PCOS Polycystic Ovarian Syndrome Dr. Dian Ginsberg, M.D., - PowerPoint PPT Presentation

PCOS Polycystic Ovarian Syndrome Dr. Dian Ginsberg, M.D., F.A.C.O.G. Board Certified in Anti-Aging and Regenerative Medicine Fellow of the American Academy of Anti-Aging Medicine

Definition PC  O  S PC S polycystic ovarian syndrome 1 a common endocrine system disorder for women of reproductive age 2 may or may not have enlarged ovaries with multiple small cysts seen on an ultrasound exam 3 symptoms vary from woman to woman

Symptoms  Irregular Menses  Scant  Prolonged, heavy  Absent  Excess Androgen  Facial + Body hair  Acne  Greasy skin

More Symptoms (Indirect)  Abnormal insulin  Abnormal blood sugar  Large waist circumference  Abnormal cholesterol and lipoproteins  Infertility  Sleep apnea  Depression and anxiety

Stein-Leventhal Syndrome  Syndrome first described in 1935 by 2 gynecologists, Irving Stein and Michael Leventhal  Associated the presence of multiple ovarian cysts in patients with anovulation For a long time, that is where the focus of treatment was …  wedge resection  laparoscopic drilling of ovaries

Causes Exact cause is unknown unknown! Genetics  Often patients have a mother or a sister with PCOS Hormone Imbalance  Elevated androgens  Harder for ovaries to release a mature egg Insulin resistance  A change in how the cells of the body react to insulin Inflammation … The final frontier

Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis It is now clear that PCOS is often associated with profound insulin resistance as well as with defects in insulin secretion. -Dunaif, A. (1997) Endocrine Reviews . 18(6): 774-800 Ehrmann, David A. (2002) Insulin Resistance and Polycystic Ovary Syndrome. Current Diabetes Reports. 2(1): 71-76. Gonz á lez, Frank. et al. (2005) Reactive Oxygen Species-Induced Oxidative Stress in the Development of Insulin Resistance and Hyperandrogenism in Polycystic Ovary Syndrome. The Journal of Clinical Endocrinology &Metabolism . 19(1). Baillargeon, Jean-Patrice. Nestler, John. E. (2005) Polycystic Ovary Sydrome: A Syndrome of Ovarian Hypersensitivity to Insulin. The Journal of Clinical Endocrinology & Metabolism. 91(1).

Why is this important?  Understand the cause  Realize what implication diet has  How nutrient deficiencies can exacerbate condition  We can reverse this naturally, without OCPs

Where d does energy go? BRAIN LIVER MUSCLE FIBER ENERGY ENERGY Perform Stored physical Glycogen activity Adipose to store for = times of famine George Gilson, MD PhD.

How d do we process sugar and modulate energy? GLUCOSE ACETYL CoA INSULIN HMG CoA Reductase KREBS CYCLE CHOLESTEROL HORMONES BRAIN ENERGY FIGHT INFLAMMATION Antioxidant

Insulin Resistant Adipose Tissue: “ Metastatic Fat ” Increased Cholesterol Synthesis Pancreas Pancreas Adipose Adipose Tissue Tissue Increased Liver Enzymes Liver Liver Muscle Muscle Muscle no longer burns fat Increased serum well – “ marbling ” triglycerides/free fatty acids - George Gilson, MD PhD.

What causes insulin resistance?  Sugar  Too Many Carbohydrates – Simple Worse than Dense  Low Muscle Mass  Inflammation  Too much adipose tissue  Too many trans fats  Nutrient deficiency – Chromium, Zinc, Selenium  Chronic High Cortisol – Dysregulation  High Fructose Corn Syrup  Lack of Sleep

The Skinny on Fat  Not just a storage depot!  When the fat to lean muscle ratio becomes too large, fat becomes an inflammatory agent.  Enlarged fat cells  Recruits macrophages  Increases secretion of TNF α  Leaks fatty acids Gustofson, B. (2010) J. Atheroscler Thromb. Adipose Tissue, Inflammation and Atherosclerosis. 17(4): 332-41.

High Cholesterol – Good!  In 2005, Boston University researchers found a link between high total cholesterol and cognitive performance.  789 men, 1005 women  Free of dementia and stroke  Followed for 16-18 years  Cognitive tests ever 4-6 years

High Cholesterol – Good!  Results – Significant positive linear association between total cholesterol and measures of verbal fluency, attention/concentration, abstract reasoning, and a composite score measuring multiple cognitive domains. – Penelope K. Elias, et al., Psychosomatic Medicine 67, no. 1 (2005); 24-30

Cholesterol is not the problem!

Energy Balance Glucose molecules Down regulates Indicates increased energy production — Palmitate HNF4  SHBG  Free Testosterone

Hypothesis  What if chronic daily inflammation created by a toxic, 24/7 high stress, sugar dysregulated, high cortisol lifestyle could cause PCOS? Dale, PO. et al. (1992) Body weight, hyperinsulinemia, and gonadotropin levels in the polycystic ovarian syndrome: evidence of two distinct populations. Fertility and Sterility. 58(3): 487-491. DeUgarte, MD. et al. (2005) Prevalence of insulin resistance in the polycystic ovary syndrome using the homeostasis model assessment. Fertility and Sterility. 83(5): 1454- 1460. Gonz á lez, Frank. et al. (2005) Reactive Oxygen Species-Induced Oxidative Stress in the Development of Insulin Resistance and Hyperandrogenism in Polycystic Ovary Syndrome. The Journal of Clinical Endocrinology &Metabolism . 19(1).

Steroidal Hormone Principle Pathways Understanding pregnenolone steal, the preferential pathway under chronic stress.

Why d do P PCOS Adrenal DHEA gland patients have patients have high high estradiol? estradiol? Increased Fatty fatty tissue tissue Upregulation of aromatization Increased androgens Androstenedione aromatization Estrone Estrone Testosterone Testosterone aromatizatio Estradiol Estradiol n Upregulation of aromatization

Progesterone and Insulin  Progesterone acts on the pancreatic beta cells to decrease insulin production.  Progesterone inhibits insulin secretion by a membrane delimited, non-genomic action. Straub, SG, et al. Biosci Rep 2001; 21:653-666.  Patients in Helene Leonetti ’ s study of progesterone cream and vasomotor symptoms who had high triglycerides (TG) at inception, had lower TG after one year of Pg cream, 20 mg qd  There are widespread, but anecdotal reports of improvement in PCOS with topical progesterone (lower androgens, resumption of regular menses)  Bottom line: Progeste Progestero rone e appears appears to to ameliora ameliorate te problems problems associated with increased insulin. In r reasonable doses, there is n no e evidence that progesterone causes or w worsens insulin resistance.

Lab Tests Serum Salivary  Cardio Metabolic Panel  Estradiol  FSH  Estrone  Fasting Insulin  Estriol  HbA 1C  Progesterone  SHBG  Testosterone  Free Testosterone  Total Testosterone

How can we reverse PCOS?  Pharmacological aids  Diet – Nutrition  Exercise  Supplements

Pharmacological Aids 1. OCP 2. Metformin 3. Progesterone 4. Clomiphene Citrate 5. Spironolactone

 NUTRITION  EXERCISE  SUPPLEMENTATION

Nutrition  Stabilize Blood Sugar -Anti-inflammatory/Real Food Diet -Sugar Elimination Diet  12 Hour Fast, 5 pm – 5 am 4 days a week -Biosphere studies  Minimize Fast Food  Minimize Eating Out - 500 more calories are consumed - More bad carbohydrates are consumed

Exercise 85% of blood sugar goes to Skeletal muscle  Resistance training  High Intensity Interval Exercise - Peak 8 - More After-Burn

Supplements Designs For Health  Ovaben  Metabolic Synergy  Chromium Synergy  Ultimate Antiox To aid in diet transition …  Paleo Cleanse Plus Detox

Conclusion  PCOS is a disease of … • Insulin resistance • Blood sugar dysregulation • Nutrient deficiencies • Heredity • Inflammation