Ethinylestradiol/cyproterone acetate
Ethinylestradiol/cyproterone acetate (EE/CPA), also known as co-cyprindiol and sold under the brand names Diane and Diane-35 among others, is a combination of ethinylestradiol (EE), an estrogen, and cyproterone acetate (CPA), a progestin and antiandrogen, which is used as a birth control pill to prevent pregnancy in women.[1] It is also used to treat androgen-dependent conditions in women such as acne, seborrhea, excessive facial/body hair growth, scalp hair loss, and high androgen levels due to ovaries with cysts.[2][3][4][5][6][7] The medication is taken by mouth once daily for 21 days, followed by a 7-day free interval.[1]
Combination of | |
---|---|
Ethinylestradiol | Estrogen |
Cyproterone acetate | Progestogen; Antiandrogen |
Clinical data | |
Trade names | Diane, Diane-35, others |
Other names | EE/CPA; Co-cyprindiol; SHB 209 AB; SHB 209 AE; SH-81041 |
Routes of administration | By mouth |
Drug class | Estrogen; Progestogen; Antiandrogen |
ATC code | |
Legal status | |
Legal status |
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Identifiers | |
CAS Number | |
PubChem CID |
Medical uses
EE/CPA is used as a combined birth control pill to prevent ovulation and pregnancy in women.[1] It is also approved and used to treat androgen-dependent conditions in women such as acne, seborrhea, hirsutism, female pattern hair loss, and hyperandrogenism due to polycystic ovary syndrome.[1][2][3][4][5][6][7]
Side effects
Side effects of EE/CPA include dysmenorrhea (10.2%), breast tension or tenderness (6.5%), headache (5.2%), nervousness (4.4%), chloasma (4.2%), depressed mood (3.4%), decreased libido (3.1%), varicosities (2.9%), nausea (1.9%), edema (1.7%), and dizziness (1.1%).[1] The incidence of depression with EE/CPA is the same as that with other birth control pills.[8][9]
The risk of venous thromboembolism with EE/CPA-containing birth control pills is similar to that with EE and gestodene-, desogestrel-, and drospirenone-containing birth control pills and about 50 to 80% higher than with EE and levonorgestrel-containing birth control pills.[10][11][12][13][14] The absolute risk of venous thromboembolism with EE/CPA-containing birth control pills is about 1.2 to 9.9 per 10,000 women-years.[15]
Pharmacology
EE is a synthetic estrogen, or an agonist of the estrogen receptors, the biological target of estrogens like estradiol.[16][3] It also has functional antiandrogenic effects by decreasing the circulating free fractions of androgens.[17] CPA is a progestin (synthetic progestogen), or an agonist of the progesterone receptors, the biological target of progestogens like progesterone.[16][3] It also acts as an antiandrogen, or as an antagonist of the androgen receptor, the biological target of androgens like testosterone and dihydrotestosterone.[16][3] However, it is thought that the antiandrogenic activity of CPA may only be significant at higher doses than are present in birth control pills.[3][18] Both EE and CPA have antigonadotropic effects and act as contraceptives in women by suppressing ovulation.[16] The antigonadotropic effects of EE and CPA also contribute to the antiandrogenic efficacy of the medication by suppressing androgen production by the ovaries.[17]
History
CPA/EE-containing birth control pills were developed by 1975[19][20] and were first introduced for medical use in 1978.[21] They originally contained 50 μg EE (Diane); subsequently, the EE dosage was decreased to 35 μg in a new "low-dose" preparation in 1986 (Diane-35).[3][22][23]
Society and culture
Generic names
Co-cyprindiol, a shortened form of combination of cyproterone acetate and ethinylestradiol, is a generic name of EE/CPA.[24][25][26] It is also known by its former developmental code names SHB 209 AB (Diane)[27][20][28] and SHB 209 AE (Diane-35).[22][23] The developmental code name SH-81041 referred to a combination of high-dose 100 mg CPA and 40–50 μg EE administered in a reverse sequential regimen.[27][19][20]
Brand names
Brand names of EE/CPA include Diane and Diane-35, as well as Adco-Fem, Alisma, Althea, Ancea, Anuar, Avancel, Axira, Bella HEXAL, Bellgyn, Bellune, Brenda-35 ED, Chloe, Clairette, Claudia, Co-Cyprindiol, Cybelle, CyEstra-35, Cypestra-35, Cyprelle, Cyprest, Cypretil, Cypretyl, Cyproderm, Cyprodiol, Cypromix, Dafne-35, Daphne, Dialider, Diane mite, Diane-35 ED, Dianette, Diclin, Dinac, Diva-35, Dixi, Dixi-35, Drina, Elestra, Elisamylan, Elleacnelle, Erika-35, Esdian, Estelle, Estelle-35, Evashine, Evépar, Evilin, Facetix, Femina, Feminac, Feminil mite, Frauline, Giane, Giane-35, Ginet, Ginette, Gynelle, Gyneplen, Gynofen, Holgyeme, Isbela, Jennifer-35, Juliet-35 ED, Juliette, Jene, Lady-Ten, Laila-35 ED, Linface, Lunar, Manoane, Midane, Mileva, Minerva, Morea sanol, Neynna, Nortin, OC-35, Selene, Sucee, Syndi, Tess, Visofid, Vreya, Xylia, Zinnia, and Zyrona.[24]
References
- https://www.bayer.ca/omr/online/diane-35-pm-en.pdf
- Miller JA, Jacobs HS (May 1986). "Treatment of hirsutism and acne with cyproterone acetate". Clin Endocrinol Metab. 15 (2): 373–89. doi:10.1016/S0300-595X(86)80031-7. PMID 2941191.
- Hammerstein, J. (1990). "Antiandrogens: Clinical Aspects". Hair and Hair Diseases. pp. 827–886. doi:10.1007/978-3-642-74612-3_35. ISBN 978-3-642-74614-7.
- Van der Spuy ZM, le Roux PA (2003). "Cyproterone acetate for hirsutism". Cochrane Database Syst Rev (4): CD001125. doi:10.1002/14651858.CD001125. PMID 14583927.
- Jing Z, Liang-Zhi X, Tai-Xiang W, Ying T, Yu-Jian J (October 2008). "The effects of Diane-35 and metformin in treatment of polycystic ovary syndrome: an updated systematic review". Gynecol. Endocrinol. 24 (10): 590–600. doi:10.1080/09513590802288242. PMID 19012104.
- Bitzer J, Römer T, Lopes da Silva Filho A (June 2017). "The use of cyproterone acetate/ethinyl estradiol in hyperandrogenic skin symptoms - a review". Eur J Contracept Reprod Health Care. 22 (3): 172–182. doi:10.1080/13625187.2017.1317339. PMID 28447864.
- Ruan X, Kubba A, Aguilar A, Mueck AO (June 2017). "Use of cyproterone acetate/ethinylestradiol in polycystic ovary syndrome: rationale and practical aspects". Eur J Contracept Reprod Health Care. 22 (3): 183–190. doi:10.1080/13625187.2017.1317735. PMID 28463030.
- Raudrant D, Rabe T (2003). "Progestogens with antiandrogenic properties". Drugs. 63 (5): 463–92. doi:10.2165/00003495-200363050-00003. PMID 12600226.
- Seaman HE, Snowball J, de Vries CS (2006). "Cyproterone Acetate + Ethinyloestradiol and the Risk of Depression". Pharmacoepidemiology and Drug Safety. 15 (S1): S25. doi:10.1002/pds.1295. ISSN 1053-8569.
- Martínez F, Ramírez I, Pérez-Campos E, Latorre K, Lete I (February 2012). "Venous and pulmonary thromboembolism and combined hormonal contraceptives. Systematic review and meta-analysis". Eur J Contracept Reprod Health Care. 17 (1): 7–29. doi:10.3109/13625187.2011.643836. PMID 22239262.
- Plu-Bureau G, Maitrot-Mantelet L, Hugon-Rodin J, Canonico M (February 2013). "Hormonal contraceptives and venous thromboembolism: an epidemiological update". Best Pract. Res. Clin. Endocrinol. Metab. 27 (1): 25–34. doi:10.1016/j.beem.2012.11.002. PMID 23384743.
- Stegeman BH, de Bastos M, Rosendaal FR, van Hylckama Vlieg A, Helmerhorst FM, Stijnen T, Dekkers OM (September 2013). "Different combined oral contraceptives and the risk of venous thrombosis: systematic review and network meta-analysis". BMJ. 347: f5298. doi:10.1136/bmj.f5298. PMC 3771677. PMID 24030561.
- de Bastos M, Stegeman BH, Rosendaal FR, Van Hylckama Vlieg A, Helmerhorst FM, Stijnen T, Dekkers OM (March 2014). "Combined oral contraceptives: venous thrombosis". Cochrane Database Syst Rev (3): CD010813. doi:10.1002/14651858.CD010813.pub2. PMID 24590565.
- Dragoman MV, Tepper NK, Fu R, Curtis KM, Chou R, Gaffield ME (June 2018). "A systematic review and meta-analysis of venous thrombosis risk among users of combined oral contraception". Int J Gynaecol Obstet. 141 (3): 287–294. doi:10.1002/ijgo.12455. PMC 5969307. PMID 29388678.
- Spitzer WO (December 2003). "Cyproterone acetate with ethinylestradiol as a risk factor for venous thromboembolism: an epidemiological evaluation". J Obstet Gynaecol Can. 25 (12): 1011–8. doi:10.1016/S1701-2163(16)30342-5. PMID 14663535.
- Kuhl H (2005). "Pharmacology of estrogens and progestogens: influence of different routes of administration" (PDF). Climacteric. 8 Suppl 1: 3–63. doi:10.1080/13697130500148875. PMID 16112947.
- Ekback, Maria Palmetun (2017). "Hirsutism, What to do?" (PDF). International Journal of Endocrinology and Metabolic Disorders. 3 (3). doi:10.16966/2380-548X.140. ISSN 2380-548X.
- 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.
- Grund E, Schmidt-Elmendorff H (November 1975). "Behandlung von Virilisierungs-Erscheinungen: vergleichende Klinische Untersuchung zweier antiandrogenwirksamer Gestagene--Cyproteronazetat, Megestrolazetat" [The treatment of virilizing syndromes. Comparative clinical studies of 2 antiandrogen-active gestagens (cyproterone acetate, megestrol acetate]. Med Welt (in German). 26 (48): 2180–7. PMID 128684.
- Hammerstein J, Meckies J, Leo-Rossberg I, Moltz L, Zielske F (June 1975). "Use of cyproterone acetate (CPA) in the treatment of acne, hirsutism and virilism". J. Steroid Biochem. 6 (6): 827–36. doi:10.1016/0022-4731(75)90311-8. PMID 126335.
- G. Plewig; A.M. Kligman (6 December 2012). ACNE and ROSACEA. Springer Science & Business Media. pp. 662, 685. ISBN 978-3-642-59715-2.
- Fedele L, Cavalli G, Marchini M, Carinelli S, Candiani GB (1986). "Effect of a new oral antiandrogen-estrogen combination on the endometrium: histological and ultrastructural scanning electron microscopy study". Acta Eur. Fertil. 17 (1): 9–13. PMID 3727896.
- Fedele L, Marchini M, Cavalli G, Baglioni A, Taccagni GL (May 1987). "Marked deciliation and insufficient secretory modification of endometrial surface during treatment with a new progestogen-estrogen combination". Contraception. 35 (5): 497–505. doi:10.1016/0010-7824(87)90086-2. PMID 3621944.
- "Cyproterone". Drugs.com.
- NADIR R. FARID; Evanthia Diamanti-Kandarakis (27 February 2009). Diagnosis and Management of Polycystic Ovary Syndrome. Springer Science & Business Media. pp. 237–. ISBN 978-0-387-09718-3.
- Adam Balen; Stephen Franks; Roy Homburg; Sean Kehoe (October 2010). Current Management of Polycystic Ovary Syndrome. Cambridge University Press. pp. 131–. ISBN 978-1-906985-41-7.
- Hammerstein, J. (1981). "Antiandrogens — Basic Concepts for Treatment". Hair Research. pp. 330–335. doi:10.1007/978-3-642-81650-5_49. ISBN 978-3-642-81652-9.
- Lachnitt-Fixson U, Kaufmann J (1977). "Zur bein flussung von androgenisierungsercheinungen-doppelblind. Studium eines cyproteronacetat-haltiges praparats (SHB 209 AB) gegen neogynon". Med. Klin. 72: 1922–1926.