Polycystic Ovarian Syndrome Omar Al Omari, MRCOG Obstetrician

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Polycystic Ovarian SyndromeOmar Al Omari,
MRCOGObstetrician GynaecologistJordan
Hospital Medical Center
FQN0009
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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

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.
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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

Azziz R, Obstetrics and Gynecology, 2003.
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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)

Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus
Workshop Group, Fertility and Sterility, 2004.
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Balen AH et al4
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Android Obesity
Genetic Predisposition Aging Pregnancy Drugs Lifes
tyle
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.
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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

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

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.
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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

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.
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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 gt50 yrs of age with endometrial cancer,
  PCOS (62.5) more prevalent than not (27.3
  P0.033)
• 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.
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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, P0.05) and
  greater insulin resistance (P0.02)

Vgontzas AN et al, Sleep Medicine Reviews, 2005.
Rasgon NL et al, Journal of Affective Disorders,
2003.
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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.
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Infertility

• gt75 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.
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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)

Ehrmann DA, New England Journal of Medicine, 2005.
Clark AM et al, Human Reproduction, 1995.
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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

Kim LH et al, Fertility and Sterility, 2000.
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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)
• IVFsingle 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

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Thank you