Weight loss

• The recommendation on weight loss for women who are overweight or obese is based on expert opinion [Lavery et al, 2005].
• Weight loss is likely to improve metabolic and endocrine parameters; however, in one study of overweight women with polycystic ovary syndrome, there was no direct effect of weight loss on hirsutism [Moran et al, 2003].

Permanent hair reduction techniques

• There are very few published studies on electrolysis; however, electrolysis has been widely used for a number of years.
• Limited evidence from a Cochrane systematic review (11 randomized controlled trials [RCTs]) suggests that some laser and photoepilation treatments may lead to short-term hair reduction. There is less evidence of long-term benefit.
• One small crossover trial suggests that laser treatment is more effective that electrolysis.

Combined oral contraceptives (COCs)

• COCs are recommended as first-line treatment for premenopausal women with hirsutism in guidelines and narrative reviews [Claman et al, 2002; Lavery et al, 2005; Martin et al, 2008; Koulouri and Conway, 2009].
• COCs decrease plasma testosterone by suppression of luteinizing hormone secretion (thereby reducing ovarian androgen secretion) and by increasing the production of sex hormone-binding globulin (thereby increasing androgen binding and reducing free androgen levels) [Martin et al, 2008].
• CKS expert reviewers recommend co-cyprindiol (Dianette^®) or a COC containing drospirenone as the preferred COCs for women with hirsutism.
• Co-cyprindiol contains the anti-androgen cyproterone acetate, which has been shown to be effective in managing hirsutism. It is licensed for the treatment of moderately-severe hirsutism [ABPI Medicines Compendium, 2008].
• Drospirenone also has anti-androgenic properties [Martin et al, 2008]. COCs containing drospirenone (such as Yasmin^®) may be an alternative to co-cyprindiol in women with hirsutism, especially as long-term treatment is often necessary.
• CKS expert reviewers did not recommend second generation COCs (containing levonorgestrel and norethisterone) and third generation COCs (containing desogestrel, norgestimate, and gestodene) for the management of hirsutism.
• COCs containing levonorgestrel and norethisterone are more androgenic and could potentially exacerbate hirsutism [Koulouri and Conway, 2009].
• There is some concern that COCs containing desogestrel, norgestimate, and gestodene may have a greater risk of venous thromboembolism than those containing drospirenone, levonorgestrel, or norethisterone, although the absolute risk is is still low (about 25 per 100,000 women per year of use) [BNF 57, 2009].
• There is limited evidence on the efficacy of COCs in the management of hirsutism.
• Evidence from a Cochrane systematic review (one RCT) suggests that co-cyprindiol is more effective than placebo at reducing hair growth in women with hirsutism.
• Evidence from one RCT suggests that COCs containing drospirenone are at least as effective at reducing hair growth as those containing cyproterone acetate.
• Evidence from one small RCT with a high drop-out rate suggests there is no difference in clinical outcomes between second and third generation COCs; further studies are needed to confirm this.

Duration of treatment

• An Endocrine Society clinical practice guideline suggests a trial of at least 6 months of treatment, based on very low quality evidence [Martin et al, 2008].
• The Committee on the Safety of Medicines recommends that co-cyprindiol should be discontinued three or four menstrual cycles after the woman's hirsutism has resolved, due to the risk of serious adverse effects such as thromboembolism [CSM, 2002].
• There is a two- to four-fold increase in the risk of venous thromboembolism with co-cyprindiol compared with conventional second-generation COCs, although the absolute risk remains low [Vasilakis-Scaramozza and Jick, 2001; Seaman et al, 2003].

Treatment of relapse when co-cyprindiol is stopped

• The advice on whether to continue to use co-cyprindiol continuously or intermittently, or to switch to an alternative COC, is advice based on the opinions of CKS expert reviewers.

Eflornithine

• Evidence from small RCTs suggests that eflornithine may improve the appearance of facial hair in the short term (up to 6 months), but its efficacy in the longer term remains unclear.
• There is weak evidence that it may be more effective than placebo when combined with laser treatment, in the short term.