1. Coagulation / Fibrinolytic Factors in PCOS

2. The Alternative Hypothesis : Conversely, PCOS women may be protected from later life onset of CHD by the altered hormonal profile that includes increased estrone from peripheral conversion of androgen in adipose and other tissue Conversely, PCOS women may be protected from later life onset of CHD by the altered hormonal profile that includes increased estrone from peripheral conversion of androgen in adipose and other tissue This profile could be responsible for the inconsistencies observed between investigations of risk factors in PCOS and the McKeigue retrospective follow-up of mortality This profile could be responsible for the inconsistencies observed between investigations of risk factors in PCOS and the McKeigue retrospective follow-up of mortality

3. Carotid IMT in PCOS Click for larger picture

4. Hemodynamic Measures in PCOS Click for larger picture

5. Correlation of Various Subclinical CHD Measures Click for larger picture

6. Interaction of PCOS and Age in IMT Click for larger picture

7. Lancet 1997; 350 (suppl I):15 Click for larger picture

8. Lancet 1997;350:21 Click for larger picture

9. Introduction Polycystic Ovary Syndrome (PCOS) is associated with an increased prevalence of cardiovascular disease risk factors (Wild, !988; Slowinska-Srezednicka, 1991; Talbott and Guzick, 1995) Polycystic Ovary Syndrome (PCOS) is associated with an increased prevalence of cardiovascular disease risk factors (Wild, !988; Slowinska-Srezednicka, 1991; Talbott and Guzick, 1995) PCOS women have evidence of metabolic derangements similar to Syndrome X (  LDLc,  HDLc,  triglycerides,  insulin,  central adiposity, hypertension, and Type II diabetes) PCOS women have evidence of metabolic derangements similar to Syndrome X (  LDLc,  HDLc,  triglycerides,  insulin,  central adiposity, hypertension, and Type II diabetes)

10. Introduction (cont.) Since LDLc is an important determinant of atherosclerosis in women, the increased LDLc levels seen in younger PCOS suggests that these women may be at increased risk for subclinical and clinical atherosclerosis at an earlier age than the general female population. Since LDLc is an important determinant of atherosclerosis in women, the increased LDLc levels seen in younger PCOS suggests that these women may be at increased risk for subclinical and clinical atherosclerosis at an earlier age than the general female population.

11. Characteristics of PCOS Chronic Anovulation Chronic Anovulation Hyperandrogenism (Elevated Testosterone) Hyperandrogenism (Elevated Testosterone) Hirsutism Hirsutism Obesity Insulin Resistance Infertility Affects 5 to 10 percent of US Women, and the condition is marked by:

12. Research Questions Do women with PCOS have evidence of subclinical atherosclerosis as demonstrated by an increase in carotid intima-media thickness? Do women with PCOS have evidence of subclinical atherosclerosis as demonstrated by an increase in carotid intima-media thickness? If so, can the increase in carotid intima- media thickness be linked to the various cardiovascular risk factors seen in PCOS women? If so, can the increase in carotid intima- media thickness be linked to the various cardiovascular risk factors seen in PCOS women?

13. Current Study Population Women participating in Phase II of the Cardiovascular Health and Risk Measurement Study (CHARM, 1997-98) Women participating in Phase II of the Cardiovascular Health and Risk Measurement Study (CHARM, 1997-98) Cases and controls represent the initial 1/3 of the women recruited for Phase II participation (46 Cases with PCOS and 59 Controls) Cases and controls represent the initial 1/3 of the women recruited for Phase II participation (46 Cases with PCOS and 59 Controls) PCOS is defined as chronic anovulation with clinical or biochemical evidence of hyperandrogenism without other identified causes PCOS is defined as chronic anovulation with clinical or biochemical evidence of hyperandrogenism without other identified causes

14. Selected Clinical and Lifestyle Factors in PCOS Cases and Controls- Preliminary Data VARIABLES (1993-94 Data) CASES (n=46) CONTROLS (n=59) * p .05 ** p .001

15. Selected Lipid and Hormone Levels in PCOS Cases and Controls- Preliminary Data VARIABLES (1993-4 Data) CASES (n=46) CONTROLS (n=59) * p .05 ** p .001

16. Differences in CAI in PCOS Cases vs. Controls by Age * p = 0.004 ** p = 0.021

17. Analysis of CAI Predictors in PCOS Cases and Controls Employed a multiple linear regression model with forced entry of predictors Employed a multiple linear regression model with forced entry of predictors Dependent variable: CAI Dependent variable: CAI Independent variables in the fixed model included: age, BMI, DBP, smoking and hormone use Independent variables in the fixed model included: age, BMI, DBP, smoking and hormone use Lipids and insulin were added separately to the fixed model to determine the change in R 2 Lipids and insulin were added separately to the fixed model to determine the change in R 2 PCOS status was added to the final model to evaluate attenuation of the relationships by case status PCOS status was added to the final model to evaluate attenuation of the relationships by case status

18. Regression - Fixed Model Predictors P-value of Predictors Model Adjusted R 2 Model Significance Forced entry of CVD risk factors: Dependent variable = CAI

19. Regression - Lipids and Insulin Predictors P-value of Predictors Model Adjusted R 2 Model Significance Individual entry of lipids and insulin to CVD fixed model: Dependent Variable = CAI

20. Regression - PCOS Status Predictors P-value of Predictors Model Adjusted R 2 Model Significance Entry of PCOS status to CVD fixed model including LDL: Dependent variable = CAI

21. Conclusions PCOS women demonstrate increased carotid intima-media thickness compared to age matched controls at a relatively young age (< 40 years). PCOS women demonstrate increased carotid intima-media thickness compared to age matched controls at a relatively young age (< 40 years). However, the most striking evidence of subclinical atherosclerosis in PCOS appears in the  40 year age group. However, the most striking evidence of subclinical atherosclerosis in PCOS appears in the  40 year age group.

22. Conclusions (cont.) Age, BMI, and diastolic blood pressure are significant predictors of CAI in women Age, BMI, and diastolic blood pressure are significant predictors of CAI in women Atherosclerotic potential in the younger PCOS women is mediated by in part by higher LDLc levels and increased BMI. Atherosclerotic potential in the younger PCOS women is mediated by in part by higher LDLc levels and increased BMI.

23. Implications Since abnormal LDLc levels and increased BMI appear to contribute to subclinical atherosclerosis in PCOS, interventions directed at decreasing LDLc and controlling weight in younger PCOS women may improve the later-life cardiovascular risk profile in this high risk population. Since abnormal LDLc levels and increased BMI appear to contribute to subclinical atherosclerosis in PCOS, interventions directed at decreasing LDLc and controlling weight in younger PCOS women may improve the later-life cardiovascular risk profile in this high risk population.

24. Evelyn O. Talbott A544 Crabtree Hall Pittsburg, PA (412) 624-3074