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Polycystic Ovarian Syndrome

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Polycystic Ovarian Syndrome 1st described by Irving Stein and Michael Leventhal as a triad of amenorrhea, obesity and hirsutism (1935) The most common endocrine disorder in women of reproductive age ~ 2%-8% of women Current suggested prevalence in the U.S. Caucasian: 4.8% African American: 8.0% Hispanic or Latino: 13% 5%-10% of women

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Review Objectives Symptom Presentation Diagnosis Definitions Potential Causes Metabolic and Reproductive Complications Infertility

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PCOS Presentation Two of the following symptoms: Polycystic ovaries (PCO) Hyperandrogenism Anovulation No single criteria is sufficient for clinical diagnosis. Additional features may include: Excessive hair growth Abnormal bleeding Obesity Hair loss Acne Infertility

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PCOS Presentation Difficult to diagnosis Heterogeneous symptoms Vary over time NIH-Sponsored Conference on PCOS (1990 Criteria) Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group (2003 Criteria)

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Early Signs: Adolescence “Polycystic ovarian syndrome is the most common endocrinopathy in adult women, and is emerging as a common cause of menstrual disturbances in the adolescent population” Normal pubertal events include: Oligomenorrhea, hirsutism, acne, and weight gain Insulin resistance has reportedly increased in last decade Pediatric Endocrinologists trending towards an earlier work-up then compared to traditional practice of waiting 2-years post-menarche

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Genetic Link Familial clustering of PCOS common 1st degree relatives of patients with PCOS may be at high risk for diabetes and glucose intolerance Mothers and sisters of PCOS patients have higher androgen levels than control subjects

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PCOS: Metabolic Disorder Insulin Resistance High association with PCOS 10% have Type 2 Diabetes 30%-35% have Impaired Glucose Tolerance (IGT) Obesity 50% of PCOD patients are obese Amplifies biochemical and clinical abnormalities of PCOS

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PCOS: Metabolic Disorder Endometrial Cancer Long-term follow-up of 786 PCOS women found an increased risk of endometrial cancer Women >50 yrs of age with endometrial cancer, PCOS (62.5%) more prevalent than not (27.3%; P=0.033) Cardiovascular Disease PCOS is characterized by endothelial dysfunction and resistance to vasodilating action of insulin Increased risk of myocardial infarction in PCOS women than age-matched controls

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PCOS: Metabolic Disorder Sleep Apnea Increased Sleep Disordered Breathing (SDB) and daytime sleepiness in PCOS vs. controls Depression Higher prevalence in PCOS patients, associated with higher body mass index (BMI, P=0.05) and greater insulin resistance (P=0.02)

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Pregnancy Complications Spontaneous Abortions Increased in high BMI/PCOS patients Impaired Glucose Tolerance Gestational Diabetes Hypertension Small for Gestational Age

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Infertility >75% of women with anovulation infertility Follicular arrest Impaired selection of dominant follicle Risk of multiple pregnancy with treatment

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PCOS: Weight Loss Frequency of obesity in women with anovulation and PCO: 30%-75% Six month weight-loss program for overweight anovulatory women Lost an average of 6.3 kg (13.9 lbs) Decreased fasting insulin and testosterone levels 92% resumed ovulation (12/13) 85% became pregnant (11/13)

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Infertility Treatments Step-by-step. . . . If BMI elevated, loss of at least 5% body weight Ovulation induction (OI) with clomiphene citrate Insulin sensitizer as single agent Insulin sensitizer + clomiphene Gonadotropin therapy, FSH hormone Gonadotropins + insulin sensitizer In vitro fertilization (IVF) …single embryo transfer

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PCOS: Stimulated Cycles PCOS patients are often high responders to medications, Clomid and FSH High risk of multiple pregnancy Ovarian hyperstimulation syndrome (OHSS) IVF…single embryo transfer

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Conclusions PCOS is a multifaceted condition Varying presentations Begins in adolescence Long-term consequences Genetic and pre-natal implications Metabolic Disorder Cosmetic issues Reproductive complications. cycle irregularity / bleeding / endometrial cancer Infertility Common endocrinopathy in pre-menopausal women, causing menstrual irregularities and hirsutism Multiple treatments available with potentially successful outcomes