A 19-year-old woman with hirsutism has been referred to the gynaecologist by her

A 19-year-old woman with hirsutism has been referred to the gynaecologist by her
GP.

(a) What important clinical signs will you look for? (6 marks)

(b) Justify the
investigations you will undertake on her. (6 marks)

Common mistakes

● Discussing the pathogenesis of hirsutism
● Listing all the causes of hirsutism
● Detailing the symptoms of PCOS and the physiological bases of hyperandrogenism in
PCOS
● Management of infertility and menstrual abnormalities
● Defining hirsutism and the use of Gallwey and Ferriman classification of hirsutism
● Advising the patient to lose weight – not told that she is obese
● Treating all the associated symptoms of PCOS, e.g. menstrual abnormalities, acne, infertility, obesity, etc.
● Use of trade names of very unfamiliar drugs
A good answer will include some or all of these points

(a) What important clinical signs will you look for? (6 marks)

● Body habitus (height, weight):
● Signs of virilisation, and in some cases features of classic endocrine disorders –
Cushing’s syndrome or acromegaly
● Breast examination – galactorrhoea (especially if menstrual abnormalities), atrophy
● Thyroid gland – enlargement
● Abdomen and pelvis for masses – adrenal or ovarian
● Acanthosis nigricans – back of neck and vulva
● Hair distribution:
● Semi-quantitative assessment of degree of hirsutism – Ferriman–Gallwey score
● Baldness, acne
● Secondary sexual characteristics

(b) Justify the investigations you will undertake on her. (6 marks)

● Blood:
● Serum testosterone – elevated in only 40 per cent of cases:
● Mainly to exclude serious disorders of androgen secretion (e.g. congenital
adrenal hyperplasia, Cushing’s syndrome, adrenal or ovarian tumours)

● Testosterone levels <3 nm/L in those with idiopathic hirsutism; levels >5 nmol/L
are rare in those with PCOS
● If >5 nmol/L, further test for adrenal function must be undertaken (computerised tomography (CT)/magnetic resonance imaging (MRI))
● Sex-hormone-binding globulin
● Follicle-stimulating hormone (FSH)/luteinising hormone (LH)
● Free androgen index
● Dehydroepiandrostendione sulphate (DHEAS),
● Radiological:
● Ultrasound scan of the ovaries and adrenals; best performed in the early follicular
phase to define ovarian morphology and exclude rare tumours
● MRI/CT scan if raised testosterone

● Reassurance – especially if familiar; no treatment needed and patient feels normal
● Mechanical (cosmetic) – waxing, shaving, electrolysis, depilatory creams, bleaching and
laser; most are cheap, patient feels normal and that she does not have a disease, not medicalised
● Medical:
● Antiandrogens:
● Cyproterone acetate (CPA) alone or in combination with oestrogens (Dianette®)
● Spironolactone
● Flutamide
● Ovarian suppression:
● Combined oral contraceptive pill
● Gonadotropin-releasing hormone (GnRH) analogues
● Eflornithine hydrochroride (Vaniqa®)
● 5-Alpha-reductase inhibitor:
● Finasteride

Sample answer

(a) What important clinical signs will you look for? (6 marks)

Physical examination will first determine her weight, height and therefore body mass index
and muscle distribution. The aim of this is to identify obesity and if present whether it is central or not. Acanthosis nigricans should be noted.

Other features that may be identified on
examination include those of virilisation and, in some cases, those of the classical
endocrinopathies such a Cushing’s syndrome (moon-face appearance). Hair distribution and
the type of hair should be noted and scored by the Ferriman–Gallwey method of semi-
quantification. Any acne or degree of baldness should also be noted. All secondary sexual char

acteristics including the Tanner stage of breast development should also be recorded. The
breasts should be examined for atrophy and discharge, while the thyroid gland is examined for
enlargement and features of thyrotoxicosis. Examination of the abdomen should aim to identify masses such as adrenal and ovarian, while a pelvic examination will confirm the presence
of ovarian masses, which may be the source of androgens causing the hirsutism.

(b) Justify the investigations you will undertake on her. (6 marks)

A blood sample should be obtained for a hormone profile (including serum testosterone, FSH
and LH, sex-hormone-binding globulin, DHEAS and free androgen index) to exclude or diagnose PCOS. A thyroid function test (free thyroxine (FT4) and thyroid-stimulating hormone
(TSH)) should also be undertaken if thyroid dysfunction is suspected.

If the testosterone level
is <5 nmol/L, then PCOS is a more likely to be a cause but if >5 nmol/L, then an adrenal
tumour would look more likely. For a raised testosterone level, an MRI/CT scan of the
abdomen should be undertaken as this is more likely to diagnose a tumour.
An ultrasound scan of the pelvis and abdomen will be essential to rule out any tumours
within the ovary and adrenals and more importantly to exclude features consistent with
PCOS. This scan is best done in the early follicular phase.

Where no obvious cause is found, it is classified as idiopathic and may well be constitutional.
The first approach is reassurance; such reassurance is much better if there is a strong family
history of hirsutism.
The next option will be shaving the excessive hair. If this is unacceptable, other mechanical
treatments such as plucking or waxing could be considered. Some of these are cheap and effective but require repeated application. The myth that shaving increases hirsutism needs to be
dismissed in order to motivate this patient appropriately.

Where she objects to this, or has previously tried these methods unsuccessfully, she should be offered bleaching and/or laser treatment. These methods are effective but are more expensive. Electrolysis is thought to be the
only permanent way of removing hair and gives the best cosmetic result.

This may be offered
as an option if the others are unsuccessful or unacceptable. However, it is expensive and needs
to be performed by an experienced operator to minimise the risks of scarring or infection.
Medical treatment will be the last option for this young woman. The first will be a combination of CPA (an antiandrogen) and an oestrogen in the form of Dianette.

This offers the
added advantage of effective contraception, if required, and also corrects any menstrual
abnormalities. It is cheap and effective, but compliance may be a problem as it has to be taken
regularly. In a young woman this may be an important consideration.

It is important to
emphasise that the effects of this treatment are not immediate and it may take up to 4 months
for a significant difference to be noticed. More than 70 per cent of women treated with this
regimen report a significant improvement in symptoms within 12 months. Side-effects, of
which the patient must be warned, include depression, weight gain and breast tenderness

More recently, eflornithine hydrochloride (Vaniqa®) has been shown to be effective, especially for facial hair, and this may therefore be offered if the patient does not require contraception. Other options to consider include CPA given on its own.

Again, motivation is
required as it is taken daily. There are side-effects of this treatment, which may be unacceptable to the patient and therefore result in poor compliance.

If this is not acceptable, spironolactone (an aldosterone antagonist with androgenic-receptor-blocking activity) or flutamide
(a non-steroidal antiandrogen) may be used.

Flutamide may also be used in combination with
a combined oral contraceptive pill to achieve results comparable to those of spironolactone or
CPA. Flutamide has several side-effects and may be poorly tolerated.

A comparative trial of
spironolactone and CPA did not show any significant difference in response between the two
groups, but spironolactone is not the drug of choice because of its side-effects and cost. In
addition, when used it must be combined with effective contraception.
Other less-effective options that may be considered include ketoconazole, a synthetic imidazole derivative, which blocks gonadal and adrenal steroidogenesis.

Unfortunately, marked
side-effects, such as nausea, asthenia and alopecia, necessitate close monitoring during treatment and may also result in poor compliance. Clinical response to this option is also relatively
poor.
Ovarian suppression with low-dose contraceptive pills and GnRH analogues are effective in
some patients. The former will be suitable in this young woman, but the latter, though effective, will have severe hypo-oestrogenic side-effects, making it less acceptable.

An important aspect of her management is the emphasis on the absence of pathology. Such
reassurance and encouraging the patient to have a more positive image of herself may be all
that is necessary