Mohammad Emam

1
Polycystic Ovary Syndrome In The Era Of Metabolic
Syndrome

• BY
• Mohammad Emam
• Prof. OB GYN
• Mansoura Faculty of Medicine
• Mansoura integrated fertility center (MIFC)
• EGYPT

2
Metabolic Syndrome ( MS) Syndrome X IR

• Is a cluster of metabolic disorders, with a
  subnormal biological response to insulin
  occurring mainly in visceral obesity.

The more components of the syndrome , the
greater the risks .
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Diagnostic Criteria for Metabolic Syndrome
Diagnosis is made when 3 or more of these risk
criteria are met

• Glucose ? 6.1mmol/L
• Waist Circumference
• ? 102cm
• ?? 88cm
• HDL-C
• 1.0 mmols/L
• ? 1.3 mmols/L
• BP ?130/?85 mmHg
• Triglycerides ? 1.7mmol/L

• Glucose
• V. Obesity
• ? HDL-C
• ? BP
• ? TG

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Definition PCOS ( Rotterdam 2003)

• Two of the following three features are present,
  after exclusion of other etiologies
• (i) Oligomenorrhoea and or Anovulation
• (ii) Hyperandrogenism and/or hyperandrogenemia.
• (iii) Polycystic ovaries (sonar).

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Phenotypes (Rotterdam)

• PCOS WITH PCO .
• PCO HYPERANDROGENISM ANOVULATION.
• PCO Hyperandrogenism.
• PCO Anovulation.
• PCOS WITHOUT PCO .
• Hyperandrogenism Anovulation.
• PCO WITHOUT PCOS.
• ( Isolated PCO Asymptomatic PCO ).

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What is The significance of PCO in PCOS??

• The presence of PCO usually correlates with the
  presence of insulin resistance
• (Richard J 2002).

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Prevalence Of MS In PCOS

• MS is present in 2/3 of the PCOS (2-fold higher
  than women in the general population).

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Pitfalls Rotterdam Definition

• doubts still exist regarding borderline groups of
  patients ,such as hirsute ovulatory
  Normoandrogenic women with PCO???.
• Neglect role of IR

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Phenotypes Of PCOS According to IR

• PCOS IR (70 ).
• PCOS without IR (Legro etal 2004).

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1) IR Phenotype of PCOS

• Abdominal obesity ( Minority may be lean)
• Acanthosis Nigericans.
• Hirsutism.
• Resistance to CC,

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2) PCOS Without IR

• Lean.
• Euinsulinemic/ Euglycemic
• Enhanced Ovarian Sensitivity to insulin
  (although no hyperinsulinemia).

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RATIONALE

• MS
• Is associated with medical and psychosocial
  co-morbidities that are both immediate and
  long-term ( PCOS Is one of these co-morbidities
  ).
• PCOS
• PCOS is now recognized as an important metabolic
  and reproductive disorder .
• So, Overlap and vicious circle can be present
  between PCOS and MS.

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Co-morbidities With IR
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Objective

• To illustrate the link between two current
  ,intimate and hidden epidemics , MS and
  PCOS .
• To pinpoint the role of gynecologists regarding
  the management of PCOS in the era of MS.

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Link between MS PCOS
PCOS
MS
IR
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The Central Player ( Insulin Resistance
Vicious circle )
Aging
Pregnancy
Drugs
Lifestyle
Insulin Resistance
Genetics
obesity
Increased lipid storage
Hyperinsulinemia
PCOS
Altered lipoprotein cholesterol metabolism
Altered steroid hormone metabolism
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IR The central paradox

• The high ovarian response to insulin.
• Opposed by the whole body resistance.

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Genetic Of (MS) PCOS

• There is evidence for linkage of the
  hyperandrogenemia phenotype with an allele of a
  marker locus on chromosome 19, in the region of
  the gene encoding the insulin receptor.

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Types of insulin resistance
Type B
Type A
Insulina
Autoantibodies to insulin receptors
Genetic defect of insulin receptor (Kahn
syndrome)
a
a
Type C
b
b
tyrozine kinase
Defect of tyrozine kinase
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How IR Can Be Confirmed ??

• Fasting glucose / insulin lt 4.5
• Fasting insulin gt 24 uU / ml
• One hour insulin post OGTT-75 gm gt 150
• uU/ml

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Targets for ttt
PCOS
IR
None IR

• Symptomatic ttt Insulin sensitizers ( prevent
  Hyperandrogenism IR Vicious circle )
• Acne.
• Hirsutism.
• INFERTILITYT

Causative ttt ( Insulin sensitizers)
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Causative ttt

• Life- style modifications
• Diet modification
• Weight loss
• Exercise
• Psychosocial support.
• Cessation smoking.
• Improve IR ( Metformin)

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Proposed Approach for ttt of Anovulation In PCOS
Baseline evaluation ( Semenogram , HSG ,
Midluteal p)
Life style modification ( Exercise , Wt loss ,
Prohibit smoking
Metformin 500mg / day x first week , then 500
bd on week 2 , then 500 tds from week 3 till
6-12 month . ( Ensure liver and renal functions
prior ttt )
Pregnant continue Metformin first trimester
Not pregnant add CC for 6 cycles
Not pregnant , consider GN , OV Drilling , IUI ,
IVF OR ICSI
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The advantages of Metformin over drilling

• continue beyond conception
• It reduces the miscarriage rate.
• Decreases the development of gestational
  diabetes.

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Indications Of Drilling

• Regressed behind.
• Failure of
• Change of life style.
• Insulin sensitizing agents.
• CC /- HMG.

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Role Of Metformin In None IR ( PCOS)

• Prevents starting vicious circle of
  hyperandrogenemia - IR .
• Improve spontaneous and CC-induced ovulation.
• Improve follicular maturation in IVF cycles.
• The continuation in the first trimester appears
  to reduce the risk of abortion
• ( Metformin FDA group B ).

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Conclusions

• We are facing two current intimate epidemics (
  MS PCOS ) which affect a large scale of
  population and also affect their reproductive
  future.

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Conclusions

• Gynecologists should categorize any case of PCOS
  ,depending on
• Rotterdam criteria.
• IR or not

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conclusions
Conclusions

• Insulin sensitizers are the milestone in ttt of
  PCOS
• whether as a causative therapy in
• ( IR) sub phenotype.
• OR AS
• A prohibitor of the starting
  Hyperandrogenemia- IR vicious circle in (none
  IR) sub phenotype

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At The End We are in need for an applicable
integrated classification of PCOS to satisfy
different specialists at the same time!!!!
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Thank you
Prof. DR. MOHAMMAD EMAM
Telfax 0020502319922 0020502312299 Email.
mae335_at_hotmail.com