Utrogestan Mechanism of Action

Pharmacotherapeutic group: urogenital system and sex hormones. ATC-code: G03DA04.
Pharmacology: Pharmacodynamics: Progesterone is the natural progestogen, the main hormone of the corpus luteum and the placenta. It reacts specifically with Progesterone receptor which regulates gene transcription through direct interaction with DNA. It acts on the endometrium by converting the proliferating phase to the secretory phase with predecidualization of the endometrium. Micronised Progesterone has all the properties of endogenous Progesterone with dose-dependent induction of a full secretory endometrium and has in particular gestagenic, antiestrogenic, slightly antiandrogenic and tranquillising through the interactions with the GABA receptors and antialdosterone effects.
Pharmacokinetics: Progesterone has a short elimination half-life and undergoes extensive first-pass hepatic metabolism when given orally; oral bioavailability is very low although it may be increased somewhat by an oily vehicle and by micronisation. Progesterone is absorbed when given buccally, rectally, or vaginally, and rapidly absorbed from the site of an oily intramuscular injection.
Various derivatives have been produced to extend the duration of action and to improve oral activity. Esters of progesterone derivatives such as hydroxyprogesterone caproate are used intramuscularly, and megestrol acetate is orally active. The ester medroxyprogesterone acetate is used orally and parenterally. 19-Nortestosterone progestogens have good oral activity because the 17-ethinyl substituent slows hepatic metabolism.
Progesterone and the progestogens are highly protein bound; progesterone is bound to albumin and corticosteroid binding globulin; esters such as medroxyprogesterone acetate are mainly bound to albumin; and 19-nortestosterone analogues are bound to sex-steroid binding globulin and albumin. Progesterone is metabolized in the liver to various metabolites including pregnanediol, which are excreted in the urine as sulfate and glucuronide conjugates. Similarly, progestogens undergo hepatic metabolism to various conjugates, which are excreted in the urine. Progesterone is distributed into breast milk.
Pharmacokinetic parameters after administration of progesterone: According to route of administration: The comparison of the pharmacokinetics showed a significant difference for mean plasma concentrations of Area Under the Curve (AUC;ng.h/ml). Mean concentration in the steady state (CSS) and Maximum concentration (Cmax) after one factor variance analysis for four groups taken together: the test was also significant. (P<0.0001), and (P<0.05 for Tmax). (See table.)

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Toxicology: Preclinical safety data: Data not supplied.