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Polycystic Ovarian Syndrome Omar Al Omari, MRCOG Obstetrician & Gynaecologist Jordan Hospital Medical Center. FQN0009. Polycystic Ovarian Syndrome. 1 st described by Irving Stein and Michael Leventhal as a triad of amenorrhea, obesity and hirsutism (1935)
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Polycystic Ovarian SyndromeOmar Al Omari, MRCOGObstetrician & GynaecologistJordan Hospital Medical Center FQN0009
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 Knochenhauer ES et al, Journal of Clinical Endocrinology & Metabolism, 1998. 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 • No single criteria is sufficient for clinical diagnosis. • Additional features may include: Excessive hair growth Abnormal bleeding Obesity Hair loss Acne Infertility Azziz R, Obstetrics and Gynecology, 2003.
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.
Android Obesity Genetic Predisposition Aging Pregnancy Drugs Lifestyle 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 post-menarche Guttmann-Bauman I, Journal of Pediatric Endocrinology & Metabolism, 2005.
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 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 • 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 Dunaif A, Endocrinology Review, 1997. Ehrmann DA et al, Diabetes Care, 1999. • Legro RS et al, Journal of Clinical Endocrinology & Metabolism, 1999. Goldzieher JW, Young RL, Endocrinology Metabolism Clinics of North America, 1992. Kiddy DS et al, Clinical Endocrinology, 1990.
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 Wild S et al, Human Fertility, 2000. Pillay OC et al, Human Reproduction, 2006. • Paradisi G et al, Circulation, 2001. • 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 • Depression • Higher prevalence in PCOS patients, associated with higher body mass index (BMI, P=0.05) and greater insulin resistance (P=0.02) Vgontzas AN et al, Sleep Medicine Reviews, 2005. Rasgon NL et al, Journal of Affective Disorders, 2003.
Pregnancy Complications • Spontaneous Abortions • Increased in high BMI/PCOS patients • Impaired Glucose Tolerance • Gestational Diabetes • Hypertension • Small for Gestational Age Wang JX et al, Human Reproduction, 2001. Turhan NO et al, International Journal of Gynecology & Obstetrics, 2003. Bjercke S et al, Gynecologic and Obstetric Investigation, 2002. Weerakiet S et al, Gynecological Endocrinology, 2004. Sir-Petermann T et al, Human Reproduction, 2005.
Infertility • >75% of women with anovulation infertility • Follicular arrest • Impaired selection of dominant follicle • Risk of multiple pregnancy with treatment Franks et al, International Journal of Andrology, 2006. Webber LJ et al, Lancet, 2003. Jonard S, Dewailly D, Human Reproduction Update, 2004.
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) Ehrmann DA, New England Journal of Medicine, 2005. 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