Interventions for hirsutism (excluding laser and photoepilation therapy alone)

Abstract

Background: Hirsutism occurs in 5% to 10% of women of reproductive age when there is excessive terminal hair growth in androgen-sensitive areas (male pattern). It is a distressing disorder with a major impact on quality of life. The most common cause is polycystic ovary syndrome. There are many treatment options, but it is not clear which are most effective.

Objectives: To assess the effects of interventions (except laser and light-based therapies alone) for hirsutism.

Search methods: We searched the Cochrane Skin Group Specialised Register, CENTRAL (2014, Issue 6), MEDLINE (from 1946), EMBASE (from 1974), and five trials registers, and checked reference lists of included studies for additional trials. The last search was in June 2014.

Selection criteria: Randomised controlled trials (RCTs) in hirsute women with polycystic ovary syndrome, idiopathic hirsutism, or idiopathic hyperandrogenism.

Data collection and analysis: Two independent authors carried out study selection, data extraction, 'Risk of bias' assessment, and analyses.

Main results: We included 157 studies (sample size 30 to 80) comprising 10,550 women (mean age 25 years). The majority of studies (123/157) were 'high', 30 'unclear', and four 'low' risk of bias. Lack of blinding was the most frequent source of bias. Treatment duration was six to 12 months. Forty-eight studies provided no usable or retrievable data, i.e. lack of separate data for hirsute women, conference proceedings, and losses to follow-up above 40%.Primary outcomes, 'participant-reported improvement of hirsutism' and 'change in health-related quality of life', were addressed in few studies, and adverse events in only half. In most comparisons there was insufficient evidence to determine if the number of reported adverse events differed. These included known adverse events: gastrointestinal discomfort, breast tenderness, reduced libido, dry skin (flutamide and finasteride); irregular bleeding (spironolactone); nausea, diarrhoea, bloating (metformin); hot flushes, decreased libido, vaginal dryness, headaches (gonadotropin-releasing hormone (GnRH) analogues)).Clinician's evaluation of hirsutism and change in androgen levels were addressed in most comparisons, change in body mass index (BMI) and improvement of other clinical signs of hyperandrogenism in one-third of studies.The quality of evidence was moderate to very low for most outcomes.There was low quality evidence for the effect of two oral contraceptive pills (OCPs) (ethinyl estradiol + cyproterone acetate versus ethinyl estradiol + desogestrel) on change from baseline of Ferriman-Gallwey scores. The mean difference (MD) was -1.84 (95% confidence interval (CI) -3.86 to 0.18).There was very low quality evidence that flutamide 250 mg, twice daily, reduced Ferriman-Gallwey scores more effectively than placebo (MD -7.60, 95% CI -10.53 to -4.67 and MD -7.20, 95% CI -10.15 to -4.25). Participants' evaluations in one study with 20 participants confirmed these results (risk ratio (RR) 17.00, 95% CI 1.11 to 259.87).Spironolactone 100 mg daily was more effective than placebo in reducing Ferriman-Gallwey scores (MD -7.69, 95% CI -10.12 to -5.26) (low quality evidence). It showed similar effectiveness to flutamide in two studies (MD -1.90, 95% CI -5.01 to 1.21 and MD 0.49, 95% CI -1.99 to 2.97) (very low quality evidence), as well as to finasteride in two studies (MD 1.49, 95% CI -0.58 to 3.56 and MD 0.40, 95% CI -1.18 to 1.98) (low quality evidence).Although there was very low quality evidence of a difference in reduction of Ferriman-Gallwey scores for finasteride 5 mg to 7.5 mg daily versus placebo (MD -5.73, 95% CI -6.87 to -4.58), it was unlikely it was clinically meaningful. These results were reinforced by participants' assessments (RR 2.06, 95% CI 0.99 to 4.29 and RR 11.00, 95% CI 0.69 to 175.86). However, finasteride showed inconsistent results in comparisons with other treatments, and no firm conclusions could be reached.Metformin demonstrated no benefit over placebo in reduction of Ferriman-Gallwey scores (MD 0.05, 95% CI -1.02 to 1.12), but the quality of evidence was low. Results regarding the effectiveness of GnRH analogues were inconsistent, varying from minimal to important improvements.We were unable to pool data for OCPs with cyproterone acetate 20 mg to 100 mg due to clinical and methodological heterogeneity between studies. However, addition of cyproterone acetate to OCPs provided greater reductions in Ferriman-Gallwey scores.Two studies, comparing finasteride 5 mg and spironolactone 100 mg, did not show differences in participant assessments and reduction of Ferriman-Gallwey scores (low quality evidence). Ferriman-Gallwey scores from three studies comparing flutamide versus metformin could not be pooled (I² = 62%). One study comparing flutamide 250 mg twice daily with metformin 850 mg twice daily for 12 months, which reached a higher cumulative dosage than two other studies evaluating this comparison, showed flutamide to be more effective (MD -6.30, 95% CI -9.83 to -2.77) (very low quality evidence). Data showing reductions in Ferriman-Gallwey scores could not be pooled for four studies comparing finasteride with flutamide as the results were inconsistent (I² = 67%).Studies examining effects of hypocaloric diets reported reductions in BMI, but which did not result in reductions in Ferriman-Gallwey scores. Although certain cosmetic measures are commonly used, we did not identify any relevant RCTs.

Authors' conclusions: Treatments may need to incorporate pharmacological therapies, cosmetic procedures, and psychological support. For mild hirsutism there is evidence of limited quality that OCPs are effective. Flutamide 250 mg twice daily and spironolactone 100 mg daily appeared to be effective and safe, albeit the evidence was low to very low quality. Finasteride 5 mg daily showed inconsistent results in different comparisons, therefore no firm conclusions can be made. As the side effects of antiandrogens and finasteride are well known, these should be accounted for in any clinical decision-making. There was low quality evidence that metformin was ineffective for hirsutism and although GnRH analogues showed inconsistent results in reducing hirsutism they do have significant side effects.Further research should consist of well-designed, rigorously reported, head-to-head trials examining OCPs combined with antiandrogens or 5α-reductase inhibitor against OCP monotherapy, as well as the different antiandrogens and 5α-reductase inhibitors against each other. Outcomes should be based on standardised scales of participants' assessment of treatment efficacy, with a greater emphasis on change in quality of life as a result of treatment.

Conflict of interest statement

There are no financial conflicts of interest; the authors, Esther van Zuuren, Zbys Fedorowicz, Ben Carter and Nik Pandis declare that they do not have any associations with any parties who may have vested interests in the results of this review.

Figures

Figure 1

Hirsutism on the chin

Figure 2

Hirsutism on the chest and breasts

Figure 3

Modified Ferriman‐Gallwey score, each of nine body areas can receive a score from 0 (no hair) to 4 (frankly virile) (van Zuuren EJ, Pijl H. Hirsutism. Ned Tijdschr Geneeskd. 2007 Oct 20;151(42):2313‐8

Figure 4

Study flow diagram.

Figure 5

'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Figure 6

'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.

Analysis 4.1

Comparison 4 Ethinyl estradiol 35 μg + cyproterone acetate 2 mg versus ethinyl estradiol 30 μg + desogestrel 0.15 mg, Outcome 1 Mean change from baseline in Ferriman‐Gallwey score.

Analysis 4.2

Comparison 4 Ethinyl estradiol 35 μg + cyproterone acetate 2 mg versus ethinyl estradiol 30 μg + desogestrel 0.15 mg, Outcome 2 Mean change from baseline in Lorenzo score.

Analysis 20.1

Comparison 20 Finasteride 5 mg to 7.5 mg/day versus placebo, Outcome 1 Adverse events.

Analysis 20.2

Comparison 20 Finasteride 5 mg to 7.5 mg/day versus placebo, Outcome 2 Mean change from baseline in Ferriman‐Gallwey score.

Analysis 27.1

Comparison 27 Metformin 500 mg to 1500 mg per day versus placebo for 12 to 48 weeks, Outcome 1 Mean change from baseline in Ferriman‐Gallwey score.

Analysis 27.3

Comparison 27 Metformin 500 mg to 1500 mg per day versus placebo for 12 to 48 weeks, Outcome 3 Mean change from baseline in BMI.

Analysis 91.1

Comparison 91 Flutamide 250 mg once to b.i.d. versus metformin 1275 mg to 1700 mg per day, Outcome 1 Mean change from baseline in Ferriman‐Gallwey score.

Analysis 92.1

Comparison 92 Finasteride 5 mg once a day versus flutamide 250 mg once to b.i.d., Outcome 1 Number of adverse events.

Analysis 92.2

Comparison 92 Finasteride 5 mg once a day versus flutamide 250 mg once to b.i.d., Outcome 2 Mean change from baseline in Ferriman‐Gallwey score.