Chlormadinone acetate (CMA) is a progesterone derivative (17α-acetoxy-6-chloro-4,6-pregnadiene-3,20-dione), first synthesized in 1961. It was used as progestin-based hormone replacement therapy; since 1999 it was first used for oral contraception combined with ethinyl estradiol (EE). CMA exerts a potent progestagenic effect, about one third higher than that observed with endogenous progesterone. CMA is also an anti-estrogen, showing no androgenic effects (at birth control dose). Unlike progesterone, it has a mild glucosteroidal effect with no anti-mineralocorticoid effect at all. These biological actions have allowed CMA to have a role for therapeutic use in dysmenorrhea, hyperandrogenism, and as a contraceptive agent. In addition, CMA has exhibited beneficial neuroendocrine effects on women's mood. CMA-EE combination has shown excellent contraceptive efficacy, high tolerability, and compliance due to its risk-benefit profile, having additional benefits on skin and hair, such as reduction of seborrhea and acne. Metabolic tolerance of CMA has been demonstrated in several clinical studies. Currently, CMA is formulated to be taken as oral caplets in a 21 caplets package containing 0.03 mg/EE and 2 mg CMA per pill with/without seven placebo additional pills. Another presentation has 24 caplets containing 0.02 mg/EE and 2 mg CMA plus four placebo pills.
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