2. Polycystic Ovary Syndrome (PCO)
By: Prof. Dr. Rizwana Chaudhri
Head of the Gynae/Obs Unit - I
Holy Family Hospital, Rawalpindi.

3. Rawalpindi Medical College, Rawalpindi.
Holy Family Hospital, Rawalpindi.
Faisal Mosque & Margalla Hills, Islamabad.
College of Physicians & Surgeons Pakistan.

4. PCO Commonest endocrine disorder in women. Prevalence- 15- 20%.
Complex Interaction of Environmental and Genetic factors.
Runs in families , effecting 50% first degree relatives.

5. DEFINITIONS OF PCOS PCO
Polycystic ovarian morphology seen by ultrasound
PCOS 1
favoured in the UK
Polycystic ovaries on ultrasound, plus: symptoms (obesity, hyper-androgenism, menstrual cycle disturbance) and/or: biochemical abnormalities (elevated serum concentrations of testosterone and/or LH)
PCOS 2
favoured in North America
Hyperandrogenism and menstrual cycle disturbance

6. DEFINITION OF PCOS NIH-Criteria 1990 Chronic anovulation
Clinical and / or biochemical signs of hyperandrogenemia and exclusion of other causes
Rotterdam-Criteria 2003
Oligo- and / or anovulation
Clinical and / or biochemical signs of hyperandrogenism
Polycystic ovaries (Ultrasound) and exclusion of other causes (Adrenal hyperplasia, androgen-producing tumor, Cushing Syndrome)
ESHRE/ ASRM-sponsored PCOS Workshop Group
Human Reprod. 19, 41, 2004

7. HETEROGENOUS SYMPTOM COMPLEX
ESHRE/ASRM Definition:
Two out of following 03 criteria:
Oligo – &/or anovulation
Hyperandrogenism (clinical/ biochem.)
Polycystic ovaries.
(≥12 follicles, 2-9 mm and ovarian volume >10 cm3)

8. SONOGRAPHIC CRITERIA OF PCOS
Classical criteria
Enlarged ovaries
At least 8-10 follocles with 2-10 mm diameter, grouped peripherally
Stromal hyperplasia
New criteria
Presence of at least one criterium:
Enlarged ovaries (>10 cm3)
Increased number of follicles (at least 12 between 2-20 mm diameter)
It is sufficient that only one ovary is changed
Adams et al BMJ 293, 355, 1986
Scematic presentation
Balen et al Human Reprod. Update 9, 505, 2003

11. PAINTINGS OF BEARDED WOMEN
Brigida del Rio (1590)
Painted by
Sanchez Cotán ( ))
Maddalena Ventura
Painted by
José de Ribera (1631)

12. PATHOPHYSIOLOGY

13. SYMPTOMS Hyperandrogenism. Menstrual disturbances. Infertility.
Obesity.
Asymptomatic.

14. FREQUENCY OF SYMPTOMS IN PCOS
Cases (n)
Average (%)
Range (%)
Infertility
596 74
35-94
Hirsutism
819 69
17-83
Amenorrhea
640 51
15-77
Obesity
600 41
16-49
Functional bleeding
547 29
6-25
Dysmenorrhea 75 23
Virilisation
431 21
0-28
Cyclic bleeding
395 12
7-28
Goldzieher und Green

15. CLINICAL FEATURES OF PCOS
PCOS is the most frequent endocrine disturbance in the reproductive phase of women
Increased ovarian androgensecretion with oligo-anovulation and signs of androgenisation
Frequently: overweight, impaired glucose tolerance, hyperlipidenemia, hypertension, increased risk of diabetes mellitus type 2, infertility
Less frequent: acanthosis nigricans, sleep-apnoe
No virilisation
Schöfl et al Dt. Ärzteblatt 101, 346, 2004
Hahn et al J. Lab. Med. 27,53,2003

17. SERUM ENDOCRINOLOGY ↑Fasting insulin ↑Androgens. ↑LH, normal FSH.
↓SHBG.
↑Oestradiol.
↑Prolactin.

18. POSSIBLE LATE SEQUELAE
Diabetes mellitus.
Dyslipidemia.
Hypertension.
Cardiovascular disease.
Endometrial carcinoma.
Breast cancer.

19. PCOS - OVERVIEW Biochemical parameter Hyper- androgenimea
Abnormalities
in reproduction
Metabolic
Disturbances
Increased LH-/
FSH-Ratio
CLI
Anovulation
Obesity
Acne
Dysfibrinolysis
Elevated
Androgens
Hirsutism
Dyslipidemea
Infertility
Perhaps elevated
Prolaktin
Seborrhoe
Diabetes mellitus
Abortion
Hypertension
SHBG ↓
Alopecia
Gestational
diabetes
Cardiovascular
Disease
IFGBP-1 ↓
Preeclampsia
Hyperinsulinemia
Dyslipidanemia
De Leo et al Minerva Ginecologica 56, 53, 2004

20. The highest reported prevalence of PCOS has been 52% amongst South Asian immigrants in Britain, of whom 49 % had menstrual irregularities.
Rodin et al Clin. Endocrinol. 49, 91, 1998

21. PCOS is likely to parallel the increase in prevalence of insulin resistance and type II diabetes, which is currently being observed in the Asian population.
Balen et al Taylor & Francis London NY, 2005, 51

22. GENETIC ASPECTS OF PCOS I
PCOS have a high heriditary component
24 % of all mothers
33 % of all sisters
do have PCOS
Kalsar-Miller et al Fert. Steril. 75, 53, 2001

23. TRIGGERING SIGNALS

24. Mainly symptom oriented
MANAGEMENT
Mainly symptom oriented

25. OBESITY Loose weight: BMI < 30 Kg/m2. Diet/Dietician help.
Exercise.
Drugs.

26. MENSTRUAL IRREGULARITY
Dianne 35
Low Dose OCP
Progestogens
Induction of ovulation

27. HYPERANDROGENISM / HIRSUTISM
Physical treatment.
Medical treatment.

28. PHYSICAL TREATMENT: Waxing Electrolysis Bleaching Laser
Photothermolysis

29. TREATMENT OF ANDROGENISATION
Estrogen/progestogen combination with an antiandrogenic progestin for instance: Diane 35®
Non-steroidal antiandrogens (spironolactone, flutamide, finasteride)
Alone
Combined with Diane 35®
Insulin sensitizing drugs e.g metformin
Sequential therapy

30. PREVALENCE OF ANDROGEN-RELATED DISORDERS IN WOMEN
Most common female endocrinopathy
affecting about % of women in the fertile age
characterized by excessive androgen action
Many women with androgenic skin changes have normal androgen levels
suggesting increased target organ (receptor) sensitivity to androgens
Hyperandrogenism may be of ovarian or adrenal origin

31. DIANE-35 INDICATION Androgen-dependent diseases in women Seborrhea
Acne
Mild to moderate cases of hirsutism
Androgenetic alopecia
In women who also need or accept contraception

32. THE 3 STEPS OF ANDROGEN METABOLISM IN WOMEN

33. REASONS FOR ANDROGEN-RELATED DISORDERS IN WOMEN
Increased secretion of testosterone from the ovaries or adrenals
Increase in the level of freely circulating androgens not bound to transport protein (SHBG)
Increased enzyme activity (5a-reductase) in target organs, i.e. increased production of biologically active dihydrotestosterone (DHT)
Increased sensitivity of the target organs to DHT

34. DIANE-35 (CPA 2 MG / EE 35 µG)
Highly effective in the treatment of androgen-related disorders
based on antiandrogenic effect of CPA
supported by antigonadotropic activity of CPA/EE combination
Very reliable contraception
based on progestogenic effect of CPA and antigonadotropic effect of CPA/EE combination
comparable to other oral contraceptives
Pearl index 0.1

35. ANTI-ANDROGENIC EFFECT OF DIANE-35
Receptor level: By competition with binding of testosterone and DHT to their nuclear receptors
Enzymatic: increasing androgen metabolic clearance at the hepatic level and reducing the peripheral activity of 5a-reductase at skin level
Antigonadotropic: Reduction of LH secretion and suppression of ovarian androgen secretion
Increase in SHBG and decrease of free testosterone
The anti-androgenic treatment used most: Diane-35

36. DIANE-35 IN ACNE: ANTIANDROGENIC EFFECT ON THE TARGET TISSUE
Acne is the most common skin disease
affecting 80% of females at some time after the onset of puberty
Most patients seem to have sebaceous glands that are hypersensitive to androgens

37. SUCCESSFUL TREATMENT OF HIRSUTISM REQUIRES MORE TIME THAN ACNE THERAPY
Reduction of overall Ferriman-Gallway score with Diane-35 (n=63) % reduction 6 cycles 24 cycles 48 cycles % -55% -72%
60 cycles treatment with Diane-35 (n=140)
Acne resolved in all cases after cycles
Hirsutism resolved in 69% of cases
Moderate hirsutism in 100% of cases
Severe hirsutism became mild to moderate in 80% of cases

38. HYPERINSULINAEMIA METFORMIN:
Ameliorates hyperinsulinaemia and hyperandrogenism.
No effect on weight loss.
Dose: 850mg bd/500mg tds.
Further long term evaluation required.

39. INFERTILITY
Ovulation Induction:
WEIGHT REDUCTION IMP, to improve the prospects of both spontaneous and drug induced ovulation.
Medical Method.
Surgical Method.

40. MEDICAL OVULATION INDUCTION
ANTIESTROGEN - (Clomiphene Citrate)
50 – 100 mg.
Ovulation – 80%.
Conception – 40%
Cumulative conception rate (CCR) continues to increase for up to cycles.

41. PARENTRAL GONADOTROPHINS:
hMG, hCG, FSH.
6 month- CCR and LBR- 62%- 54% resp.
12 month-CCR and LBR-73%- 62% resp

42. SIDE EFFECTS:
Multiple pregnancy; %.
Ovarian Hyperstimulation syndrome (OHSS); %.

43. SURGICAL OVULATION INDUCTION
Ovarian Wedge Resection.
Ovarian Diathermy

44. OVARIAN WEDGE RESECTION:
Used to be done in 1970’s.
Abandoned b/c:
* Extensive tissue loss.
* Extensive periovarian and tubal adhesions.

45. Laparoscopic Ovarian Diathermy (LOD)
Technique 40w, 04points, 04sec.
Unilateral/Bilateral.

46. Laparoscopic Ovarian Diathermy

47. Laparoscopic Ovarian Diathermy

48. MECH. OF ACTION OF LOD Exactly not known:
Ruptures thick ovarian capsule.
Sensitizes ovary to endogenous /exogenous FSH.
End result is a decrease in LH and androgen levels, restoring normal ovulation.

49. ADVANTAGES OF LOD Improved endocrine profiles. Spontaneous ovulation.
Reduction in gonadotropin doses for ovulation induction and hence reduction in cost of further stimulated cycles.
Reduction in multiple pregnancy rates.
Reduction in first trimester abortions.
Continued:

50. Reduction in ovarian hyper stimulation.
No prolonged USG follow ups.
Tubal patency checked at the same time.
A meta analysis showed pregnancy rates greater with 06 months gonadotrophins treatment, compared with LOD but same after 12 months.
Conception rate with LOD in 12 months is 60-80%.

51. DISADVANTAGES OF LOD Risk of anaesthesia. Risk of minimal adhesions.
Requires expertise.

52. CONCLUSION
PCO syndrome is a mixed clinical entity and should be dealt with according to the problems of the patients

53. hope we all have a better tomorrow
Thank You