Polycystic Ovarian Syndrome

1. Polycystic Ovarian Syndrome Dr Louise Knowles 12/12/16

2. PCOS; points to cover today • Diagnosis • Clinical Features; presentation and long term consequences • Hormonal Disturbances • Subtypes PCOS • Investigations • Management.

3. PCOS • Originally described 1935 by Stein and Leventhal. • Redefined 2003 by American and European Societies reproductive medicine • Patient likely to present with menstrual disturbance, acne, hirsutism, infertility.

4. PCOS; genetics • Heterogenous; familial clustering. • Autosomal dominant inheritance, variable penetrance in females; 50% chance of offspring being affected • Phenotype manifests itself via raised androgen levels secreted by ovarian theca cells. • Severity seems to be determined by factors such as obesity

5. PCOS Statistics Incidence: 15-25% UK Women 50% UK Asian Women South Asian women present at younger age and often have more severe symptoms

6. USS assessment 20-30% Caucasian women have PCO 5-15% Caucasian women have PCOS Polycystic ovaries not necessary to make diagnosis of PCOS

7. 12 or more follicle measuring 2-9mm and/or Increased ovarian volume (>10cm3) ASRM Consensus 2003 Ultrasound assessment of the polycystic ovary: international consensus

8. Diagnostic Criteria Two out of three criteria required 1.Anovulation or oligo-anovulation 2.Hyperandrogenism Clinical (hitsuitism, acne) Biochemical (raised testosterone) 3.Polycystic ovaries(12 or more follicles,2-9mm diameter)

9. Diagnostic criteria • Other causes of menstrual disturbance and hyperandrogenism must be excluded.

10. Hyperandrogenism Alopecia Hirsuitism Acne

11. Differential Diagnoses Cushings Adrenal/Ovarian tumours ( virilisation) Congenital adrenal hyperplasia Menopause/Ovarian failure Exogenous- anabolic steroid, testosterone medication Hypothalamic/pituitary disorders

12. Long Term Consequences • Metabolic syndrome, with increased risk type 2 diabetes, hyperlipidaemia • Fertility problems • Psychological distress • Endometrial cancer • Increase risk sleep apnoea

13. Endocrinology • Normal function of the pituitary and ovary • Hormonal abnormalities underlying PCOS

14. PCOS; the hormones • In women with PCOS, the theca cells of the ovary produce excess androgens, which may be due to hyperinsulinaemia or increased serum levels of luteinizing hormone (LH)

15. Insulin Resistance Weight gain Insulin  Fat storage Inhibits SHBG Testosterone  Androgenic Effects Acne Hirsuitism Irreg periods Infertility

16. PCOS; the hormones • Insulin resistancehyperinsulinaemia as a key factor in PCOS for many women •  Insulin and LH lead to  androgen production from theca cells. •  androgen leads to follicular arrest and anovulation

17. Subtypes of PCOS LH Driven Insulin Driven

18. LH Driven Slim High LH High Impaired GTT (10%) Responds to ovarian diathermy

19. Insulin Driven XS Centripetal fat Acanthosis Nigricans Longer inter-menstrual interval

20. Investigations; PCOS • LH;  or normal • FSH often normal. • Total testosterone; normal or slightly raised ( if >5 nmol/l exclude androgen secreting tumours) • Free testosterone may be  • SHBG normal or  • Free androgen index normal or

21. Investigations • Free androgen index FAI •  FAI =Total testosteronex100/SHBG • Or;  Free Testosterone.

22. Investigations for diff. diagnosis • TSH • Prolactin • 17-hydroxyprogesterone ( CAH) • DHEA-S and FAI ( androgen secreting tumours) • 24 hr urinary cortisol ( Cushings)

23. Investigations PCOS In addition to hormone profile; need to check • Lipid profile • LFT’s if high BMI • HBa1C/GTT ( fasting glucose not sensitive enough)

24. Other Menstrual Irregularities FSH + LH + E 

25. Other Menstrual Iregularities FSH + LH + E  Ovarian failure/ menopause

26. Other Menstrual Iregularities FSH + LH + E  Ovarian failure/ menopause FSH + LH + E

27. Other Menstrual Iregularities FSH + LH + E  Ovarian failure/ menopause FSH + LH + E Hypothalamic/pituitary Underweight Overexercise Chronic Illness

28. Management Aims: Managing symptoms Reducing long term consequences

29. Management Weight management/ psychological support Hair removal. Oligo/amenorrhoea Infertility

30. Weight Management Aim: 5-10% wt loss (can achieve 30% loss of visceral fat) Empower the patient Be kind Discuss long term health Depression in 70%

31. Oligo/amenorrhoea • Need to bleed every 3-4m to avoid unopposed oestrogen, increased risk endometrial cancer. • Endometrial protection will be provided by desogestrel/implant/ Mirena. • Consider COCP

32. COCP • Oestrogens increase SHBG • Dianette • Yasmin • Any cocp will help prevent androgenic effects and give regular bleed enabling endometrial protection

33. Fertility, when BMI>30 • Clomiphene citrate • Ovarian drilling( useful in LH driven PCOS) • Ovulation induction • IVF • Weight loss alone may be enough.

34. Goal weight • 5-10% weight loss reduces visceral fat by 30%..... Beware of pregnancy • Impact on insulin levels • Give realistic goals; eg 1kg per week. • Orlistat • Bariatric surgery.

35. What about metformin? • Ineffective for hyperandrogenism • Ineffective for anovulation • Use for IGT( & continue if conceives?) • May be used to reduce risk of ovarian hyperstimulation in IVF • May be used in sec care in treatment infertility (Nice 2013)?

36. Hirsutism • Eflornithine ( Vaniqua); 4m trial.....£55 per tube!! Can be prescribed as NHS drug in PCOS/hirsutism • (Spironolactone) • Laser treatment

37. Pregnancy and PCOS • Gestational diabetes( OR 3.6)Do GTT at 24-28w • Increased risk hypertension, preclampsia. • Increased risk preterm birth/ small for dates infants. • Increased risk PCOS in offspring • 14% will have a major pregnancy related complication

38. West Yorkshire! South Asian women resident in Yorkshire with anovular PCOS; • Present younger • Develop oligomenorrhoea younger • Have more T2DM in families • Have more acanthosis nigricans & hirsutism • Have higher insulin resistance.

39. PCO and the future • Increasing incidence • Needs holistic approach • Primary care pivotal role with support specialists; gynaecology, dietician, counsellors, beauticians.

40. Patient support groups • www.verity-pcos.org.uk • www.soulcysters.com American

41. Useful references • Polycstic Ovary Syndrome; Nice CKS Feb 2013 • RCOG Green Top guideline No 33; Long Term Consequences of PCOS (2014) • Hirsutism; Nice CKS Dec 2014 • https://www.womens-health-concern.org have an excellent fact sheet for patients.