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.[2] 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 associated with ovaries with cysts.[3][4][5][6][7][8] The medication is taken by mouth once daily for 21 days, followed by a 7-day free interval.[2]
EE/CPA is used as a combined birth control pill to prevent ovulation and pregnancy in women.[2] 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.[2][3][4][5][6][7][8]
Available forms[]
EE/CPA comes in the form of oraltablets and contains 35 or 50 μg EE and 2 mg CPA per tablet.[2] It is taken once daily for 21 days, followed by a 7-day free interval.[2]
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%).[2] The incidence of depression with EE/CPA is the same as that with other birth control pills.[9][10]
Blood clots[]
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.[11][12][13][14][15] 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.[16]
v
t
Risk of venous thromboembolism (VTE) with hormone therapy and birth control (QResearch/CPRD)
Notes: (1) Nested case–control studies (2015, 2019) based on data from the QResearch and Clinical Practice Research Datalink (CPRD) databases. (2) Bioidenticalprogesterone was not included, but is known to be associated with no additional risk relative to estrogen alone. Footnotes: * = Statistically significant (p < 0.01). Sources: See template.
Pharmacology[]
Main article: Ethinylestradiol § Pharmacology of cyproterone acetate
EE is a syntheticestrogen, or an agonist of the estrogen receptors, the biological target of estrogens like estradiol.[17][4] It also has functional antiandrogenic effects by decreasing the circulating free fractions of androgens.[18] CPA is a progestin (synthetic progestogen), or an agonist of the progesterone receptors, the biological target of progestogens like progesterone.[17][4] It also acts as an antiandrogen, or as an antagonist of the androgen receptor, the biological target of androgens like testosterone and dihydrotestosterone.[17][4] However, it is thought that the antiandrogenic activity of CPA may only be significant at higher doses than are present in birth control pills.[4][19] Both EE and CPA have antigonadotropic effects and act as contraceptives in women by suppressing ovulation.[17] The antigonadotropic effects of EE and CPA also contribute to the antiandrogenic efficacy of the medication by suppressing androgen production by the ovaries.[18]
History[]
CPA/EE-containing birth control pills were developed by 1975[20][21] and were first introduced for medical use in 1978.[22] 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).[4][23][24]
Society and culture[]
Generic names[]
Co-cyprindiol, a shortened form of combination of cyproterone acetate and ethinylestradiol, is a generic name of EE/CPA.[25][26][27] It is also known by its former developmental code names SHB 209 AB (Diane)[28][21][29] and SHB 209 AE (Diane-35).[23][24] 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.[28][20][21]
Availability of CPA in countries throughout the world (as of March 2018). Turquoise is combined with an estrogen at a low dose, dark blue is alone at a high dose, and light blue is both available.
EE/CPA is available widely throughout the world, including in Europe, North America, South America, East Asia, South Asia, Southeast Asia, and Oceania.[25] It is notably not available in the United States or Japan.[25]
^ abMiller 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. PMID2941191.
^ abcdefgHammerstein, J. (1990). "Antiandrogens: Clinical Aspects". Hair and Hair Diseases. pp. 827–886. doi:10.1007/978-3-642-74612-3_35. ISBN978-3-642-74614-7.
^ abVan der Spuy ZM, le Roux PA (2003). "Cyproterone acetate for hirsutism". Cochrane Database Syst Rev (4): CD001125. doi:10.1002/14651858.CD001125. PMID14583927.
^ abJing 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. PMID19012104. S2CID38997400.
^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. ISSN1053-8569. PMID16986216. S2CID3586619.
^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. PMID22239262. S2CID20299968.
^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. PMID23384743.
^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. PMID14663535.
^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. PMID9476091.
^ abcHammerstein 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. PMID126335.
^G. Plewig; A.M. Kligman (6 December 2012). ACNE and ROSACEA. Springer Science & Business Media. pp. 662, 685. ISBN978-3-642-59715-2.
^ abFedele 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. PMID3727896.
^ abFedele 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. PMID3621944.
^ abHammerstein, J. (1981). "Antiandrogens — Basic Concepts for Treatment". Hair Research. pp. 330–335. doi:10.1007/978-3-642-81650-5_49. ISBN978-3-642-81652-9.
^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.
External links[]
"Ethinylestradiol". Drug Information Portal. U.S. National Library of Medicine.
Anabolic steroids (e.g., testosterone and esters, methyltestosterone, metandienone (methandrostenolone), nandrolone and esters, many others; via estrogenic metabolites)