For the full versions of these articles see bmj.com CLINICAL REVIEW Management of hirsutism Olympia Koulouri, Gerard S Conway Department of Endocrinology, Hirsutism is the presence of excess hair growth in that secrete androgens are rare and tend to cause severe University College London women, and the term usually refers to excessive hirsutism. Adrenal tumours usually co-secrete cortisol Hospitals, London NW1 2PQ growth of terminal hair in an androgen dependent dis- and the clinical picture is that of Cushing’s syndrome. Correspondence to: G S Conway [email protected] tribution. Although it is often thought to be a cosmetic At the time of the menopause, hair growth is pro- problem, unwanted hair growth adversely affects psy- moted by a fall in the production of ovarian oestradiol Cite this as: BMJ 2009;338:b847 chological wellbeing.1 It can have a similar effect on but relatively well maintained testosterone production. doi:10.1136/bmj.b847 quality of life scores to that of asthma, epilepsy, and In some instances, rising concentrations of luteinising diabetes,2 and effective treatments reverse these hormone lead to stromal hyperplasia, high testoster- adverse scores.3 one concentrations, and severe menopausal hirsutism. Several new treatments have emerged in recent years, including the wider availability of laser depilation, topi- What aspects of the history and examination are cal suppressors of hair growth (eflornithene), and a pro- important? gestogen with antiandrogenic properties (drospirenone). For research purposes, hair growth can be measured In this review, we assess the evidence base for new treat- using a scoring system established by Ferriman and ments in the context of established treatments, although Gallwey.5 In clinical practice, subjective assessment is the worldwide availability of these preparations varies usually adequate, although personal perception of greatly. The overall quality of primary evidence of the body hair can vary greatly among individuals.6 Insulin relative efficacy of treatments for hirsutism is weak and is resistance may be clinically evident as acanthosis based on small studies of short duration that lack quality nigricans. of life outcomes. Recently, however, systematic reviews The most important clinical feature to be aware of is have amalgamated this evidence and new guidelines are the recent onset and rapid progression of hair growth now available.4 seen with the rare androgen secreting tumours. Conversely, onset of mild hirsutism around the time What are the possible causes of hirsutism? of the menarche implies that androgen excess has Most women with hirsutism have polycystic ovary syn- a non-tumour ovarian origin, as in polycystic ovary drome or idiopathic hirsutism (box 1). Treatment syndrome (box 2). options are the same for both, so ovarian ultrasound is not essential in many cases. What investigations are needed? Mild to late onset adrenal hyperplasia is a rare cause Measurement of serum testosterone concentrations of hirsutism that overlaps clinically with polycystic helps identify the occasional case of severe androgen ovary syndrome. Classic congenital adrenal hyperpla- excess that needs further investigation, but it is not sia is obvious because it presents in infancy, and it com- essential in women with a clearly benign presentation, monly causes severe hirsutism, particularly if especially as testosterone assays perform poorly in the 7 adherence to glucocorticoids is poor. Ovarian tumours female range. According to current guidelines, testos- terone measurement is needed only for women with moderate to severe hirsutism, when other symptoms Box 1 Main causes of hirsutism of polycystic ovary syndrome are present, or when Polycystic ovary syndrome there is rapid progression of hirsutism or other signs of virilisation.4 Obese women with polycystic ovary syn- Idiopathic hirsutism drome, particularly those with a family history of type Congenital adrenal hyperplasia 2 diabetes, should be assessed for metabolic syndrome Androgen secreting tumours (ovarian or adrenal) with an oral glucose tolerance test and cholesterol Cushing’ssyndrome profile.8 Hirsutism is the subject of a Biochemical screening for non-classic adrenal forthcoming article on Rational Acromegaly hyperplasia with measurement of serum 17 hydroxy- Testing, a new BMJ series starting Drugs this month progesterone concentrations is not usually productive BMJ | 4 APRIL 2009 | VOLUME 338 823 CLINICAL REVIEW noted that the long term efficacy of these treatments is Box 2 Important aspects of the history not well established.9 Laser treatment is less effective in How quickly has the hair growth progressed? darker skin because a contrast is needed between skin What measures have been used to control excess hair? and hair pigments, but some types of photoepilation Does the woman have any other features of androgen can be of benefit for darker skin. excess (acne or alopecia)? Eflornithine, a topical agent, inhibits the enzyme What is the pattern of menstruation? ornithine decarboxylase, which in turn reduces matrix cell proliferation in the hair follicle. A large sponsored Has her weight changed recently? randomised trial showed a 26% reduction in facial hair What is the history of use of the oral contraceptive pill? after 24 weeks of treatment, with most of the benefit Is there a family history of type 2 diabetes? achieved in eight weeks.10 What about systemic treatments? because glucocorticoids are rarely the optimal treat- Systemic treatments aim to suppress ovarian androgen ment even in confirmed cases; most women do better secretion or reduce the action of testosterone on the with ovarian suppression with or without an anti- androgen receptor. In a systematic review of 28 rando- androgen. Late onset congenital adrenal hyperplasia mised trials of systemic treatments for hirsutism that is, however, important to exclude in hirsute women included 1227 women, we found that the following wishing to conceive when glucocorticoids are the treat- drugs were effective: metformin (19.1% suppression ment of first choice during periconception. Screening of hirsutism over baseline over six months compared ’ for Cushing s syndrome by 24 hour urine collection with placebo), finasteride (20.3%), oral contraceptive for free cortisol or dexamethasone suppression tests is pills (27%), thiazolidinediones (31.5%), cyproterone indicated if clinical features are present. Laboratory acetate and ethinylestradiol in combination (36%), tests to investigate the causes of hirsutism will be cov- spironolactone (38.4%), and flutamide (41.3%).11 The ered in more detail in an upcoming rational testing arti- beneficial effects of cyproterone acetate and spirono- cle on hirsutism. Computed tomography imaging of lactone have also been confirmed by individual sys- the adrenal glands should be undertaken only if the tematic reviews.12 13 index of suspicion of a tumour is high—for example, The primary driver of ovarian androgen secretion is when hair growth is particularly sudden and heavy. luteinising hormone, which can be suppressed using a Imaging results are often normal in mild forms of adre- combined oral contraceptive pill. The effectiveness of nal hyperplasia and there is the added complication of oral contraceptives in suppressing hirsutism will identifying an incidentoloma. depend on the content of ethinylestradiol (20-35 μg) and on the nature of the progestogen. Pills containing What are the principles of treatment? progestogens with antiandrogenic properties (such as Most women can be treated in primary care. Box 3 lists Dianette and Yasmin) are effective in hirsutism,14 the indications for specialist referral. Most therapeutic whereas those containing levonorgestrel and norethis- trials have lasted for six to 12 months only, so we do not terone are more androgenic and could potentially know how long it takes for many treatments to reach exacerbate hirsutism.15 Third generation progestogens their maximal effect. such as desogestrel or gestodene have relatively neu- Hair grows in cycles, and it can take months for an tral androgenic effects,16 and oral contraceptives con- individual hair follicle to proceed through catagen, taining these compounds can usefully be combined anagen, and telogen phases. All systemic treatments with an antiandrogen such as spironolactone. Only reduce stimulation of the anagen growth phase by tes- one small randomised controlled trial has compared tosterone, and enough follicles have to pass through different oral contraceptive pills, and current guide- anagen before a clinically obvious effect is seen. In lines do not recommend one specific pill for treating other words, progress can be slow and little improve- hirsutism.4 ment is seen within four months. Once satisfactory sup- Insulin, which acts as a co-gonadotrophin and pression of unwanted hair has been achieved, the goal amplifies luteinising hormone induced testosterone of management is to find the lowest effective dose of any agent that maintains the benefit gained in the first phase of treatment. Box 3 When to refer to a specialist What non-systemic treatments are available? If hirsutism is particularly severe Many women will be familiar with routine methods of If hair growth is of recent onset and rapid progression hair removal such as shaving, threading, waxing, and If first and second line treatments have not been effective using depilatory creams and can be reassured that over six to 12 months these methods do not exacerbate hair growth. Electro- If