Hirsutism

What is hirsutism?

Hirsutism is defined as the excessive growth of thick dark hair in an androgen-dependent pattern where hair growth in women is usually minimal or absent - eg, the face, the chest and the areolae. It occurs as a result of increased androgen production, increased skin sensitivity to androgens, or both.¹ Hirsutism is different to hypertrichosis, which is increased hair growth in a generalised non-sexual distribution and is unrelated to androgens. Idiopathic hirsutism and polycystic ovary syndrome (PCOS) are the most common causes.² When hirsutism in women is accompanied by other signs of virilism, it may be a manifestation of a more serious underlying disorder causing hyperandrogenism, such as an ovarian tumour or adrenal neoplasm.

How common is hirsutism? (Epidemiology)³

• Hirsutism is a common disorder affecting between 5% and 10% of women of reproductive age.⁴

• It is less common in Asian people.

• There is variation in amount of terminal body hair amongst different ethnicities.⁵

• In addition, cultural factors affect the perception of what is considered 'excessive' hair growth for women.

• The Ferriman-Gallwey score is used in evaluation of hirsutism. It reflects the amount of hair over different body areas. This may require adjustment for ethnic group.

• Obesity is associated with increased hirsutism.

Hirsutism causes (aetiology)

• Idiopathic hirsutism:
  

  • Common and often familial.

  • Is a diagnosis of exclusion and thought to be related to disorders in peripheral androgen activity.

  • Onset occurs shortly after puberty with slow progression.

  • There are no other signs of virilism. Menstrual function and investigations are normal.

• Drug-induced hirsutism - eg, glucocorticoids, danazol, sodium valproate and androgenic progestogens.

• Ovarian causes:
  

  • PCOS: virilisation is minimal and hirsutism is often prominent. This is the most common cause and is present in approximately 70% of cases.^{3 4}

  • Menopause.

  • Androgen-producing ovarian tumours - eg, luteoma of pregnancy, arrhenoblastomas, Leydig cell tumours, hilar cell tumours, thecal cell tumours.

• Adrenal causes:
  

  • Androgen-producing adrenal tumour.

  • Congenital adrenal hyperplasia (CAH).

  • Cushing's syndrome.

• Other causes include severe insulin resistance, anorexia nervosa, prolactinoma, acromegaly, hypothyroidism and porphyria.

Hirsutism in children

• Familial or ethnic hirsutism usually begins during puberty. Therefore, hirsutism in prepubertal children may be a sign of precocious puberty and may signify a serious underlying disease (all relevant conditions listed above should be considered).

• Hirsutism resulting from CAH begins early in childhood, while late-onset CAH presents with hirsutism after puberty.

• Rare 46, XY chromosomal disorders can cause hirsutism at puberty with primary amenorrhoea and clitoromegaly⁶ .

Hirsutism symptoms

• Excess terminal hair in a masculine pattern: face (particularly the moustache, beard and temple areas), chest, areolae, linea alba, upper and lower back, buttocks, inner thighs, external genitalia.

• Signs of associated virilism (hyperandrogenism) may be present. They include:⁷
  

  • Acne.

  • Alopecia, temporal hair recession.

  • Male-pattern (truncal) obesity.

  • Clitoromegaly.

  • Deepening of voice.

  • Increased libido.

  • Increased muscle mass (primarily shoulder girdle).

  • Loss of breast tissue or normal female body contour.

  • Malodorous perspiration.

  • Infertility.

  • Menstrual dysfunction.

• Other abnormalities associated with excessive levels of androgen are cardiovascular disease, dyslipidaemia, glucose intolerance/insulin resistance and hypertension. Acanthosis nigricans, a marker for insulin resistance, may also be present.

• Pelvic mass: originating from an ovary (on bimanual vaginal examination) or adrenal tumour.

Differential diagnosis

Hypertrichosis: this is androgen-independent and causes uniform growth of vellus hair over the body, especially in non-sexual areas. The aetiology of hypertrichosis includes:

• Familial.

• Related to medication - eg, phenytoin, ciclosporin, minoxidil or topical steroids.

• Non-endocrine causes, such as anorexia nervosa.

Investigations

It is important to investigate to establish the cause of hirsutism, even when mild, as the degree of hirsutism does not correlate well with the magnitude of androgen excess.³ However, the first stage is careful history and examination. If there is no suggestion of hyperandrogenism, full endocrine evaluation may not be required.⁸

History

• Age of onset, rate of progression.

• Menstrual history, age of menarche.

• Medication, including over-the-counter preparations and anabolic steroids.

• Family history of hirsutism.

• Level of distress caused by hirsutism.

• Associated symptoms (eg, acne, weight gain, androgenic alopecia, galactorrhoea, visual disturbance, headache, deepened voice).

Examination

• For signs of hyperandrogenism as above.

• For signs of Cushing's syndrome (moon face, stretch marks, easy bruising, proximal muscle weakness).

• For skin changes such as acanthosis nigricans or acne.

• To exclude pelvic masses.

• Blood pressure.

• BMI.

The task is then to establish whether the hirsutism is androgen-mediated and if so, the cause of excess androgen.

Further investigation is indicated if there are features of androgen excess, rapid progression, infertility or menstrual irregularity.

Initial investigations
These include:^{4 9}

• Testosterone:

  • If the total testosterone is raised, further investigations for androgen excess should be conducted (see below

  • If the total testosterone is normal, and the hirsutism mild and isolated, a trial of treatment can be considered.

  • If the total testosterone is normal, but the hirsutism is moderate-to-severe, or there are other signs of hyperandrogenic endocrine disorder (for example, sudden-onset or rapidly-progressing hirsutism, irregular menstruation, infertility, galactorrhoea, features of hypothyroidism or Cushing's syndrome, acromegaly, or central obesity), measure an early morning serum total and free testosterone.

  • Free testosterone is more sensitive and may be raised in PCOS.

  • If the free testosterone is normal, this suggests idiopathic hirsutism.

  • If free testosterone is elevated, further investigations for androgen excess should be conducted (see below).

• 17-hydroxyprogesterone:

  • This is raised in non-classical CAH.

  • It can be measured in women with hyperandrogenaemia, and should be considered in all women with hirsutism at high risk of non-classical CAH, regardless of testosterone levels. High-risk features for CAH include those with a family history of the condition, and women from certain high-risk ethnic groups (such as Ashkenazi Jewish, Hispanic, and Eastern European people)

  • This test needs to be measured in the early morning, during the follicular phase.

Further investigations for hyperandrogesteronism will depend on the clinical picture and may need to take place in secondary care (see 'Indications for referral' below).

• Follicle stimulating hormone (FSH), luteinising hormone (LH): women with PCOS may have an increased LH/FSH ratio (>2 is common).

• 24-hour urine cortisol (to rule out Cushing's syndrome if suspected):
  

  • Cushing's syndrome is a rare cause of hirsutism and exclusion is not necessary unless the patient has Cushingoid features.

• Pregnancy should be ruled out in women with irregular or absent menstrual cycles.

• Prolactin:
  

  • Prolactin affects the menstrual cycle and hyperprolactinaemia can be associated with hirsutism.

  • If prolactin concentrations are more than 1.5-2 times the upper limit of normal, other causes of hyperprolactinaemia should be considered.

• TFTs: thyroid dysfunction can affect menstruation and hypothyroidism is associated with changes in hair.

• Ultrasound: patients with either menstrual disturbances or clinical or biochemical evidence of hyperandrogenism alone should have transvaginal ultrasound imaging of the ovaries.

• Further investigations as indicated:
  

  • Glucose tolerance test with serial growth hormone measurements if acromegaly is suspected.

  • Lipid profile.

  • HbA1c.

  • Ultrasound, CT, MRI: if an adrenal or ovarian tumour is suspected. MRI brain scan: if a pituitary tumour is suspected.

Hirsutism treatment^{4 9}

Treatment for hirsutism is unnecessary if no abnormal aetiology can be diagnosed and if the patient is not concerned about the cosmetic appearance. Management is mainly directed at any underlying cause if present. Treatment of hirsutism is not usually curative, unless a treatable underlying cause has been found. Because of the cyclical nature of hair growth, any systemic treatment may take up to six months to be effective.

Lifestyle modification

• Encourage weight loss if overweight:
  

  • Weight loss increases steroid hormone-binding globulin levels and decreases insulin resistance and the levels of serum androgens and luteinising hormones.

  • Obesity has an adverse effect on the outcome of all systemic treatments.¹⁰

  • Women who are overweight, hyperandrogenic or hyperinsulinaemic are at increased risk of diabetes mellitus and cardiovascular disease.

• Smoking cessation advice.

Indications for referral

• Features of Cushing's syndrome (weight gain, stretch marks, easy bruising, proximal muscle weakness).

• Abnormal results of levels of testosterone, 17-hydroxyprogesterone, prolactin, etc.

  • NICE recommends referring to endocrinology if testosterone levels are >4 nanomol/L, and referring urgently if testosterone levels are >6-7 nanomol/L.

• Hirsutism not controlled by measures advised in primary care.

• Features of an androgen-secreting tumour (two-week wait referral):

  • Sudden onset or rapidly-progressing hair growth.

  • Signs of virilisation (voice deepening, increased muscle bulk, clitoromegaly).

  • Pelvic or abdominal mass.

Topical cosmetic therapies

Shaving, threading, waxing, using depilatory creams, electrolysis and laser epilation or photo-epilation do not exacerbate hair growth and are effective, at least in the short term.¹⁰ Hair removal therapies are not usually available on the NHS.

• Bleaching.

• Shaving: removes all hairs superficially but regrowth produces a rough stubble. Most women prefer not to shave facial hair.

• Chemical depilation may be suited to treatment of large hairy areas in patients unable to afford more expensive treatments such as electrolysis and laser epilation.

• Temporary epilation:
  

  • Plucking: this may result in irritation, damage to the hair follicle, folliculitis, hyperpigmentation, and scarring.

  • Waxing: this can be painful and sometimes results in folliculitis. With repeated treatments it may reduce the number of hairs permanently.

  • Home epilating devices that remove hair by rotation or friction: these may produce traumatic folliculitis.

• Permanent epilation:
  

  • Electrolysis and thermolysis:
    

    • Thermolysis (diathermy) is much faster than the traditional electrolysis method.

    • Electrolysis and thermolysis can be used on all skin and hair colours; however, they require multiple treatments.

    • Results depend on the skill of the operator.

    • Electrolysis and thermolysis can be uncomfortable and may produce folliculitis and post-inflammatory pigmentary changes in the skin.

  • Laser epilation:
    

    • Can treat larger areas faster than electrolysis and thermolysis.

    • Is most effective on dark hairs in fair-skinned people.

    • Multiple treatments may be necessary for long-term hair destruction.

    • Folliculitis, discomfort and pigmentary changes may occur.

Pharmacotherapy

• Eflornithine, a topical hair growth retardant, inhibits the enzyme ornithine decarboxylase. It may reversibly slow facial hair growth in up to 70% of patients; however, evidence is weak. Local prescribing policies may not recommend its use:

  • It must be used indefinitely to prevent regrowth. Once discontinued, hair growth returns to pre-treatment levels within eight weeks.

  • It is only licensed for facial hair.

  • Continuous use for eight weeks is required before benefit is seen.

  • It should be discontinued in the absence of improvement after treatment for four months.

  • It should not be used in pregnant or breastfeeding women or in those younger than 19 years.

• Combined oral contraceptives:
  

  • Recommended as first-line treatment. There is evidence of limited quality that they are effective for mild hirsutism.¹¹

  • Pills containing progestogens with anti-androgenic properties (eg, Co-cyprindiol (Dianette®) or Yasmin®) are effective but those containing levonorgestrel and norethisterone are more androgenic and could potentially exacerbate hirsutism. Dianette® is licensed for this purpose and can be used first-line. Use of Yasmin®, or other combined oral contraceptives containing drospirenone, is off-licence.

  • Co-cyprindiol may be effective when hirsutism co-exists with acne (eg, in PCOS).

• Anti-androgens:
  

  • Flutamide, finasteride and spironolactone have all been used in the management of hirsutism. There is some low-quality evidence for efficacy of flutamide and spironolactone but results for finasteride were found to be inconsistent in a Cochrane review.¹¹

  • May be combined with oral contraceptives for the treatment of hirsutism.

  • Cannot be used in pregnancy and should be prescribed with secure contraception.

  • May be associated with side-effects.

• Gonadotrophin-releasing hormone (GnRH) agonists:
  

  • For severe cases, these are occasionally used in secondary care.

  • GnRH agonists such as leuprorelin or goserelin should be reserved for use in women who do not respond to combination hormonal therapy or those who cannot tolerate oral contraceptives.

  • Long-term adverse effects include hot flushes, bone demineralisation, atrophic vaginitis.

• Metformin and other insulin-sensitisers have been shown to improve insulin sensitivity and decrease testosterone levels in patients with PCOS. They may have a limited role in management of subfertility in this context but the evidence is currently against them being used for hirsutism alone.^{11 13}

Complications

• Hirsutism may have a detrimental impact on a woman's body image.

• Facial hirsutism may cause considerable emotional distress and social embarrassment to women; hirsutism exceeding culturally normal levels can be very distressing.

• Hirsutism is commonly associated with lower quality of life and symptoms of anxiety and depression.¹⁴