1. Polycystic ovarian syndrome: an Asian phenomenon?
Premila Jeevan Kollipara MD FRCOG
Clinical Director & Consultant in Obstetrics and Gynaecology
Queen’s Hospital, London, England

2. Defining polycystic ovarian syndrome (PCOS)
Identified by Slein & Leventhal (1935)
Oligo/amenorrhoea
Bilateral polycystic ovaries on surgery
NIH definition (1990)
Hyperandrogenism
Ovarian dysfunction
Presence of PCO morphology not required
Rotterdam Consensus Workshop (2003)
Presence of PCO morphology
Any 2 of these 3 could lead to a diagnosis

3. Incidence
Reported incidence ranges from 10% to 80% across epidemiological studies
Seen in women of all races and nationalities
Very common in the South Asian population, including many from the Indian subcontinent

4. Symptoms
Oligomenorrhea (>35 day cycle) / Amenorrhoea (>6 months)
Either may be associated with heavy bleeding
Difficulty in losing weight
Infertility
Hirsutism
Dyspareunia
Androgenic alopecia
Acne
Seborrhea
Acanthosis nigricans
Acrochordons
Prolonged periods of PMS like symptoms (bleeding, mood swings, pelvic pain, backache)
Obstructive sleep apnoea

5. Presentation Women may present with these symptoms: at any age
to a gynaecologist, dermatologist or endocrinologist

6. Signs On biochemical tests:
LH to FSH ratio greater than 1 on day 3 of the menstrual cycle
High level of testosterone
High level of sex hormone binding globulin
Hyperinsulinaemia
On scan:
10 or more peripherally located small follicles in ovary (echogenic ‘string of pearls’ appearance)
Ovary enlarged 1.5 to 3 times normal
On laparascopy:
Multiple smooth, thickened, pearl-white areas on the outer surface of the ovary

7. Risks Endometrial hyperplasia and cancer
Insulin resistance and type II diabetes
Gestational diabetes
Weight gain
Infertility
Miscarriage
Hypertension
Dyslipidaemia
Cardiovascular disease
Stroke

8. Diagnosing PCOS
Difficult and therefore characterised as a syndrome and not as a disease
Standard diagnostic assessments:
History – 4 key questions:
Menstrual patterns
Obesity
Hirsutism
Absence of breast discharge
Sensitivity 77.1% and specificity 93.8%
Transvaginal ultrasound scan
Serum testosterone level
Free more sensitive than total
Free androgen index = free testosterone/SHBG x 100

9. Diagnosing PCOS (continued)
Common assessments for associated conditions or risks:
Fasting biochemical screen
Lipid profile
2 hour oral GTT
Impaired GTT in 15-30%
Frank diabetes in 65-68%
Insulin resistance in both normal and overweight
Exclusions:
Prolactin level
TSH / Free thyroxine
17 hydroxyprogesterone
DHEAS
Androstenedione

10. Diagnosing PCOS (continued)
Controversial tests
Fasting insulin level
GTT with insulin level – IGTTT
HOMAI – mathematical derivation calculated from the fasting values of glucose and insulin allows a direct and moderately accurate measure of insulin sensitivity
LH/FSH ratio not very specific – present in less than 50% in 1 study

11. Differential diagnosis
CAH
Cushing’s
Hyperprolactinaemia
Other pulmonary and adrenal disorders
PCOS has been reported in patients with acromegaly, an insulin resistant condition

12. Pathogenesis PCOS develops when:
Ovaries are stimulated to produce more androgens through the release of LH by the anterior pituitary
Ovaries are stimulated to produce more androgens through high levels of insulin

13. ↓ follicular maturation
Aetiology
Cause still unknown as it involves a diverse and complex set of symptoms
However, a number of theories have been put forward
Insulin resistance hypothesis:
Hyperinsulinaemia ↓
↑ GHRH pulse frequency
LH over FSH dominance
↑ovarian androgens
↓ follicular maturation
↓ SHBG binding
PCOS

14. Aetiology (continued)
Genetic hypothesis:
Interpopulation variation in the frequency of phenotypic expression of PCOS
Disease familial
More common in monozygotic twins
Some link to the D dinucleotide repeat marker linked to insulin receptor gene on chromosome 19p13.2

15. Aetiology (continued)
Environmental hypothesis:
Low birth weight females have a higher chance of precocious pubarche, hyperinsulinaemia and hyperandrogenism
Hypothesized that poor foetal and infant growth can promote development of PCOS in individuals with genetic susceptibility when exposed to a nutritional environment of excess later in life
Exposure to androgens during pregnancy
Animal studies in rhesus monkeys and sheep

16. Aetiology (continued)
Evolutionary hypothesis:
At some point in evolution PCOS may have been selectively advantageous
Women with PCOS have a high chance of being obese and anovulatory during times of normal or excess food availability
During periods of food shortage and weight loss they begin to ovulate
Selective advantage in being able to reproduce when other women become anovulatory
With a modern Westernised lifestyle with abundant food and limited physical activity these thrifty genes have become disadvantageous
High waist to hip ratio and carbohydrate intolerance in many hunter-gatherer populations throughout the world
The suggestion is that a thrifty gene would code for famine resistant glucose metabolism
Genotype leads to anabolic metabolism and fat deposition
Traditionally not obese when living in their own lifestyle where food supplies are at or just above subsistence level or seasonally available

17. Aetiology (continued)
Food deprivation hypothesis:
Weight loss results in spontaneous medically unassisted pregnancies in 33% of cases
Thus the onset of severe food deprivation, whether incidental or seasonal, might present reproductive advantage to women with the PCOS genotype

18. Aetiology (continued)
Re-feeding hypothesis:
Chronic food deprivation leads to famine related amenorrhoea
Amenorrhoeic women, when fed, will reach the critical BMI
This will open the leptin gate
This will favour earlier ovulation

19. Aetiology (continued)
Trans-generational privation hypothesis
Nutrition of mothers and grandmothers has a profound influence on the health of the offspring in adulthood

20. Treatment of PCOS The mainstay of treatment is:
To start the patient on a weight loss diet
A low glycaemic index (GI) diet is the ideal
A significant part of carbohydrate should be from fruit, vegetable and wholegrain sources
To ensure good aerobic exercise for 30 minutes every day

21. Aims of medical treatment
Medical treatment of PCOS should be tailored to the patients’ goals:
Restoration of menstruation
Prevention of endometrial hyperplasia
Prevention of endometrial cancer
Restoration of fertility
Treatment of hirsutism or acne

22. Correction of insulin levels
Drugs that reduce insulin resistance are helpful:
Metformin hydrochloride
Proglitazone hydrochloride
Rosiglitazone maleate
Combined with exercise and low GI diet, 85% of patients will improve in terms of menstrual cycle regularity and ovulation

23. Restoration of menstruation and prevention of endometrial hyperplasia
Combined contraceptive pill
Mirena IUD
Oral progesterone taken every 3 months to induce a predictable menstrual bleed
D-chiro-inositol
Naturally occurring human metabolite known to be involved in insulin metabolism
Available as a nutritional supplement in the US

24. Treatment of infertility
Clomiphene citrate +/- metformin
Drastic increase in ovulation occurs with a combination of diet, moderate weight loss and the above drugs
Controlled ovarian hyperstimulation
In vitro fertilisation
In vitro maturation
Ovarian drilling
Laparoscopic electrocauterisation
Ovarian wedge resection

25. Treatment of androgenic symptoms
Cyproterone acetate (contained in Dianette)
Spiranolactone
Eflornithine
Electrolysis / laser therapy

26. Summary
PCOS is an enormous problem, with significant effects on both body morphology and fertility
Its incidence could be as high as 80% in the Indian female population
Although its aetiology is not fully understood, a low GI diet and regular exercise may help to ameliorate symptoms

27. Thank you!