Key messages
• There were no important differences in unwanted hair growth or hormone levels between cyproterone acetate and most of the treatments with which it was compared.
• There were differences in the hormonal impact of the various medications, which can be explained by how they work.
What is cyproterone acetate?
Unwanted hair growth on the face, tummy or chest of women results from raised levels of sex hormones, the most important being testosterone. This hormone is produced in the ovaries. A medicine called cyproterone acetate lowers levels of testosterone in the body and reduces unwanted hair growth, but it has unwanted effects including weight gain, depression (feeling sad), fatigue (feeling tired), breast swelling or tenderness, scalp hair loss and problems with sexual activity. Other treatments have been introduced more recently, and this review reports the evidence from studies comparing these treatments.
What did we want to find out?
We wanted to find out whether cyproterone acetate was better than other types of medication in reducing unwanted hair growth, measured by tests, or as reported by the women having the treatment, and by hormone levels. We also noted unwanted effects and if women decided to stop having the treatment.
What did we do?
We searched for studies that looked at cyproterone acetate and other types of medication in women with unwanted hair on the face, tummy or chest. We compared and summarised the results of the studies and rated our confidence in the evidence, based on factors such as study methods and sizes.
What did we find?
We found 23 mostly small studies that involved 1557 women with unwanted hair growth.
In women requiring therapy for unwanted hair growth either of unknown cause or caused by high levels of testosterone, there was no evidence of a difference between cyproterone acetate and most other medications used in reducing hair growth, lowering hormone levels or causing unwanted effects.
Cyproterone acetate was likely more effective after six months of treatment compared with a medicine called spironolactone (when both groups also received ethinylestradiol (a female hormone that is frequently used in contraceptive pills)) and more effective at 24 months compared with a medicine called finasteride (when both groups also received ethinylestradiol). Another medicine, flutamide, was more effective in one study at 12 months compared to cyproterone acetate.
What are the limitations of the evidence?
There was variability in the number of women, and the type and timing of measurements between studies, so we could not always compare the studies. Many of the studies included few women.
There is insufficient evidence to compare the unwanted effects of the treatments.
Larger studies are needed to provide more meaningful results. The present evidence supports the use of cyproterone acetate or spironolactone ideally combined with ethinylestradiol as the best treatment for unwanted hair growth.
How up to date is this evidence?
The information is current to December 2022.
Lire le résumé complet
Hirsutism (excessive and unwanted hair growth) is a distressing and relatively common endocrine problem in women that may prove difficult to manage. Cyproterone acetate (CPA), an antiandrogen, is frequently used to treat hirsutism, usually in combination with ethinylestradiol. This is an update of a Cochrane review first published in 2003.
Objectifs
To assess the benefits and harms of cyproterone acetate (CPA) alone, or in combination with ethinylestradiol, and other medication in reducing hair growth and improving the endocrine profile in women with hirsutism secondary to ovarian hyperandrogenism as well as idiopathic hirsutism.
Stratégie de recherche documentaire
We searched the Cochrane Gynaecology and Fertility specialised register, CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL to 20 December 2022. We also searched the reference lists of relevant papers and clinical trial registries.
Critères de sélection
We included randomised controlled trials (RCT) examining women of reproductive age with either idiopathic hirsutism or hirsutism secondary to ovarian hyperandrogenism. Hirsutism was defined as a Ferriman Gallwey (FG) score greater than 7.
Recueil et analyse des données
We included 23 studies. Only one study had more than 100 women included in the analysis. The primary outcomes were the objective and subjective assessment of clinical parameters (FG scores, linear hair growth and hair shaft diameter, women's feedback and frequency of hair removal). Secondary outcomes included endocrine parameters, side effects and withdrawals during therapy.
Résultats principaux
Cyproterone acetate greater than 2 mg plus ethinylestradiol compared to cyproterone acetate 2 mg or less plus ethinylestradiol (dose comparison)
After six months of treatment, we are uncertain of any difference in effect on FG scores (mean difference (MD) 0.63, 95% confidence interval (CI) −1.02 to 2.28; I2 = 0%; 2 RCTs, 145 women; very low-certainty evidence). There was likely little to no difference in free testosterone (MD 0.35 pmol/L, 95% CI −0.61 to 1.31; 1 RCT, 113 women; moderate-certainty evidence).
Cyproterone acetate alone (no ethinylestradiol) compared to other interventions alone (no ethinylestradiol)
There was little or no difference for CPA compared with gonadotropin-releasing hormone (GnRH) analogues on total testosterone at three months (MD 0.17 nmol/L, 95% CI −0.15 to 0.49). There was little or no evidence of an effect for CPA compared with GnRH agonist on androstenedione at three months (MD 0.66 nmol/L, 95% CI −0.44 to 1.76). Both results from one RCT (20 women; very low-certainty evidence).
Cyproterone acetate plus ethinylestradiol compared to other interventions alone (no ethinylestradiol)
There was little to no difference in effect for CPA plus ethinylestradiol on FG scores at six months compared with finasteride (MD 4.70, 95% CI −1.86 to 11.26; 1 RCT, 27 women; low-certainty evidence), spironolactone (MD 0.90, 95% CI −2.86 to 4.66; 1 RCT, 77 women; moderate-certainty evidence), ketoconazole (MD 0.70, 95% CI −0.84 to 2.24; 1 RCT, 81 women; moderate-certainty evidence), or pioglitazone plus flutamide plus metformin (Pio-Flu-Met) (MD 0.90, 95% CI −0.79 to 2.59; 1 RCT, 34 women; low-certainty evidence). CPA plus ethinylestradiol may improve hirsutism slightly compared with flutamide (MD 4.00, 95% CI 0.10 to 7.90; 1 RCT, 28 women).
CPA plus ethinylestradiol likely results in little to no difference in total testosterone at six months compared with spironolactone (MD −0.06 nmol/L, 95% CI −1.25 to 1.13; 1 RCT, 77 women; moderate-certainty evidence), ketoconazole (MD −0.02 nmol/L, 95% CI −0.37 to 0.33; 1 RCT, 81 women; moderate-certainty evidence), or Pio-Flu-Met (MD −0.39 nmol/L, 95% CI −0.82 to 0.04; 1 RCT, 81 women; low-certainty evidence). CPA plus ethinylestradiol may be more effective than finasteride at six months (MD −1.60 nmol/L, 95% CI −2.39 to −0.81; 1 RCT, 27 women; low-certainty evidence).
CPA plus ethinylestradiol may lower free testosterone slightly at six months compared to finasteride (MD −9.02 nmol/L, 95% CI −12.44 to −5.60; 1 RCT, 27 women; low-certainty evidence) or flutamide (MD −4.16 nmol/L, 95% CI −6.62 to −1.70; 1 RCT, 28 women; low-certainty evidence). There was little to no difference between CPA plus ethinylestradiol and spironolactone (MD 0.35 nmol/L, 95% CI −0.62 to 1.32; 1 RCT, 77 women; low-certainty evidence). CPA plus ethinylestradiol may be less effective than ketoconazole (MD 1.39 nmol/L, 95% CI 0.43 to 2.35; 1 RCT, 81 women; low-certainty evidence).
Cyproterone acetate plus ethinylestradiol compared to other interventions plus ethinylestradiol
CPA plus ethinylestradiol likely results in little to no difference in effect on FG scores at six months compared with finasteride plus ethinylestradiol (MD −0.91, 95% CI −1.82 to 0; 1 RCT, 26 women; moderate-certainty evidence) or spironolactone plus drospirenone plus ethinylestradiol (MD 0.69, 95% CI −0.80 to 2.18; 1 RCT, 89 women; high-certainty evidence). However, CPA plus ethinylestradiol may lower FG scores compared to spironolactone plus ethinylestradiol, but the evidence is very uncertain (MD −0.93, 95% CI −1.68 to −0.19; 3 RCTs, 103 women; very low-certainty evidence).
There was probably little to no difference in effect for CPA plus ethinylestradiol on total testosterone at six months compared with spironolactone plus ethinylestradiol (MD −0.20 nmol/L, 95% CI −0.64 to 0.24; 1 RCT, 45 women; moderate-certainty evidence), and likely results in little to no difference compared with drospirenone plus ethinylestradiol (MD 0.15 nmol/L, 95% CI 0.08 to 0.22; 1 RCT, 91 women; moderate-certainty evidence).
Six months of CPA plus ethinylestradiol treatment likely lowered free testosterone levels compared to drospirenone plus ethinylestradiol (MD −0.31 pmol/L, 95% CI −0.53 to −0.09; 1 RCT, 91 women; moderate-certainty evidence).
Data were lacking for all other outcomes in our main review comparisons.
Conclusions des auteurs
There were some differences in clinical outcome between CPA and spironolactone, CPA and flutamide, and CPA and finasteride. There were no clinical differences between CPA and the other medical therapies, possibly because of small study size, lack of standardised assessment and objective determinants of improvement in many studies. There are insufficient data presented to compare the adverse effects of all the treatment options.
Larger, carefully designed studies are needed to compare efficacy and safety profiles between the therapeutic options available.
