1. Prevention & Management of PCOS Rashmi Kudesia, M.D. M.Sc. Icahn School of Medicine at Mount Sinai November 18, 2015

2. Objectives To highlight the dilemmas in PCOS management in the primary care setting To address barriers to comprehensive PCOS care for the female through the lifecourse

3. PCOS Lifecourse Birth Infancy & Childhood Adolescence Reproductive years Pregnancy Menopause & Beyond

4. Management of PCOS Most important goals – Avoiding over- and under-diagnosis – Counseling – Prioritize specific aspects affecting health and quality of life for each individual – Optimize fertility and pregnancy (prevention) – Minimize cardiometabolic sequelae

5. Diagnosis Dilemma 1: What are the best diagnostic criteria? – NIH – Rotterdam – Androgen Excess

6. Diagnosis – Dilemma 1 Common Pitfalls – Not adhering to strict criteria Gestalt impressions Applying sonographic criteria – Failure to recognize lean PCOS women – Failure to recognize racial & ethnic variations in phenotype and risk profile

7. Diagnosis Dilemma 2: What is the best approach to the child or adolescent with suspected PCOS? Pubertal symptoms overlap with PCOS criteria – Irregular menstruation – Acne – Weight gain

8. Diagnosis – Dilemma 2 Common Pitfalls: – Labeling an adolescent too early – And yet: failure to identify a child who has multiple risk factors – In a girl with suspected PCOS, failure to identify risk and provide counseling regarding: How the diagnosis might be confirmed Broad strokes of what diagnosis would mean Allay concerns and provide reassurance

9. Diagnosis – Dilemma 2 Routine fertility counseling for adolescents Teens with PCOS have greater fertility concerns than peers without PCOS

10. Counseling Dilemma 3: What are the most salient points in patient counseling once the diagnosis is established? The quality of PCOS care provided is largely determined by the quality of patient counseling

11. Counseling Common Pitfalls: – Only addressing patient’s acute concerns – Failure to counter misinformation from non- medical sources – Failure to explain which medications address which aspects of PCOS management

12. Lifelong Management Dilemma 4: In the era of personalized medicine, how best can one individualize PCOS care? OR, how can one take a patient-centered approach to the care of PCOS women?

13. Lifelong Management PCOSQ Questionnaire* helps identify which domains are most affecting current QOL – Emotions – Body hair – Weight – Infertility – Menstrual problems *Cronin et al JCEM 1998

14. Lifelong Management Consensus Guidelines from Endocrine Society (2010): – All PCOS women be assessed for CVD risk – BP, waist circumference & BMI at every visit – Complete lipid profile (target LDL) Reassess every 2 years or sooner if weight gain – 2h 75g OGTT in women with BMI>30 or in lean women with age>40, h/o GDM, FH of T2DM Reassess every 2 years or sooner if new risk factors A1c has promise – Assessment for depression, anxiety, QOL

15. Lifelong Management Common Pitfalls: – Failure to recognize shifting priorities – Discomfort with lifestyle counseling – Time limitations – Failure to emphasize or provide multi-disciplinary care with a team-based approach: Nutrition Exercise Bariatric surgery Endocrinology & cardiology

16. Lifelong Management Common Pitfalls: – Over-reliance on metformin

17. Lifelong Management Potential roles of metformin: – A meta-analysis of 31 trials concluded that metformin increases insulin sensitivity up to 20%, decreases weight and BMI by 3–5%, decreases fasting glucose by about 5%, and increases HDL-cholesterol and decreases triglycerides by approximately 10% in patients Weight loss enhances the effects of metformin Appears to decrease levels of C-reactive protein (low level chronic inflammation) May improve vascular endothelial function and coronary flow rate

18. Lifelong Management Common Pitfalls: – Over-reliance on metformin – Specific Indications for its usage: Prevent or slow progression to type 2 DM and long- term risks for cardiovascular disease) Women with IGT or DM, those with evidence of severe insulin resistance (acanthosis nigricans) and women having features of metabolic syndrome (central obesity, HTN, dyslipidemia) – Does not replace lifestyle modifications!

19. Lifelong Management Dilemma 5: How best to optimize fertility and pregnancy? Is there potential for prevention in the next generation?

20. Lifelong Management Common Pitfalls: – Failure to optimize health prior to conception Requires a detailed plan – Failure to select the most effective fertility treatment Clomiphene more effective (22.5%) than metformin monotherapy (7.2%) for live birth (Legro et al, NEJM 2007) PPCOS II demonstrated a rate ratio for live birth 1.44 [95% CI 1.1,1.9] with letrozole rather than clomiphene (Legro et al, NEJM 2014) Avoiding gonadotropins in non-IVF settings

21. Lifelong Management Common Pitfalls: – Failure to provide preemptive counseling regarding the elevated risks to PCOS women: Excessive pregnancy weight gain Gestational diabetes Gestational hypertension/preeclampsia Preterm labor Increased C-section rate Abnormal birthweight and impact on ultimate cardiometabolic health of their child

22. Lifelong Management Dilemma 6: How best to mitigate cardiometabolic sequelae for the woman with PCOS? What do we know about the risk?

23. Lifelong Management The impact of PCOS by time of menopausal transition is still poorly understood, however: *Kudesia et al Semin Repro Med 2014

24. Lifelong Management Thus, the overarching goals could be: – Stave off development of cardiometabolic co- morbidities in middle age – Emphasize lifestyle modification – Prevent or treat obesity – Such that, PCOS women enter post-menopause at similar risks to non-PCOS women

25. Conclusions The comprehensive management of PCOS requires: – A patient-centered approach – Significant time dedicated to thorough education and counseling – A network of referrals and local resources – Remaining up-to-date on newest advances in the literature – Improvement in health of the PCOS woman in pregnancy could help “prevent” disease in the next generation