Progestogen ester

A progestogen ester is an ester of a progestogen or progestin (a synthetic progestogen). The prototypical progestogen is progesterone, an endogenous sex hormone. Esterification is frequently employed to improve the pharmacokinetics of steroids, including oral bioavailability, lipophilicity, and half-life. In addition, with intramuscular injection, steroid esters are often absorbed more slowly into the body, allowing for less frequent administration. Many (though not all) steroid esters function as prodrugs. Esterification is particularly salient in the case of progesterone because progesterone itself shows very poor oral pharmacokinetics and is thus ineffective when taken orally. Unmodified, it has a half-life of only 5 minutes, and is almost completely inactivated by the liver during first-pass metabolism.Micronization, however, has allowed for progesterone to be effective orally, although oral micronized progesterone was not developed until recent years.

Estradiol was discovered in 1929, and beginning in 1936, a variety of estradiol esters, such as estradiol benzoate and estradiol dipropionate, were introduced for clinical use.Testosterone esters, such as testosterone propionate and testosterone phenylacetate, were also introduced around this time. In contrast to estradiol and testosterone, progesterone proved more difficult to esterify. In fact, esterification involves the replacement of a hydroxy group with an alkoxy group, and unlike estradiol and testosterone, progesterone does not possess any hydroxy groups, so it is actually not chemically possible to esterify progesterone itself. The first progestogen esters were not introduced until the mid-1950s, and were esters of 17α-hydroxyprogesterone (which, unlike progesterone, has a hydroxy group available for esterification) rather than of progesterone; they included 17α-hydroxyprogesterone caproate (Delalutin, Proluton) and 17α-hydroxyprogesterone acetate (Prodrox). The following quote of de Médicis Sajous et al. (1961) details the development of progestogen esters:

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