradiol undecylate in humans have been studied and reported.
Chemistry
Estradiol undecylate is an estrane (C18) steroid and the C17β undecylate (or undecanoate) fatty acid ester of estradiol. It is also known as estra-1,3,5(10)-triene-3,17β-diol 17β-undecanoate. A few related estradiol esters include estradiol decanoate, estradiol diundecylate, and estradiol diundecylenate.
Estradiol undecylate is a relatively long-chain ester of estradiol. Its ester chain contains 11 carbon atoms. For comparison, the ester chains of estradiol acetate, estradiol valerate, and estradiol enanthate have 2, 5, and 7 carbon atoms, respectively.
History
Estradiol undecylate was developed, along with estradiol valerate, in 1954.