Hirsutism is defined as the presence of excess hair growth in women occurring in an androgen-dependent pattern (top lip, chin, chest, periumbilical, inner thigh; Figure 26.1). It should be distinguished from hypertrichosis which is an excess of long fine vellus hairs and is not androgen-dependent. Hirsutism occurs as a result of increased androgen production and/or increased skin sensitivity to androgens. Androgens are produced from the ovaries and adrenal glands in equal amounts in pre-menopausal women. Common causes of androgen excess are PCOS and idiopathic hyperandrogenism (more common in Mediterranean, South Asian and Middle Eastern populations). Rarer causes are Cushing’s syndrome (Chapter 4), congenital adrenal hyperplasia (CAH), ovarian or adrenal tumours, and medication (e.g. danazol) (Table 26.1).
Investigation and management
An evaluation of hirsutism should look for other features of hyperandrogenism (acne, frontal balding, oligo-/amenorrhoea), with a particular focus on signs of virilisation (deepening of the voice, clitoromegaly, marked frontal balding, increased muscle bulk) as this can point to an underlying tumour. The history should also focus on duration of hirsutism (rapid onset suggests a virilising tumour) and the time spent on hair removal each day as a guide to severity and impact upon the patient.
Investigation is mainly to exclude virilising tumours and other rare causes of hyperandrogenism, such as Cushing’s syndrome which requires a different approach to management from PCOS or idiopathic hyperandrogenism. A biochemical screen must include measurement of testosterone, because levels 5 nmol/L should lead to ovarian and adrenal imaging (MRI or CT) to exclude virilising tumours. Only 50% of patients with PCOS have elevated testosterone values, hence a normal reading does not exclude the diagnosis. Other helpful biochemical tests are LH, FSH (the LH : FSH ratio is often raised in PCOS), ovarian/adrenal androgens (androstenedione/DHEAS) and 09.00 17-hydroxyprogesterone (17-OHP; to screen for CAH). In patients with features of Cushing’s syndrome, one or more of an overnight DST, late night salivary cortisol and 24-hour UFC should be undertaken as a screen.
Treatment is directed at the underlying cause. General treatments for hirsutism include mechanical approaches (waxing, plucking, shaving, depilatory creams), laser removal and electrolysis, eflornithine cream (which slows down hair follicle growth), oestrogens (e.g. the combined oral contraceptive pill) and anti-androgens (e.g. cyproterone acetate, spironolactone). Because hair grows slowly, any treatment will need to be used for at least 6 months to judge efficacy.
Polycystic ovary syndrome
PCOS is a common endocrine condition that affects 5–10% of young women. It is characterised by hyperandrogenism, oligo-/amenorrhoea and polycystic appearances to the ovaries on ultrasound (Figure 26.2). Two out of three of the above features are needed to support a diagnosis, provided other mimicking conditions (e.g. Cushing’s syndrome, CAH, hyperprolactinaemia) are excluded.
Insulin resistance is a key underlying defect in both obese and lean women with PCOS, and leads to an increased lifetime risk of type 2 diabetes in addition to the well-recognised reproductive consequences (subfertility, oligo-/amenorrhoea) of the disorder.
Transvaginal ultrasound can show a polycystic ovarian appearance of multiple small subcapsular follicles and an increased central stroma, but a normal scan does not exclude the diagnosis. Equally, ultrasonic appearance of polycystic ovaries is common in the general population (up to 20% of young women) but on its own is insufficient to establish a diagnosis of PCOS. Biochemical tests, undertaken as for hirsutism, can support the diagnosis but are not specific.
Treatment is predominantly directed at the principal complaint. Because >70% of patients are overweight or obese, weight loss is important, not only to improve clinical symptoms, but also to reduce the long-term metabolic health risks. Hirsutism is treated as for any other cause whereas menstrual irregularity can be treated with the combined oral contraceptive pill, cyclical progestogens or metformin (to improve insulin sensitivity) if fertility is not desired. Clomiphene is first line treatment to induce ovulation in women who desire pregnancy.
Congenital adrenal hyperplasia
CAH is a family of inherited disorders of adrenal steroidogenesis, the most common of which is 21-hydroxylase deficiency (90% of cases). This enzyme defect leads to a block in cortisol (± aldosterone) synthesis, consequent hypersecretion of ACTH, a build-up of precursors upstream of the defect (e.g. 17-OHP) and excess hormone synthesis (especially androgens) in pathways unimpaired by the enzyme defect (Figure 26.3).
In ‘classic’ CAH, patients usually present in the neonatal period or as children with virilisation (e.g. causing ambiguous genitalia in girls) ± salt wasting (due to aldosterone deficiency). ‘Non-classic’ CAH, characterised by partial enzyme inactivity, presents later in life with features akin to PCOS (hirsutism, oligomenorrhoea). Demonstration of a raised 17-OHP value, either at baseline or in response to synthetic ACTH (Synacthen), confirms the diagnosis.
Treatment comprises replacement therapy with glucocorticoids (e.g. hydrocortisone or prednisolone); patients with salt-wasting also require mineralocorticoid replacement with fludrocortisone.