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Chemistry

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Also known as: 302-22-7, Gestafortin, Menstridyl, Normenon, Matrol, Cero
Molecular Formula
C23H29ClO4
Molecular Weight
404.9  g/mol
InChI Key
QMBJSIBWORFWQT-DFXBJWIESA-N
FDA UNII
0SY050L61N

Chlormadinone Acetate
An orally active synthetic progestational hormone used often in combinations as an oral contraceptive (CONTRACEPTIVES, ORAL).
1 2D Structure

Chlormadinone Acetate

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
[(8R,9S,10R,13S,14S,17R)-17-acetyl-6-chloro-10,13-dimethyl-3-oxo-2,8,9,11,12,14,15,16-octahydro-1H-cyclopenta[a]phenanthren-17-yl] acetate
2.1.2 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/s1
2.1.3 InChI Key
QMBJSIBWORFWQT-DFXBJWIESA-N
2.1.4 Canonical SMILES
CC(=O)C1(CCC2C1(CCC3C2C=C(C4=CC(=O)CCC34C)Cl)C)OC(=O)C
2.1.5 Isomeric SMILES
CC(=O)[C@]1(CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2C=C(C4=CC(=O)CC[C@]34C)Cl)C)OC(=O)C
2.2 Other Identifiers
2.2.1 UNII
0SY050L61N
2.3 Synonyms
2.3.1 MeSH Synonyms

1. Chlormadinon Acetate

2. Chlormadinone

3. Chlormadinone Acetate, (9 Beta,10 Alpha)-isomer

4. Neo Eunomin

5. Neo-eunomin

6. Neoeunomin

7. Pregna-4,6-diene-3,20-dione, 17-(acetyloxy)-6-chloro-

2.3.2 Depositor-Supplied Synonyms

1. 302-22-7

2. Gestafortin

3. Menstridyl

4. Normenon

5. Matrol

6. Cero

7. Chlormadinon Acetate

8. Pregna-4,6-diene-3,20-dione, 17-(acetyloxy)-6-chloro-

9. Nsc-92338

10. Bovisynchron

11. Chlordion

12. Clordion

13. Fertiletten

14. Minipill

15. Lutinyl

16. Skedule

17. Traslan

18. Retex

19. Synchrosyn P

20. Skedule Tm

21. Lutoral (syntex)

22. Chloramdinone Acetate

23. Synchrosyn

24. Chloromadinone Acetate

25. 17-(acetyloxy)-6-chloropregna-4,6-diene-3,20-dione

26. 17alpha-acetoxy-6-chloro-6-dehydroprogesterone

27. Chloromadinone 17-acetate

28. Chlormadinonu

29. Mls000028451

30. Mls001148653

31. 6-chloro-17-hydroxypregna-4,6-diene-3,20-dione Acetate

32. 6-chloro-17alpha-hydroxypregna-4,6-diene-3,20-dione Acetate

33. Chebi:31394

34. 0sy050l61n

35. Ay 13390-6

36. [(8r,9s,10r,13s,14s,17r)-17-acetyl-6-chloro-10,13-dimethyl-3-oxo-2,8,9,11,12,14,15,16-octahydro-1h-cyclopenta[a]phenanthren-17-yl] Acetate

37. Ncgc00022680-04

38. Chlormadinone (acetate)

39. Smr000058325

40. 17-acetoxy-6-chloro-6-dehydroprogesterone

41. Dsstox_cid_274

42. Dsstox_rid_75478

43. 6-chloro-3,20-dioxopregna-4,6-dien-17-yl Acetate

44. 6-chloro-6-dehydro-17.alpha.-acetoxyprogesterone

45. Dsstox_gsid_20274

46. 6-chloro-6-dehydro-17.alpha.-hydroxyprogesterone Acetate

47. Chlormadinonu [polish]

48. Clormadinone Acetate

49. Progesterone, 6-chloro-6-dehydro-17-hydroxy-, Acetate

50. Pregna-4,6-diene-3,20-dione, 17-(acetoxy)-6-chloro-

51. (8r,9s,10r,13s,14s,17r)-17-acetyl-6-chloro-10,13-dimethyl-3-oxo-2,3,8,9,10,11,12,13,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-17-yl Acetate

52. Cas-302-22-7

53. Ccris 129

54. Hsdb 3591

55. Einecs 206-118-0

56. 6-chloro-delta6-17-acetoxyprogesterone

57. Nsc92338

58. Pregna-4,6-diene-3,20-dione, 6-chloro-17-hydroxy-, Acetate

59. Unii-0sy050l61n

60. 6-chloro-delta6-(17alpha)acetoxyprogesterone

61. 6-chloro-6-dehydro-17alpha-acetoxyprogesterone

62. 6-chloro-delta(sup 6)-17-acetoxyprogesterone

63. Chlormadinone Acetate [progestins]

64. 17-alpha-acetoxy-6-chloro-6-dehydroprogesterone

65. 6-chloro-6-dehydro-17-alpha-acetoxyprogesterone

66. 6-dehydro-6-chloro-17-alpha-acetoxyprogesterone

67. 17-alpha-acetoxy-6-chloro-6,7-dehydroprogesterone

68. 6-chloro-.delta.6-17-acetoxyprogesterone

69. Chlormadinone-acetate

70. Delta(sup 6)-6-chloro-17-alpha-acetoxyprogesterone

71. Delta(sup 6)-6-chloro-17alpha-acetoxyprogesterone

72. Lutoral (tn)

73. 6-chloro-delta-6-17alpha-hydroxyprogesterone Acetate

74. Chlormadinone Acetate [usan:jan:nf]

75. 6-chloro-6-dehydro-17alpha-hydroxyprogesterone Acetate

76. 6-chloro-delta(sup 6)-dehydro-17-acetoxyprogesterone

77. 17-alpha-acetoxy-6-chloro-4,6-pregnadiene-3,20-dione

78. 6-chloro-17-alpha-acetoxy-4,6-pregnadiene-3,20-dione

79. 6-chloro-6-dehydro-17-alpha-hydroxyprogesterone Acetate

80. 6-chloro-pregna-4,6-dien-17alpha-ol-3,20-dione Acetate

81. 6-chloro-17-alpha-hydroxy-delta(sup 6)-progesterone Acetate

82. 6-chloro-pregna-4,6-dien-17-alpha-ol-3,20-dione Acetate

83. Opera_id_343

84. 17.alpha.-acetoxy-6-chloro-6-dehydroprogesterone

85. 6-chloro-.delta.6-[17.alpha.]acetoxyprogesterone

86. Acetic Acid Chlormadinone

87. .delta.(sup 6)-6-chloro-17.alpha.-acetoxyprogesterone

88. 6-chloro-delta(sup 4,6)-pregnadiene-17-alpha-ol-3,20-dione 17-acetate

89. Schembl15046

90. Chembl110691

91. Chlormadinone Acetate, >=98%

92. Dtxsid6020274

93. Chlormadinone Acetate [mi]

94. Hms2231j04

95. Hms3715e19

96. Chlorinated Phenylmethylpolysiloxane

97. Chlormadinone Acetate [jan]

98. Bcp28307

99. Hy-b1095

100. Zinc3876041

101. Chlormadinone Acetate (jp17/usan)

102. Chlormadinone Acetate [hsdb]

103. Chlormadinone Acetate [usan]

104. Tox21_110881

105. Tox21_200665

106. Mfcd00056471

107. S4593

108. 6-chloro-pregna-4,20-dione Acetate

109. Chlormadinone Acetate [mart.]

110. Akos015955610

111. Chlormadinone Acetate [who-dd]

112. Tox21_110881_1

113. Ccg-220989

114. Cs-4683

115. Ks-5157

116. Rs-1280

117. Ay-13390-6

118. Ncgc00022680-05

119. Ncgc00258219-01

120. (1s,11s,15s,2r,10r,14r)-14-acetyl-8-chloro-2,15-dimethyl-5-oxotetracyclo[8.7.0 .0<2,7>.0<11,15>]heptadeca-6,8-dien-14-yl Acetate

121. 17.alpha.-acetoxy-6-chloro-4,20-dione

122. 6-chloro-17.alpha.-acetoxy-4,20-dione

123. Chlormadinone Acetate [ep Monograph]

124. Chlormadinone Acetate For System Suitability

125. 17.alpha.-acetoxy-6-chloropregna-4,20-dione

126. 6-chloro-.delta.(sup 4,20-dione 17-acetate

127. 6-chloro-17-hydroxypregna-4,20-dione Acetate

128. C74552

129. D01299

130. 6-chloro-.delta.(sup 6)-17-acetoxyprogesterone

131. Pregna-4,20-dione, 17-(acetyloxy)-6-chloro-

132. 302c227

133. Sr-01000003040

134. Pregna-4,20-dione, 6-chloro-17-hydroxy-, Acetate

135. Q-200829

136. Q5102980

137. Sr-01000003040-2

138. 6-chloro-17.alpha.-hydroxypregna-4,20-dione Acetate

139. 17alpha-acetoxy-6-chloropregna-4,6-diene-3,20-dione

140. 6-chloro-.delta.(sup 6)-dehydro-17-acetoxyprogesterone

141. 17.alpha.-acetoxy-6-chloro-6,7-dehydroprogesterone

142. 6-chloro-.delta.-6-17.alpha.-hydroxyprogesterone Acetate

143. Chloromadinone 17-acetate 100 Microg/ml In Methanol/water

144. Wln: L E5 B666 Ov Ku Mutj A1 E1 Fv1 Fov1 Lg

145. 6-chloro-17.alpha.-hydroxy-.delta.(sup 6)-progesterone Acetate

146. Chlormadinone Acetate, European Pharmacopoeia (ep) Reference Standard

147. (8r,9s,10r,13s,14s,17r)-17-acetyl-6-chloro-10,13-dimethyl-3-oxo-2,3,8,9,10,11,12,13,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-17-ylacetate

2.4 Create Date
2005-03-26
3 Chemical and Physical Properties
Molecular Weight 404.9 g/mol
Molecular Formula C23H29ClO4
XLogP33.6
Hydrogen Bond Donor Count0
Hydrogen Bond Acceptor Count4
Rotatable Bond Count3
Exact Mass404.1754371 g/mol
Monoisotopic Mass404.1754371 g/mol
Topological Polar Surface Area60.4 Ų
Heavy Atom Count28
Formal Charge0
Complexity827
Isotope Atom Count0
Defined Atom Stereocenter Count6
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count1
4 Drug and Medication Information
4.1 Therapeutic Uses

Contraceptives, Oral, Synthetic; Progestational Hormones, Synthetic

National Library of Medicine's Medical Subject Headings online file (MeSH, 2009)


Chlormadinone acetate has not been used in the United States since 1970, when the only product (an oral contraceptive) was removed from the market. Its use in the United Kingdom was suspended in the same year. Before suspension, chlormadinone acetate was used in oral contraceptives either together with mestranol as a "sequential" contraceptive or as a "progestogen only" oral contraceptive. Chlormadinone acetate has been used (frequently in combination with mestranol) for treatment of threatened abortion and dysmenorrhea.

IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V72 584 (1999)


Ethinylestradiol/chlormadinone acetate 0.03/2mg (EE/CMA) is a combined monophasic contraceptive pill with anti-androgenic properties. In a large, non-comparative, multicentre trial (< or =24 cycles of treatment per woman) and two (6- and 12-cycle) post-marketing surveillance studies, EE/CMA was effective in preventing pregnancy. EE/CMA was significantly more effective than EE/levonorgestrel 0.03/0.15 mg/day in treating women with mild-to-moderate papulopustular acne of the face and related disorders in a randomized, single-blind, multicentre trial. EE/CMA was well tolerated in clinical trials and the post-marketing surveillance studies. Adverse events were those commonly reported with oral contraceptives. As expected, the most common menstrual disturbances were breakthrough bleeding, spotting and amenorrhea.

PMID:15025547 Curran MP, Wagstaff AJ; Drugs 64 (7): 751-62 (2004)


Orally active progestogen with antiandrogenic activity; has been used in combinations as an oral contraceptive.

O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Whitehouse Station, NJ: Merck and Co., Inc., 2006., p. 348


For more Therapeutic Uses (Complete) data for CHLORMADINONE ACETATE (7 total), please visit the HSDB record page.


5 Pharmacology and Biochemistry
5.1 MeSH Pharmacological Classification

Androgen Antagonists

Compounds which inhibit or antagonize the biosynthesis or actions of androgens. (See all compounds classified as Androgen Antagonists.)


Contraceptives, Oral, Synthetic

Oral contraceptives which owe their effectiveness to synthetic preparations. (See all compounds classified as Contraceptives, Oral, Synthetic.)


Contraceptives, Oral, Hormonal

Oral contraceptives which owe their effectiveness to hormonal preparations. (See all compounds classified as Contraceptives, Oral, Hormonal.)


5.2 Absorption, Distribution and Excretion

... Pharmacokinetic studies have shown rapid and almost complete absorption after oral administration, and chlormadinone acetate is being bound to albumin rather than SHBG (Sex-Hormone-Binding-Globulin). Multiple dosing studies have demonstrated that steady state is reached by day 7 after oral administration with peak plasma concentrations in the region of 2 ng/mL. ...

PMID:16356876 Bouchard P; Eur J Contracept Reprod Health Care 10 Suppl 1: 7-11 (2005)


The half-life and metabolic clearance rate of chlormadinone acetate were computed after a single iv injection of 60 to 90 mcCi 1-alpha-tritiated-chlormadinone acetate (specific activity 222 mcCi/mg) into 7 women aged 34-52 years. Plasma was extracted with acetone:MeOH for total radioactivity; then extracted with water and ether for free steroid radioactivity; then with n-butanol for conjugated steroid radioactivity; and finally extracted with chloroform:MeOH and chromatographed on thin layer with ether:benzene for specific radioactivity due to chlormadinone acetate. Blood samples were taken at 0 .25, 0.5, 1, 8, 24 hours and every 24 hours for 5 days. ... All 4 curves, total radioactivity, conjugated steroids, free steroids, and specific activity had the same biphasic form: a rapid loss for about 24 hours, and an approaching equilibrium after 24 hours. The metabolic clearance rate was 42.61 liters per day... These data generate an estimate of the concentration of chlormadinone acetate in plasma of women taking 0.5 mg daily: about .45 ng/mL, i.e. about one-thirteenth the concentration of progesterone.

PMID:4134033 Dugwekar YG et al; Contraception 7 (1): 27-45 (1973)


Published data on pharmacokinetic parameters for chlormadinone acetate (CMA) are in part contradictory, especially with regard to terminal half-life (t(1/2,z)). Single and multiple doses of CMA (2 mg) and ethinylestradiol (EE; 0.03 mg) were administered to healthy female volunteers for six menstrual cycles. Plasma concentrations of CMA and EE were determined by gas chromatography-mass spectrometry. Single-dose and steady-state pharmacokinetic parameters were calculated. In a separate study, healthy female volunteers were given a single 2-mg dose of radiolabeled CMA. Concentrations of radioactivity in fecal and urine samples were determined via liquid scintillation. Excretion of total radioactivity was calculated as percentage of administered dose. Eighteen women completed the repeated-dose study. Peak plasma concentrations for CMA and EE were reached within 1 and 2 hr after taking the study drug. Peak plasma concentrations of CMA were approximately 1600 pg/mL after single-dose administration and 2000 pg/mL after multiple dosing. CMA and EE showed linear pharmacokinetics throughout six cycles, with constant trough values of approximately 400-500 pg/mL for CMA and 20-40 pg/mL for EE. Mass balance factors were 1.2-1.4 for CMA and 1.6-1.7 for EE, and accumulation factors were 1.7-2 for CMA and 1.7-1.8 for EE. Mean t(1/2,z) of CMA was approximately 25 hr after single dosing and 36-39 hr at steady state. In the excretion balance study, mean dose of CMA recovered was 87.3+/-6.4%, with urinary and fecal excretion accounting for 45% and 42%, respectively. The pharmacokinetics of CMA and EE is linear after multiple dosing and remains stable during long-term administration, once steady state is reached. The t(1/2,z) of CMA was 36-39 hr after multiple dosing, which is considerably shorter than the 80 hr often quoted in the literature.

PMID:16904418 Terlinden R et al; Contraception 74 (3): 239-44 (2006)


The bioavailability and bioequivalence of two different film coated tablets containing ethinylestradiol and chlormadinone acetate (Bellissima as test and the respective preparation from the originator as reference) were investigated in 20 healthy female volunteers after oral single-dose administration. The study was performed according to a single-center, randomised, single-dose, 2-way cross-over design with a wash-out phase of 28 days. Blood samples for pharmacokinetic profiling were taken up to 168 hr post-dose, and ethinylestradiol and chlormadinone acetate plasma concentrations were determined with a validated LC-MS/MS method. The observed mean maximum plasma concentrations (Cmax) of ethinylestradiol were 124.96 pg/mL (test) and 129.12 pg/mL (reference). In the case of chlormadinone acetate, Cmax averaged 6.9566 ng/mL (test) and 6.6663 ng/mL (reference). The geometric means of area under the plasma concentration-time curve (AUC(0-infinity)) of ethinylestradiol were 1292.35 pg/mL x hr (test) and 1380.49 pg/mL x hr (reference). For chlormadinone acetate, geometric means of AUC(0-infinity) were 53.322 ng/mL x hr (test) and 58.111 ng/mL x hr (reference). The median of tmax of ethinylestradiol was 1.5 hr for both test and reference and the median of tmax of chlormadinone acetate 1.0 hr (test) and 1.5 hr (reference). Plasma elimination half-lives (t1/2) of ethinylestradiol were 14.96 hr (test) and 15.41 hr (reference) and of chlormadinone acetate 56.63 hr (test) and 56.17 hr (reference), respectively. Both primary target parameters AUC(0-infinity) and Cmax were tested parametrically by analysis of variance (ANOVA). The point estimator and the 90% confidence intervals for the AUC(0-infinity) ratio (test/reference: 93.72% [86.62%-101.39%]) indicate high similarity of both formulations with respect to the extent of ethinylestradiol exposure. A high degree of similarity was also observed for Cmax of ethinylestradiol, as the point estimator and the 90% confidence interval for the Cmax ratio are 96.18% (90.82%-101.86%). Regarding the AUC(0-infinity) ratio of chlormadinone acetate, the point estimator is 91.60% and the 90% confidence interval 84.08%-99.79%. Furthermore, exchangeability of both formulations is also suggested by the point estimator and 90% confidence of Cmax of this active agent (104.72% [95.76%-114.53%]). Bioequivalence between test and reference formulation was demonstrated since for both ethinylestradiol and chlormadinone acetate all 90% confidence intervals of AUC(0-infinity) and Cmax fall into the generally accepted range of 80%-125%.

PMID:20108652 Bonn M et al; Arzneimittelforschung 59 (12): 651-8 (2009)


After intravenous injection of radiolabelled chlormadinone acetate, the steroid and its metabolites have an initial rapid half-life of 2.4 hours, followed by a slow half-life of 80.1 hours. The mean metabolic clearance rate is 126 L/day for chlormadinone acetate and 42.6 L/day for chlormadinone acetate and its metabolites. The long half-life and slow elimination rate are probably due to accumulation of the drug in fat tissue.

IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V72 226 (1999)


5.3 Metabolism/Metabolites

The major metabolites of chlormadinone acetate are 2alpha- hydroxychlormadinone acetate and 3beta-hydroxychlormadinone acetate. Incubation of chlormadinone acetate with human or rat liver microsomes produces mainly the 3beta-hydroxy metabolite. In contrast, incubation with microsomes from phenobarbital-treated rats produces the 2alpha-hydroxy metabolite, indicating that the metabolite pattern is dependent on the hepatic monoxygenase state.

IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V72 226 (1999)


5.4 Biological Half-Life

... After a single dose of CMA the half-life time is around 34 hours and after multiple dose administration approximately 38 hours. ...

PMID:16356876 Bouchard P; Eur J Contracept Reprod Health Care 10 Suppl 1: 7-11 (2005)


Published data on pharmacokinetic parameters for chlormadinone acetate (CMA) are in part contradictory, especially with regard to terminal half-life (t(1/2,z)). Single and multiple doses of CMA (2 mg) and ethinylestradiol (EE; 0.03 mg) were administered to healthy female volunteers for six menstrual cycles. ... Mean t(1/2,z) of CMA was approximately 25 hr after single dosing and 36-39 hr at steady state. ... The t(1/2,z) of CMA was 36-39 hr after multiple dosing, which is considerably shorter than the 80 hr often quoted in the literature.

PMID:16904418 Terlinden R et al; Contraception 74 (3): 239-44 (2006)


The half-life and metabolic clearance rate of chlormadinone acetate were computed after a single iv injection of 60 to 90 mcCi 1-alpha-tritiated-chlormadinone acetate (specific activity 222 mcCi/mg) into 7 women aged 34-52 years. Plasma was extracted with acetone:MeOH for total radioactivity; then extracted with water and ether for free steroid radioactivity; then with n-butanol for conjugated steroid radioactivity; and finally extracted with chloroform:MeOH and chromatographed on thin layer with ether:benzene for specific radioactivity due to chlormadinone acetate. Blood samples were taken at .25, .5, 1, 8, 24 hours and every 24 hours for 5 days. The mean half-life of radioactivity specifically indentified as chlormadinone acetate for the first 24 hours was 2.6 hours, and after 24 hours was 81.8 hours, calculated by TAIT and BURSTEIN's method. ...

PMID:4134033 Dugwekar YG et al; Contraception 7 (1): 27-45 (1973)


After intravenous injection of radiolabelled chlormadinone acetate, the steroid and its metabolites have an initial rapid half-life of 2.4 hours, followed by a slow half-life of 80.1 hours.

IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V72 226 (1999)


5.5 Mechanism of Action

Chlormadinone acetate (CMA) is a derivative of naturally secreted progesterone that shows high affinity and activity at the progesterone receptor. It has an anti-estrogenic effect and, in contrast to natural progesterone, shows moderate anti-androgenic properties. CMA acts by blocking androgen receptors in target organs and by reducing the activity of skin 5alpha-reductase. It suppresses gonadotropin secretion and thereby reduces ovarian and adrenal androgen production. CMA shows high contraceptive efficacy by inhibiting ovulation due to its ability to suppress or disrupt endogenous gonadotropin secretion and, by this, inhibits follicular growth and maturation. In addition, it suppresses endometrial thickness and increases the viscosity of cervical mucus. ...

PMID:16356876 Bouchard P; Eur J Contracept Reprod Health Care 10 Suppl 1: 7-11 (2005)


The ovulation response to electrical stimulation of the median eminence, or to the intrapituitary infusion of median eminence extract, was observed in control rabbits and animals pre-treated with chlormadinone acetate. Chlormadinone acetate pre-treatment did not significantly reduce the proportion of rabbits ovulating in response to electrical stimulation. However, there was a significant reduction in the average number of ruptured follicles when compared with the animals in the control group. Chlormadinone acetate pre-treatment significantly reduced the proportion of animals ovulating in response to the intrapituitary infusion of median eminence extract as compared with the control series. However, there was no significant reduction in the average number of ruptured follicles (in those rabbits that ovulated) when compared with the control groups. Chlormadinone acetate pre-treatment produced no significant effect upon either the proportion of animals ovulating, or the average number of ruptured follicles, following i.v. injection of 50 ug LH.5. The conclusion drawn is that chlormadinone acetate blocks copulattion-induced ovulation in the rabbit by action at a site in the central nervous system located above the median eminence. The possible effects of chlormadinone acetate upon the secretion of FSH, the pituitary sensitivity to releasing factors and the ovarian sensitivity to LH are discussed.

PMID:4186126 Full text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1351513 Harris GW, Sherratt RM et al; J Physiol 203 (1): 59-66 (1969)


Studies with the human breast cancer cell line ZR-75-1, which contains functional estrogen, progesterone and androgen receptors, suggest that chlormadinone acetate inhibited the growth of these cells by an interaction of androgen and progesterone receptor-mediated mechanisms.

IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V72 240 (1999)


Groups of 8-12 male Sprague-Dawley Crl:CD(SD)Br rats were castrated and injected immediately thereafter twice daily for 14 days with one of a number of synthetic progestogens, including chlormadinone acetate, used in the treatment of prostate cancer. Controls received the vehicle, 1% gelatine in 0.9% saline... Dihydrotestosterone was injected at a dose of 150 ug twice daily for 14 days as a positive control. All animals were killed on the morning after the last day of treatment, and the ventral prostate and adrenals were removed and weighted; furthermore, the prostatic content of ornithine decarboxylase was measured, as it is consider to be a highly specific, sensitive of androgenic activity in the prostate. Dihydrotestosterone increased the ventral prostate weight to 43% above that of castrated controls. Chlormadinone acetate was less potent than dihydrotestosterone but caused significant increases in prostate weight, by about 22% at 3 mg and 36% at 10 mg per injection. Whereas dihydrotestosterone caused a 14-fold increase in ornithine decarboxylase activity in the prostate, chlormadinone acetate caused a 5.3-fold increase at 3 mg and an 11.8-fold increase at 10 mg. Chlormadinone acetate thus has weak but significant androgenic activity in the rat ventral prostate.

IARC. Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans. Geneva: World Health Organization, International Agency for Research on Cancer, 1972-PRESENT. (Multivolume work). Available at: https://monographs.iarc.fr/ENG/Classification/index.php, p. V72 280-1 (1999)


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CEP 2018-122 - Rev 03
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Chemical
2023-09-07
2702
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Certificate Number : CEP 2018-122 - Rev 03

Status : Valid

Issue Date : 2023-09-07

Type : Chemical

Substance Number : 2702

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Chlormadinone Acetate

Registration Number : 218MF10991

Registrant's Address : Via Pavia, 1-27027 Gropello Cairoli, Pavia, Italy

Initial Date of Registration : 2006-12-18

Latest Date of Registration : 2019-07-04

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Japanese Pharmacopoeia Chlormadinone Acetate

Registration Number : 218MF10701

Registrant's Address : 1-8-2 Marunouchi, Chiyoda-ku, Tokyo

Initial Date of Registration : 2006-08-11

Latest Date of Registration : 2006-08-11

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Chlormadinone Acetate

Registration Number : 217MF10977

Registrant's Address : 235 East 42nd Street, New York, NY 10017

Initial Date of Registration : 2005-11-14

Latest Date of Registration : 2009-05-27

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