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

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 .

Diagnostic Criteria for Metabolic Syndrome

Diagnosis is made when 3 or more of these risk criteria are met
oGlucose V. Obesity q HDL-C HDLo BP o TG
Glucose u 6.1mmol/L Waist Circumference bu 102cm cu 88cm HDL-C b 1.0 mmols/L c 1.3 mmols/L BP u130/u85 mmHg Triglycerides u 1.7mmol/L

Definition PCOS ( Rotterdam 2003) 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).

Phenotypes (Rotterdam)

PCOS WITH PCO .

PCO + HYPERANDROGENISM + ANOVULATION. PCO + Hyperandrogenism. PCO + Anovulation.

PCOS WITHOUT PCO .

Hyperandrogenism + Anovulation.

PCO WITHOUT PCOS.

( Isolated PCO = Asymptomatic PCO ).

What is The significance of PCO in PCOS??

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

Prevalence Of MS In PCOS

MS is present in 2/3 of the PCOS (2-fold higher than

women in the general population).

Pitfalls Rotterdam Definition

1. doubts still exist regarding borderline groups of patients ,such as hirsute ovulatory Normoandrogenic women with PCO???. 2. Neglect role of IR

Phenotypes Of PCOS According to IR

PCOS + IR (70 % ). PCOS without IR
(Legro etal 2004).

1) IR Phenotype of PCOS
 Abdominal obesity ( Minority may be lean)  Acanthosis Nigericans.  Hirsutism.  Resistance to CC,

2) PCOS Without IR
Lean. Euinsulinemic/ Euglycemic Enhanced Ovarian Sensitivity to insulin
(although no hyperinsulinemia).

RATIONALE

MS
Is associated with medical and psychosocial comorbidities 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.

Co-morbidities With IR

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.

Link between MS & PCOS

MS

PCOS

IR

The Central Player ( Insulin Resistance & Vicious circle )

Pregnancy

Aging

Drugs

Lifestyle
obesity
Increased lipid storage

Genetics

Insulin Resistance

Hyperinsulinemia

PCOS
Altered steroid hormone metabolism Altered lipoprotein & cholesterol metabolism

IR : The central paradox

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

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.

Types of insulin resistance

Type A
Genetic defect of insulin receptor (Kahn syndrome)

Type B
Insulina

Autoantibodies to insulin receptors

E
F
Type C

F
tyrozine kinase
Defect of tyrozine kinase

How IR Can Be Confirmed ??

Fasting glucose / insulin < 4.5 Fasting insulin > 24 uU / ml One hour insulin post OGTT-75 gm > 150 uU/ml

Targets for ttt

PCOS
IR
None IR

Symptomatic ttt + Insulin sensitizers ( prevent Hyperandrogenism IR Vicious circle ) :

Causative ttt ( Insulin sensitizers)

Acne. Hirsutism. INFERTILITYT

Causative ttt
Life- style modifications:
Diet modification Weight loss Exercise Psychosocial support. Cessation smoking.

Improve IR ( Metformin)

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 ) Not pregnant add CC for 6 cycles
Not pregnant , consider GN , OV Drilling , IUI , IVF OR ICSI

Pregnant: continue Metformin first trimester

The advantages of Metformin over drilling

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

Indications Of Drilling

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

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 ).

Conclusions

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

Conclusions
Gynecologists should categorize any case of PCOS ,depending on :

1. Rotterdam criteria.

2.IR or not

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

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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