Hirsutism and Virilism

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, e.g. face, chest, and areolae. It is caused either by increased circulating levels of androgens or increased sensitivity of hair follicles to normal levels of circulating androgens. 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 or adrenal neoplasm.¹

• Hirsutism is a common disorder affecting between 5% and 10% of women.² It is uncommon in sub-Saharan and East Asian people.
• Familial hirsutism is most often seen in southern European and South Asian countries.
• Dark-haired and dark-skinned whites tend to be more hirsute than blond or fair-skinned people.
• Obesity is associated with increased hirsutism.

• 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, normal menstrual function and normal investigations
• Drug-induced hirsutism: e.g. anabolic steroids, danazol, minoxidil, metoclopramide, methyldopa, phenothiazines, progestogens and reserpine
• Ovarian causes:
  • Polycystic ovary syndrome (PCOS): virilisation is minimal, and hirsutism often is prominent
  • Menopause
  • Androgen-producing ovarian tumours: e.g. luteoma of pregnancy, arrhenoblastomas, Leydig cell tumors, hilar cell tumors, 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 congenital adrenal hyperplasia begins early in childhood, while late-onset CAH presents with hirsutism after puberty.

• Excess terminal hair in a masculine pattern: face (particularly, moustache, beard and temple areas), chest, areolae, linea alba, upper and lower back, buttocks, inner thighs, external genitalia.
• Other signs of virility include:
  • 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: ovarian (bimanual vaginal examination) or adrenal tumour

Hypertrichosis: excess hair (terminal or vellus) in areas that are not predominantly androgen dependent, i.e. any part of the body.

• Investigations in primary care:
  • Pelvic ultrasound
  • Serum testosterone, free testosterone and dehydroepiandrosterone sulphate (DHEAS): raised levels indicate the need for further investigation. High levels of DHEAS suggest a possible ovarian or adrenal neoplasm.
  • Thyroid function
  • Follicle stimulating hormone, luteinising hormone: women with PCOS have an increased LH/FSH ratio (>2 is common)
  • Prolactin
• Investigations in secondary care:
  • Dehydroepiandrosterone (DHEAS)
  • Androstenedione
  • 17-alpha hydroxy progesterone: screening test for late-onset congenital adrenal hyperplasia
  • 24-hour urinary cortisol or an overnight dexamethasone suppression test: if Cushing's syndrome is suggested
  • Glucose tolerance test with serial growth hormone measurements
  • Abdominal ultrasound, CT, MRI: if suspected polycystic ovary syndrome, adrenal or ovarian tumour. MRI brain scan if suspect pituitary tumour

• 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.
• The management of virilism is based on the diagnosis and management of the underlying cause.
• Encourage weight loss if overweight: increases steroid hormone binding globulin levels and decreases insulin resistance and the levels of serum androgens and luteinising hormones. Women who are overweight, hyperandrogenic or hyperinsulinaemic are at increased risk of diabetes mellitus and cardiovascular disease.

Topical cosmetic therapies¹

• 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: may result in irritation, damage to the hair follicle, folliculitis, hyperpigmentation, and scarring.
  • Waxing: 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: 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, but 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 can electrolysis and thermolysis.
    • 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.

Drug therapy

• Combined oral contraceptives: low-dose combined oral contraceptives containing less androgenic progestogens (e.g. norgestimate, gestodene and desogestrel) or dianette (containing cyproterone) are recommended but all combined oral contraceptives may be equally effective.^1,4
• Anti-androgens:
  • May be combined with oral contraceptives for the treatment of hirsutism.²
  • In most patients, low doses of antiandrogens (e.g. flutamide, spironolactone) are used with few adverse effects and good results.^5,6
  • Patients with severe hyperandrogenic hirsutism may require larger doses of antiandrogens.⁶
  • Response to antiandrogens is slow and may take up to 18 months. Stopping treatment is usually followed by recurrent hair growth.
  • Finasteride, which inhibits 5 alpha-reductase activity, may be used as alternative to low dose antiandrogen therapy but the results are often less satisfactory.⁶
• Dexamethasone: may be used at low doses with an antiandrogen to prolong the length of the remission.⁶
• Gn-RH agonists:
  • Leuprolide 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.
• Antifungal:
  • Effective but side effects include alopecia, dry skin, abdominal pain and hepatotoxicity.
  • Should be reserved for patients with severe hirsutism that have not responded to other therapeutic options.
  • Liver function testing should be performed before and at periodic intervals during prolonged treatment.
• Insulin-sensitising agents: metformin has been shown to improve insulin sensitivity and decrease testosterone levels in patients with polycystic ovary syndrome.
• Eflornithine: topical hair growth retardant.
  • Must be used indefinitely to prevent regrowth.
  • Continuous use for 8 weeks is required before benefit is seen.
  • Should be discontinued in the absence of improvement after treatment for 4 months.
• Co-cyprindiol may be effective when hirsutism co-exists with acne (e.g. in polycystic ovary syndrome).

• Hirsutism may have a detrimental impact on a woman's body image and quality of life.
• Facial hirsutism may cause considerable emotional distress and social embarrassment to women., hirsutism exceeding culturally normal levels can be very distressing.³