1. Polycystic Ovary Syndrome Jamal Zaidi Consultant Obstetrician & Gynaecologist East Sussex Healthcare NHS Trust

2. Objectives Definition & Prevalence Pathogenesis Diagnosis
Clinical Features
Management
Long term consequences

3. Definition ASRM/ ESHRE
Rotterdam: May 2003
Two of three: Oligomenorrhoea & or anovulation
Hyperandrogenism; Clinical/biochemical
PCO on USG; 12 or more follicles in each ovary, 2-9mm,and/ or increased ovarian volume to over 10cm3
Single PCO
The follicle distribution & increase in stromal echogenicity & volume should be omitted
Chronic anovulation & hyperandrogenism in absence of other endocrine disorders
January issue of Fertility & Sterility J, 2004

4. Ultrasound

6. Gross appearance of ovaries
Enlarged bilaterally and have a smooth thickened avascular capsule
On cut section, subcapsular follicles in various stages of atresia are seen
Microscopically luteinizing theca cells are seen

9. Prevalence PCO on ultrasound - 20%-33% Oligomenorrhoea - 4 – 21 %
Oligomenorrhoea + hyperandrogenism – 9 %
PCOS – approx 18% (community-based prevalence study based on Rotterdam criteria). Importantly, 70% of women in this recent study were undiagnosed

10. Pathogenesis Insulin resistance ? Hypersecretion of adrenal androgens?
Hypersecretion of ovarian androgens?
A genetic disorder with an autosomal dominant mode of inheritance?
A multifactorial genetic disorder?

11. SHBG Obesity Insulin Free testosterone IGF-1
5-alfa reductase activity is stimulated
Free testosterone
IGF*** insulin like growth factor

12. Insulin Resistance Hyperinsulinaemia ↑Pulse Freq
↑Thecal cell & adrenal androgens
↑Free IGF-1
Hepatic SHBG production
LH production
FSH production
IGF-BP-1; insulin growth factor binding protein: IGF-1; insulin growth factor 1: SHBG; Sex hormone binding globulin: LH; Luteinising Hormone: FSH; Follicle Stimulating Hormone. - +
↑ Oestrogens
↑ Free testosterone
↑Adipose tissue leptin
Hepatic IGF-BP-1 production
Insulin Resistance
Atresia
Hirsutism

13. Diagnosis History Taking Menarche Menstrual pattern Weight issues
Hirsutism
Other aspects of gynae history

14. Diagnosis Biochemical tests
The best biochemical markers of hyperandrogenism are
Increased free testosterone levels or free androgen index;
Reduced SHBG levels
Not all patients with PCOS have elevated circulating androgen levels
DHEAS is raised in small fraction of patient with PCOS levels (measured to exclude adrenal causes)

15. Diagnosis Biochemical Tests
LH/FSH ratios can be elevated in up to 95% of women with PCOS if women with recent ovulation are excluded
LH levels are not necessary for clinical diagnosis of PCOS
May have increased Prolactin levels
Increased oestradiol/oestrone levels
Normal TFTs
Increased fasting insulin

16. PCOS should be excluded from other disorders in which hirsutism and menstrual irregularities are prominent
Congenital adrenal hyperplasia
Cushing's syndrome
Androgen-secreting tumors
In oligo/anovulation:
E2 & FSH to exclude hypogonadotrophic hypogonadism (central origin of ovarian dysfunction)

17. Diagnosis Pelvic Ultrasound
Small ovarian follicles; result of disturbed ovarian function
In PCOS, there is a so called "follicular arrest", i.e., several follicles develop to a size of 5–7 mm, but not further.
According to the Rotterdam criteria, 12 or more small follicles should be seen in an ovary on ultrasound examination. The follicles may be oriented in the periphery, giving the appearance of a ‘string of pearls’

18. Clinical Features Amenorrhoea Oligomenorrhoea Irregular periods
Infertility
Hirsutism
Obesity
Acne Vulgaris
Asymptomatic

19. Management Symptom control Diet & exercise Wt. loss
Improves both symptoms & endocrine profile
Aim for BMI < 30kg/ m2
Keep CHO content down, avoid fatty food
Obesity clinics

20. Contd Menstrual irregularities OCP- COCP, Yasmin, Dianette
Withdrawal bleed – regular bleed with progestagen
Consider Endometrial sampling

21. STEPWISE APPROACH FOR OVULATION INDUCTION IN PCOS (ACOG,2002)
1. Weight loss: If BMI >30 Kg/m2
2. Clomiphene citrate
3. CC +/- Metformin
4. Low dose step up protocol - FSH injection
5. Ovarian drilling
8. IVF

23. Mx of Hirsutism Cosmetic Medical- 6-7 months
Cyproterone acetate+ EE, Spironolactone
Reliable contraception
Flutamide & Finasteride - Rare

24. Reproductive Endocrinologist / Gynaecologist
S.testosterone > 5nmol/L
Rapid onset hirsutism
IGT/ Type2 DM
Refractory symptoms
Amen. > 6 months
Subfertility

25. Long term risks in PCOS Definite Type 2 diabetes(15%), IGT( 18-20%)
Dyslipidemia (Hypercholesterolemia with diminished HDL2 and increased LDL)
Endometrial cancer (OR % CI )

26. Possible
Hypertension
Cardiovascular disease
Gestational diabetes mellitus
Pregnancy-induced hypertension
Unlikely
Breast cancer

27. Guidelines (RCOG, May 2003)
1-Patients presenting with PCOS particularly if they are obese, should be offered measurement of fasting blood glucose and urine analysis for glycosuria. Abnormal results should be investigated by a glucose tolerance test
Such patients are at increased risk of developing type II diabetes (Evidence level IIb[C])
2- Women diagnosed as having PCOS before pregnancy should be screened for gestational diabetes in early pregnancy
Refer to specialized obstetric diabetic service if abnormalities detected (evidence level IIb[B])

28. Guidelines (RCOG, May 2003)
3-Measurement of fasting cholesterol, lipids and triglycerides should be offered to patients with PCOS, since early detection of abnormal levels might encourage improvement in diet and exercise (Evidence level III[C])
4- Olig- and amenorrhoeic women with PCOS may develop endometrial hyperplasia and later carcinoma. It is good practice to recommend treatment with progestogens to induce withdrawal bleed at least every 3-4 months (Evidence level IIa[B])

29. Guidelines (RCOG, May 2003)
5- Evidence has accumulated demonstrating safety and efficacy of insulin-sensitizing agents in the management of short-term complications of PCOS, particularly anovulation. Long-term use of these agents for avoidance of metabolic complications of PCOS cannot as yet be recommended (Evidence level IV[B])
6- No clear consensus regarding regular screening of women with PCOS for later development of diabetes and dyslipidemia
Obese women with strong family history of cardiac disease or diabetes should be assessed regularly in a general practice or hospital outpatient setting. Local protocols should be developed and adapted (Evidence level IV[C])

30. Guidelines (RCOG, May 2003)
Young women diagnosed with PCOS should be informed of the possible long-term risks to health that are associated with their condition. They should be advised regarding weight and exercise (Evidence level III[C])

31. Thank you