Estrogen ester

Not to be confused with Esterified estrogens or Conjugated estrogens.

An estrogen ester is an ester of an estrogen, most typically of estradiol but also of other estrogens such as estrone, estriol, and even nonsteroidal estrogens like diethylstilbestrol.[1][2][3] Esterification renders estradiol into a prodrug of estradiol with increased resistance to first-pass metabolism, slightly improving its oral bioavailability.[1][2][4] In addition, estrogen esters have increased lipophilicity, which results in a longer duration when given by intramuscular or subcutaneous injection due to the formation of a long-lasting local depot in muscle and fat.[1][2][3] Conversely, this is not the case with intravenous injection or oral administration.[1][5] Estrogen esters are rapidly hydrolyzed into their parent estrogen by esterases once they have been released from the depot.[1][2] Because estradiol esters are prodrugs of estradiol, they are considered to be natural and bioidentical forms of estrogen.[2][1][6]

Estrogen esters are used in hormone therapy, hormonal contraception, and high-dose estrogen therapy (e.g., for prostate cancer and breast cancer), among other indications.[1][2] The first estrogen ester to be marketed was estradiol benzoate in 1933, which was followed by many more.[7][8] One of the most widely used estradiol esters is estradiol valerate, which was first introduced in 1954.[9] Other major estradiol esters that are or have been used in medicine include estradiol acetate, estradiol cypionate, estradiol dipropionate, estradiol enantate, estradiol undecylate, and polyestradiol phosphate (an estrogen ester polymer), as well as the nitrogen mustard alkylating antineoplastic agent estramustine phosphate (estradiol normustine phosphate).[2][10]

The most common vehicles for injections of steroids and steroid esters are oil solutions, but aqueous solutions, aqueous suspensions, and emulsions have also been used.[11][additional citation(s) needed] The durations of estrogen esters are not prolonged if they are given orally, vaginally, or by intravenous injection.[11]

  1. ^ a b c d e f g Kuhl H (2005). "Pharmacology of estrogens and progestogens: influence of different routes of administration" (PDF). Climacteric. 8 (Suppl 1): 3–63. doi:10.1080/13697130500148875. PMID 16112947. S2CID 24616324.
  2. ^ a b c d e f g Michael Oettel; Ekkehard Schillinger (6 December 2012). Estrogens and Antiestrogens II: Pharmacology and Clinical Application of Estrogens and Antiestrogen. Springer Science & Business Media. pp. 235–237, 261, 271. ISBN 978-3-642-60107-1. Natural estrogens considered here include: [...] Esters of 17β-estradiol, such as estradiol valerate, estradiol benzoate and estradiol cypionate. Esterification aims at either better absorption after oral administration or a sustained release from the depot after intramuscular administration. During absorption, the esters are cleaved by endogenous esterases and the pharmacologically active 17β-estradiol is released; therefore, the esters are considered as natural estrogens.
  3. ^ a b R. S. Satoskar; S. D. Bhandarkar &nirmala N. Rege (1969). Pharmacology And Pharmacotherapeutics (New Revised 21 St Ed.). Popular Prakashan. p. 24. ISBN 978-81-7991-527-1. Retrieved 29 May 2012.
  4. ^ Gordon L. Amidon; Ping I. Lee; Elizabeth M. Topp (2000). Transport Processes in Pharmaceutical Systems. CRC Press. pp. 188–189. ISBN 978-0-8247-6610-8. Retrieved 29 May 2012.
  5. ^ Parkes AS (February 1938). "Effective Absorption of Hormones". Br Med J. 1 (4024): 371–3. doi:10.1136/bmj.1.4024.371. PMC 2085798. PMID 20781252.
  6. ^ Düsterberg B, Nishino Y (December 1982). "Pharmacokinetic and pharmacological features of oestradiol valerate". Maturitas. 4 (4): 315–24. doi:10.1016/0378-5122(82)90064-0. PMID 7169965.
  7. ^ J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 897–. ISBN 978-1-4757-2085-3.
  8. ^ Index Nominum 2000: International Drug Directory. Taylor & Francis US. 2000. pp. 404–406. ISBN 978-3-88763-075-1. Retrieved 13 September 2012.
  9. ^ William Andrew Publishing (22 October 2013). Pharmaceutical Manufacturing Encyclopedia, 3rd Edition. Elsevier. pp. 1477–. ISBN 978-0-8155-1856-3.
  10. ^ Oriowo MA, Landgren BM, Stenström B, Diczfalusy E (April 1980). "A comparison of the pharmacokinetic properties of three estradiol esters". Contraception. 21 (4): 415–24. doi:10.1016/s0010-7824(80)80018-7. PMID 7389356.
  11. ^ a b C. W. Emmens (22 October 2013). Hormone Assay. Elsevier Science. pp. 394–395. ISBN 978-1-4832-7286-3.