Interventions for Hirsutism Excluding Laser and Photoepilation Therapy Alone

Abridged Cochrane Systematic Review Including GRADE Assessments

E.J. van Zuuren; Z. Fedorowicz

Disclosures

The British Journal of Dermatology. 2016;175(1):45-61. 

In This Article

Discussion

Principal Findings

This review of 157 studies evaluated a variety of treatments. Several of the studies examining insulin-sensitizing agents, statins or laparoscopic diathermy did not focus on hirsutism as a primary outcome. We did not identify RCTs that addressed cosmetic measures, i.e. electrolysis, waxing and bleaching, while laser and intense pulsed-light therapy are covered in another Cochrane review.[17] Although it is well recognized that hirsutism has a profound impact on a woman's quality of life, it was unfortunate that relevant patient-reported outcomes were addressed in very few studies.

Most OCPs reduced FG scores, but the degree of reduction was inconsistent across comparisons. Pooling of data was possible for only two OCPs (ethinyl oestradiol 35 μg + cyproterone acetate 2 mg and ethinyl oestradiol 30 μg + desogestrel 0·15 mg), and both demonstrated a clinically important reduction in FG score, although this is based on low-quality evidence. The two antiandrogens flutamide 250 mg twice daily and spironolactone 100 mg over a period of at least 6 months were effective but the quality of evidence for these studies was rated as very low and low, respectively. Finasteride reduced FG scores, but the reductions were inconsistent across studies and varied from limited to substantial decreases. Similar inconsistencies in effectiveness were seen with GnRH-A.

Metformin appeared to be ineffective for treating hirsutism, based on low-quality evidence, albeit having a beneficial effect on glucose metabolism.

Fewer studies than expected evaluated combinations of OCP with cyproterone acetate, flutamide, spironolactone or finasteride. The addition of cyproterone acetate to an OCP was associated with greater reductions in FG scores. Finasteride 5 mg and spironolactone 100 mg demonstrated similar effectiveness but the quality of evidence was rated low. The results from four studies that compared flutamide with finasteride were inconsistent; two studies favoured flutamide but the other two studies did not identify a statistically significant difference.

Strengths and Limitations

Despite the large number of studies included, the pooling of data was limited because very few studies investigated similar comparisons and also because of interstudy clinical or methodological heterogeneity. Most studies were assessed as having a 'high risk' of bias mainly owing to performance and detection bias (open-label studies) and attrition bias (high number of dropouts). Trial investigators failed to recognize the importance of patient-reported outcomes. These assessments could help fill gaps regarding which treatments are more likely to be preferred by women with hirsutism and which treatments might improve their quality of life, both of which are key prerequisites for shared decision making. The comprehensive search, thorough assessment for risk of bias, systematic data extraction, detailed GRADE approach in the assessment of the quality of evidence combined with a transparent and reproducible report of the results lends credence to the strength of the review.

Our inability to include laser therapy and intense pulsed-light treatment is indicative of the incompleteness of this review, but these were covered in another Cochrane review and we did not identify any RCTs evaluating electrolysis.

Agreements and Disagreements With Other Reviews

We identified a number of systematic reviews, narrative reviews and clinical guidelines that reported on some of the interventions covered in this systematic review.[2,3,6,178–204] Notwithstanding some minor concerns with the methodological robustness of some of these reviews, we were broadly in agreement with the conclusions that were drawn.

Conclusion, Unanswered Questions and Future Research

Treatment for women with hirsutism necessitates a holistic approach that not only involves pharmacological treatments, but also cosmetic measures, psychological support, incorporates women's preferences and, if associated with PCOS, also addresses and monitors other signs and symptoms of this syndrome. In conclusion, OCPs, preferably with antiandrogenic activity can be regarded as first-line treatment for mild hirsutism.

For moderate-to-severe hirsutism, the antiandrogens flutamide 250 mg twice daily and spironolactone 100 mg are effective and safe with the quality of evidence rated very low and low, respectively. Both finasteride and GnRH-A showed inconsistent results varying from small to substantial beneficial effects. Combining OCPs with cyproterone acetate might lead to greater reductions in FG score, but more research is needed regarding this treatment. However, antiandrogens, finasteride and GnRH-A all have well-known side-effects, and this should be taken into consideration in clinical decision making. As women with hirsutism are often of childbearing age, proper contraceptive advice should be given for all these treatments and biochemical monitoring during treatment is necessary.

Metformin was shown to be ineffective for hirsutism and there was a lack of evidence showing that lifestyle modification improves hirsutism.

As most treatments need to be continued for 6–12 months before an effect can be observed, women need to be appropriately counselled to prevent disappointment and should also be encouraged to use interim cosmetic measures.

More head-to-head trials are necessary, especially those that compare OCP monotherapy with OCPs combined with an antiandrogen such as flutamide, spironolactone and cyproterone acetate or finasteride. Trials are also required to compare the different antiandrogens or finasteride with each other. Future studies should include more detailed patient-reported outcomes and better reporting of adverse events.

A recent blog posting by a woman with hirsutism reinforces the deep-seated personal side-effects associated with this condition and points a finger at several salient aspects of living with this condition: 'As for the rest of us that have already descended into this lonely, black abyss of shame and secrecy, not to mention a lack of intimacy with our romantic partners; all we can do is band together. I think part of the problem is the isolation we all suffer from. We wonder if anyone else we know suffers from hirsutism but we're afraid to ask'.[205] The noticeable absence of assessments of patient-reported outcomes in the studies included in this review illustrates a serious underestimation of the impact of this condition on women and should be viewed as a significant omission.

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