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

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)
Clinical signs hyperandrogenism; excess facial and body hair, midline hair growth.

9. Diagnostic criteria
Other causes of menstrual disturbance and hyperandrogenism must be excluded.
Conditions such as thyroid dysfunction, hyperprolactinaemia may present with cycle disturbance.

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
Cushings; proximal muscle weakness, plethoric round face, sriae, bruising, supraclavicular fat pad
Virilisation; deep voice, smaller breasts, bulky muscles,clitromegaly.
High total testosterone levels (>5nmol/l)may indicate a differnet diagnosis

12. Long Term Consequences
Metabolic syndrome, with increased risk type 2 diabetes, hyperlipidaemia
Fertility problems
Psychological distress
Endometrial cancer
Increase risk sleep apnoea
CVD is one of the leading casues of death in women with PCOS.
Assess CVD risk; measure BP, lipids, HBa1c. Conventional CVD risk tables have not however been validated in these women.
Increased visceral fat; check waist circumference.

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 Androgenic Effects Weight gain Insulin 
Fat storage
Inhibits SHBG
Testosterone 
Insulin in hibits production SHBG by the liver.
Testosterone is bound to SHBG; total testosterone may be normal but free testosterone is typicaly high.
Even women with normal BMI have insulin resistance. South Asian women with PCOS should have OGTT even if BMI normal (RCOG)
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
If not having a bleed every 3 months consider inducing bleed with progesterone; eg medroxyprogesterone 10 mg bd for 10 days per cycle
If amenorrhoea consider USS to check endometrial thickness. If >7mm consider referral for ? Endometrial biopsy.
For every 1mm increase in endometrial thickness the risk of endomethrial hyperplasia increases by odds ratio of 1.5

32. COCP Oestrogens increase SHBG Dianette Yasmin
Any cocp will help prevent androgenic effects and give regular bleed enabling endometrial protection
Dianette licensed for hirsutism/acne of any cause; not just for PCOS.Because it is being used for licensed use other than contraception the rules about BMI are more flexible than COCP UKMEC rules.
It is advised to stop 3-4m after the problem has improved.
Its VTE risk is comparable to coc’s containing gestodene, drosperinone and desogestrel.
Nice guidance suggest treating for 12m , having 6m break then treating another 12m.( due to life cycle of hair follicle a minimum ofr 6m treatment needed to make discernible difference)

33. Fertility, when BMI>30
Clomiphene citrate
Ovarian drilling( useful in LH driven PCOS)
Ovulation induction
IVF
Weight loss alone may be enough.
Clomiphene can by used up to 6 months; but there is an increased risk multiple pregnancy; need scans; secondary care.
Gonadatrophins may be used if failed clomiphene.
Drilling/electrocautery should be considered for selected anovulatory patients specially with normal BMI

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.
Consider bariatric surgery if BMI.40 and failed other weight loss measures or if BMI>35 with co-existent T2D/ hypertension
This will improve daibetes, hypertension and dyslipidaemia, reducing mortality from CVD and cancer.

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)?
Metformin is not licensed for treatment of PCOS so if used women need careful counselling to make informed choice.
There is some evidence that it can modestly reduce androgen levels by 11% in women with PCOS compared to placebo and some studies show reduction in body weight but variable evidence.

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
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
have an excellent fact sheet for patients.