Cyclogest Mechanism of Action

Pharmacotherapeutic group: Sex hormones and modulators of the genital system; Progestogens; Pregnen-(4) derivatives. ATC code: G03DA04.
Pharmacology: Pharmacodynamics: Progesterone is a naturally occurring steroid that is secreted by the ovary, placenta, and adrenal gland. In the presence of adequate estrogen, progesterone transforms a proliferative endometrium into a secretory endometrium. Progesterone is necessary to increase endometrial receptivity for implantation of an embryo. Once an embryo is implanted, progesterone acts to maintain the pregnancy.
Clinical efficacy and safety: In a Phase III clinical trial in pre-menopausal women subjected to ART and IVF the pregnancy rates after vaginally applied Cyclogest suppository (400 mg twice daily) was found to be 38.3% (FAS) and 38.1% (PP) after 38 days of luteal phase support. The clinical pregnancy rate was 34.5% after 70 days of luteal phase support.
Pharmacokinetics: Absorption: Vaginal administration of Cyclogest 400 mg every 12 h in healthy women has been shown effective in rapidly achieving and maintaining serum progesterone concentrations at physiological levels appropriate to the midluteal phase of the ovarian cycle and early pregnancy.
The mean C_max after 10 days of multiple dosing was 18.4 [ng/mL] and C_trough was 10.5 [ng/mL].
Distribution: Progesterone is approximately 96% to 99% bound to serum proteins, primarily to serum albumin and corticosteroid binding globulin.
Biotransformation: Progesterone is metabolized primarily by the liver largely to pregnanediols and pregnanolones. Pregnanediols and pregnanolones are conjugated in the liver to glucuronide and sulfate metabolites.
Progesterone metabolites that are excreted in the bile may be deconjugated and may be further metabolized in the gut via reduction, dehydroxylation, and epimerization.
Elimination: Progesterone undergoes renal and biliary elimination.
Toxicology: Preclinical safety data: There are no preclinical data of relevance to the prescriber which are additional to those already included in other sections of the monograph.