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Millennium Disease and Reproductive Health

Millennium Disease and Reproductive Health. Geva E. The Noi-Katovich Women’s Health Center, Clalit Health Services, Department of Obstetrics and Gynecology, Edith Wolfson Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

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Millennium Disease and Reproductive Health

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  1. Millennium Disease and Reproductive Health Geva E The Noi-Katovich Women’s Health Center, Clalit Health Services, Department of Obstetrics and Gynecology, Edith Wolfson Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

  2. Prevalence of At Risk for Overweight and Overweight in Children and Adolescents: United States, 1999-2002 Prevalence, % (SE) Hedley AA et al, JAMA 2004

  3. Prevalence of Overweight and Obesity in Adults: United States, 1999-2002 Prevalence, % (SE) Hedley AA et al, JAMA 2004

  4. Obesity Epidemic Kopelman PG, Nature 2000

  5. Prevalence of Overweight and Obesity in Adults by Sex and Age: Israel, 1999-2001 Obesity (BMI ≥ 30) Overweight (BMI ≥ 25) 33.0 % 25.8 % ICDC 2003

  6. The Modern Epidemic From adolescence and throughout the reproductive life Childhood Adolescence Reproductive Postmenopausal Premature puberty Anovulatory Cycle Infertility Reproductive Hyperandrogenism Obstetric outcome Metabolic Insulin resistance and DM Obesity CVS disease Dyslipidemia Breast Endometrial Colon Cancer

  7. The Relation of Menarcheal Age to Obesity in Childhood and Adulthood Freedman DS et al, BMC Pediatr 2003

  8. Age at Menarche, Abnormal Glucose Tolerance and Type 2 Diabetes Mellitus The Rancho Bernardo Study, 1984-87 Saquib N et al, Climacteric 2005 Data are presented as mean ± SE

  9. The Modern Epidemic From adolescence and throughout the reproductive life Childhood Adolescence Reproductive Postmenopausal Premature puberty Anovulatory Cycle Infertility Reproductive Hyperandrogenism Obstetric outcome Metabolic Insulin resistance and DM Obesity CVS disease Dyslipidemia Breast Endometrial Colon Cancer

  10. The association between a disorder of carbohydrate metabolism and hyperandrogenism was first describe in 1921 by Achard and Thiers and was called “diabete des femmes a barb” The Diabetes of Bearded Women Achard C and Thiers J 1921 Le virilisme pilaire et son association a l’insuffisance glycolytique (diabete des femmes a barb) Bull Acad Natl Med 86:51–64

  11. ESHRE / ASRM CRITERIA 2003 PCOS Revised Definition Hyperandrogenism PCO morphology Anovulation • + • Exclusion of related disorders Fertil Steril & Hum Reprod, 2004

  12. Prevalence of Obesity in a Large Cohort of 320 Women with PCOS Pasquali Ret al, Int J Obstet Gynecol 2006 WHR, waist-to-hip ratio

  13. Prevalence of Overweight and Obesity in a Cohort of 147 Israeli Women with PCOS 12.92 10.88 Geva E, Gutman G, Amster RE, unpublished data; The Noi-Katovich Women’s Health Center, Clalit Health Services

  14. PCOS: Insulin Sensitivity Insulin sensitivity Dunaif A, 1987 Lean Normal Obese Normal Lean PCOS Obese PCOS

  15. Pathophysiology of Obesity-PCOS Association Insulin resistance Beta-cell dysfunction Genetic factors Obesity PCOS Hyperestrogenism Acquired factors Hyperandroginemia

  16. Prevalence of type 2 DM and IGT in PCOS 254 affected women Obese Not obese 88.2% 61.4% Prevalence of glucose intolerance by WHO criteria 31.1% Legro R, 1999 10.3% 7.5% 1.5% NGT IGT Type 2 DM

  17. Metabolic Syndrome • Abdominal obesity • Insulin resistance ± glucose • intolerance • Atherogenic dyslipidemia • Elevated blood pressure • Proinflammatory state • Prothrombotic state

  18. ATP III Clinical Identification of the Metabolic Syndrome* *Any 3 of 5 constitute diagnosis The National Cholesterol Education Program’s Adult Treatment Panel III report (ATP III), 2005 American Heart Association/National Heart, Lung, and Blood Institute/American Diabetes Association

  19. Metabolic Syndrome in PCOS • The prevalence of MS is 41 - 47% • 91% had at least one metabolic abnormality: • - decreased HDL levels 68% • - obesity 67% • - HTN 45% • The major predictors of MS were: • serum free T and SHBG levels Dokras A, 2005 Apridonidze T, 2005

  20. Glucose intolerance in Israeli PCOS Patients Geva E, Gutman G, Amster RE, unpublished data; The Noi-Katovich Women’s Health Center, Clalit Health Services

  21. Prevalence of HTN and DM Type II in PCOS PCOS Control 40% % 15% Dahlgren E, 1992 10% 3% HTN NIDDM

  22. Prevalence of DM Type II in PCOS with DM Type II FHx % % PCOS DM Type II FHx 100 100 50 50 Ehrmann DA, 1999 N IGT DM type II N IGT DM type II

  23. Increase of CRP* Concentrationsin Women With PCOS PCOS Control 36.8% P < 0.001 % 9.6% n = 116 n = 94 Boulman N, 2004 *high CRP level (>5 mg/liter)

  24. Increase of Leukocytesin PCOS Orio F, 2005

  25. Elevated Plasma Homocysteinein PCOS 155 PCOS infertile women PCOS Control P < 0.001 P < 0.003 12.4 ± 8.4 Homocysteine levels (µmol/l) 11.5 ± 7.4 9.6 ± 4.4 7.4 ± 2.1 + IR - IR Schachter M, 2003

  26. PCOS Greater Carotid Intima-Media Thickness (IMT)in PCOS Control 0.85 IMT (mm) 0.65 0.50 30-39 40-44 45-49 ≥50 Age (y) Talbott EO, 2000

  27. Greater Coronary Artery Calcium (CAC) in PCOS PCOS Control 40% % CAC 20% Christian RC, 2003

  28. Echocardiographic findings in PCOS and controls Left Ventricular Hypertrophyin PCOS Orio F, 2004

  29. Metabolic Profile and CVS Risk Factors in Women with and without PCOS Orio F, 2004

  30. Syndrome XX PCOS Insulin resistance and hyperinsulinemia DM Type II HTN Dyslipidemia Atherosclerosis Prognosis ? A documentation of a clear association between PCOS and CVS events or mortality is lacking

  31. The Modern Epidemic From adolescence and throughout the reproductive life Childhood Adolescence Reproductive Postmenopausal Premature puberty Anovulatory Cycle Infertility Reproductive Hyperandrogenism Obstetric outcome Metabolic Insulin resistance and DM Obesity CVS disease Dyslipidemia Breast Endometrial Colon Cancer

  32. The Association Between BMI at Age 18 and Subsequent Primary Ovulatory Infertility 2527 married infertile nurses *Referent BMI Richedwards JW et al, Am J Obstet Gynecol 1994

  33. Association of Obesity with Treatment Outcomes in Ovulatory Infertile Women Mean (± SD) ovarian response to stimulation by BMI groups Dodson WC et al, Fertil Steril 2006

  34. The Effect of BMI on the Outcome of IVF and ET Clinical pregnancy rate per fresh treatment cycle BMI < 25 BMI ≥ 25 51% % 35% n = 102 n = 81 Mitwally MF et al, O-161, ASRM 2006

  35. Body Weight (BMI) of Recipient is Important for Oocyte Donation *p < 0.05 BMI Bellver J et al, Fertil Steril 2003

  36. The Modern Epidemic From adolescence and throughout the reproductive life Childhood Adolescence Reproductive Postmenopausal Premature puberty Anovulatory Cycle Infertility Reproductive Hyperandrogenism Obstetric outcome Metabolic Insulin resistance and DM Obesity CVS disease Dyslipidemia Breast Endometrial Colon Cancer

  37. Obstetric Complications by Maternal BMI Morbidly obese vs control Obese vs control Weiss JL et al, Am J Obstet Gynecol 2006

  38. Obstetric Outcomes Associated with Increase in BMI Category in Women Who Were Overweight at First Prenatal Visit Kabiru W et al, Am J Obstet Gynecol 2004

  39. Preterm Delivery Associated with Prepregnancy BMI among Women Delivering Singleton Infants* in Sweden in 1992 and 1993 Nulliparous BMI Parous Events /1000 Events /1000 OR OR 95% CI 95% CI *no. = 167,750 Cnattingius S et al, N Eng J Med 1998

  40. Late Fetal Death Associated with Prepregnancy BMI among Women Delivering Singleton Infants* in Sweden in 1992 and 1993 Nulliparous BMI Parous Events /1000 Events /1000 OR OR 95% CI 95% CI *no. = 167,750 Cnattingius S et al, N Eng J Med 1998

  41. The Modern Epidemic From adolescence and throughout the reproductive life Childhood Adolescence Reproductive Postmenopausal Premature puberty Anovulatory Cycle Infertility Reproductive Hyperandrogenism Obstetric outcome Metabolic Insulin resistance and DM Obesity CVS disease Dyslipidemia Breast Endometrial Colon Cancer

  42. Relation Between BMI and the Risk of Death among Women McTigue K et al, JAMA 2000

  43. Mortality and Fasting Serum Glucose Level n = 468,615 1200 800 Rate per 100,000 women 400 0 90-109 < 90 110-125 126-139 ≥ 140 Fasting serum glucose (mg/ml) Jee SH et al, JAMA 2005

  44. Relation Between BMI and the RR of Type 2 DM, HTN, CHD, and Cholelithiasis Willett WC et al, N Eng J Med 1999

  45. Mortality from Cancer According to Body-Mass Index for U.S. Women The Cancer Prevention Study II, 1982-98 1,184,617 participants P < 0.05 for all cancer sites Reference category: BMI 18.5 - 24.9 Calle EE et al, N Engl J Med 2003

  46. Associations Between Anthropometric Measurements and Endometrial Cancer Risk Controls no. Cases no. OR 95% CI <0.01 1.0 p for trend <0.01 Xu WH et al, Am J Epidemiol 2005

  47. Obesity as a Medical Problem The OB/GYN evaluation • Risk factors • - Age • - FHX • - Blood pressure • - Oligo/anovulation • Anthropometric measurements • - BMI • - W/H ratio • Blood test • - CBC • - Lipid profile • - Glucose, insulin, GCT • - CRP

  48. Obesity as a Medical Problem The OB/GYN recommendations • Diet • Physical activity • Family physician • Medical treatment

  49. Thanks You for Your Attention

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