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Cyproterone
acetate for hirsutism
Cyproterone acetate (CPA) was first used to treat hirsutism experimentally
in 1965 and was brought to the attention of dermatologists by Hammerstein
and colleagues in Germany. Since then it has become a very popular
oral antiandrogen in Europe, Canada, and South America. Flutamide
may have slightly a superior ability to reduce hirsutism as compared
to CPA, but CPA is significantly cheaper than Flutamide and so is
a popular choice in those countries where CPA is available.
Several different treatment approaches have been tried with CPA.
50-100mg per day of CPA orally on days 1-10 of the menstrual cycle
along with a triphasic oral contraceptive is a popular treatment
regime with some dermatologists, particularly in Mediterranean countries.
However, this is regarded as overkill by some Northern European
dermatologists who specialize in treating hair conditions. Dosages
of 100mg CPA per day are used for people with ovarian tumors or
for sex offenders, but may not be necessary for treating idiopathic
hirsutism. Several studies comparing different CPA dosage rates
have shown no significant difference in the treatment of hirsutism
when using 100mg or 2mg of CPA. A few dermatologists use high dose
CPA initially and then drop the dosage for long term use.
Low dose CPA treatment protocols include; oral ingestion of 2mg
CPA plus estradiol on days 5-25 of the menstrual cycle, or just
1mg of CPA on days 12 to 21 of the menstrual cycle plus estradiol
for 21 days. Low dose CPA use reduces the risk of side effects while
having similar positive benefits in treating hirsutism. There are
many other protocols for treating hirsutism using different CPA
doses or different times of application during the monthly cycle.
No clear advantage has been demonstrated for a particular CPA treatment
regime and the personal preference of the dermatologist seems to
be the greatest factor in deciding CPA dose levels.
CPA is not available in the US in any form and only certain formulations
of CPA are available in other countries. The most commonly available
form of CPA is in combination with estradiol in tablets called Diane
(Diane 35) or Dianette (Diane 50) both of which are advertised for
treating acne in women, but have been utilized for treating other
androgen based conditions such as hirsutism. However, while both
Diane and Dianette are available in Canada, only Diane is available
in the UK. CPA in its various forms is made by the Germany based
Schering AG pharmaceutical company.
Both Diane and Dianette contain 2mg of CPA but Diane contains
35mg of estradiol and Dianette contains 50mg of estradiol. The Dianette
tablets have a significant property in that they increase sex hormone
binding globulin (SHBG) levels in the blood whereas the lower estradiol
dose in Diane does not. The increase in SHBG has a positive benefit
as SHBG binds to testosterone and stops it from being converted
to dihydrotestosterone and having an affect on hair follicles. However,
high dose estradiol is potentially toxic and some women are unable
to tolerate the negative effects of Dianette.
CPA and estradiol combined also has potential to induce other side
effects. Some suspicions have been cast on long term CPA and estradiol
use and the potential for a reduction in bone mass. However, recent
research studies suggest there are no apparent negative effects.
Other side effect risks include weight gain, fatigue, nausea, headaches,
depression, and impairment of liver function. Some dermatologists
recommend testing vitamin B12 levels in CPA users. CPA can cause
B12 levels to drop and this can lead to depression or anxiety problems.
Vitamin B12 supplements can rectify the problem.
As with all systemic antiandrogens, serious side effects will develop
in a male embryo of a pregnant user. Although CPA is a powerful
proestrogen it does not necessarily stop ovulation. Consequently,
contraception with cyclical estrogen supplements is vital when using
CPA.
Cyproterone
acetate for hirsutism references
- Tartagni
M, Schonauer LM, De Salvia MA, Cicinelli E, De Pergola G, D'Addario
V. Comparison of Diane 35 and Diane 35 plus finasteride in the
treatment of hirsutism. Fertil Steril. 2000 Apr;73(4):718-23.
- Yucelten
D, Erenus M, Gurbuz O, Durmusoglu F. Recurrence rate of hirsutism
after 3 different antiandrogen therapies. J Am Acad Dermatol.
1999 Jul;41(1):64-8.
- Pazos F,
Escobar-Morreale HF, Balsa J, Sancho JM, Varela C. Prospective
randomized study comparing the long-acting gonadotropin-releasing
hormone agonist triptorelin, flutamide, and cyproterone acetate,
used in combination with an oral contraceptive, in the treatment
of hirsutism. Fertil Steril. 1999 Jan;71(1):122-8.
- Castelo-Branco
C, Martinez de Osaba MJ, Pons F, Vanrell JA. Effects on bone mass
of two oral contraceptives containing ethinylestradiol and cyproterone
acetate or desogestrel: results of a 2-year follow-up. Eur J Contracept
Reprod Health Care. 1998 Jun;3(2):79-84.
- Sahin Y,
Bayram F, Kelestimur F, Muderris I. Comparison of cyproterone
acetate plus ethinyl estradiol and finasteride in the treatment
of hirsutism. J Endocrinol Invest. 1998 Jun;21(6):348-52.
- Venturoli
S, Ravaioli B, Bagnoli A, Colombo FM, Macrelli S, Iadarola I,
Vianello F, Mancini F, Flamigni C. Contraceptive and therapeutic
effectiveness of two low-dose ethinylestradiol and cyproterone
acetate regimens in the treatment of hirsute patients. Eur J Contracept
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F, Sahin Y. Comparison of Diane 35 and Diane 35 plus spironolactone
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O, Senoz S, Gulekli B, Isik AZ. Comparison of four different treatment
regimes in hirsutism related to polycystic ovary syndrome. Gynecol
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M, Yucelten D, Gurbuz O, Durmusoglu F, Pekin S. Comparison of
spironolactone-oral contraceptive versus cyproterone acetate-estrogen
regimens in the treatment of hirsutism. Fertil Steril. 1996 Aug;66(2):216-9.
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RG, van den Ende A. Experience in the long-term treatment of patients
with hirsutism and/or acne with cyproterone acetate-containing
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Cherry CA, Wojnarowska F, Dawber RP. Cyproterone acetate for severe
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Endocrinol (Oxf). 1991 Jul;35(1):5-10.
- Adamopoulos
DA, Kampyli S, Georgiacodis F, Kapolla N, Abrahamian-Michalakis
A. Effects of antiandrogen-estrogen treatment on sexual and endocrine
parameters in hirsute women. Arch Sex Behav. 1988 Oct;17(5):421-9.
- Belisle
S, Love EJ. Clinical efficacy and safety of cyproterone acetate
in severe hirsutism: results of a multicentered Canadian study.
Fertil Steril. 1986 Dec;46(6):1015-20.
- Galindo PA, Borja J, Feo F, Gomez E, Chamorro
R, Encinas C, Garcia R. Fixed drug eruption caused by cyproterone
acetate. Allergy. 1998 Aug;53(8):813.
- Similowski T, Orcel B, Derenne JP.CD8+
lymphocytic pneumonitis in a patient receiving cyproterone acetate.
South Med J. 1997 Oct;90(10):1048-9.
- Hammerstein J, Moltz L, Schwartz U. Antiandrogens
in the treatment of acne and hirsutism. J Steroid Biochem. 1983
Jul;19(1B):591-7.
- Hammerstein J, Cupceancu B. The treatment
of hissutism with cyproterone acetate. Ger Med Mon. 1969 Dec;14(12):599-602.
- Hammerstein J, Cupceancu B. [Management
of hirsutism using cyproterone acetate]. Dtsch Med Wochenschr.
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