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Premenstrual syndrome: making sense of the options

Dermatologist Dr Tony Downs outlines the causes of hirsutism and hypertrichosis and discusses treatments

We have always been preoccupied about the removal or presence of hair in both sexes. Hair or lack of it can define our acceptance, role and status within society. There is no gold standard treatment for what a person or society deems as inappropriate or excessive hair. But a wide range of treatment options can make the management of this problem successful in most cases.

The causes of unwanted hair

·Hypertrichosis

Hypertrichosis is defined as excess hair on any part of the body compared with a person of the same age, sex and race, excluding androgen-induced growth.

It causes a cosmetic embarrassment and is a significant burden for adults and children. Patients should be investigated for underlying acquired causes.

Generalised hypertrichosis

Genetic causes include universal congenital hypertrichosis (UCH), congenital hypertrichosis lanuginosa (CHL), prepubertal hypertrichosis (PH), or as part of complex syndrome disorders. All have widespread dramatic presentations. CHL spontaneously improves.

Acquired causes include drug-induced hypertrichosis. Typical drugs include phenytoin, ciclosporin A, minoxidil, and steroids. Other acquired causes include hepatic porphyria, brain injury, anorexia/ malnutrition, juvenile hyperthyroidism, juvenile dermatomyositis, AIDS, and paraneoplastic hypertrichosis.

Localised hypertrichosis

Genetic causes include congenital melanocytic naevi, Becker's naevi, nevoid hypertrichosis, and localised symmetrical hypertrichosis. Acquired hypertrichosis may occur over longstanding inflammatory changes within the skin, with or without the application of topical steroid. An artefactual hypertrichosis is caused by hair-bearing skin grafts or skin flaps.

It can take up to two years for drug-induced hypertrichosis to settle on withdrawal of the drug. Traditional physical methods of hair removal are perhaps the best form of treatment in motivated patients and parents.

Small congenital melanocytic naevi can be excised. Laser epilation will only work on dark hairs, but many congenital forms of hypertrichosis initially start with blond, fine hairs that become darker and coarser as the child matures.

Lasers can also treat underlying pigmentation in many of the localised forms. Topical eflornithine cream (Vaniqa) is limited to localised forms of hypertrichosis. There is no role for the use of systemic anti-androgen drugs.

·Hirsutism

Hirsutism is defined as an excess of terminal hairs in women, which are androgen-induced and have a distribution typical of adult men.

Patients are arbitrarily classified as mild, moderate and severe. The Ferriman-Gallaway score is a research tool used to measure the extent of hirsutism and hair growth, but not of practical use in a clinical setting.

Hair density, extent of hair coverage in androgen-inducible skin sites, rate of hair growth (for instance, frequency of physical depilation), and psychological impact are much easier to measure objectively and subjectively in a clinic.

Perception of abnormality is important ­ there are significant racial and ethnic differences in hair growth.

Society plays a big role in defining what is a normal amount of hair for women and men. For example, 5-10 per cent of women, depending on racial grouping, are classified as hirsute. But in a 2001 US survey, 45 per cent of women complained of having unwanted facial hair.

Hirsutism can be a marker for underlying hormonal disease or idiopathic ­ with no underlying endocrine abnormality detectable after investigation.

Polycystic ovary syndrome (PCOS) is the commonest cause. Some 5-10 per cent of women of a fertile age have PCOS and of these, 60-80 per cent are hirsute. Other causes include late onset congenital adrenal hyperplasia, Cushing's disease or syndrome, and androgen- secreting tumours. In women who have features of PCOS (such as hirsutism) but a normal androgen profile, androgen receptor sensitivity is felt to be the cause.

This is likely to be the case in many women labelled as idiopathic hirsutes because systemic anti-androgens work just as well in classic PCOS cases, and so-called idiopathic cases.

Patients with congenital adrenal hyperplasia will present before the age of puberty. Ovarian or adrenal tumours either have moderate to severe hirsutism, usually with a sudden onset of the condition. A full history and examination will differentiate between hirsutism and hypertrichosis. Longstanding mild hirsutism requires no investigations.

PCOS and tumours should be identified with an initial screening test of serum testosterone, FSH, LH and oestradiol measurements. Abdomino-pelvic ultrasound scan to exclude tumour is only usually considered if testosterone level is above 5IU. A serum 17-hydroxyprogesterone level will exclude late onset congenital adrenal hyperplasia.

If any of these investigations are abnormal, then advice regarding further tests or referral to an endocrinologist or gynaecologist should be sought.

Treating the underlying cause of the hirsutism should improve androgen-dependent hair growth. Many cases with mild PCOS with few or no problems, do not actually require medical treatment. Hirsutism alone may be insufficient grounds to embark on medical treatment.

·Inflammatory hair conditions

Pilonidal sinus disease (PSD) occurs in the hair-bearing antenatal cleft of men and women. Thanks to laser the hair follicles are destroyed or miniaturised and this puts the condition into long-term remission.

Pseudofolliculitis occurs because of a natural tendency of curly hair to become in-growing after shaving, or as a result of damage to the hair tunnel by waxing or plucking. A 'foreign-body' type inflammatory reaction is set up within the skin causing painful papules, pustules, nodules, and abscesses, with or without scar formation. Typically affected areas include the beard area, nape of the neck, and the bikini line.

There are a number of options for this condition, including allowing the hair to grow long, laser epilation (if the hair is dark) and long-term anti-inflammatory antibiotics. Laser treatment is particularly successful in the bikini area.

Treatments

Only laser hair removal for PSD is a cost-effective treatment that reduces patient morbidity and reverses physical complaints.

·Shaving

This is quick, effective, cheap and self-funding. Shaving the face is intensely disliked by women due to the strong masculine connotation. Trimming and shaving of congenital forms of hypertrichosis are more readily accepted by parents and patients. The hair-free interval is short and, contrary to popular belief, hairs do not grow back thicker after shaving. Stubble can be a problem.

·Waxing or plucking

Both methods are time-consuming and painful. The hair-free interval, however, is longer than shaving but there is no stubble to see or touch. These methods can cause burns, hyperpigmentation, bacterial folliculitis, pseudofolliculitis and contact dermatitis.

·Bleaching

In certain lights, blond facial hair can look less noticeable than dark facial hair. The camouflage effect is only truly helpful in mild hirsutism of the upper lip. Bleaching can cause irritation and contact dermatitis.

·Electrolysis

An electric current is passed down each individual hair shaft with an electric probe. It is expensive and time-consuming, and the results wholly dependent on the technician performing the procedure. A combination of thermolysis (heat) and diathermy (electrical burn) damage the hair bulb. Folliculitis and erythema can occur.

Scarring is rare in trained hands. Patients and less-skilled technicians are often unaware of the long-term intensive treatment schedules required for optimal results. For heavy facial hair growth, two to three hours per week for two years are required, dropping down to a 30-minute treatment every two weeks.

·Laser epilation

Lasers utilise the theory of selective photothermolysis. The desire is to achieve thermal damage to the hair without thermal damage to the surrounding skin by the appropriate selection of wavelength, pulse width and fluency. A number of lasers are used, such as the ruby alexandrite, and diode.

The ND:Yag is meant for darker skin types. It is thought to target the vascular network around the hair bulb, but this is not proven.

Blond, grey, white and red hair respond poorly with complete recovery of the hair within six to eight weeks, depending on the natural hair cycle for that particular section of skin.

The paler the skin and darker the hair, then the more effective the treatment. This is because a larger fluency (energy) can be delivered without burning the skin. Deeper-lying hair bulbs can therefore be captured by heat conduction down the hair shaft.

More modern devices with larger spot size without loss of fluency also allow deeper laser light penetration, and quicker treatment times.

The alexandrite is the most popular laser for pale skins, and the ND:Yag or diode for darker skin types. Intense pulsed light (IPL) systems are non-laser broadband energy devices. User-friendly software has made the co-ordination of the various parameters on these devices much easier ­ they are popular in beauty salons.

It is more complex to get as good a result with lasers but not impossible. Erythema, discomfort during treatment, folliculitis, and blistering are all potential side-effects. Sun-induced temporary hyperpigmentation means patients must avoid suntans for up to one year after laser or IPL treatment.

Studies show only a small percentage of patients achieve complete hair loss with laser. But hair regrowth delay and a prolonged decrease in hair density are very achievable outcomes. Of 13 patients treated with the ruby laser, four still had significant obvious hair loss two years later; while among another 43 patients treated with the ruby laser, there was a 66 per cent hair count reduction after three months.

Using the Alexandrite laser on 126 patients achieved a 75-95 per cent hair reduction after three months; and of 38 patients treated with the diode, 59 per cent had sparse hair regrowth1,2.

Another effect of laser is that coarse hairs become finer, hair grows more slowly and often regrows as blond hair. Male hairs are more resistant to laser treatment, except in males undergoing complete trans-gender remodification. Laser miniaturisation of the hair follicles may decrease the capacity of the hair to utilise androgens.

Topical treatments

Thioglycolates are available OTC. On the face, they tend to cause irritation. They fracture the hair shaft just below the surface of the skin on repeat application. There is no data on their efficacy.

Eflornithine cream 15 per cent is very well tolerated with minimal topical side-effects, and minimal systemic absorption. It is an irreversible inhibitor of ornithine decarboxylase, which is needed by hair follicles for cell division and differentiation. It now has a worldwide licence.

Pregnancy safety data is insufficient, so it should be avoided in women who are likely to become pregnant unless they are taking adequate contraception. A placebo- controlled randomised study of 596 patients with six months' use showed 39 per cent versus 9 per cent (vehicle group) having a marked improvement. Of these, 5 per cent were completely clear3.

An open non-blind study of 215 patients at one year showed 3 per cent to be clear, 15 per cent marked improvement, 55 per cent some improvement, 20 per cent no improvement. Noticeable hair reduction occurs at eight weeks and plateaus at six months4. A split face right-left facial study comparing alexandrite laser alone versus the alexandrite laser and eflornithine cream in 28 patients showed at six months that there was 68 per cent clearance of hair versus 96 per cent clearance (laser plus eflornithine cream5).

·Diet

Obesity, insulin resistance and hyperinsulinaemia play a much wider role than is generally appreciated. Weight loss should be the initial approach to hirsute women who are overweight. Metformin can help reduce excess weight in women with PCOS and improve hirsutism in some instances6.

·Combined oral contraceptive (COC)

Long-term treatment with a COC is an effective treatment for mild to moderate hirsutism. Hair growth scores have been reported as giving 100 per cent reduction by two years. A six-month trial of treatment, therefore, is not a sufficient evaluation point.

·Cyproterone acetate

Many reports confirm this as an effective treatment. It should be used in combination with a contraceptive oestrogen such as Dianette. Dianette plus additional cyproterone acetate allows for a quicker hair reduction, but hair loss rates are evenly matched at six months treatment7,8. A 100 per cent clearance is expected in mild to moderate hirsutism by two years. Only a decrease from severe to moderate hirsutism occurs in 70 per cent of women, with 30 per cent of severe cases not responding at al · 1.

Side-effects include nausea, weight gain, breast tenderness, thromboembolic events, migraine, decreased libido, hepatitis, depression and hypertension. It should be avoided in patients with a history of thromboembolic disease, coronary artery disease, stroke, breast cancer, abnormal vaginal bleeding, migraines, smokers and women over 35.

·Spironolactone

This diuretic with anti-androgen activity is as effective as cyproterone acetate. Because of the potential feminisation of the male fetus, a COC should be given to sexually active, fertile, women. Side-effects included hyperkalaemia, polyuria and polydipsia. The drug is dose-dependent ­ 200mg a day is twice as effective as 100mg a day. Using 200mg a day 78 per cent clearance is achieved at six months in mild to moderate hirsutism9.

·Flutamide

This drug is comparable in efficacy with cyproterone acetate. Up to 70 per cent clearance is achieved in one year in studies9,10. Idiopathic hirsutes seem to respond better than patients with proven PCOS. Side-effects include dry skin, decreased libido, headache, GI upset, and hepatotoxicity. Regular liver function blood monitoring is mandatory. It should be combined with a COC in sexually active, fertile, women because of the potential of feminising a male fetus.

·Finasteride

This drug is well tolerated, with minimal adverse effects. Although efficacy studies vary, it is regarded as the least effective oral anti-androgen and 40-50 per cent hair reduction at one year would be a reasonable response10,11. It, too, should be combined with a COC in sexually active, fertile, women.

·Gonadotrophin receptor hormone agonists

These are effective, but expensive and complicated to use. They should be reserved for severe cases of ovarian hyper-androgenism under specialist supervision8.

Summary

Hypertrichosis and hirsutism cause psychological morbidity that can be difficult to quantify. Physicians who trivialise these conditions run the risk of failing to identify underlying disease.

Shaving is cheap, simple and harmless but detested by female patients.

Effective laser treatment is limited to dark hair, and those who can afford to pay.

It is a very safe treatment for localised and widespread hypertrichosis, and mild to severe hirsutism. Medical devices such as laser do not require a licence for treatment.

Eflornithine cream is prescription only, which may limit its availability. It can be combined with a COC, oral anti-androgen, and laser treatment to maximise efficacy.

It can be successfully used for localised hypertrichosis, and in mild to moderate hirsutism as a single agent, with minimal side-effects. COCs are excellent for mild hirsutism, if continued for two years. Vaniqa and Dianette are the only two drugs licensed to treat hirsutism.

Oral anti-androgens are effective for mild-moderate hirsutism, and partially effective for moderate to severe hirsutism. Side-effects are, however, common and potentially serious.

Take-home points

·In hirsutism, it is imperative all endocrine abnormalities are excluded by history, examination and investigation. Depending on results, further investigations or advice from an endocrinologist may be needed.

·Long-standing mild hirsutism does not require further investigation.

·Establishing PCOS may be helpful because of other possible medical consequences.

·Most treatments directed against aspects of PCOS will improve hirsutism.

·Diet, COC, systemic anti-androgens and metformin have no place in the treatment of hypertrichosis.

·It is important to investigate all possible causes of acquired hypertrichosis.

·Treatment cost is an important consideration. Safety may be more important given that hirsutism or hypertrichosis alone cause psychological morbidity only.

·The safest treatments are diet (hirsutism only), laser (dark hair only) and topical eflornithine cream (localised areas only).

·Some treatments can be combined to maximise results.

·Lasers should be the first choice treatment for PSD.

·Clinicians need to be aware of the range, usefulness and limitations of all possible treatments or patients will not be given an informed choice.

·All treatment options (excluding over-the-counter depilators and electrolysis) should be made equally available if NHS treatment is deemed appropriate.

References

11 Chana JS et al. The long-term results of ruby laser epilation in a consecutive series of 346 patients. Plastic Reconstr Surg 2002:110;254-60

12 Lanigan SW. Management of unwanted hair in females.

Clin Exp Dermatol 2001:26;644-7

13 Schrode K. Randomised double-blind vehicle controlled safety and efficacy evaluation of eflornithine 15% cream in treating women with excessive facial hair [ABSTRACT]. Am Acad Dermatology annual meeting 2000

14 Schrode K. Evaluation of the long-term safety of eflornithine 15% cream in treating women with excessive facial hair [ABSTRACT]. Am Acad Dermatology annual meeting 2000

15 Hamzani I et al. Combined treatment with laser and topical eflornithine is more effective than laser treatment alone for removing unwanted facial hair ­ a placebo-controlled trial [ABSTRACT]. Am Soc Laser Med & Surg annual meeting 2004

16 Lord J et al. Metformin in polycystic ovary syndrome: results of a double-blind dose ranging study.

Clin Endocrinol 1991;35:5-10

17 Barth JH et al. Cyproterone acetate for severe hirsutism: results of a double-blind dose ranging study.

Clin Endocrinol 1991;35:5-10

18 Downs AMR, Palmer J. Hair removal laser for the treatment of pilonidal sinus disease. J Cosmetic Laser Ther 2002;4:91

19 Triieb Rm et al. Causes and management of hypertrichosis.

Am J Clin Dermatol 2002;3:617-27

10 Muderris II et al. A prospective, randomised trial comparing flutamide and finestride in the treatment of hirsutism. Fert Sterility 2000; 73:984-7

11 Beigi A et al. Finasteride vs cyproterone acetate-estrogen regimens in the treatment of hirsutism.

Int J Gynecol 2004:87:29-33

Tony Downs is consultant dermatologist, Royal Devon & Exeter NHS Foundation Trust

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