In The Name Of God

1. In The Name Of God

2. PCO AND METABOLIC SYNDROM

3. Polycystic ovarian syndrome (PCOS) is an extremely common disorder affecting 4% to 12% of women of reproductive age. Despite being heterogeneous in nature, the hallmarks of the disease are hyperandrogenism and chronic anovulation

4. What's name? • . Is it PCO or polycystic ovary disease (PCOD) or polycystic ovary syndrome (PCOS)? Since the name includes the word "polycystic" does that mean that all women with this problem have cysts in their ovaries? • Not all women with polycystic ovary syndrome (PCOS) will present the same way or have the same symptoms or laboratory findings. Confused?

5. The poly cystic ovary • The characteristic polycystic ovary emerges when a state of anovulation persists for any length of time. • Because there are many causes of anovulation there are many causes of polycystic ovaries.

6. Ovarian hystologic characteristics • The surface area is doubled • average volume increases 2.8 times. • The number of growing and atretic follicles doubled. • Each ovary may contain 20- 100 cystic follicles(2-10mm) • The thickness of tunica is increased by 50%. • A 5-fold increase in stroma are noted.

8. Ultrasonography Finding • Enlarged ovaries and necklace –like pattern • Large number (>10) of tiny follicles (cysts) just under the surface of the ovaries • The center of the ovaries is echogenic (highly reflective on ultrasound) and with very few follicles seen. • Women with ultrasound findings are said to have polycystic appearing ovaries (PAO).

9. Ultrasonography as a diagnostic tool for PCOs is unnecessary. • Frome %8 - %25 of normal women will demonstrate ultrasonographic picture. • This woman are endocrinology normal and polyscystic ovaries observed with ulteasonography are associated with impaired fertility only when accompanied by symptoms of menstural irregularities and hyperandrogenism.

10. The cause of PCOS is most likely multiple factors, and genetic abnormalities may be involved PCOS as a heterogeneous disorder of unknown cause with various clinical features that can be divided into 3 categories: clinical, endocrine, and metabolic.

11. What signs and symptoms can be found in women with polycystic ovary syndrome (PCOS)? Ovulation problemsAnovulation • Oligo-ovulation • Infrequent or irregular ovulation • Irregular menstrual cycles (results from not ovulating regularly)Amenorrhea • Oligomenorrhea 20%-50% • Infrequent periods • Hypermenorrhea • Metorrhagia 30% • Menometorrhagia

12. Elevated androgen levels can result in the development of some signs and symptoms in women Hirsutism: • Unwanted hair growth. Usually on the lip- cheeks- chin neck-in between the breasts(70%). • Acne • Alopecia

13. Endocrin abnormality • Steady state of gonadotropins and sex stroids • The higher mean concentrations of LH but low or low-normal levels of FSH.( LH/FSH ) • The average daily productin of Estrogen and Androgens is increased and dependent on LH stimulation • 50% reduction in circulating levels of SHBG

14. The higher concentration of Testestron • Andrestendion • DHA- DHEAS • 17OHP • EStron.

15. The circulating estron levels are due to peripheral conversion of the increased amounts of androstendion to estron.

16. Etiology of increasing LH/FSH Increased frequency of GNRH pulsatile secretion. • Increase in LH pulse frequency and pituitary response to GNRH are characteristic of the anovulatory state and are independent of obesity.

17. Because the FSH levels are not totally depressed ,new follicular growth is continuosly stimulated but not to the point of full maturation and ovulation. • FSH new follicular growth and atresy

18. Theca cell LH Granolosa cell FSH Cholestronl testestron Andrestandion Estron Estradiol

21. Hyperandrogenism effect in ovary • Androgens convertion to 5a-reduced metabolites that inhibit aromatase avtivity • Preventing normal cycle and ovulation • Preventing follicular development and indusing premature atresia of follicul

22. Hyperandrogenism effect in ovary Atresia degenerating granulosa leaving the theca cells to the stromal Andrgens

23. Increaseed free estradiol and estron • FSH LH/FSH

24. Genetic concideration • X- linked dominant transmission • Autosomal- dominant and Premature bladness in males • The stimulatory effect of insulin on ovarian androgen production is influenced by gegnetic predisposition

25. Insulin Resistance and Hyperandrogenism • The association between increased insulin resistance and PCO is now well – recognized.

26. Questions 1- Which coms first , the hyperinsulinemia or the hyperandrogenism? 2- How does hyperinsulinemia produce hyperandrogenism? 3- Are all women with PCOS have hyperinsulinemia?

27. 1_ Hyper insulinemia is the primery factor • GNRH agonist and correction hyper androgenism • Administeration of insulin and glucose • Weight loss • Invitro , insulin stimulates theca cell androgen production

28. 2_ How does hyperinsulinemia produce hyperandrogenism? Insulin binds to IGF-1 reseptors increase androgen product in theca cells

31. Are all women with PCOS have hyperinsulinemia? Not every women with PCOS has hyperinsulinemia not even every overweigt. • Hyperinsulinemia can be an underlying disorder.

32. 4 - why not all women who are insulin resistant are hyperandrogenic? • The answer to this question is not known. But a logical speculation is that an ovarian genetic susceptibility is required or existence of long-term anovulation must be present and even preced huperinsulinemia.

33. Obesity • Central body (android) obesity is associated with cardiovascular risk factors: • Waist/hip >0/85 • Waist circumference >100cm (40inches) in men • and>90cm(35 inches) in women.

34. Obesity Prevalance: (35%-60%) • Hyperinsulinemia and hyprandrogenism are not confined to anovulatory women who are overweight. • The obes unovulatory women : • Insulin - LH - SHBG -IGFBG-1 • In normal weight women: • Insulin - LH

35. Metabolic Syndrom

37. Prevalence • Overall estimated: 24% higher in women( 40% by age 60) • In normal GTT : 10% • Imppaired GGT :40% • Type 2 diabet : 85% • Normal weight :5% • Obes :60%

38. Metabolic syndrom • multiple studies indicate that women with PCO are at increased risk for the development of glucose intolerance or frank type 2 diabetes mellitus, hypertension, dyslipidemia, and atherosclerosis. • In recent studies, the prevalence of MS in women with PCOS is approximately 43–47%.

39. Hyperinsulinemia and coronary disease • HT • Triglycerides • HDL • PAI-1

40. Clininical consequens • Infertility • AUB • Hirsutism-acne and alopecia • Endometrial cancer and perhaps breast cancer. • Cardiovascular disease • Diabetes melituse in patients with insulin resistant

41. Cardiovascular disease • Advers lipid and lipoprotein profile • Subclinical atherosclerosis by corotid ultra sonography in premenoppausal women with PCO. • In women who undergoing cronary angiography the prevalence of PCO is increased.

42. Laboratory tests to exclude other problem • TSH • Prolactin • Lipid and lipoprotein profile • Screen for Cushing s • Endometrial biopsy • If presence of signs of exess androgens: • Total testestron • 17-OHP

43. Who should be tested for Hyperandrogenism • In anovulatory women and their brother and sisters • Central obesity

44. How to test • Measurement of 2- hours glucose and insulin level after a 75gr glucose. • Glucose response • Normal <140mg/dl • Impaired 140-199 mg/dl • Diabet typ 2 >200 mg/dl • Insulin response • Insulin resistant very likely 100-150 uU/ml • Insulin resistant 151-300uU/ml • Sever insulin resisrant >300 uU/ml

47. Treatment Hyperandrogenism Endometrium protect Hyperinsulinemia prevent of CVD Induced ovulation

48. Endometrium protection • Endometrial Biopsy 1- Duratin of exposure to unopposed estrogen is critical. 2- Endometrial Thickness is greater than 12mm

49. Medroxy progestron: 14 days every month • OCP 1- Androgen suppression 2- Improvement in lipid profile 3 - protectin of endometrium

50. Insulin Resistance • The best therapy is weight loss>5% • BMI<27 • Lifestyle improvement with proper diet and exercise • Druge agent : Metformin and Glitazones