Metabolic Syndrome InPolycystic Ovarian Syndrome

Patients

Presented By: Brittany Atkins

What is Polycystic Ovarian Syndrome?

• Common disorder of women of reproductive age

• Uniform definition does not exist!

• Belief that PCOS should be defined by 1)ovulatory dysfunction 2) hyperandrongenism 3) exclusion of other disorders

Pathophysiology of PCOS

• Etiology Unknown• Evidence supports the hypothesis that decreased

peripheral insulin sensitivity and consequent hyperinsulinemia are pivotal in the pathogenesis of PCOS

• Evidence of autosomal transmission related to strong familial clustering

• Possible hypothalamic Defect• A post-receptor defect in adipose tissue has been

identified

Pathophysiology of PCOS

• Post Receptor Defect

• Insulin Resistance

Pathophysiology of PCOS

• Suggestion of the presence of a hypothalamic defect

• Elevated LH levels

• Hyperandrogenism

• Anovulation

How PCOS May Present in Patients

Endocrine Abnormalities

• Elevated luteinizing hormone concentration with normal follicle stimulating hormone concentration

• Increased testosterone activity (often expressed as raised free androgen index)

• Insulin Resistance with compensatory hyperinsulinemia

How PCOS May Present in Patients

Clinical Features:• Acanthosis Nigricans• Acne• Alopecia• Amenorrhea, oligomenorrhea, or dysfunctional

uterine bleeding• Anovulatory infertility• Central Obesity • Hirsutism

How PCOS May Present in Patients

How PCOS May Present in Patients

Other:

Ultrasonographic evidence of polycystic ovaries

Diagnosing PCOS

1. Symptoms 2. Ultrasound Examination Positive = diagnosis Confirmed

3. Biochemical Examinations Negative

elevated serum testosterone elevated free androgen index elevated LH concentrations Fasting glucose:insulin <4.5

INSULIN RESISTANCE!!!

• Insulin Resistance being the key pathogenic factor in PCOS, it also appears to play a pathogenic role in the metabolic syndrome!!!

• Metabolic syndrome is more prevalent in women with PCOS then in the general U.S. population

• One study found that the prevalence of Metabolic syndrome in women with PCOS was 43%

Metabolic SyndromeNCEP ATP III

Hypertension Current antihypertensive therapy and/or BP>130/85mmHg

Dyslipidemia Plasma Triglyceride level >150mg/dl and/or HDL level <50 mg/dl

Obesity Waist Circumference >88cm

Glucose Fasting Blood Glucose level >110mg/dl

Requirements for Diagnosis Any 3 of the above disorders

Important!

• Recognize that PCOS patients are at a high risk for developing metabolic syndrome

• Take measures to delay or arrest metabolic sequelae

Cardiovascular Disease

• PCOS patients have a 7-fold increased risk for a myocardial infarction

• PCOS patients have lowered HDL levels and increased LDL levels

Cardiovascular Disease

• PCOS patients have an increased activity of hepatic lipase

• Altered lipolytic response to insulin

• Impaired fibrinolytic activity due to increased circulatory levels of PAI-1

Type 2 Diabetes

• Metabolic syndrome population have an increased prevalence of glucose intolerance

• Increased risk for type 2 diabetes

• In presence of insulin resistance pancreatic b cell insulin secretion increases in a compensatory fashion

• Type 2 diabetes develops when the compensatory increase is no longer sufficient to maintain euglycemia

Current Treatments

• Lifestyle Modification – Physical exercise

– Altered dietary composition

• Weight Loss– Low fat

– Low Carbohydrate

Current Treatments

Insulin Sensitizing Agent– Biguanide (metformin)

– Thiazolidinediones (Troglitazone, pioglitazone, rosiglitazone)

Weight Loss Medications– Phentermine

– Sibutramine and Orlistat

Conclusion

• PCOS is a commonly encountered endocrinopathy in women of reproductive age

• Providers need to appreciate that the syndrome is associated with significant morbidity in terms of reproductive as well as nonreproductive events

• Recognize these patients• Use precautionary measures to prevent

cardiovascular disease and type 2 diabetes

References

Apridonidze T., Essah P., Iuorno M., Nestler J. Prevalence and characteristics of the metabolic syndrome in women with polycystic ovary syndrome. The Journal of Clinical Endrocrinology and Metabolism. 2005; 90(4):1929-1935.

Carmina E., Lobo R., Polycystic ovary syndrome (PCOS): Arguably the most common endocrinopathy is associated with significant morbidity in women. The Journal of Clinical Endocrinology and Metabolism 1999; 84(6):1897-1899.

Dunaif A., Scott D., Finegood D., Quintana B., Whitcomb R. The insulin-sensitizing agent troglitazone improves metabolic and reproductive abnormalities in the polycystic ovary syndrome. Journal of Clinical Endocrinology and Metabolism. 1996; 81(9):3299-3306.

  Ehrmann D., Liljenquist D., Kasza K., Azziz R., Legro R., Ghazzi M. Prevalence and

predictors of the metabolic syndrome in women with polycystic ovary syndrome. Journal of Clinical Endocrinology and Metabolism. 2006; 91(1): 48-53.

  Flegal et. al. CDC, National Center for Health Statistics, National Health and Nutrition survery. JAMA. 2002;288: 1723-1727  Glueck C.J., Papanna R., Wang P., Goldenberg N., Sieve-Smith L. Incidence and

treatment of metabolic syndrome in newly referred women with confirmed polycystic ovarian syndrome. Metabolism. 2003; 52(7);908-915.

 Hopkinson Z., Sattar N., Fleming R., Greer I. Polycystic ovarian syndrome: the metabolic syndrome comes to gynaecology. BMJ. 1998; 317:329-332.  Kendall D., Harmel A. The metabolic syndrome, type 2 diabetes, and cardiovascular

disease: understanding the role of insulin resistance. The Amecican Journal Of Managed Care. 2002; 8(20): 635-653.

References  Marx T. Mehta E. Polycystic ovary syndrome: Pathogenesis and treatment over the short and long term. Cleveland Clinic Journal of Medicine. 2003;70(1).   Moghetti P., Castello R., Negri C., Tosi F., Perrone F., Caputo M., et al. Metformin

effects on clinical features, endocrine and metabolic profiles, and insulin sensitivity in polycystic ovary syndrome: a randomized, double-blind, placebo-controlled 6-month trial, followed by open, long-term clinical evaluation. The Journal of Clinical Endocrinolgy and Metabolism. 2000; 85(1): 139-146.

  Morin-Papunen L., Vauhdonen I., Koivunen R., Ruokonen A., Martikainen H.,

Tapanainen R., et al. Endocrine and metabolic effects of metformin versus ethinyl estradiol-cyproterone acetate in obese women with polycystic ovary syndrome: a randomized study. The Journal of Clinical Endrocrinology and Metabolism. 2000; 85(9): 3161-3168.

 Sheehan M. Polycystic ovarian syndrome: diagnosis and management. Clinical Medicine and Research. 2004; 2(1); 13-27.  Sharpless JL., Polycystic ovary syndrome and the metabolic syndrome. Clinical Diabetes. 2003; 21(4) 154-161.  Volek J., Feinman R., Carbohydrate restriction improves the features of metabolic

syndrome. Metabolic syndrome may be defined by the response to carbohydrate restriction. Nutrition and Metabolism. 2005; 2(31).

  Vural B., Caliskan E., Turkoz E., Kilic T., Demirci A. Evaluation of metabolic

syndrome frequency and premature carotid atherosclerosis in young women with polycystic ovary syndrome. Human Reproduction. 2005; 20(9): 2409-2413.

  Zoe E. C. Hopkinson, Naveed Sattar, Richard Fleming, Ian A. Greer, Polycystic

ovarian syndrome: the metabolic syndrome comes to gynaecology. BMJ. 1998; 317: 329-332)