chlormadinone acetate chlormadinone acetate chlormadinone acetate (cma), sold under the brand names belara, gynorelle, lutéran, and prostal among others, is a progestin and antiandrogen medication which is used in birth control pills to prevent pregnancy, as a component of menopausal hormone therapy, in the treatment of gynecological disorders, and in the treatment of androgen-dependent conditions like enlarged prostate and prostate cancer in men and acne and hirsutism in women. it is available both at a low dose in combination with an estrogen in birth control pills and, in a few countries like france and japan, at low, moderate, and high doses alone for various indications. it is taken by mouth. chlormadinone acetateclinical datatrade namesbelara, lutéran, prostal, othersother namescma; rs-1280; ici-39575; stg-155; nsc-92338; 17α-acetoxy-6-chloro-6-dehydroprogesterone; 17α-acetoxy-6-chloropregna-4,6-diene-3,20-dioneroutes ofadministrationby mouthdrug classprogestogen; progestin; progestogen ester; antigonadotropin; steroidal antiandrogenatc codeg03db06 (who) legal statuslegal status in general: ℞ (prescription only) pharmacokinetic databioavailability100%protein binding96.6–99.4% (to albumin and not to shbg or cbg)metabolismliver (reduction, hydroxylation, deacetylation, conjugation)metabolites• 3α-hydroxy-cma• 3β-hydroxy-cma• otherselimination half-life25–89 hoursexcretionurine: 33–45%feces: 24–41%identifiers iupac name phenanthren-17-yl] acetate cas number302-22-7 1961-77-9 (chlormadinone)pubchem cid9324drugbankdb15903chemspider8963unii0sy050l61nkeggd01299chebichebi:31394chemblchembl110691comptox dashboard (epa)dtxsid6020274 echa infocard100.005.563 chemical and physical dataformulac23h29clo4molar mass404.93 g·mol−13d model (jsmol)interactive image smiles cc(=o)1(cc21(cc32c=c(c4=cc(=o)cc34c)cl)c)oc(=o)c inchi inchi=1s/c23h29clo4/c1-13(25)23(28-14(2)26)10-7-18-16-12-20(24)19-11-15(27)5-8-21(19,3)17(16)6-9-22(18,23)4/h11-12,16-18h,5-10h2,1-4h3/t16-,17+,18+,21-,22+,23+/m1/s1key:qmbjsibworfwqt-dfxbjwiesa-n side effects of the combination of an estrogen and cma include menstrual irregularities, headaches, nausea, breast tenderness, vaginal discharge, and others. at high dosages, cma can cause sexual dysfunction, demasculinization, adrenal insufficiency, and changes in carbohydrate metabolism among other adverse effects. the drug is a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone. it is also an antiandrogen, and hence is an antagonist of the androgen receptor, the biological target of androgens like testosterone and dihydrotestosterone. due to its progestogenic activity, cma has antigonadotropic effects. the medication has weak glucocorticoid activity and no other important hormonal activity. cma was discovered in 1959 and was introduced for medical use in 1965. it may be considered a "first-generation" progestin. the medication was withdrawn in some countries in 1970 due to concerns about mammary toxicity observed in dogs, but this turned out not to apply to humans. cma is available widely throughout the world in birth control pills, but is notably not marketed in any predominantly english-speaking countries. it is available alone in only a few countries, including france, mexico, japan, and south korea. medical uses cma is used at a low dose in combination with ethinylestradiol (ee), an estrogen, in combined birth control pills. it has also been used in the treatment of gynecological conditions including vaginal bleeding, oligomenorrhea, polymenorrhea, hypermenorrhea, dysmenorrhea, secondary amenorrhea, and endometriosis and in france (under the brand name lutéran) in menopausal hormone therapy in combination with an estrogen. cma is used at dosages of 1 to 2 mg/day in combined birth control pills and at dosages of 2 to 10 mg/day in the treatment of gynecological disorders. combined birth control pills containing ee and cma have been found to be useful in reducing androgen-dependent symptoms such as skin and hair conditions. dosages of cma of 15 to 20 mg/day have been found to improve hot flashes. high-dose cma-only tablets are used as a form of progestogen-only birth control, although they are not specifically licensed as such. cma has been widely used as a means of androgen deprivation therapy in the treatment of prostate cancer and benign prostatic hyperplasia (bph) in japan and south korea, but has seen little use for these indications elsewhere in the world. it is used at dosages of 50 to 100 mg/day in the treatment of prostate diseases. similarly to cyproterone acetate (cpa), cma shows a lower risk of hot flashes than gonadotropin-releasing hormone analogues (gnrh analogues). the medication is the only other steroidal antiandrogen besides cpa that has been approved and used for the treatment of prostate cancer; megestrol acetate has also been researched, but has not been approved. cma has also been found to be effective in the treatment of other androgen-dependent conditions such as acne, seborrhea, hirsutism, and pattern hair loss in women, similarly to cpa. it has been studied at moderate dosages of 4 to 12 mg/day in the treatment of precocious puberty in girls. it showed similar benefits as those of medroxyprogesterone acetate in these girls and was found to reduce, but not abolish premature development such as breast growth and menstruation. only slight or no axillary hair growth was observed in the girls. cma has also been used as a component of hormone therapy for transgender women, similarly to cpa and spironolactone, albeit mostly only in japan. cma has been used to prevent the testosterone flare at the start of gonadotropin-releasing hormone agonist therapy in men with prostate cancer. available forms cma is available in the form of oral tablets at low doses (2 mg) in combination with ee in birth control pills (e.g., as belara in germany and brazil), at low to moderate doses (2, 5, 10, 25 mg) alone (e.g., as lutéran in france and lutoral in mexico), and at high doses (50 mg) alone (e.g., as prostal in japan and prostal-l in south korea). contraindications contraindications of combined birth control pills, such as those containing ee and cma, include known or suspected pregnancy, lactation and breastfeeding, a history of or known susceptibility to thromboembolism, cholestasis (but not liver cirrhosis or chronic hepatitis), and breast cancer among others. cma is a teratogen in animals and may have the potential to cause fetal harm, such as feminization of male fetuses among other defects. side effects