These recommendation are based on advice in guidelines from the Royal College of Obstetricians and Gynaecologists [RCOG, 2007], a non-systematic review [Koulouri and Conway, 2009], a textbook [Balen et al, 2005], and guidelines from the Endocrine Society (US) [Endocrine Society, 2008].

Causes of hirsutism

• The most common underlying causes for hirsutism are polycystic ovary syndrome (PCOS) or idiopathic hirsutism [Koulouri and Conway, 2009].
• Hirsutism is present in 60–80% of women with PCOS [Archer and Chang, 2004].
• Other causes of hirsutism are rare and include late-onset congenital adrenal hyperplasia, androgen-secreting tumours (ovarian or adrenal), Cushing's syndrome, acromegaly, or drugs.

Test for elevated androgens

• This recommendation is based on guidelines from the Royal College of Obstetricians and Gynaecologists [RCOG, 2007].

Advise weight loss if the woman is obese

• Good evidence from a systematic review suggests that obesity negatively influences treatment for hirsutism.

Cosmetic measures

• Cosmetic measures may be helpful because drug treatments may take 6–9 months or longer before any improvement is noticed [Balen et al, 2005].
• Limited evidence from a Cochrane systematic review suggests that some laser and photoepilation treatments may lead to temporary short-term hair removal.

Treatment of hirsutism

• As hirsutism is caused by excess circulating androgenic hormones, it can be treated with anti-androgenic agents. Other topical and systemic drugs can also be used to treat the specific symptoms. The principal treatment for hirsutism caused by PCOS is to reduce or block the effect of circulating androgenic hormones.

Choice of hormonal treatment

• Oestrogen and progestins suppress gonadotrophin secretion from the pituitary, resulting in decreased androgenic hormones. In addition, oestrogen increases sex hormone-binding globulin levels, which results in decreased free testosterone levels. Progestins can act as an androgen antagonist.
• Combined oral contraceptives (COCs) may be used to reduce ovarian androgen production and treat hyperandrogenism. Some COCs may be more effective than others because of their progestogen content (although there is little direct evidence to support this idea) [Archer and Chang, 2004]. No specific COC has been shown to be superior in treating hirsutism in PCOS, and the best COC for women with PCOS is unknown [Balen et al, 2005].
• The rationale for using COCs to treat the symptoms of PCOS remains controversial. Whilst treatment is undoubtedly of benefit for many symptoms, there is some concern that use of COCs may negatively affect insulin resistance, glucose tolerance, vascular reactivity, and blood coagulation [Ehrmann, 2005].
• 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.
• Cyproterone acetate inhibits 5-alpha reductase activity, increases sex hormone-binding globulin levels, and has significant anti-gonadotrophin effects.
• There is limited evidence from a Cochrane systematic review that suggests that co-cyprindiol is more effective than placebo for treating hirsutism.
• Co-cyprindiol 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.
• There is conflicting poor quality evidence for its use in women with PCOS.
• 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].

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.

Onset of improvement with drug treatment

• An individual hair follicle takes months to pass through the anagen (active growing), catagen (involutional), and telogen (resting) phases. All systemic treatments for hirsutism reduce stimulation of the anagen growth phase by testosterone, but enough follicles must enter the anagen phase before a clinical effect is noticeable [Koulouri and Conway, 2009].

Length of hormonal treatment

• Co-cyprindiol (Dianette^®) may take 6 months or longer to produce an improvement in hirsutism, so advise the woman to be patient during this period [Balen et al, 2005; Butts and Driscoll, 2006].
• The Committee on Safety of Medicines has recommended that co-cyprindiol should be discontinued three or four menstrual cycles after the woman's acne or hirsutism has resolved, owing 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].
• The recommendation to continue to use co-cyprindiol continuously or intermittently, or to switch to an alternative COC, is pragmatic advice from CKS.

Eflornithine

• Eflornithine is an irreversible inhibitor of ornithine decarboxylase, an essential enzyme involved in the production of hair [Moghetti et al, 2000]. Inhibition of this enzyme reduces hair growth.
• Limited evidence from randomized controlled trials suggests that it is effective at reducing hirsutism, although this effect is rapidly reversed after stopping treatment [Moghetti and Toscano, 2006].
• No data are available on the long-term safety of eflornithine [Butts and Driscoll, 2006].
• The advice to consider prescribing topical eflornithine for women in whom standard treatment is ineffective, contraindicated, or considered inappropriate is consistent with the restricted use advice given by the Scottish Medicines Consortium [Scottish Medicines Consortium, 2005].
• Limited evidence from a Cochrane systematic review suggests that some laser and photoepilation treatments may lead to temporary short-term hair removal.

Treatments available in secondary care

• Weak evidence from systematic reviews suggests that spironolactone and other anti-androgens are effective in the treatment of hirsutism.
• Spironolactone has moderate anti-androgenic effects. It is not licensed in the UK for the treatment of hirsutism.

Referral

• These recommendations are based on expert advice in a review article [Koulouri and Conway, 2009].