Diet & PCOS

1. Diet & PCOS presented by Martha McKittrick RD, CDE Website: MarthaMcKittrickNutrition.comBlog: CityGirlBites.com Contact: mmckittnyc@gmail.comTwitter: @citygirlbites

2. Goals of Discussion • Provide background information on PCOS • Discuss the role of insulin resistance in PCOS • Diagnosing & treating PCOS • Provide the RD with guidance for lifestyle education for the patient with PCOS

4. Part One: Background Information on PCOS

5. PCOS was first identified by Stein & Leventhal in 1935 • They described a group of women who were obese and infertile, with enlarged ovaries and multiple cysts • Few of these original features are now considered consistent findings in PCOS

6. More Common Than You Think • PCOS is possibly the most common hormone abnormality that exists! • Up to 10% of all females have PCOS • 6 million American women have PCOS • #1 cause of anovulatory infertility

7. What is PCOS ?????

8. What is PCOS? • PCOS is a complex hormonal disturbance that affects the entire body • It has numerous implications for general health and well being • It can affect all females – from adolescence to post menopause • Accounts for ~ $40 billion yearly in the U.S. Dr. Azziz

9. Statistics • 80%+ show PCO on ultrasound (but having PCO does not mean PCOS!) • 40 – 80% will have a fertility problem • 60 - 80% hirsuitism • 40 - 70% scalp hair thinning (alopecia)

10. Statistics • 75 - 90% irregular menstrual periods • 40 - 60% acne • 70% - hyperlipidemia (often low HDL, high LDL)* • 10% - acanthosisnigricans * Legro RS, et al, Am. J. Med. 111, 607-613 (2001).

11. Acanthosis nigricans Hirsutism Alopecia

12. Health Risks That May Be Associated with PCOS • Insulin resistance (up to 80% of women with PCOS) • Metabolic syndrome (~ 1 in 3 women with PCOS) • Increased risk of diabetes/prediabetes (> 50% will get this by age 40) • Obesity (~ 50% of women with PCOS)

13. Health Risks That May Be Associated with PCOS • Endometrial Cancer • Obstructive sleep apnea • HTN • Mood disorders

14. Mood Disorders and PCOS • Increased incidence of mood disorders (i.e. depression or anxiety, or to engage in bingeing). Certain features of PCOS may contribute to the increased risk of mood disorders. For example: • Abnormal levels of androgens and other hormones are related to mood disorders • Obesity is linked to mood disorders as well as to abnormal hormone levels. Studies show that the risk of mood disorders is even greater among women with PCOS who are also obese • http://www.nichd.nih.gov/health/topics/PCOS/conditioninfo/Pages/default.aspx

15. Health Risks That May Be Associated with PCOS • Heart disease • Inflammation • Pregnancy complications

16. Consensus Statement by the Androgen Excess PCOS Society re: Cardiovascular Risk &Prevention of Cardiovascular Dz in Women with PCOS: Conclusions: Women with PCOS • Obesity, Cig. Smoking, Dyslipidemia, HTN, IGT, Subclinical Vascular Dz = At risk • Whereas those with metabolic syndrome and/or type2 DM = High risk http://www.pcoschallenge.org/symposium/2014-presentations/pcos-preventing-cardiovascular-disease-gregorry-pokrywka.pdf

17. Lean PCOS and Heart Disease Risk? • The absence of the important cardiometabolicrisk factor represented by obesity often misguides clinicians when lean PCOS patients are evaluated • Actually, IR even in lean women represents an important risk factor for glycometabolic and cardiovascular sequelae http://www.sciencedirect.com/science/article/pii/S001502821400315X

18. Inflammation and PCOS • Research suggests that PCOS associated with long-term, low-grade inflammation polycystic ovaries to produce androgens • Inflammation is associated with hardened arteries major risk factor for heart attack & stroke. • ? inflammation results from obesity and metabolic dysfunction or whether it’s an independent symptom of the disorder

19. PCOS & Pregnancy Complications • Spontaneous Abortions- increased in high BMI/PCOS pts • Impaired Glucose Tolerance • Gestational Diabetes • HTN • Small for Gestational Age http://www.pcoschallenge.org/symposium/2014- presentations/pcos-improving-feritliy-mark-perloe.pdf

20. Etiology – not 100% Clear Likely a Genetic & Environmental component

21. Etiology • Genetic. Research has found subtle changes in insulin receptor gene which may alter its function in the ovaries. It is known that insulin is capable of stimulating the ovaries to produce testosterone which causes many of the symptoms of PCOS • Combination effect of pituitary lutenizing hormone (LH) & insulin on stimulating the ovary to produce excessive male hormone (androgens). Obesity magnifies this. • Intrinsic enzymatic abnormalities have been demonstrated in the ovaries as well as the adrenal glands

22. Part Two: Role of Insulin Resistance in PCOS

23. What is Insulin Resistance? • IR is a condition where cells do not adequately respond to insulin • IR appears to result from several defects in the relationships among insulin, its receptor, and the genome • IR increases with age and is aggravated by obesity • IR is exacerbated at puberty and in pregnancy

24. Insulin Resistance http://www.pcospregnancy.net/insulin-resistance.htm

25. Effects of IR & Hyperinsulinemia and/or Visceral Obesity • Stimulation of ovarian and adrenal androgen production • Stimulation of pituitary luteinizing hormone (LH) secretion • Inhibition of hepatic sex hormone binding globulin (SHBG) production, leading to a reduced total testosterone in men and increased free testosterone in women • Increased risk of miscarriage

26. Effects… continued • Increased BP • Low HDL, high TG • Increased apolipoprotein B levels • Small dense LDL cholesterol particles • Increased fibrinogen levels • Increased C reactive protein and other inflammatory markers • Increased thickening and pigmentation of skin (acanthosis nigricans) • Premature atherosclerosis

27. Insulin Resistance in PCOS Can also lead to • Increased food cravings • Weight gain and/or difficulty losing weight

28. Diagnosing Insulin Resistance • Diagnosing Insulin Resistance is tricky!! • Insulin levels vary throughout the day • Normal range is up to 18, however many experts feel any number over 8 is high

29. Labs: IR / Glucose Intolerance Test Interpretation Fasting insulin 8-14 mU/L mild IR (not very accurate test!)> 14-18 moderate – severe Fasting glucose/insulin <4.5 (< 7.0 in adolescents) ratio Oral glucose tolerance Normal: 2 hr < 140 test Impaired: 2 hr 140-199 Diabetes: 2 hour glucose ≥200

30. Labs: IR / Glucose Intolerance • HOMA (Homeostasis Model Assessment) < 2 = normal, 2.2 - 3 = moderate, > 3 = severe • Hyperinsulinaemic glucose clamp “gold standard” – but rarely used • Other clues of IR: Elevated LH/FSH ratio Low SHBG Low HDL and/or TG Upper-body obesity Acanthosis nigricans BMI > 25 (or waist circumference > 35” in women) Fam hx of type 2 diabetes or glucose intolerance Age > 40

31. Do Lean Women with PCOS Have Insulin Resistance?

32. Insulin Resistance in Lean PCOS • Study: 72% of overweight/obese pts with PCOS were IR compared to 26% lean • Hypothesized that lean PCOS pts could be affected by an “intrinsic” form of IR whereas obese patients have a combined form of IR due in part to the syndrome itself and in part to the weight excess. In fact, lean PCOS patients could be considered to be a “unique model” to study the natural history of IR per se, because the IR occurs in the presence of normal glucose http://www.sciencedirect.com/science/article/pii/S001502821400315X

33. Non-Obese PCOS Patients • 10.3% of lean PCOS have IGT and 1.5% have diabetes. In long-term f/u, 16% of women who had been treated for PCOS 20–30 yrs. earlier had developed DM by menopause. The etiology of the insulin resistance is unclear, but suppression of the excess androgens does not alter the insulin resistance • Even in lean PCOS, a higher waist-to-hip ratio is seen in those with PCOS compared to those without PCOS. This is supported by the higher proportion of visceral adiposity measured by ultrasound in lean PCOS patients compared to weight-matched control subjects • Obese women with PCOS have greater insulin resistance than weight-matched control subjects or lean PCOS subjectshttp://clinical.diabetesjournals.org/content/21/4/154.full

34. Part Three : Diagnosing and Treating PCOS

35. Diagnosing PCOS • Symptoms and physical exam • Hormonal testing • Ultrasound

36. Diagnosing PCOS Much controversy on what the proper diagnostic criteria are! Using the Rotterdam criteria, a woman with 2 of the 3 cardinal features that characterize PCOS may have the condition: • Hyperandrogenism (androgen excess) based on: -sx: acne, excessive hirsutism or male-patternhair loss -elevated circulating levels of androgens (usually testosterone) • Ovulatory dysfunction – can be manifested as oligomenorrhea or infrequent menstruation • Small cysts on the ovaries as seen on ultrasound. Legro BMC Medicine (2015) 13:64

37. Polycystic Ovaries http://womenshealth.gov/publications/our-publications/fact-sheet/polycystic-ovary-syndrome.html#j

38. Goals of Treatment Individualization is essential • Regulation of cycle • Promote weight loss • Correction of metabolic abnormalities - Cholesterol, glucose, insulin resistance, blood sugar, HTN • Decrease androgens - Skin, hair • Improve Fertility • Improve overall well-being

39. Treatment • Traditional: the individual symptoms were treated • BCP, anti-androgens, fertility treatments • More recent: targets insulin resistance as well as the individual symptoms • Traditional treatments as above as well as weight loss/exercise and insulin sensitizing agents (ISA)

40. Metformin: Insulin SensitizerBrand names Glucophage, Glucophage XR, Fortamet, Riomet, Glumetza, and others • Lowers blood glucose • Slows release of glucose from liver • Decreases insulin resistance in muscle • Lowers androgen and insulin levels • May lower LDL • May aid in weight loss • Off label usage in PCOS • Helps overweight and normal weight women achieve ovulation

41. Metformin Dosing & Safety Info • Gastrointestinal intolerance in 30% (take with meal) • Contraindications: - Creatinine ≥1.4 mg/dL (for women)- Liver disease (or risk thereof: alcohol abuse/binge drinking)- Other risks for lactic acidosis: pulmonary disease, congestive heart failure • Dosages range from 500-1000 mg bid. Start slow!! • May need B12 supplement

42. Efffects of Metformin on Fertility • Has been shown to restore regular menstruation in > 90% amenorrheic adolescents, restoring ovulation in 80% • More effective at restoring ovulation than clomiphene • Potentiates the effect of clomiphene • Taken during the 1st trimester, reduces miscarriage rate by 80% However – not every women needs Metformin!

43. First Step in Treatment… Diet & Exercise!!! Benefits Include: • Increased regularity of menstrual cycles • Decreased levels of androgens • Improvement in lipid levels • Decreased risk of diabetes • Improves insulin sensitivity

44. Part Four: LifestyleCounseling Tips- exercise- nutrition- counseling session - practical tips

45. Which is best? Cardio? Weight training ? Movement ? HIIT?

46. How Exercise Improves Insulin Sensitivity - Enhances both GLUT4-dependent and hypoxia-dependent glucose transport in skeletal muscle - Increases skeletal muscle vascularization, mitochondrial neobiogenesis and eventually tissue mass - Repartitions intracellular fat, thereby improving its utilization - Fat mass loss Physical Activity and Insulin Sensitivity The RISC Study Diabetes. 2008 Oct; 57(10): http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2551669/

48. Aerobic Exercise • Aerobic exercise increases insulin sensitivity (especially in skeletal muscle) from ~ 25-50% in all ages, gender, body weights

49. Resistance Training • A systemic review of 20 studies found that supervised resistance training improved glycemic control and insulin sensitivity in a wide variety of study groups *however this review showed that RT compliance and glycemic control are generally less without supervision http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4129661/#R278

50. High-Intensity Interval Training HIIT demonstrates improved insulin sensitivity http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4129661/#R278