Hirsutism in women

Excessive hair growth in women is usually a psychological concern, but it may indicate underlying morbidity. Nadia Soliman and Peter Wardle consider the options for treatment

Hirsutism in women is the presence of unwanted coarse body hair in a male distribution. It affects 5-15% of women,¹ and it can have profound psychological sequelae. It undermines the woman's confidence and self esteem, and its effect on quality of life should not be underestimated. Some women live apparently normal lives but may spend two or three hours a day using cosmetic or camouflage methods. Other women may become reclusive and only venture out after dark. In teenagers, hirsutism can be a cause of bullying, social isolation, and poor educational performance. By the time they seek medical advice, many women will have reached a point of desperation.

Hirsutism is usually caused by increased production of androgen (a collective term for male sex hormones) or increased sensitivity of hair follicles to androgens. The condition is often associated with acne and seborrhoea. Management of female hirsutism requires, first of all, the exclusion of any underlying sinister cause, such as an androgen secreting tumour, by confirmation that the history is not acute and is not associated with amenorrhoea or virilisation. Measurement of serum testosterone alone is sufficient for basic screening. Urgent referral to a specialist clinic is indicated if the concentration of serum testosterone is more than 5 nmol/l. The other investigations which might be needed are listed in box 1.

More than 90% of women with hirsutism will have polycystic ovary syndrome.²Treatments include suppression of androgen, peripheral androgen blockade, and mechanical or cosmetic treatment. Recently, new treatments have been introduced, and their use needs to be appraised. In addition, a review of some established treatments shows that lower doses may give equally effective control.^{3 4}  A summary of possible treatments is given in box 2.

Popular combination

Combined oral contraceptive pills are the most popular treatment for hirsutism. The oestrogen component increases the concentrations of sex hormone binding globulin and so decreases the amount of free androgens in circulation. The progestogen component suppresses luteinising hormone, which is produced in the anterior pituitary, and consequently the production of androgen. Drosperinone, the progestogen component of Yasmin (Schering, Burgess Hill), which also contains ethinylestradiol, is derived from spironolactone, an aldosterone antagonist. It has antiandrogenic properties, which increases its effectiveness in treating hirsutism in women with polycystic ovary syndrome.⁵

Cyproterone acetate is a strong progestogen with peripheral antiandrogenic activity. It blocks androgen receptors on the surface on potential target cells. A systematic review by the Cochrane Collaboration showed that compared with placebo the combination of cyproterone acetate and ethinylestradiol resulted in a subjective improvement of hirsutism.⁶Cyproterone acetate can cause dose related side effects such as depression and loss of libido. However, the effectiveness of an oral contraceptive pill containing 35 mg ethinylestradiol and 2 mg cyproterone acetate per day (Dianette, Schering) is not increased by giving additional cyproterone acetate for the first 10 days of the cycle.³

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Fewer options for treatment existed then

Block them

Finasteride (Proscar, Merck Sharp & Dohme, Hoddesdon), a potent 5 α-reductase inhibitor, reduces the conversion of testosterone to its active metabolite dihydrotestosterone in peripheral cells. Although not licensed for use in women, its effectiveness has been shown in many trials.^{7 8} Finasteride is well tolerated with minimal side effects at the standard dose of 5 mg a day. Because of the bioactivity and slow accumulation of metabolites, a low dose (2.5 mg a day) or even intermittent doses (2.5 mg every three days) are equally effective.^{4 9} This has safety and cost effectiveness implications, especially because long term treatment is often required.

Spironolactone inhibits production of androgen and blocks androgen receptors. A systematic review by the Cochrane Collaboration showed that six months of treatment with 100 mg a day of spironolactone significantly reduced hair growth, compared with placebo-but this study had low statistical power.¹⁰ Although widely used worldwide, spironolactone is not generally a first line treatment in the United Kingdom, partly the result of a warning from the Committee on the Safety of Medicines in 1988 of possible carcinogenicity in mice.¹¹ Dysfunctional uterine bleeding is a common side effect, which can be managed with concomitant use of combined oral contraceptive pills.

Metformin, a peripheral insulin sensitising agent, reduces hyperandrogenaemia in women with polycystic ovary syndrome. A systematic review found a significant improvement in hirsutism with use of metformin compared with placebo, but, again, the statistical power was low (weighted mean difference 5.12, 95% confidence interval -8.77 to -1.47, P= 0.006).¹² A randomised controlled trial showed subjective and objective improvement with metformin compared with Dianette.¹³ Although further data are necessary, metformin seems to be of benefit for hirsute women with reduced peripheral insulin sensitivity because of polycystic ovary syndrome.

New adjuvants

Eflornithine cream (Vaniqa, Shire, Basingstoke) is licensed in the UK for the treatment of facial hirsutism. It inhibits the enzyme ornithine decarboxylase, which is involved in controlling hair growth and proliferation. A randomised double blind controlled trial found a significant reduction in facial hair growth within eight weeks compared with placebo, with additional psychological benefits (Schrode K et al, and Huber F et al, 58th annual meeting of the American Academy of Dermatology, 10-15 March, 2000, San Francisco). Eflornithine is most effective when combined with local cosmetic or depilatory treatments, which will then be needed much less often. If hirsutism is not reduced in four months, the treatment is unlikely to be effective and should be stopped. Once eflornithine is stopped, hair growth will usually return within eight weeks. For this reason, eflornithine might best be used for initial local control of hirsutism while awaiting the benefits of systemic treatment. Systemic absorption of eflornithine after topical use is very low (less than 1%),¹⁴ and side effects and local reactions or phototoxicity are rare and transient.¹⁵

Laser treatment

Advances in the use of laser offer a new option for hirsutism treatment by selective photothermolysis of dark pigmented hairs and has been shown to be effective in controlled trials.¹⁶ Best results are achieved with dark hair on fair skin. It is generally less helpful in dark skinned women, such as women of South Asian origin. Few studies have extended their observations beyond one year, and more prolonged studies are needed. Repeated treatments by laser are necessary, and the high cost can limit its use.

Lasers are a potential hazard to the eyes or skin if used by inexperienced operators. The use of laser in the independent sector in the UK is governed by the National Care Standards Act 2000. The Health Care Commission undertakes inspections of private healthcare facilities. When considering an individual clinic, patients should ensure that it has been assessed to this standard. In advising patients, a general practitioner might seek guidance about clinics from the International Skinlaser Directory see www.timewarp.demon.co.uk/skinlase.html

Concluding remarks

The growth cycle of facial hair is relatively long-about four years. For this reason, it will often take 4-6 months before any objective improvement in hirsutism is seen with systemic treatment, and up to four years to achieve the maximum effect. For women with mild hirsutism, individual treatments might be used initially, with additional drugs introduced after 4-6 months if the improvement in symptoms is inadequate.

For women with severe hirsutism, a combination of treatments, targeting different sites of action, will probably be the best option. This might include metformin to reduce hyperinsulinaemia, a combined preparation oral contraceptive pill to increase sex hormone binding globulin and reduce production of luteinising hormone; cyproterone acetate to block androgen receptors on peripheral cells; and finasteride to reduce intracellular conversion of testosterone to dihydrotestosterone.

Antiandrogens are teratogenic, and reliable contraception is essential when they are used. As these systemic treatments may take 6-12 months to give noticeable improvement in hirsutism, topical eflornithine cream can be used during this time to give earlier control of symptoms. As the majority of women with hirsutism have polycystic ovary syndrome, many will be overweight. Lifestyle changes in diet, exercise, and weight reduction, perhaps with the help of orlistat (Xenical, Roche, Welwyn Garden City; a lipase inhibitor), will improve the efficacy and duration of benefit from drug treatments. Obesity also influences the options for treatment. For example, the use of oral contraceptive pills, such as Dianette, may be contraindicated, and preparations such as metformin may be preferred.

In the UK though, with the exception of eflornithine and Dianette, all other drugs are not licensed for treatment of hirsutism despite published evidence of their effectiveness.

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