Examination and investigation of patients with PCOS and secondary amenorrhoea

A thorough history and a careful examination should always be carried out before investigations are instigated -looking particularly at stature and body form, signs of endocrine disease, secondary sexual development and the external genitalia. A history of secondary amenorrhoea may be misleading, as the 'periods' may have been the result of exogenous hormone administration in a patient who was being treated with hormone replacement therapy (HRT) for primary amenorrhoea. In most cases, however, a history of secondary amenorrhoea excludes congenital abnormalities. A family history of fertility problems, autoimmune disorders or premature menopause may also give clues to the aetiology.

EXCLUDE PREGNANCY

It is always important to exclude pregnancy in women of any age and whereas some may think that this statement superfluous, it is usual to see one or two patients a year who are pregnant despite denying the possibility.

EXAMINATION

Measurement of height and weight should be done in order to calculate a patient's body mass index (BMI). The normal range is 20-25 kg/m2, and a value above or below this range may suggest a diagnosis of weight-related amenorrhoea (which is a term usually applied to underweight women).

Signs of hyperandrogenism (acne, hirsutism, balding (alopecia)) are suggestive of the PCOS, although biochemical screening helps to differentiate other causes of androgen excess. It is important to distinguish between hyperandrogenism and virilization, which is additionally associated with high circulating androgen levels and causes deepening of the voice, breast atrophy, increase in muscle bulk and cliteromegaly (see Virilization p. 378). A rapid onset of hirsutism suggests the presence of an androgen secreting tumour of the ovary or adrenal gland. Hirsutism can be graded and given a 'Ferriman-Gallwey Score', by assessing the amount of hair in different parts of the body (e.g. upper lip, chin, breasts, abdomen, arms and legs). It is useful to monitor the progress of hirsutism, or its response to treatment, by making serial records, either using a chart or by taking photographs of affected areas of the body.

A total testosterone is adequate for general screening (Table 39.1). It is unnecessary to measure other androgens

Table 39.1 Endocrine normal ranges

Follicle stimulating harmone

1-10 IU/l (early follicular)

(FSH)*

Luteinizing hormone (LH)*

1-10 IU/l (early follicular)

Prolactin*

<400 mIU/l

Thyroid stimulating hormone*

0.5-5.0 IU/l

Thyroxine (T4)

50-150 nmol/l

Free T4

9-22 pmol/l

Tri-iodothyronine (T3)

1.5-3.5 nmol/l

Free T3

4.3-8.6 pmol/l

Thyroid binding globulin (TBG)

7-17 mg/l

Testosterone (T)*

0.5-3.5 nmol/l

Sex hormone binding globulin

16-120 nmol/l

(SHBG)

Free androgen index ([T x 100] ^

<5

SHBG)

Dihydrotestosterone

0.3-1 nmol/l

Androstenedione

2-10 nmol/l

Dehydroepiandrosterone

3-10 ^mol/l

sulphate

Cortisol: 8 a.m.

140-700 nmol/l

midnight

0-140 nmol/l

24 h urinary

<400 nmol/24h

Oestradiol

250-500 pmol/l

Oestrone

400-600 pmol/l

Progesterone (mid-luteal)

>25 nmol/l to indicate

ovulation

17-hydroxyprogesterone

1-20 nmol/l

* Denotes those tests performed in routine screening of women with amenorrhoea.

* Denotes those tests performed in routine screening of women with amenorrhoea.

unless total testosterone is >5 nmol/l. Insulin suppresses SHBG, resulting in a high free androgen index (FAI) in the presence of a normal total T. The measurement of SHBG is not required in routine practice and will not affect management.

One should be aware of the possibility of Cushing's syndrome in women with stigmata of the PCOS and obesity as it is a disease of insidious onset and dire consequences; additional clues are the presence of central obesity, moon face, plethoric complexion, buffalo hump, proximal myopathy, thin skin, bruising and abdominal striae (which alone are a common finding in obese individuals). Acanthosis nigricans is a sign of profound insulin resistance and is usually visible as hyperpigmented thickening of the skin folds of the axilla and neck; it is associated with PCOS and obesity (Fig. 39.1).

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