Hirsutism

Written by: Billy Chung from Manchester University,

Introduction

Definition: Excess facial hair or body hair in women.

Incidence: Relatively common at 10% of all women in developed countries.

 

Without the basic core knowledge of the female androgen system, it can be hard to remember or understand all the causes of hirsutism. Thus making it difficult for you to manage the hirsute patient effectively.

Causes

95% of hirsutism cases are caused by PCOS. So when asked by an examiner, this should always be your first answer. However, you also need to be aware of some of the rarer, but sinister causes of hirsutism. There are many and they can be seperated into 4 groups:

  • Ovarian in origin
  • Adrenal in origin
  • External Source
  • Suppressed SHBG levels.

 

Causes

History

You should first assess the likelihood of the hirsutism being caused hyperandrogenemia. Taking into account factors such as history of onset and rate of progression of hirsutism, ethnicity, regularity of menstrual cycles, presence of other features of hyperandrogenemia, BMI, response to previous treatments and family history of Type II diabetes. Also take time to rule out the use of androgenic medications.

Examination

  • Grade the hirsutism – This can be done subjectively or objectively using the Ferriman-Gallwey Score. A score of more than 8 is considered as being caused by hyperandrogenemia.

 

  • Look for other signs of hyperandrogenemia (i.e. acne, excess sebum secretion)

 

  • Look for virilisation (i.e. male pattern muscle bulk, deepening of the voice, balding and clitomegaly). Virilisation indicates severe hyperandrogenemia and is usually caused by an androgen secreting tumour, not PCOS.

 

  • Acanthosis Nigricans – This is hyperpigmentation of the skin folds, this can indicate hyperinsulinemia/an insulin resistant state. There is also an association of Acanthosis Nigricans with neoplasms.

 

  • Blood Pressure – Raised in Acromegaly and Cushings disease but decreased in CAH and hypothyroidism.

 

Investigations

Patients who have isolated mild hirsutism without signs of virilisation, have not been previously treated and clinical suspicion is low for underlying hyperandrogenemia, may be started on a trial of treatment to test for response without investigation.

 

In others, they should have their morning testostestrone measured initially. If raised then a full work up should be sought to look for the source of androgen production:

 

  • DEHAS & 17 hydroxyprogesterone (Raised in adrenal causes)
  • OGTT (Type II Diabetes)
  • Transvaginal Ultrasound (PCOS and ovarian neoplasms)
  • Full endocrine work up: hypothyroidism, prolactinemia, acromegaly etc.

 

First line Management

For all benign causes and idiopathic hirsutism:

 

Cosmetic measures:

  • Shaving – Effective. No major side effects. Does not change the quality, quantity or texture of hair. It leaves a blunt tip where growing hair protrudes through the skin surface which may give the illusion of thicken hair.

 

  • Bleaching – Masks undesired hair. Side effect includes skin irritation, discolouration of the skin.
  • Plucking/Waxing – Removes hair down to the bulb, safe and cheap. It can cause discomfort, scarring, folliculitis and sometimes hyperpigmentation.

 

  • Electrolysis and laser hair removal – Very effective. Under magnification, each hair follicle is destroyed individually. Very expensive compared to other cosmetic measures. Evidence of long term effecticacy is not available and its' cost and availability unfortunately limits its' use.

 

Life style changes:

  • Weight reduction - for those who have raised BMI. This is an important but perhaps under-recognised treatment of hyperandrogenemia. Weight reduction reduces insulin, increases production of SHBG and reduces the insulin resistance state of the obese body. Patient compliance can be an issue so thorough counselling to improve patient’s understanding of their condition may be needed.

Medications:

  • Combined Oral Contraceptive Pill (COCP) – Reduces hair growth in over 60% of patients. Oestrogen component increases SHBG productions and inhibits 5 alpha reductase. Progestogen component inhibits secretion of LH. Third generation combined pills are most effective. Additional benefits include contraception and reduced menstrual blood loss. COCP's are associated with a risk of developing hypertension, diabetes mellitus, hypercholestrolaemia and DVT. In addition, the side effects of COCP include bloating, breast discomfort and increasing appetite causing weight gain.

 

  • Cryproterone acetate (CPA) – an anti-androgen, also a progesterone. It is widely used in the UK to treat Hirsutism. It dual compound properties means it inhibits androgen receptors, inhibits 5 alpha reductase as well as suppressing gonadotrophin and androgen levels. It is given in conjunction with ethnyl-estridiol to prevent menstral disturbances. Typical starting dose of CPA is between 50-100mg daily. Maintenance dose can then be used once maximal effect has been achieved. CPA is well tolerated and side effects are similar to those of oral contraceptives. 

 

Second line management

Medical

  • Spironolactone: An aldosterone antagonist. Reduces Hitsutism through competitive inhibition of DHT, reduces CYP enzyme and increases peripheral aromatisation of testosterone and inhibition of skin 5 alpha reductase. Evidence shows at least modest improvement in over 70% of patients after treatment with 200mg/day for 6 months. Its therapeutic dose varies and typical dosage ranges from 50 to 100 mg twice per day. Contraception must be taken at the same time as spironolactone has effects on the genitalia of the foetus. Side effects include menstrual irregularity, polyuria, postural hypotension and rarely hyperkalaemia.

 

  • Finasteride – A specific inhibitor of 5 alpha reductase (type 2). Studies have shown a significant reduction of hirsutism score after 3-6 months of treatment. Typical dose is 5mg per day. It has minimal side effects but is teratogenic so contraception is needed.

 

  • Flutamide – a pure nonsteroidal anti-androgen, works by inhibition of androgen receptors. Less potent than sprionolactone or CPA. Side effects include dry skin, blue discolouration of urine and elevated liver enzymes. It has repeatedly been reported to cause liver failure so monitoring is needed.

 

  • Insulin lowering drugs –Metformin: primarily used to treat patients with PCOS. Its use in hirsutism without menstrual or metabolic disturbances remains controversial. Insulin stimulates androgen production in theca cells as well as suppresses SHBG production. Metformin inhibits hepatic release of glucose, thereby lowering insulin level, thus lowering androgen production and levels of free androgens. Metformin is not be used in patients with renal impairments. Side effects include diarrhoea, nausea and vomiting.

 

  • GnRH agonists- Only used if hirsutism is gonadotrophin dependent.  The use of GnRH agonsts is expensive, requires injections and requires oestrogen replacements meaning it is not recommended for the treatment of hirsutism in most women.

 

  • Ketoconazole - An anti-fungal agent. Used here to induce P450 metabolic enzymes of the liver. So metabolism of testosterone is increased. This is only to be used when other options have failed or are contraindicated for the patient as Ketoconazole can cause hepatotoxicity. Regular monitoring is needed; side effects include alopecia and abdominal pain.

References

1)Collins S, Arulkumeran S, Hayes K, et al. Oxford Handbook of Obstetrics and Gynaecology, 2nd ed. Oxford. Oxford University Press 2008. p.548-555

2)Berek, J.S., Berek & Novak's Gynaecology 2007, Lippincott Willams & Wilkins, a Wolters Kluwer business: Philadelphia. p. 1069-1089

3)Hatch, R., et al., Hirsutism: implications, etiology, and management. Am J Obstet Gynecol, 1981. 140(7): p. 815-30.