Rotterdam Criteria 9/30/2017. A Changing Paradigm in PCOS. Polycystic Ovary Syndrome - Is the Cardiometabolic Risk Increased After Menopause?

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1 Disclosure Polycystic Ovary Syndrome - Is the Cardiometabolic Risk Increased After Menopause? Fractyl laboratories, Inc Anuja Dokras, MD., Ph.D. Professor of Obstetrics and Gynecology Director PENN PCOS Program University of Pennsylvania Rotterdam Criteria A Changing Paradigm in PCOS 1. Oligo-ovulation or anovulation 2. Clinical or biochemical signs of hyperandrogenism 3. Polycystic ovaries on ultrasound any two of above three (exclusion of TSH, Prolactin, 17 OH progesterone, DHEAS) Most common endocrine disorder in reproductive age 6-15% Human Reproduction Vol.19, No.1 pp , 2004 Fertil Steril 81 (2004), pp Human Reproduction 27:14-24 (2012) 1

2 PCOS in the Perimenopause PCOS n=681, controls n=230 % women with ovulatory cycles increased from 52 to 85% Age in years Carmina et al, 2012, Obstetrics and Gynecology Pinola et al, JCEM, 2015 Infertility Hirsuitism Oligomenorrhea Preeclampsia PCOS OBESITY Endometrial hyperplasia Wiser et al, RBO, 2013 Glucose intolerance Hyperlipidemia Cardiovascular disease risk 2

3 Obesity in PCOS Obesity in PCOS Adolescents OR 2.77 (95%CI ) Lin et al, HRU, 2012 Hickey et al, 2011, Hum Reprod Obesity Not Part of the Diagnosis of PCOS Abdominal Adiposity in PCOS Prevalence of abdominal adiposity in normal and overweight women Yildiz et al, JCEM, 2008 Teede et al, Obesity, 2013 Jovanovic et al. Fert Steril 2010 Aug 3

4 PCOS Impaired Glucose Tolerance Risk of Gestational Diabetes OR 2.48 ( ) Prevalence 6-35% Moran et al, 2010, Hum Reprod OR 3.58 (95% CI ) Qin et al, 2013 PCOS - Type 2 Diabetes Diabetes Risk Independent of Age and BMI HR 3.07 (95% CI ) OR 4.43 ( ) Prevalence 2-10% Moran et al, 2010, Hum Reprod Morgan et al, 2012, JCEM 4

5 Dyslipidemia - Triglycerides Dyslipidemia - HDL-C Mean difference 26.6mg/dl (95%CI ) Only 3 studies were TG >150mg/dl HDL-C is lower in PCOS by 6.41mg/dl (95%CI ) Reverse Cholesterol Transport & Efflux Cholesterol Efflux Capacity & Coronary Artery Disease Khera et al, NEJM,

6 Cholesterol Efflux Capacity and Incident Heart Disease Dallas Heart Study, According to Models Based on High-Density Lipoprotein (HDL) Cholesterol Level and Cholesterol Efflux Capacity. Rohatgi A et al. N Engl J Med 2014;371: Roe et al, 2014, JCEM Women with PCOS had an 11% decrease in normalized cholesterol efflux capacity Dyslipidemia - LDL-C Lipid Profile Overview LDL-C levels were higher by 12.6mg/dl (%95 CI ) 6

7 Lipoprotein Subclass Particles - NMR Spectroscopy Risk of Metabolic Syndrome **p<0.01, *p<0.05 Roe et al, 2014, JCEM OR 2.88 (95% CI ) Moran et al, 2010, Hum Reprod Androgen Levels and Cardiometabolic Risk Factors Metabolic Syndrome in PCOS phenotypes PCOS n=170 Normal n=170 Fauser et al, Hum Reprod

8 Impact of Race on Metabolic Risk PCOS US White US Black India Brazil Finland Norway Is PCOS a Lifetime Metabolic Disorder? * n Metabolic Syndrome 52 (28%) 52 (51.5%) BMI criterion (47.9%) (73.3%) TG criterion (20.4%) (9.9%) BP criterion (36.6%) (58.4%) Glucose criterion (11.8%) (21.8%) HDL criterion (41.4%) (71.3%) 65 (29.6%) 82 (37.3%) 59 (26.8%) 37 (16.8%) 63 (28.6%) 214 (97.3%) 70 (29.4%) 26 (27.7%) 106 (26.5%) (42%) (47.9%) (47%) (26.9%) (11.7%) (20.2%) (34.9%) (36.2%) (45.6%) (17.7%) 16 (17%) (26.1%) (59.7%) (43.6%) (56.1%) * * ** * * * * * Chan et al, AJOG, 2017 Human Reprod 2012 Sprung et al, Clin Endo

9 Coronary Artery Calcification (CAC) & PCOS Does the CVD Risk Persist in the Menopause? Author Year Shroff, 2007 Christian, 2003 Talbott, 2004 Talbott, 2008 Chang, 2011 Calderon-Margalit 2014 n 24 cases controls 36 cases 71 controls 61 cases 85 controls 149 cases 166 controls 144 PCOS 170 controls 55 PCOS 668 controls Study Population/ Study Design Outcome Measure/ Results Obese, Prevalence of CAC (>0) premenopausal OR=5.5 (1.03, 29.45) [cross-sectional] p<0.03 Premenopausal, Prevalence of CAC (>0) age OR=1.99 (0.68,5.82) [cross-sectional] p=0.21 (NS) BMI < 35 [prospective] Age Prevalence of CAC (>0) OR=2.31 (1.00, 5.33) p=0.049 All BMI Prevalence of CAC >10 [cross-sectional] OR=1.90 (1.04, 3.48) p=0.037 Age 37-45years Cross sectional Prevalence of CAC (>10) PCOS 5.4% controls 6.3% p=0.74 Mean age 45.3 Prevalence of CAC (>0) OR 2.7 ( ) 33 Coronary Artery Disease Timeline Change in Metabolic Risk over 20 years Diabetes Hypertension A, Diabetes prevalence in 2008 and 1987; B, prevalence of treated hypertension in 2008 and *, P < 0.05; **, P < 0.01; ***, P < Schmidt J et al. JCEM 2011;96:

10 Does the CVD Risk Persist in the Menopause? Perimenopause and Metabolic Syndrome SWAN n=2543, mean age 45.8years Wang et al, 2010 Obstet Gynecol Polotsky et al, 2012, JCEM Metabolic Risk after Menopause Metsyn Stroke MI Obesity and smoking were strongest predictors Patel et al, Endo care,

11 Non fatal stroke Non fatal CHD Hart et al, 2015, JCEM Oncotarget,

12 Recommendations JCEM, May 2010 Acknowledgements PENN Andrea Roe Jessica Chan Jennifer Hillman Laura Cooney Hershey Richard Legro NHLBI Nehal Mehta Martin Playford AEPCOS Society Terhi Piltonen Sujata Kar Ezster Vanky Gustavo Marciel 12

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