Poly Cystic Ovary Syndrome

Background

PCOS is very common, with prevalence in women of reproductive age of 5-10% – and some estimate much higher. It is probably more common in women of South Asian origin. Many women with the condition are overweight or obese.

Women with PCOS have an increased risk of insulin resistance which, with the high prevalence of obesity, is a powerful risk factor for progression to Type 2 diabetes: note that insulin resistance is raised even in women with PCOS and a normal BMI.

There is also an increased long-term risk of endometrial hyperplasia/cancer, but no apparent increased risk of breast or ovarian cancer. Currently, despite having a number of risk factors for cardiovascular disease, it is unclear whether the actual risk is increased.

Diagnosis of PCOS

A diagnosis of PCOS requires at least 2 of the following 3 criteria: –

• Infrequent menses (>35 days between menses) or amenorrhoea >3 years post menarche
• Clinical and / or biochemical signs of excessive androgen secretion, i.e. hirsutism, acne, raised total testosterone or a raised Free Androgen Index (FAI). Although raised LH, with a normal FSH, may be found in PCOS, gonadotrophin results no longer form part of the diagnostic criteria.
• Presence of at least 12 follicles measuring 2-9 mm in diameter, an ovarian volume > 10ml³, or both by ultrasound (preferably transvaginal). This criterion does not apply to adolescents, for whom ultrasound is less helpful.

Lothian guidance is that a scan for suspected PCOS is not required unless there are other indications e.g. pelvic symptoms: THE DIAGNOSIS IS PRIMARILY MADE ON CLINICAL AND BIOCHEMICAL FEATURES.

Other possible causes of presenting features should be considered and excluded:

• congenital adrenal hyperplasia (CAH)
• androgen secreting tumour
• Cushing’s syndrome
• thyroid dysfunction
• hyperprolactinaemia and perimenopause etc.

These generally are excluded with basic blood tests and clinical features. The most important pointer to the possibility of CAH, androgen secreting tumour or Cushing’s syndrome is Testosterone >4nmol/l* or clinical features such as rapidly-developing hirsutism.

Laboratory investigation of patients with suspected PCOS

Sample Timing

Unless the patient is amenorrhoeic, the sample should be taken on days 1-5 of the menstrual cycle (misleading increases in testosterone may occur later in the cycle).

Clinical details

• State the LMP
• If there is amenorrhoea, state this on the request form.
• Provide clinical details e.g. hirsutism, irregular periods etc.: these are crucial as the laboratory may add additional tests.

Test requests

• LH, FSH, Estradiol, Testosterone & Prolactin as first line
• TFTs if thyroid status unknown
• random glucose (if BMI is > 30 kg/m² or family history of diabetes), and HbA1c if glucose is borderline as per Lothian guidelines.

The laboratory will add any necessary additional tests (e.g. free androgen index (FAI), dehydroepiandrosterone sulphate (DHEAS), 17 hydroxyprogesterone, androstenedione) in the light of the results and the clinical details provided. To facilitate this it is crucial to provide all relevant clinical details.

Reports

An Endocrine Biochemist will issue an interpretative comment on all results – if adequate clinical details have been provided – and indicate what additional action regarding further sampling etc. is advised. The Endocrine Duty Biochemist can be contacted on 0131 242 6880

* It is unusual for PCOS to present with a testosterone of >4 nmol/L: in such patients the test should be repeated as soon as possible. If confirmed on repeat sampling, the patient should be referred for an endocrine opinion.  

Additional notes for interpretation of blood results in PCOS

LH

• Increases in LH & LH/FSH ratio occur in many women with PCOS
• However LH is often normal in PCOS and is not required for the diagnosis
• Measurement of LH (and FSH and estradiol) can be useful in identifying other causes of amenorrhoea eg the low gonadotrophins & estradiol of ‘functional’ or ‘hypothalamic’ amenorrhoea associated with weight loss, stress and excess exercise. In these conditions, LH is generally more suppressed than FSH, and FSH concentrations can be normal.

Prolactin

• Up to 40% of women with PCOS have mildly elevated prolactin concentrations – generally <750 mIU/l (relating to unopposed estrogen).
• In PCOS the LH will be higher than the FSH – unlike true hyperprolactinaemia where the LH concentrations are lower than the FSH concentrations (and estradiol concentration may also be low).
• Prolactin can be increased due to pituitary adenomas
• Multiple other causes for increased prolactin – including stress, drug treatment (dopamine antagonists), hypothyroidism and unopposed estrogen.
• See Endocrine guidance for investigation of hyperprolactinaemia Endocrinology if Prolactin >1000mIU/l

Testosterone and free androgen index (FAI)

• Testosterone production roughly doubles in the early follicular phase when it may rise above the upper reference limit. Therefore if a patient is having periods, a sample taken during/shortly after menses (day 1-5 of cycle) is the most suitable for PCOS diagnosis to avoid a misleadingly-high testosterone result later in the cycle
• A large proportion of circulating testosterone is bound to sex hormone binding globulin (SHBG).
• SHBG-bound testosterone is biologically inactive cf its unbound or ‘free’ form
• Serum SHBG is decreased (and therefore active testosterone increased) in: PCOS, insulin resistance, obesity, hyperprolactinaemia, hypothyroidism and when there are high serum androgens.
• Serum SHBG is increased (and active testosterone reduced) by: estrogen, pregnancy, hyperthyroidism, excess alcohol, liver disease and anticonvulsants. 

The free androgen index (FAI) is a simple method of estimating the circulating free testosterone in women but may be unreliable in situations where there are extreme abnormalities in the concentration of SHBG.

• The FAI is more sensitive at detecting hyperandrogenism than total testosterone, and may be helpful in assessing androgen status where total testosterone is in the upper half of the reference range.
• If total testosterone is in the lower part of the reference range, FAI is generally not raised.
• As PCOS is associated with reduced SHBG levels, this increases the FAI (i.e. active, free hormone), while total testosterone can remain normal.

See   Gynaecological Radiology &  Poly Cystic Ovary Syndrome