Polycystic Ovarian
Syndrome
Omar Al Omari, MRCOG
Obstetrician & Gynaecologist
Jordan 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
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
No 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 al4
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
– 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
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
Thank you