PCOS Polycystic Ovary Syndrome

Objectives Know the clinical definition of PCOS Know the typical physical and laboratory findings associated with PCOS Be familiar with the current management options

Definition Polycystic ovary syndrome is a clinical diagnosis 2 or more of the following features: Chronic oligo-ovulation or anovulation Androgen excess Polycystic ovaries

Epidemiology Affects 5-10% of women of childbearing age Most common cause of anovulatory infertility in developed countries Prevalence of the metabolic syndrome is 2-3x higher among women with PCOS

Theories to Etiology of PCOS Genetic predisposition Most likely although no gene isolated Premature adrenarche (<8 y/o) Heterozygosity for congenital adrenal hyperplasia (CAH) Intrauterine Growth Retardation (IUGR)

Pathophysiology Majority of women with PCOS (regardless of weight), have insulin resistance Association with: type 2 diabetes, dyslipidemia, and hypertension Effects of hyperinsulinemia Ovaries remain sensitive to insulin (maybe hypersensitive)  Androgen excess Inhibits hepatic production of sex hormone binding globulin  increases circulating free testosterone Impedes ovulation

Nestler J. N Engl J Med 2008;358:47-54

Cascade leading to excess androgens

CYCLE STARTS Vicious Cycle of PCOS

Clinical Findings Anovulation  amenorrhea & infertility Hirsuitism Acne Vulgaris Male pattern baldness/thinning Obesity- android-type with waist-hip ratios Cancer- endometrial

Evaluation: Differential Dx MORE LIKELY LESS LIKELY Pregnancy PCO Hypothyroidism Ovarian tumor Pituitary tumor CAH Female Athlete Triad (hypothalamic amenorrhea) Turner’s syndrome Testicular Feminization

Knowing all of this, what laboratory tests would you order for a patient you are suspecting of PCOS?

Laboratory Tests to Consider in Evaluation Process B-HCG Thyroid LH/FSH Prolactin Free/total testosterone Fasting 17-OPH and cortisol Fasting glucose Fasting Insulin level Fasting Lipid profile Androstenedione DHEAS Karyotype RED - those tests most critical to diagnosis of PCOS GREEN – consider these tests as associated problems with PCOS

Ultrasound Findings

Problems associated with high levels of sex hormones: Insulin resistance Hyperinsulinemia Diabetes Cardiovascular disease

Management: Non-medical Weight control Low carb diets Exercise reduce weight and CV risk factors Increase insulin sensitivity

Management: Medical OCP’s: suppress LH  androgens SHBG  free testosterone adrenal production of androgen  5alpha-reductase Spironolactone Cyclic progestins GnRH agonists

Management: Metformin Reduces hyperinsulinemia Decreases risk factors for CHD Improved weight-loss Normalization of circulating androgens Resumption of normal ovulatory menses and therefore reversal of infertility