Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.



Published on

Published in: Health & Medicine


  1. 1. <ul><li>BY </li></ul><ul><li>Mohammad A. Emam </li></ul><ul><li>Prof. OB& GYN </li></ul><ul><li>Mansoura Faculty of Medicine </li></ul><ul><li>Mansoura integrated fertility center (MIFC) EGYPT </li></ul><ul><li> </li></ul>Progress In PCOS
  2. 2. History <ul><li>Stein and Leventhal </li></ul><ul><li>Polycystic Ovarian disease. </li></ul><ul><li>Polycystic ovarian syndrome </li></ul><ul><li>Syndrome O </li></ul><ul><li>( Metabolic) </li></ul>
  3. 3. Prevalence <ul><li>About 20% of reproductive age women demonstrate the ultrasound picture of polycystic ovaries. </li></ul><ul><li>About 5- 10 % have clinical or biochemical signs of Anovulation and androgen excess (dunaif 1995 , Norman etal 2002) </li></ul>
  4. 4. Rationale <ul><li>Knowledge base for PCOS is rapidly revived and revised Not end story </li></ul>Creation of significant Developments
  5. 5. Objective <ul><li>To highlight the progress in PCOS regarding : </li></ul><ul><ul><li>Definition . </li></ul></ul><ul><ul><li>Etiology </li></ul></ul><ul><ul><li>Path physiology. </li></ul></ul><ul><ul><li>Diagnosis </li></ul></ul><ul><ul><li>Heterogeneity of clinical presentations </li></ul></ul><ul><ul><li>Management. </li></ul></ul><ul><ul><li>Health risks. </li></ul></ul>
  6. 6. <ul><li>F rom recent publications in the relevant subjects of endocrinology, reproductive medicine, and gynaecology. </li></ul><ul><li>Medline search from 1994 till 2005 for English language articles related to PCOS and &quot;metabolic syndrome in women.&quot; </li></ul>Methods
  7. 7. Definition of PCOS
  8. 8. Definition of PCOS <ul><li>Europe view: - Ultrasound profile. </li></ul><ul><li>USA view (NIH ): - Endocrine Profile. </li></ul><ul><li>Rotterdam definition PCOS (2003). </li></ul>
  9. 9. <ul><li>PCOS could be defined when at least two of the following three features are present, after exclusion of other etiologies : </li></ul><ul><li>(i) Oligomenorrhea and or Anovulation </li></ul><ul><li>(ii) Hyperandrogenism and/or hyperandrogenemia. </li></ul><ul><li>(iii) Polycystic ovaries (sonar). </li></ul>Rotterdam , May 2003 Definition
  10. 10. <ul><li>Hyperandrogenism is the clinical manifestation of hyperandrogenemia. </li></ul><ul><li>Hyperandrogenism can exist in absence of hyperandrogenemia e.g. enhanced tissue sensitivity to androgens in many premenopausal women </li></ul>What is T he D ifference B etween Hyperandrogenism & Hyperandrogenemia?
  11. 11. Ultrasonic Criteria of PCO <ul><li>At least one of the following: </li></ul><ul><ul><ul><li>12 or more follicles measuring 2–9 mm in diameter, </li></ul></ul></ul><ul><ul><ul><li>increased ovarian volume (>10 cm 3 ). </li></ul></ul></ul><ul><li>If there is a follicle >10 mm in diameter, the scan should be repeated at a time of ovarian quiescence in order to calculate volume and area . </li></ul><ul><li>The presence of a single PCO is sufficient to provide the diagnosis. </li></ul><ul><li>The distribution of follicles and a description of the stroma are not required for diagnosis. </li></ul>
  12. 12. <ul><li>Significant intra-observer and inter-observer variability . </li></ul>What are The Pitfalls Of Ultrasonic Criteria ?
  13. 13. What are Trials To Standardize Ultrasonic Criteria PCO? <ul><li>Ratio between ovarian stromal area and total area of ovarian section ( S/A)..with cut –off 0.34 for PCO diagnosis (Belasi etal 2004). </li></ul><ul><li>The use of high resolution 3D. </li></ul>
  14. 14. <ul><li>Polycystic ovaries ( PCO ), observed on ultrasound are a sign of PCOS and not by themselves diagnostic of the syndrome. </li></ul>PCO & PCOS
  15. 15. PCO VS. Multicystic Ovaries <ul><li>Polycystic ovaries </li></ul><ul><ul><li>Bilateral </li></ul></ul><ul><ul><li>Multiple cysts </li></ul></ul><ul><ul><li>Cyst diam 2-<10 mm </li></ul></ul><ul><ul><li>Stroma increased </li></ul></ul><ul><li>Multicystic ovaries </li></ul><ul><ul><li>Bilateral </li></ul></ul><ul><ul><li>Multiple cysts </li></ul></ul><ul><ul><li>Cyst diam > 10 mm </li></ul></ul><ul><ul><li>Stroma not increased </li></ul></ul><ul><ul><li>I t is better to call it Polyfollicular syndrome not PCOS </li></ul></ul>
  16. 16. Emerging & Created Phenotypes &????? Regarding Roterdam 2003 Definition
  17. 17. Phenotypes (Rotterdam) Not P C O S +/- + +/- - + Norm N. Androgen + ovulatory +PCO + + ++ ++ +++ CVS risk + + - - Abn DD - - -/+ ++ - Abn Hyperando + Anov + N.ov + + + + Norm Hyperandrogen+PCO + Ovul. * + -/+ - - Norm Anov+ PCO + N.androgen + + ++ - Irreg Classic PCOS NB PCO I.R Androgens Ovulation Menses
  18. 18. What is The significance of polycystic-appearing ovaries versus normal appearing ovaries in patients with PCOS?? <ul><li>The presence of polycystic-appearing ovaries usually correlates with the presence of insulin resistance ( Richard J 2002) . </li></ul>
  19. 19. <ul><li>Late onset congenital adrenal hyperplasia </li></ul><ul><li>DHEAS > 18mmol/l </li></ul><ul><li>17 OH Prog > 6 mmol/l </li></ul><ul><li>Ovarian + adrenal androgen secreting tumours </li></ul><ul><li>V. high teslosterone > 6mmol/l </li></ul><ul><li>Cushings Syndrome </li></ul><ul><li>- Dexamethsone suppression test </li></ul><ul><li>- 24 hours urinary cortisol </li></ul><ul><li>- DHEAS > 13 mmol/l </li></ul>Anovulation & Hyperandrogenism What is DD?
  20. 20. <ul><li>Iatrogenic and illegal androgen ingestion </li></ul><ul><li>Hypothyroidisms </li></ul><ul><li>Hyperprolactinemia. </li></ul>Anovulation & Hyperandrogenism What is DD?
  21. 21. Is Fertility Normal in patients With Ovulatory PCOS? <ul><li>These patients should be regarded as fertile but many studies have shown that women with ovulatory PCOS have luteal phase defect (Joseph H etal 2002). </li></ul>
  22. 22. Asymptomatic PCO (Ovulatory + Normoandrogenic ) <ul><li>There is significantly lower levels of progesterone in the early Luteal phase. </li></ul><ul><li>This may contribute to the delay in conception in these patients. </li></ul><ul><li>May be the starting cascade of Pcos !!!!!!!!! </li></ul>
  23. 23. Pitfalls Rotterdam Definition <ul><li>doubts still exist regarding borderline groups of patients ,such as hirsute ovulatory Normoandrogenic women with PCO???. </li></ul><ul><li>Neglect role of IR </li></ul>
  24. 24. Etiology <ul><li>Speculation: </li></ul><ul><li>Complex interaction of genetic ,epigenetic and environmental factors. </li></ul><ul><li>Recently ,PCOS is mediated by ghrelin </li></ul><ul><li>( gastric peptide which is orexigenic and adipogenic) </li></ul>
  25. 25. Pathogenesis <ul><li>Three major hypothesis ( culprits ) may all interact: </li></ul><ul><ul><ul><li>Insulin resistance ( central player). </li></ul></ul></ul><ul><ul><ul><li>Hyperandrogenism & (altered Gonadotropins) </li></ul></ul></ul><ul><ul><ul><li>Recently ( target genes) : </li></ul></ul></ul><ul><ul><ul><ul><li>Genes encoding Inflammatory cytokines. </li></ul></ul></ul></ul><ul><ul><ul><ul><li>INSR genes. </li></ul></ul></ul></ul>
  26. 26. IR ( Metabolic or Syndrome x ) What is? <ul><li>Insulin acts like a key which can open a door on the cell's surface. </li></ul><ul><li>cells do not have enough insulin receptor sites and cannot effectively burn glucose . </li></ul><ul><li>this excess glucose is then sent to the liver where it is converted to fat. </li></ul>
  27. 27. PCOS, starts in adolescence. But Unfortunately, not always diagnosed at that age.
  28. 28. The Central Player ( Insulin Resistance ) Genetics Aging Pregnancy Drugs Lifestyle Upper abdominal obesity Hyperinsulinemia Increased lipid storage Altered lipoprotein & cholesterol metabolism Altered steroid hormone metabolism PCOS Insulin Resistance
  29. 29. <ul><ul><li>The high ovarian response to insulin. </li></ul></ul><ul><ul><li>Opposed by the whole body resistance. </li></ul></ul>IR : The central paradox
  30. 31. How IR Can Be Assessed ?? <ul><li>OGTT ( the best ). </li></ul><ul><li>Fasting insulin (mu/ L) to fasting glucose (mmol/L) ( Hyperinsulinemic – euglycemic). </li></ul>
  31. 32. Emerging & Created PHENOTYPES &????????????? Regarding Pathogenesis
  32. 33. <ul><li>PCOS + IR ( 50-70 % ). </li></ul><ul><li>PCOS without IR. </li></ul>Phenotypes According to IR
  33. 34. 1) IR Phenotype of PCOS: What are the characteristics ? <ul><ul><li>Obese ( may be lean ) </li></ul></ul><ul><ul><li>Acanthosis Nigerians. </li></ul></ul><ul><ul><li>Hirsutism. </li></ul></ul><ul><ul><li>Resistance to CC, </li></ul></ul>
  34. 35. 2) PCOS Without IR: What are characteristics? <ul><li>Lean. </li></ul><ul><li>Euinsulinemic/ Euglycemic </li></ul><ul><li>Enhanced Ovarian Sensitivity to insulin ( although no Hyperinsulinemia ). </li></ul>
  35. 36. Diagnosis <ul><li>In the past (before 2003) Necessary Lab Tests or sonar </li></ul><ul><li>Recently ( after 2003)… clinically. </li></ul>
  36. 37. What is needed after clinical diagnosis PCOS? <ul><li>Body weight </li></ul><ul><li>Ideal body weight </li></ul><ul><li>Body Mass Index (BMI) </li></ul><ul><li>Lipid profile </li></ul><ul><li>Fasting blood glucose </li></ul><ul><li>Fasting insulin levels </li></ul><ul><li>Blood pressure </li></ul><ul><li>Medications </li></ul>
  38. 39. 1) Symptomatic PCOS : What is the most important parameter ? <ul><li>Any or all of these symptoms may be present: </li></ul><ul><ul><ul><li>Irregular menstrual cycles. </li></ul></ul></ul><ul><ul><ul><li>Weight gain. </li></ul></ul></ul><ul><ul><ul><li>Abnormal hair growth on the face or the body. </li></ul></ul></ul><ul><ul><ul><li>Infertility. </li></ul></ul></ul><ul><li>Increased BMI ( severity of the PCOS). </li></ul>
  39. 40. 2) Asymptomatic PCOS <ul><li>Very lean </li></ul><ul><li>Athletic women </li></ul><ul><li>May be underweight. </li></ul><ul><li>This may mask the PCOS . </li></ul><ul><ul><ul><ul><ul><li>The less symptoms, the better response to medication and treatment. </li></ul></ul></ul></ul></ul>
  40. 41. Controversy <ul><ul><li>Epilepsy & PCOS </li></ul></ul><ul><ul><li>Miscarriage & PCOS </li></ul></ul>
  41. 42. Long term risks in PCOS <ul><li>Definite </li></ul><ul><li>Type 2 diabetes </li></ul><ul><li>Dyslipidemia (Hypercholesterolemia with diminished HDL2 and increased LDL) </li></ul><ul><li>Endometrial cancer. </li></ul>
  42. 43. <ul><li>Possible </li></ul><ul><li>Hypertension </li></ul><ul><li>Cardiovascular disease </li></ul><ul><li>Gestational diabetes mellitus </li></ul><ul><li>Pregnancy-induced hypertension </li></ul><ul><li>Ovarian cancer </li></ul><ul><li>Unlikely </li></ul><ul><li>Breast cancer </li></ul>Long term risks in PCOS
  43. 44. Long Term Risks Of PCOS PCOS CVD Gout Obesity Hypertension Infertility Endometrial Cancer Gallbladder Disease NIDDM
  44. 45. How is PCOS treated? <ul><li>Till now there is no cure for PCOS . </li></ul><ul><li>The target is to: </li></ul><ul><ul><ul><ul><ul><li>Try causative ttt. </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>prevent further problems. </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>HOW????? </li></ul></ul></ul></ul></ul>
  45. 46. Causative ttt <ul><li>Life- style modifications: </li></ul><ul><ul><ul><li>Diet modification </li></ul></ul></ul><ul><ul><ul><li>Weight loss </li></ul></ul></ul><ul><ul><ul><li>Exercise </li></ul></ul></ul><ul><ul><ul><li>Psychosocial support. </li></ul></ul></ul><ul><ul><ul><li>Cessation smoking. </li></ul></ul></ul><ul><ul><li>Improve IR ( Metformin) </li></ul></ul>
  46. 47. Targets for treatment PCOS
  47. 48. A weight loss of only 5% of total body weight is associated with: <ul><li>Decreased insulin levels </li></ul><ul><li>improved menstrual function </li></ul><ul><li>reduced hirsutism and acne </li></ul><ul><li>lower testosterone levels. </li></ul>
  48. 49. Drug Therapy: Insulin-Sensitizing Agents (Metformin) <ul><li>Potential Disadvantages </li></ul><ul><li>Gastrointestinal disturbance in 1/3 of patients </li></ul><ul><li>Generalized feeling of unwell ness </li></ul><ul><li>Decreased absorption of vitamin B-12 </li></ul><ul><li>Lactic acid buildup </li></ul><ul><li>Potential Advantages </li></ul><ul><li>↑ glucose tolerance </li></ul><ul><li>↑ insulin sensitivity </li></ul><ul><li>↓ blood lipid levels </li></ul><ul><li>↑ weight loss or stabilization </li></ul><ul><li>Improved fat distribution </li></ul><ul><li>↓ blood pressure </li></ul><ul><li>↓ androgen levels </li></ul><ul><li>Restoration of regular menses </li></ul><ul><li>Postponement of diabetes </li></ul>
  49. 50. Laparascopic Treatment of Polycystic Ovaries: Is Its Place Diminishing? <ul><li>Laparascopic ovarian drilling and Metformin improve ovulatory dysfunction and pregnancy rate to a similar extent. </li></ul><ul><li>The advantages of Metformin continue beyond conception: </li></ul><ul><ul><ul><li>It reduces the miscarriage rate </li></ul></ul></ul><ul><ul><ul><li>Decreases the likelihood of developing gestational diabetes. </li></ul></ul></ul>
  50. 51. Proposed APPROACH FOR ttt of PCOS
  51. 52. <ul><li>Gynecologists should categorize any case of PCOS ,depending on : </li></ul><ul><li>Rotterdam definition </li></ul><ul><li>IR or not </li></ul><ul><li>Asymptomatic or symptomatic </li></ul>Conclusions
  52. 53. Conclusions <ul><li>Treatment of PCOS should be directed towards causative rather than symptomatic especially if IR is proved as the central player !!!! </li></ul>Conclusions
  53. 54. <ul><li>NOW We Can Decide That Polycystic Ovary Syndrome is An Open Door for Dietetics Professionals </li></ul>Conclusions
  54. 55. <ul><li>The pathogenesis of altered ovarian morphology in asymptomatic PCO should be evaluated by 3D and Doppler ultrasonic in those apparently normal women where up to 20% of fertile women have PCO on ultrasound </li></ul>Recommendations
  55. 56. T elfax 0020502319922 & 0020502312299 Email. [email_address] Prof. DR. MOHAMMAD EMAM Thank you