Chlormadinone acetate (CMA) is a derivative of
progesterone (17alpha-acetoxy-6-chloro-4,6-pregnadiene-3,20-dione), first synthesized in 1961 and is used as an orally effective
progestogen in
hormone replacement therapy (HRT), and in combination with
ethinyl estradiol (EE) in
contraception since 1999.
Chlormadinone acetate has a strong progestogenic effect - about one-third higher than that of
progesterone - and may vary depending on the previous effect of an
estrogen, i.e.,
estrogens may promote the formation of
progesterone receptors and proliferation of the endometrium. Like
progesterone, it is anti-estrogenic and has no partial androgenic effect (at the doses used for
contraception and HRT). In contrast to
progesterone, it has a slight
glucocorticoid effect, a pronounced anti-androgenic effect and no anti-
mineralocorticoid effect. No pregnancy-maintaining effect of CMA has been demonstrated in humans. The anti-androgenic effect of CMA is presumed to be the result of both its binding to
androgen receptors - competitively inhibiting the effect of endogenous
testosterone and
dihydrotestosterone - and the competitive inhibition of 5alpha-reductase. In this respect, dosing of CMA is crucial; agonistic effects are observed when doses are increased from those optimal for an antagonistic effect.
Chlormadinone acetate has a strong anti-gonadotropic effect, through negative feedback on
gonadotropin secretion, and has been used for more than 20 years alone for
contraception in arterial risk patients. The clinical and metabolic tolerability of CMA has been demonstrated in numerous clinical studies with
duration of treatment of up to 2.5 years. The more recent application of CMA as an
oral contraceptive in combination with EE (
Neo Eunomin,
Belara) has proven highly successful, with studies reporting excellent
contraceptive efficacy, high tolerability and adherence due to a good side effect profile and positive effects on preexisting
dysmenorrhea, skin and hair conditions.