Exprogest Mechanism of Action

Pharmacotherapeutic group: Sex hormones and modulators of the genital system, progestogens. ATC code: G03DA04.
Pharmacology: Pharmacodynamics: Progesterone (Exprogest), which contains micronised progesterone, significantly raises plasma progesterone concentrations after oral use. It therefore corrects progesterone deficiencies.
The active ingredient, progesterone, is chemically identical to the progesterone produced by the corpus luteum during the female ovarian cycle. It exerts many biological actions, mainly on target tissues previously sensitized by estrogens. Progesterone transforms proliferative endometrium into secretory state.
In postmenopausal women, estrogens promote the growth of the endometrium and unopposed oestrogens increase the risk of endometrial hyperplasia and cancer. The addition of a progesterone greatly reduces the estrogen induced risk of endometrial hyperplasia in non-hysterectomised women.
During pregnancy, progesterone increases endometrial receptivity for implantation of an embryo. Once the embryo has been implanted, progesterone acts to maintain the pregnancy. Progesterone also relaxes uterine smooth muscle.
Pharmacokinetics: Absorption: Absorption through the vaginal mucosa is rapid, producing high plasma concentrations of progesterone after 1 hour.
Distribution: Peak plasma concentration is reached 2-6 hours after application. After administration of 100 mg in the morning and 100 mg at night, a mean plasma concentration of 9.7 ng/ml (30.9 nmol/l) is obtained for 24 hours. This dosage of 200 mg per day induces stable physiological plasma concentrations of progesterone, similar to those observed during the luteal phase of a menstrual cycle with normal ovulation. Inter-individual variations of progesteronaemia are less with vaginal administration and results can therefore be better predicted using this route. With doses of over 200 mg per day, progesterone plasma concentrations comparable to those described during the first trimester of pregnancy are obtained.
Metabolism: The plasma concentration of 5β-pregnenolone does not increase with this route of administration.
Elimination: Urinary elimination is primarily in the form of 5α,5β-pregnanediol (pregnandiol), as shown by the rise in its concentration (which reaches its peak level of 142 ng/ml (415.6 nmol/l) at 6 hours).
Toxicology: Preclinical safety data: Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction.