All progestins are not created equal

Frank Z. Stanczyk
In: Steroids · 2003 · vol. 68(10-13) , pp. 879–890 · doi:10.1016/j.steroids.2003.08.003 · PMID:14667980 · W2037043326
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Progestins, classified by their chemical relation to progesterone or testosterone, exhibit diverse structures, metabolism, pharmacokinetics, and potencies, leading to significant differences in their therapeutic effects.

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Abstract

A variety of progestins are available for therapeutic use. It is convenient to classify them into those related in chemical structure to progesterone or testosterone. Progestins related to progesterone can be subdivided into pregnanes and 19-norpregnanes, whereas those related to testosterone can be subdivided into those with and without a 17-ethinyl group. 17-Ethinylated progestins consist of the families of norethindrone (estranes) and levonorgestrel (13-ethylgonanes). Progestins administered orally undergo extensive hepatic first pass metabolism primarily by reduction and conjugation, and in most instances, relatively high progestin doses are required for therapeutic use. There are limited reliable data on the pharmacokinetics of most progestins. Some progestins are prodrugs, requiring transformation prior to exhibiting progestational activity. Qualitative and quantitative tests utilizing either human or animal species have been used to establish progestin potency. However, profound differences in progestational activity are often observed between human and animal tissues. Also, there is a misconception about androgenicity of progestins due largely to extrapolation of data from rat studies to the human. Progestins differ widely in their chemical structures, structure-function relationships, metabolism, pharmacokinetics, and potencies; they are not created equal.

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