Polycystic Ovarian Syndrome FQN 0009 Polycystic Ovarian

Polycystic Ovarian Syndrome FQN 0009

Polycystic Ovarian Syndrome • 1 st 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 Knochenhauer ES et al, Journal of Clinical Endocrinology & Metabolism, 1998. • Current suggested prevalence in the U. S. – – Caucasian: 4. 8% African American: 8. 0% Hispanic or Latino: 13% 5%-10% of women Azziz R et al, Journal of Clinical Endocrinology & Metabolism, 2004. Goodarzi MO et al, Fertility and Sterility, 2005. Ehrmann DA, New England Journal of Medicine, 2005.

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

PCOS Presentation • Two of the following symptoms: –Polycystic ovaries (PCO) –Hyperandrogenism –Anovulation ØNo single criteria is sufficient for clinical diagnosis. • Additional features may include: Excessive hair growth Abnormal bleeding Obesity Acne Infertility Azziz R, Obstetrics and Gynecology, 2003. Hair loss

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) Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group, Fertility and Sterility, 2004.

Balen AH et al 4

Genetic Predisposition Aging Pregnancy Drugs Lifestyle Android Obesity Insulin Resistance ↑ Lipid Storage Hyperinsulinemia Altered Fat Metabolism Altered Steroid Hormone Metabolism PCOS: Acne, hirsutism, hyperandrogenism infertility Adapted from Cristello F et al, Gynecological Endocrinology, 2005.

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 postmenarche Guttmann-Bauman I, Journal of Pediatric Endocrinology & Metabolism, 2005.

Genetic Link • Familial clustering of PCOS common – 1 st 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 Yildiz BO et al, Journal of Clinical Endocrinology & Metabolism, 2003. “PCOS is a genetically determined ovarian disorder… the heterogeneity can be explained on the basis of interaction of the disorder with other genes and with the environment. ” Franks S et al, International Journal of Andrology, 2006.

PCOS: Metabolic Disorder • Insulin Resistance – High association with PCOS Dunaif A, Endocrinology Review, 1997. – 10% have Type 2 Diabetes – 30%-35% have Impaired Glucose Tolerance (IGT) Ehrmann DA et al, Diabetes Care, 1999. Legro RS et al, Journal of Clinical Endocrinology & Metabolism, 1999. • Obesity – 50% of PCOD patients are obese Goldzieher JW, Young RL, Endocrinology Metabolism Clinics of North America, 1992. – Amplifies biochemical and clinical abnormalities of PCOS Kiddy DS et al, Clinical Endocrinology, 1990.

PCOS: Metabolic Disorder • Endometrial Cancer – Long-term follow-up of 786 PCOS women found an increased Wild S et al, Human Fertility, 2000. risk of endometrial cancer – Women >50 yrs of age with endometrial cancer, PCOS (62. 5%) more prevalent than not (27. 3%; P=0. 033) Pillay OC et al, Human Reproduction, 2006. • Cardiovascular Disease – PCOS is characterized by endothelial dysfunction and resistance Paradisi G et al, Circulation, 2001. to vasodilating action of insulin – Increased risk of myocardial infarction in PCOS women than age-matched controls Dahlgren E et al, Acta Obstetricia et Gynecologica Scandinavica, 1992.

PCOS: Metabolic Disorder • Sleep Apnea – Increased Sleep Disordered Breathing (SDB) and daytime sleepiness in PCOS vs. controls Vgontzas AN et al, Sleep Medicine Reviews, 2005. • Depression – Higher prevalence in PCOS patients, associated with higher body mass index (BMI, P=0. 05) and greater insulin resistance (P=0. 02) Rasgon NL et al, Journal of Affective Disorders, 2003.

Pregnancy Complications • Spontaneous Abortions – Increased in high BMI/PCOS patients Wang JX et al, Human Reproduction, 2001. • Impaired Glucose Tolerance Turhan NO et al, International Journal of Gynecology & Obstetrics, 2003. • Gestational Diabetes Bjercke S et al, Gynecologic and Obstetric Investigation, 2002. • Hypertension Weerakiet S et al, Gynecological Endocrinology, 2004. • Small for Gestational Age Sir-Petermann T et al, Human Reproduction, 2005.

Infertility • >75% of women with anovulation infertility Franks et al, International Journal of Andrology, 2006. Webber LJ et al, Lancet, 2003. • Follicular arrest – Impaired selection of dominant follicle Jonard S, Dewailly D, Human Reproduction Update, 2004. –Risk of multiple pregnancy with treatment

PCOS: Weight Loss • Frequency of obesity in women with anovulation and PCO: 30%-75% Ehrmann DA, New England Journal of Medicine, 2005. • 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) Clark AM et al, Human Reproduction, 1995.

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 Kim LH et al, Fertility and Sterility, 2000.

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 .

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

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