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.

[1] Side effects of the combination of an estrogen and CMA include menstrual irregularities, headaches, nausea, breast tenderness, vaginal discharge, and others.

[2] At high dosages, CMA can cause sexual dysfunction, demasculinization, adrenal insufficiency, and changes in carbohydrate metabolism among other adverse effects.

[5][25] 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.

[24] 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.

[7][29] 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.

[7] 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.

[31] CMA has been used to prevent the testosterone flare at the start of gonadotropin-releasing hormone agonist therapy in men with prostate cancer.

[11][37] 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.

[39][40] The most common side effects of birth control pills containing EE and low-dose CMA have been found to include menstrual abnormalities, headache (37%), nausea (23%), breast tenderness (22%), and vaginal discharge (19%) among others.

[2] These formulations do not adversely affect sexual desire or function in women and show little or no risk of depression, mood swings, or weight gain.

[23] Similarly to other progestins but in contrast to progesterone, CMA has been found to significantly increase the risk of breast cancer when used in combination with an estrogen in menopausal hormone therapy.

[41] No abnormalities in liver function tests have been observed in women taking combined birth control pills containing CMA or CPA.

[45] CMA has been studied in men with advanced prostate cancer at massive dosages of 1,000 to 2,000 mg/day orally and 100 to 500 mg/day via intramuscular injection, without serious adverse effects or toxicity described.

[2][53][12] As a result, CMA suppresses ovulation and gonadal sex hormone production and can strongly decrease circulating testosterone and estradiol levels at sufficiently high dosages.

[1][2][5] Unlike progesterone but similarly to other progestins, CMA has no known neurosteroid activity (e.g., GABAA receptor modulation) or sedative effects.

[5][2] Certain progestins have been found to stimulate the proliferation of MCF-7 breast cancer cells in vitro, an action that is independent of the classical PRs and is instead mediated via the progesterone receptor membrane component-1 (PGRMC1).

[60] It is unclear if these findings may explain the different risks of breast cancer observed with progesterone and progestins in clinical studies.

[1][2] Reduction occurs at the C3 ketone with preservation of the δ4(5) double bond, hydroxylation is at the C2α, C3α, C3β, and C15β positions, and conjugation includes glucuronidation and sulfation.

[17][18] It was the first sequential contraceptive pill to be introduced in the U.S.[18] CMA has also been marketed in combination with mestranol under the brand names Ovosiston, Aconcen, and Sequens.

[67][68] Due to findings of mammary gland nodules in beagle dogs (see below), C-Quens was voluntarily withdrawn from the U.S. market by Eli Lilly in 1971 and all oral contraceptives of CMA were discontinued in the U.S. by 1972.

[69] However, subsequent research found that there is no such risk in humans,[70] and CMA has continued to be widely used in oral contraceptives in many other countries, such as Germany and China.

[71] The antiandrogenic activity of CMA was first described in 1966,[5][72] and the medication was subsequently developed for use alone at high dosages in the treatment of androgen-dependent conditions like prostate cancer.

[20][21] Tumors were also observed with progesterone, as well as with ethynerone and chloroethynylnorgestrel, but notably not with the non-halogenated 19-nortestosterone derivatives norgestrel, norethisterone, noretynodrel, or etynodiol diacetate, which remained on the market.

[11] CMA has been marketed under a variety of brand names throughout the world including Clordion, Gestafortin, Gestogan, Lormin, Lutéran, Lutoral, Menstridyl, Non-Ovlon, Normenon, Prococyd, Progestormon, Prostal, Synchrogest, Verton, and many others.

[24][74][11][63] It is available in many countries in combination with EE, including throughout most of Europe and Latin America, and in Japan, Thailand, Israel, Lebanon, Tunisia, and Oman (but notably not South Korea).