11th October, 2018, Dr Chee L Khoo
The original diagnostic criteria for polycystic ovary syndrome (PCOS) put forward after the first international conference on PCOS in 1990 was oligo-anovulation and hyperandrogenism or hyperandrogenaemia in the absence of all other endocrinopathies. This was based on expert consensus rather than clinical research data. The Rotterdam criteria 2003 added ultrasound as a third diagnostic marker and to allow for a diagnosis of PCOS if two of the three criteria were met. The Rotterdam criteria are controversial but remain the most widely adopted.
Exclusion of thyroid disease (thyroid stimulating hormone), hyperprolactinemia (prolactin) and non-classic congenital adrenal hyperplasia is recommended with further evaluation in those with amenorrhea and more severe clinical features including consideration of hypogonadotropic hypogonadism, Cushing’s disease or androgen producing tumours.
Diagnosis and treatment of PCOS using the Rotterdam criteria is challenging because of the difficulty defining individual components within the diagnostic criteria, significant clinical heterogeneity generating a range of phenotypes with or without obesity, ethnic differences and variation in clinical features across the life course. These factors contribute to variation in diagnosis and care across geographical regions and health professional groups.
The Australian Centre for Research Excellence in PCOS, funded by the National Health and Medical Research Council (NHMRC), partnered with European Society of Human Reproduction and Embryology and the American Society for Reproductive Medicine recently put together an evidence-based guideline for the assessment and management of PCOS. It is a comprehensive 201 page guideline!
Four phenotypes are identified:
- Androgen excess + ovulatory dysfunction + polycystic ovarian morphology (Phenotype A)
- Androgen excess + ovulatory dysfunction (Phenotype B)
- Androgen excess + polycystic ovarian morphology (Phenotype C)
- Ovulatory dysfunction + polycystic ovarian morphology (Phenotype D)
Screening & Diagnosis
They endorsed the Rotterdam diagnostic criteria in adults of two of:
- clinical or biochemical hyperandrogenism,
- ovulatory dysfunction, or
- polycystic ovaries on ultrasound
Irregular menstrual cycles are defined as:
- normal in the first year post menarche as part of the pubertal transition
- 1 – 3 years post menarche: < 21 or > 45 days
- > 3 years post menarche to perimenopause:
- <21 or >35 days or < 8 cycles per year
- > 1 year post menarche > 90 days for any one cycle
- Primary amenorrhea by age 15 or > 3 years post thelarche (breast development)
Biochemical hyperandrogenism
Assessment of biochemical hyperandrogenism is most useful in establishing the diagnosis of PCOS and/or phenotype where clinical signs of hyperandrogenism (in particular hirsutism) are unclear or absent. Calculated free testosterone, free androgen index or calculated bioavailable testosterone should be used to assess biochemical hyperandrogenism in the diagnosis of PCOS. Androstenedione and dehydroepiandrosterone sulfate (DHEAS) could be considered if total or free testosterone are not elevated; however, these provide limited additional information in the diagnosis of PCOS. In women on an combined oral contraceptive pill (COCP), drug withdrawal is recommended for three months or longer before measurement with use of other non-hormonal contraceptive.
Clinical hyperandrogenism
A comprehensive history and physical examination should be completed for symptoms and signs of clinical hyperandrogenism, including acne, alopecia and hirsutism and in adolescents, severe acne and hirsutism.
Ultrasound Morphology
The threshold for polycystic ovary morphology (PCOM) should be on either ovary, a follicle number per ovary of > 20 and/or an ovarian volume ≥ 10ml, ensuring no corpora lutea, cysts or dominant follicles are present.
Where irregular menstrual cycles and hyperandrogenism are present, ultrasound is not necessary in diagnosis. However, within 8 years of menarche, both hyperandrogenism and ovulatory dysfunction are required, with ultrasound not recommended.
Where the diagnosis is not clear (which means do not have the full criteria met), then these young women are deemed “at risk” and further follow up assessment is recommended. Serum anti-mullerian hormone (AMH) levels should not yet be used as an alternative for the detection of PCOS or as a single test for the diagnosis of PCOS. Neither should insulin levels be used for diagnosis of insulin resistance.
Risk Assessment
Education, self-empowerment, multidisciplinary care and lifestyle intervention for prevention or management of excess weight are important. Depressive and anxiety symptoms should be screened, assessed and managed with the need for awareness of other impacts on emotional wellbeing.
All women should be monitored regularly for weight gain, CV risks, GDM, IGT and T2D. Glycaemic status should be assessed at baseline in all women with PCOS. Thereafter, assessment should be every one to three years, influenced by the presence of other diabetes risk factors. Women with PCOS have a two to six-fold increased risk of endometrial cancer, which often presents before menopause although the absolute risk of endometrial cancer remains relatively low.
There is a high prevalence of moderate to severe anxiety and depressive symptoms in adults and a likely increased prevalence in adolescents.
Management
COCP are first line pharmacological management for menstrual irregularity and hyperandrogenism, with no specific recommended preparations and general preference for lower dose preparations. The 35 microgram ethinyloestradiol plus cyproterone acetate preparations should not be considered first line in PCOS as per general population guidelines, due to adverse effects including venous thromboembolic risks. Only where COCPs are contraindicated or poorly tolerated, in the presence of other effective forms of contraception, should anti-androgens be considered to treat hirsutism and androgen-related alopecia.
Metformin in addition to lifestyle, could be recommended in adult women with PCOS, for the treatment of weight, hormonal and metabolic outcomes.
Letrozole is first-line pharmacological infertility therapy. Clomiphene citrate could be used alone in women with PCOS with anovulatory infertility and no other infertility factors to improve ovulation and pregnancy rates. Metformin could be used alone in women with PCOS, with anovulatory infertility and no other infertility factors, to improve ovulation, pregnancy and live birth rates, although women should be informed that there are more effective ovulation induction agents.
In women with PCOS and anovulatory infertility, gonadotrophins are second line. In the absence of an absolute indication for IVF, women with PCOS and anovulatory infertility, could be offered IVF third line where other ovulation induction therapies have failed.
Post menopausal women
A diagnosis of PCOS post-menopause could be considered if there is a past diagnosis of PCOS, a long-term history of irregular menstrual cycles and hyperandrogenism and/or PCOM, during the reproductive years. Postmenopausal women presenting with new-onset, severe or worsening hyperandrogenism including hirsutism, require further investigation to rule out androgen-secreting tumours and ovarian hyperthecosis.
Thus, in patients in general practice with PCOS, there are four elements to consider:
- Ovarian dysfunction (may or may not have infertility),
- Hyperandrogenism,
- Body image/mental health issues and
- Cardio-metabolic risks.
The diagnosis is quite easily made in general practice. Management is also easily achieved in general practice. The management and prevention of the metabolic risks can only be done in general practice.
Access the full evidence based guideline here.