Assessment of severity

• The recommendation to assess severity is based on expert opinion in guidelines and narrative reviews [Lavery et al, 2005; Martin et al, 2008; Kumar et al, 2009].

Definition of excessive hair growth

• There is no clear cut-off for defining excessive hair growth. Although many clinical trials use a Ferriman–Gallwey score of eight or more to indicate hirsutism, many women with a lower score consider themselves hirsute.
• In a prospective observational study in 633 women, a Ferriman–Gallwey score of two or less was observed in approximately 75% of women; 16% of these women considered themselves to be hirsute [DeUgarte et al, 2006].
• Of the 25% of women with a Ferriman–Gallwey score of three or more, 70% considered themselves to be hirsute.
• Similarly, 70% of women with a Ferriman–Gallwey score of eight or more considered themselves to be hirsute.
• Overall there were no differences between black and white women.
• The Ferriman–Gallwey scoring system is a validated tool. However, it has a number of limitations, and although it is valuable as a clinical research tool, it is generally not considered to be practical for use in primary care [Lavery et al, 2005; Martin et al, 2008; Koulouri and Conway, 2009; Kumar et al, 2009].

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.

Treatment of postmenopausal women

• CKS found no evidence specifically on the management of hirsutism in postmenopausal women. Recommendations are based on the opinion of CKS expert reviewers.

Androgen secreting tumour

• Hair growth of recent onset and rapid progression, signs of virilization, particularly severe hirsutism, and a pelvic or abdominal mass are indications of a more serious underlying cause, such as an androgen-secreting (ovarian or adrenal) tumour.
• A high total testosterone concentration may indicate an androgen-secreting tumour [Sathyapalan and Atkin, 2009].
• If the total testosterone is normal (< 4.1 nanomol/L) or only slightly increased (< 5 nanomol/L), an androgen secreting tumour can be excluded.

When treatment in primary care has been ineffective

• Hirsutism that has failed to respond to treatment in primary care may respond to systemic treatments such as anti-androgens, insulin-sensitizing drugs, and gonadotrophin-releasing hormone agonists [Lavery et al, 2005; Martin et al, 2008; Koulouri and Conway, 2009].
• Because these drugs are not licensed for the treatment of hirsutism and have potentially serious adverse effects, CKS recommends that they should only be used under specialist supervision.

Hirsutism that has failed to respond to treatment in primary care may respond to systemic treatments such as anti-androgens, insulin-sensitizing drugs, and gonadotrophin-releasing hormone agonists [Lavery et al, 2005; Martin et al, 2008; Koulouri and Conway, 2009].

• Because these drugs are not licensed for the treatment of hirsutism and have potentially serious adverse effects, CKS recommends that they should only be used under specialist supervision.
• Weak evidence from a systematic review and meta-analysis (12 randomized controlled trials [RCTs]) suggests that anti-androgens are effective for the treatment of hirsutism [Swiglo et al, 2008].
• Compared with placebo, anti-androgens reduced Ferriman–Gallwey scores by 3.9 points (95% CI 2.3 to 5.4).
• Weak evidence from a systematic review and meta-analysis (16 RCTs) suggests that insulin-sensitizing drugs have limited efficacy in the treatment of hirsutism [Cosma et al, 2008].
• Compared with placebo, insulin sensitizers reduced Ferriman–Gallwey scores by 1.5 points (95% CI 0.3 to 2.8).
• There was no evidence of a significant difference between insulin sensitizers and oral contraceptives (weighted mean difference [WMD] 0.5 points; 95% CI 3.9 to 5.0).
• Metformin was less effective than both spironolactone (WMD 1.3; 95% CI 0.03 to 2.6) and flutamide (WMD 5.0; 95% CI 3.0 to 7.0).