GynProgesterone Mechanism of Action

Pharmacotherapeutic group: Urogenital system and sex hormones. ATC: G03DA04.
Pharmacology: Pharmacodynamics: Mechanism of action: Progesterone is a progestinic hormone secreted mainly from the corpus luteum of the ovary during the latter half of the menstrual cycle. Progesterone is formed from steroid precursors in the ovary, testis, adrenal cortex, and placenta. Luteinizing hormone (LH) stimulates the synthesis and secretion of progesterone from the corpus luteum. Progesterone is necessary for nidation (implantation) of the ovum and for maintenance of pregnancy.
Progesterone shares the pharmacologic actions of the progestins. Progesterone stimulates the growth of mammary alveolar tissue and relaxes uterine smooth muscle. Progesterone has minimal estrogenic and androgenic activity.
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-nortertosterone 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.
Toxicology: Preclinical safety data: The carcinogenic and mutagenic potentials of progesterone have not been specifically determined.