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 PCOS 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. González, 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

• f 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

ENERGY ENERGY BRAIN LIVER Stored Glycogen =

Adipose to store for times of famine

MUSCLE FIBER Perform physical activity

George Gilson, MD PhD.

Where d does energy go?

GLUCOSE ACETYL CoA KREBS CYCLE INSULIN

HMG CoA Reductase

CHOLESTEROL

HORMONES FIGHT INFLAMMATION Antioxidant BRAIN

ENERGY How d do we process sugar and modulate energy?

Insulin Resistant Adipose Tissue: “Metastatic Fat”

Pancreas Pancreas Adipose Adipose Tissue Tissue Muscle Muscle Liver Liver

Increased Cholesterol Synthesis Increased Liver Enzymes

Muscle no longer burns fat well – “marbling” Increased serum 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 TNFα  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 Palmitate

Indicates increased energy production

HNF4 —

 SHBG  Free Testosterone

Down regulates

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. González, 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.

Adrenal gland DHEA Fatty tissue Increased fatty tissue Increased androgens Androstenedione Testosterone Testosterone

aromatizatio n

Upregulation of aromatization Estradiol Estradiol

aromatization

Upregulation of aromatization Estrone Estrone

Why d do P PCOS patients patients have have high high estradiol? estradiol?

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

• ne 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

 Cardio Metabolic Panel  FSH  Fasting Insulin  HbA1C  SHBG  Free Testosterone  Total Testosterone

Salivary

 Estradiol  Estrone  Estriol  Progesterone  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