Cyproterone acetate

Cyproterone acetate
Clinical data
Trade namesAndrocur, Androcur Depot, Cyprostat, Siterone, others
Other namesSH-80714; SH-714; NSC-81430; 1α,2α-Methylene-6-chloro-17α-hydroxy-δ6-progesterone acetate; 1α,2α-Methylene-6-chloro-17α-hydroxypregna-4,6-diene-3,20-dione acetate
AHFS/Drugs.comMicromedex Detailed Consumer Information
Pregnancy
category
  • X
Routes of
administration		By mouth, intramuscular injection
Drug classSteroidal antiandrogen; Progestogen; Progestin; Progestogen ester; Antigonadotropin
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
BioavailabilityOral: 68–100%[1][2]
Protein bindingAlbumin: 93%
Free: 7%[3][4][5][6]
MetabolismHepatic (CYP3A4)[11][12]
Metabolites• 15β-OH-CPATooltip 15β-Hydroxycyproterone acetate (major)[1][7]
• Cyproterone (minor)[8]
• Acetic acid (minor)[8]
Elimination half-lifeOral: 1.6–4.3 days[8][9][10]
IM: 3–4.3 days[2][8][10]
ExcretionFeces: 70%[8]
Urine: 30%[8]
Identifiers
  • (2aR,3aS,3bS,3cS,5aS,6R,8aS,8bR)-6-acetyl-10-chloro-3b,5a-dimethyl-2-oxo-2,2a,3,3a,3b,3c,4,5,5a,6,7,8,8a,8b-tetradecahydrocyclopenta[a]cyclopropa[g]phenanthren-6-yl acetat
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.006.409 Edit this at Wikidata
Chemical and physical data
FormulaC24H29ClO4
Molar mass416.94 g·mol−1
3D model (JSmol)
Melting point200 to 201 °C (392 to 394 °F)
  • CC(=O)[C@]1(CC[C@@H]2[C@@]1(CC[C@H]3[C@H]2C=C(C4=CC(=O)[C@@H]5C[C@@H]5[C@]34C)Cl)C)OC(=O)C
  • InChI=1S/C24H29ClO4/c1-12(26)24(29-13(2)27)8-6-16-14-10-20(25)19-11-21(28)18(15)23(19,4)17(14)5-7-22(16,24)3/h10-11,14-18H,5-9H2,1-4H3/t14-,15+,16-,17-,18-,22-,23-,24-/m0/s1
  • Key:UWFYSQMTEOIJJG-FDTZYFLXSA-N
  (verify)

Cyproterone acetate (CPA), sold alone under the brand name Androcur or with ethinylestradiol under the brand names Diane or Diane-35 among others, is an antiandrogen and progestin medication used in the treatment of androgen-dependent conditions such as acne, excessive body hair growth, early puberty, and prostate cancer, as a component of feminizing hormone therapy for transgender individuals, and in birth control pills.[1][9][13][14][15] It is formulated and used both alone and in combination with an estrogen. CPA is taken by mouth one to three times per day.

Common side effects of high-dose CPA in men include gynecomastia (breast development) and feminization. In both men and women, possible side effects of CPA include low sex hormone levels, reversible infertility, sexual dysfunction, fatigue, depression, weight gain, and elevated liver enzymes. At very high doses in older individuals, significant cardiovascular complications can occur. Rare but serious adverse reactions of CPA include blood clots, liver damage and brain tumors. CPA can also cause adrenal insufficiency as a withdrawal effect if it is discontinued abruptly from a high dosage. CPA blocks the effects of androgens such as testosterone in the body, which it does by preventing them from interacting with their biological target, the androgen receptor (AR), and by reducing their production by the gonads, hence their concentrations in the body.[1][13][16] In addition, it has progesterone-like effects by activating the progesterone receptor (PR).[1][13] It can also produce weak cortisol-like effects at very high doses.[1]

CPA was discovered in 1961.[17] It was originally developed as a progestin.[17] In 1965, the antiandrogenic effects of CPA were discovered.[18] CPA was first marketed, as an antiandrogen, in 1973, and was the first antiandrogen to be introduced for medical use.[19] A few years later, in 1978, CPA was introduced as a progestin in a birth control pill.[20] It has been described as a "first-generation" progestin[21] and as the prototypical antiandrogen.[22] CPA is available widely throughout the world.[23][24] An exception is the United States, where it is not approved for use.[25][26]

  1. ^ a b c d e f Kuhl H (2005). "Pharmacology of estrogens and progestogens: influence of different routes of administration". Climacteric. 8 (Suppl 1): 3–63. doi:10.1080/13697130500148875. PMID 16112947. S2CID 24616324.
  2. ^ a b Huber J, Zeillinger R, Schmidt J, Täuber U, Kuhnz W, Spona J (November 1988). "Pharmacokinetics of cyproterone acetate and its main metabolite 15 beta-hydroxy-cyproterone acetate in young healthy women". Int J Clin Pharmacol Ther Toxicol. 26 (11): 555–61. PMID 2977383.
  3. ^ Bińkowska M, Woroń J (June 2015). "Progestogens in menopausal hormone therapy". Przegla̜d Menopauzalny = Menopause Review. 14 (2): 134–43. doi:10.5114/pm.2015.52154. PMC 4498031. PMID 26327902.
  4. ^ Schindler AE, Campagnoli C, Druckmann R, Huber J, Pasqualini JR, Schweppe KW, Thijssen JH (December 2003). "Classification and pharmacology of progestins". Maturitas. 46 (Suppl 1): S7–S16. doi:10.1016/j.maturitas.2003.09.014. PMID 14670641. Since there is no binding of CPA to SHBG and CBG in the serum, 93% of the compound is bound to serum albumin.
  5. ^ Wakelin SH, Maibach HI, Archer CB (1 June 2002). Systemic Drug Treatment in Dermatology: A Handbook. CRC Press. pp. 32–. ISBN 978-1-84076-013-2. Archived from the original on 14 January 2023. Retrieved 27 September 2016. It is almost exclusively bound to plasma albumin.
  6. ^ Hammond GL, Lähteenmäki PL, Lähteenmäki P, Luukkainen T (October 1982). "Distribution and percentages of non-protein bound contraceptive steroids in human serum". Journal of Steroid Biochemistry. 17 (4): 375–80. doi:10.1016/0022-4731(82)90629-X. PMID 6215538.
  7. ^ Frith RG, Phillipou G (1985). "15-Hydroxycyproterone acetate and cyproterone acetate levels in plasma and urine". J. Chromatogr. 338 (1): 179–86. doi:10.1016/0378-4347(85)80082-7. PMID 3160716.
  8. ^ a b c d e f Weber GF (22 July 2015). Molecular Therapies of Cancer. Springer. pp. 316–. ISBN 978-3-319-13278-5. The terminal half-life is about 38 h. A portion of the drug is metabolized by hydrolysis to cyproterone and acetic acid. However, in contrast to many other steroid esters hydrolysis is not extensive, and much of the pharmacological activity is exerted by the acetate form. Excretion is about 70% in the feces, mainly in the form of glucuronidated metabolites, and about 30% in the urine, predominantly as non-conjugated metabolites.
  9. ^ a b Barradell LB, Faulds D (July 1994). "Cyproterone. A review of its pharmacology and therapeutic efficacy in prostate cancer". Drugs Aging. 5 (1): 59–80. doi:10.2165/00002512-199405010-00006. PMID 7919640. S2CID 260845477.
  10. ^ a b AAPL Newsletter (PDF). The Academy. 1998. Archived (PDF) from the original on 30 August 2017. Retrieved 16 August 2016. CPA is 100% bioavailable when taken orally with a half life of 38 hours. The injectable form reaches maximum plasma levels in 82 hours and has a half life of about 72 hours.
  11. ^ Dickman A (27 September 2012). Drugs in Palliative Care. OUP Oxford. pp. 137–138. ISBN 978-0-19-966039-1.
  12. ^ Boarder M, Newby D, Navti P (25 March 2010). Pharmacology for Pharmacy and the Health Sciences: A Patient-centred Approach. OUP Oxford. pp. 632–. ISBN 978-0-19-955982-4. Archived from the original on 6 July 2024. Retrieved 27 September 2016.
  13. ^ a b c Neumann F (1994). "The antiandrogen cyproterone acetate: discovery, chemistry, basic pharmacology, clinical use and tool in basic research". Exp. Clin. Endocrinol. 102 (1): 1–32. doi:10.1055/s-0029-1211261. PMID 8005205.
  14. ^ Neumann F (January 1977). "Pharmacology and potential use of cyproterone acetate". Horm. Metab. Res. 9 (1): 1–13. doi:10.1055/s-0028-1093574. PMID 66176. S2CID 7224893.
  15. ^ Neumann F, Töpert M (November 1986). "Pharmacology of antiandrogens". Journal of Steroid Biochemistry. 25 (5B): 885–95. doi:10.1016/0022-4731(86)90320-1. PMID 2949114.
  16. ^ Berek JS (2007). Berek & Novak's Gynecology. Lippincott Williams & Wilkins. p. 1085. ISBN 978-0-7817-6805-4.
  17. ^ a b Pucci E, Petraglia F (December 1997). "Treatment of androgen excess in females: yesterday, today and tomorrow". Gynecol. Endocrinol. 11 (6): 411–33. doi:10.3109/09513599709152569. PMID 9476091.
  18. ^ Cite error: The named reference pmid5989926 was invoked but never defined (see the help page).
  19. ^ Wakelin SH (1 June 2002). Systemic Drug Treatment in Dermatology: A Handbook. CRC Press. p. 32. ISBN 978-1-84076-013-2. Archived from the original on 14 January 2023. Retrieved 27 September 2016.
  20. ^ Cite error: The named reference Plewig-2012 was invoked but never defined (see the help page).
  21. ^ Cite error: The named reference pmid27616670 was invoked but never defined (see the help page).
  22. ^ Jameson JL, De Groot LJ (25 February 2015). Endocrinology: Adult and Pediatric E-Book. Elsevier Health Sciences. pp. 2293, 2464, 2479, 6225. ISBN 978-0-323-32195-2. Archived from the original on 6 July 2024. Retrieved 2 August 2018.
  23. ^ Cite error: The named reference Drugs.com-Cyproterone was invoked but never defined (see the help page).
  24. ^ Cite error: The named reference IndexNominum2000 was invoked but never defined (see the help page).
  25. ^ Cite error: The named reference Schechter-2016 was invoked but never defined (see the help page).
  26. ^ Deleve LD (2013). "Cancer Chemotherapy". Drug-Induced Liver Disease. Academic Press. pp. 541–567. doi:10.1016/B978-0-12-387817-5.00030-3. ISBN 9780123878175.