1. Polycystic Ovary Syndrome: An overview
Welcome
Dr. Julie Tomlinson
PhD MSc BSc(Hons) PgDipClinEd PgCert SCPHN RGN QN
Consultant Nurse & Advanced Nurse Practitioner

2. Intended learning outcomes
To understand how Polycystic Ovary Syndrome is diagnosed.
To develop a greater understanding of the significance that Polycystic Ovary Syndrome has on individual women and society.
To develop understanding of the clinical management of women with Polycystic Ovary Syndrome

3. Polycystic Ovary Syndrome
Overview of
Polycystic Ovary Syndrome

4. WHAT IS POLYCYSTIC OVARY SYNDROME (PCOS)?
The most common female endocrine disorder, 15% prevalence rate1
Characterised by androgen excess during the reproductive years.
Different diagnostic criteria in use: NIH versus Rotterdam consensus3
Treatment usually revolves around resolving acne, hirsutism or infertility4
Overview of polycystic ovary syndrome
1. Fauser et al. (2012) Consensus on women’s health aspects of polycystic ovary syndrome. Fertil Steril 97:28-38
2.Zawadski J, Dunaif A(1992) Diagnostic criteria for polycystic ovary syndrome. In: Dunaif, A et al (eds) Polycystic Ovary Syndrome. Blackwell Scientific Publications, Boston
3. Rotterdam/ESRE Workshop Group(2004) Revised 2003 consensus on diagnostic criteria and long term health risks related to polycystic ovary syndrome. Human Reprod 19: 41-7
4. Tomlinson JA & Pinkney JH (2007) Diabetes and polycystic ovary syndrome. Practice Nurse. 34 (10): 43-7

5. WHAT IS POLYCYSTIC OVARY SYNDROME (PCOS)?
PCOS is associated with increased metabolic risk (Type 2 diabetes [T2D] and cardiovascular disease)4
Increasing prevalence of childhood obesity is resulting in increased referral of teenage girls with PCOS related hirsutism, acne, oligomenorrhoea, IGT and T2D5
What is less well-known about PCOS..
4. Gluek CJ et al (2003) Incidence and treatment of metabolic syndrome in newly referred women with confirmed polycystic ovarian syndrome Metaboilsm; 52:908-15
5. Palmert MR, Gordon CM, Kartashov AI, Legro RS, Ermans SJ, Dunaif A. (2002) Screening for abnormal glucose tolerance in adolescents with polycystic ovary syndrome. J Clin Endocrinol Metab 87,

6. Polycystic Ovary Syndrome – historical aspects
400 BC – Hippocrates reportedly described 2 cases of hirsute women with amenorrhea
1921 –report of bearded woman with diabetes
1935 ‐ Stein & Leventhal described 7 women with amenorrhea, hirsutism, obesity, and enlarged polycystic ovaries

7. Polycystic ovary syndrome is a complex condition involving an interplay of various organs and hormonal regulation systems in the body. This results in a variety of chemical and physical changes including hyperandrogenism, insulin resistance, increased free fatty acids and hyperglycaemia.

8. The aetiological, hormonal and clinical features of PCOS
Teede et al. 2011

9. Polycystic Ovary Syndrome
Learning outcome 1:
To understand how
Polycystic Ovary Syndrome
is diagnosed

10. Defining Polycystic Ovary Syndrome
Prior to 1990, no agreed diagnostic criteria
NIH 1990 diagnosis ( US and most literature)
Rotterdam 2003 consensus ( Europe)
Androgen Excess Society recommendations
Endocrine Society 2014 (USA) recommends use of Rotterdam in USA.

11. A diagnosis of PCOS may be made if there is both:
The NIH 1990 criteria for the diagnosis of PCOS
A diagnosis of PCOS may be made if there is both:
Presence of hyperandrogenism with either clinical signs (hirsutism, acne, or male pattern balding) or biochemical signs of hyperandrogenaemia (high serum androgen concentrations)
and
Presence of chronic menstrual irregularity due to oligomenorrhoea / amenorrhoea (authors comment: usually accepted to be 6 or fewer periods per year)
after
Excluding other known disorders such as Cushing’s syndrome, Congenital Adrenal Hyperplasia, androgen-secreting tumours, and hyperprolactinaemia

12. The Rotterdam 2003 criteria for the diagnosis of PCOS
A diagnosis of PCOS may be made if any TWO of the following features are present:
The presence of menstrual irregularities - oligomenorrhoea and/or annovulation
The presence of clinical and/or biochemical signs of hyperandrogenism
The presence of polycystic ovaries
After
Excluding other potential causes of menstrual irregularity or hyperandrogenism

13. In essence, the Rotterdam 2003 expanded the NIH 1990 definition creating two new phenotypes:
ovulatory women with polycystic ovaries and hyperandrogensm
and
oligo-anovulatory women with polycystic ovaries, but without hyperandrogenism

14. Prevalence rates vary according to diagnostic criteria
Rotterdam Criteria
PCOS prevalence 15%
NIH Criteria
PCOS prevalence 5-6%
“The Rotterdam criteria are inclusive of National Institutes of Health (NIH) criteria in that a woman diagnosed with PCOS using the NIH criteria will also meet Rotterdam criteria; however, a woman diagnosed with PCOS using Rotterdam criteria may not meet NIH criteria.” Teede et. al, 2011

15. The Androgen Excess Society have suggested a further amendment…
A diagnosis of PCOS may be made if the following features are present:
The presence of hyperandrogenism (clinical and/or biochemical)
and
The presence of ovarian dysfunction (oligo-anovulation and/or polycystic ovaries)
after
Excluding other causes
*Most of the U.S. uses 1990 criteria and Europe uses 2003 criteria

16. different diagnostic criteria
different phenotype & genotype
different health needs & prevalence rates
urgent need to standardise diagnostic criteria!

17. FINALLY, WHEN DIAGNOSING PCOS IN YOUNG WOMEN…
Caution should be applied if diagnosing PCOS in young women. Multiple ovarian follicles, acne and irregular periods are common in teenagers, so avoid diagnosis in under 18’s or within first two years of menarche.

18. Diagnostic features of PCOS

19. Clinical features of PCOS Clinical hyperandrogenism: hirsutism

20. Ferriman Gallwey score – a clinical aid?

21. Clinical features of PCOS Clinical hyperandrogenism: androgenic alopecia (AA)
Gradual onset
Hair loss on vertex (top of head) & angles of the front-line (‘triangular thinning”)
AA is less commonly used for diagnostic criteria
Reproduced with permission: Futterweit at

22. Clinical features of PCOS Clinical hyperandrogenism: acne
Acne is common in the young and difficult to measure
Image reproduced from:

23. Biochemical hyperandrogenism
Ideally use a calculated measure to investigate biochemical hyperandrogenism, i.e.
a raised Free Androgen Index (FAI)
FAI derived through a calculation between total testosterone and Sex Hormone Binding Globulin (SHBG)
Remember if SHBG is raised, ie with combined pill use, this will lower the bioavailable serum testosterone. Therefore a raised total-testosterone might not produce hirsutism etc.
Obesity lowers SHBG, therefore more testosterone is bioavailable and women become more hirsute/oligomenorrhoeic etc.

24. Serum Testosterone/SHBG
Bound (inactive) Testosterone
SHBG
Unbound (active) Testosterone

25. Beware the polycystic ovaries!
Women don’t need polycystic ovaries to diagnose PCOS
Women can have multiple cysts but not have PCOS (i.e. teenagers,OCP)

26. ultrasound to diagnose:
IF you use
ultrasound to diagnose:
>12 follicles 2-9 mm in at least one of the ovaries
Increased volume (>10cc)
Excluded are those on OCPs and those with follicle >10mm) – can be reason for misdiagnosis!
“Chain of Pearls sign” is not required

27. Common phenotypical features
of PCOS
Obesity

28. phenotypical features of PCOS
Common
phenotypical features of PCOS
Acanthosis nigricans
Axillary skin tags

29. Differential diagnoses of PCOS
Cushing’s syndrome
Diabetes
Thyroid disease- hypo or hyper
Hyperprolactinaemia
Hypothalamic dysfunction
Pituitary gland dysfunction
Adrenal gland dysfunction or tumour
Congenital Adrenal Hyperplasia
Acromegaly
Ovarian failure or tumour
Medication effects
Pregnancy

30. Learning outcome 2:
To develop a greater understanding of the significance that Polycystic Ovary Syndrome has on individual women and society.

31. Individual concerns may include:
Reproductive - fertility issues
Psychosocial -self esteem issues (poor body image or feminine identity issues through acne, excess weight), lower quality of life, anxiety and depression, psychosexual dysfunction, eating disorders
Metabolic – increased cardiovascular risk factors and type 2 diabetes

32. PCOS – a public health priority
What is the extent of the problem?
Prevalence rate currently ± 15%
Likely to increase prevalence with rising levels of obesity
PCOS is associated with increasing cardiometabolic risk and type 2 diabetes

33. The PCOS iceberg Cardiometabolic risk Infertility and hirsutism
Glucose intolerance
Dyslipidaemia
Inflammation
Copyright © Tomlinson & Pinkney

34. Evidence that PCOS is associated with T2D and impaired glucose tolerance
Insulin resistance found in lean and obese women with PCOS1
7.5 – 10% PCOS have T2D and 31-35% IGT2
Lean PCOS have higher prevalence T2D than weight matched controls, but obesity increases their risk further3
1Dunaif et al., 1989
2Ehrmann et al. 1999; Legro et al., 1999
3Tomlinson et al. In press

35. Learning outcome 3:
To develop understanding of the clinical management of women with Polycystic Ovary Syndrome

36. Recommended treatment guidelines for PCOS
(Australia)
Ref: Teede et al, 2011

37. Hirsutism
Choice of options depends on patient preferences; impact on wellbeing; access and affordability: First line:
Self-administered and professional cosmetic therapy (laser therapy recommended)
Eflornithine (Vaniqa) cream can be added and may induce a more rapid response If cosmetic therapy is not adequate, pharmacological therapy can be considered
Second line: pharmacological therapy if patient is concerned and cosmetic therapy is ineffective/inaccessible/unaffordable
Primary therapy is the OCP (monitor glucose tolerance in those at risk of diabetes)
Anti-androgen monotherapy (eg, spironolactone or cyproterone acetate) *not be used
without adequate contraception
Trial therapies for ≥ 6 months before changing dose or medication Combination therapy — if ≥ 6 months of OCP is ineffective, add anti-androgen to OCP
(twice daily spironolactone > 50 mg or cyproterone acetate 25 mg/day, days 1–10 of OCP)  

38. Oligomenorrhoea/amenorrhoea
Lifestyle change (5%–10% weight loss + structured exercise)
Oral contraceptive pill (OCP) (low oestrogen doses [eg, 20 μg] may have less impact on insulin resistance)
Cyclic progestins (eg, 10 mg medroxyprogesterone acetate 10–14 days every 2–3 months)
Unlicensed metformin (improves ovulation and menstrual cyclicity)-but works better if clomiphene is added in secondary care.

39. Infertility
Lifestyle intervention (to optimise preconception health and fertility and reduce pregnancy and long-term complications). LOSE WEIGHT!
Advise on folate, smoking cessation and optimal weight and exercise before conception
Given age-related infertility, advise women to optimise family initiation
Infertility therapies may include clomiphene citrate, (?) unlicensed metformin, gonadotrophins, surgery and in-vitro fertilisation.

40. Cardiometabolic risk
Lifestyle change: WEIGHTLOSS! >5%weight loss in those who are overweight reduces diabetes risk by approximately 50%–60% in high-risk groups
Assess for and optimise cardiovascular risk factors – OGTT for diabetes (?best test for PCOS), lipids, BP, smoking cessation, age, BMI, waist circumference,
Consider unlicensed metformin
(reduces the risk of diabetes by ~50% in adherent high-risk groups)

41. Psychosocial and emotional wellbeing
Assess and offer help for psychosexual problems including anxiety, depression, psychosexual dysfunction, poor body image, eating disorders

42. In Conclusion, PCOS…
Is a very common condition but poorly identified and managed
Is prevalent in 15% women and likely to rise with obesity
Is often complicated to diagnose; urgent need for standardisation
Has can have dramatic consequences on the individual and on society
Is a risk factor for T2D and increased cardiovascular risk
Can have a negative impact on emotional as well as physical wellbeing

43. Recommended Reading
1. Fauser BC et al. (2012) Consensus on women’s health aspects of polycystic ovary syndrome (PCOS): the Amsterdam ESHRE/ASRM- Sponsored 3rd PCOS consensus workshop group. Fertility and Sterility, 97,28-38 e25
2. Teede, H et al. (2011) Evidence-based guideline for the assessment and management of polycystic ovary syndrome.[online pdf]
3.Teede, H et al (2011) Assessment and management of polycystic ovary syndrome: summary of an evidence based guideline [online]

44. Thank you for listening
contact: