Vous êtes sur la page 1sur 36

Polycystic Ovary Syndrome

PCOS)

Lenny Lisal,SpOG
Division of Reproductive Endocrinology
& Fertility
Department of Obstetrics and Gynecology
Medical Faculty Hasanuddin University
Makassar
Introduction
Irving Stein and Michael Levental, first
diagnosed PCOS
Seven women infertility and amenorrhea
Pelvic X-ray enlarged ovaries that
contained several cystic structures
Wedge resections removed obstructions
from the ovary, normal ovarian fuction
resumed!
Five of them conceived!
INTRODUCTION
The four main symptoms of PCOS, Stein
and Leventhal :
Irreguler menstruation,
Infertility,
Obesity, and
Hirsutism
PREVALENCE
About 20 % of reproductive age women
demonstrate the USG picture of PCO.
About 5-10 % have clinical of biochemichal sign
of anovulation and androgen excess.
Dunaif 1995, Norman et al 2002
Estimation of true prevalence PCOS must be
made with caution since there is on overall
consensus on the diagnostic criteria that must be
satisfied to make a diagnosis.
Ledger and Clark 2003
Criteria for diagnosis of PCOD
Major criteria
Chronic anovulation
Clinical sign of androgen excess
Hirsutism
Acne
Alopecia
Menstrual disturbance
Infertility
Virilization
Excelussion of alternative causes androgen excess

Minor criteria
Insulin resistenace
Onset at puberty
Elevated LH: FSH ratio > 2.5-3.0
Ultrasonographic evidence of plycistic ovaries
Obesity BMI > 27.5 kg/cm2
NIH-NICHD 1997
Anovulation Insulin Resistance
Hirsutism

1 MAJOR CRITERIA 2 MAJOR CRITERIA PCOS

LH/FSH >3
Obesity
Hiperandrogenemia PCO (USG)

1. Usg
2. Hormonal Examination
3. Insulin Resistance
The European Society for Human
Reproduction and Embriology (ESHRE) &
American Society for Reproductive Medicine
(ASRM)

PCOS Consensus Workshop Group Rotterdam 2003


Irregular or absent ovulation
Hyperandrogenism with or without laboratory finding
Ultrasound finding of PCO
DEFINITION
PCOS: A metabolic disorder characterized
by ovulatory dysfunction,
hyperandrogenism, and exclusion of other
endocrinopathies
PCO: The presence of multiple ovarian
cysts 2-8 mm in diameter and increased
ovarian stroma; this condition is not
intrinsically pathologic
ETIOLOGY
3 MAJOR HYPOTHESIS :
Familial
Strong family hystory
Ovarian & adrenal steroidogenesis disorder
An abnormality of gene
Hyperinsulinaemia occurs much more
commonly in PCOS.

MAY ALL INTERACT


OTHER CAUSES
High androgen & LH causes granulosa cells
to fail perpetuating anovulation
Intra-ovarian endocrine & paracrine
disorder
Exogenous or excess endogenous androgens
will produce PCOS (inutero, at puberty or in
adult life)
ETIO-PATHOPHYSIOLOGY
PCOS

CLINICAL SIGNS

PATHOPHYSIOLOGY
Pathophysioloy of
Polycistic Ovary Syndrome
Pituitury

LH Secration
FSH Secretion

Adipose Ovary
Tissue Chromis
Extraglandular Anovulation Impaired
Aromatization Development
Of Follicle

Obesity

Hyperandrogenism

Hirsutism
Hyperinsulinemia Acne
Insulin Resistance Alopecia

Source : Rasgon NL (2001)


PCOS
IGF-1
Theca cells Activity
LH R
+ R

IGFBP-1
Insulin
R
(Insulin Resisten) +
Androgen

- R FSH
IGFBP-1
Hyperandrogenism Production
Aromatase
+

Estradiol R Insulin
Granolosa Cells Defective
Folicular
maturation

Wang HS, Chard T.J Of Endocrinology 1999. 161:1-13


Polycistic
Ovarian syndrome

Insulin
resistance

Hyperinsulinaemia

Insuline like Ovary


Liver Growth factor 1 Thecal cell
Hyperplasia
Luteinising
Sex hormone Insuline like hormone Anovulation
Binding Growth factor 1
globulin Binding protein

Androgen Activity
Insulin resistance

Endocrine Central obesity Metabolic


Manifestations Manifestations

Insulin
? Glucose intolerance
Liver Adrenal
Gland
Ovary
Hypertension
Sex hormone
binding
globulin
Dyslipidaemia
Androgen Activity

Clinical Long term


presentation sequelae
Infertility
Menstrual disturbance Vascular disease
Hirsutism
INVESTIGATIONS
Ultrasound transvaginal ultrasound is best
LH/FSH
Free testosterone
SHBG
Hypothalamic Adrenal

Ovary

Inherent defect in Obesity


androgen-secreting
tissue Insulin resistance
Hyperinsulinemic state
Insulin resistance Compensatory
Hyperinsulinemia

?
Androgens
Ovary

Cause-and-effect
relationship

Serum insulin
Obesity
Insulin

SHBG
Free
testosterone
PCOD
Non-obese Obese

GH Insulin resistance
LH LH and IGF-I Hyperinsulinemia
effect
IGFBP-I
on theca cells
IGF-I
Cytochrome
p-450c 17-alpha activity SHBG
Androgen secretion
Long term Risk PCOS

Hypertention
Altered lipid level
Hyperinsulinemia Fibrinolysis, vasodilation
Insulin resistance Hirsutism
Hyperandrogenism Myocard infarc
Chronic an-ovulation Type 2 DM
Endometrial Cancer
Frekwency of SIGNS and
SYMPTOMS
Hirsutism
Oligomenorrhea 60 90 %
Infertility 50 90 %
55 75 %
Polycistic on USG
50 75 %
Obesity
40 60 %
Amenorrhea
26 51 %
Acne 24 27 %
DUB 29 %
Normal Menstruan pattern 22 %
Virilization 0 28 %
Pituitary

Altered GnRH pulse LH/FSH


Frequency/amplitude
Muscle/Adipose

Insulin
Resitance

Insulin
Ovary
Liver
Estrogen Activin
IGF1 & IGF II
IGFBP-1 Inhibin
SHBG
Free estradiol Androgens
Adipose

Estrogen Free androgen

Pathophysiology of polycystic ovary syndrome (FSH=Follicle stimulating hormone; IGF= insulin-like growth factor: IGFBP = insulin-
Like growth factor-binding protein; LH= luteinizing hormone; SHBG= sex hormone binding globulin)
Revised 2003 consensus on diagnostic
criteria and long-term health risks related
to plycystic ovary syndrome
The Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group
Rotterdam, The Netherlands

TABLE 3
Criteria for the metabolic syndrome in women with
polycystic ovary syndrome. (Three of five quality for the
syndrome.)
Risk Factor Cuto off
1. Abdominal obesity (waist > 88 cm (>35 inch)
circumference)
2. Triglycerides > 150 mg/dL
3. HDL-C < 50 mg/dL
4. Blood pressure > 130/> 85
5. Fasting and 2-h glucose from 110-126 mg/dL and/or 2-h
oral glucose tolerance test glucose 140-199 mg/dL

2003 Rotterdan PCOS consensus, Fertil Steril 2004


Pathways to Insulin Resistance and
Polycistic Ovary Syndrome
Increased peripheral cortisol metabolism as a proposed
mechanism for the development of PCOS

5a-Reductase 11b-HSD1
Activity Activity

Cortisol
Metabolism

ACTH

Adrenal Normal Serum


Androgens Cortisol

PCOS
PATHOPHYSIOLOGY OF PCOs
(HYPOTHESIS

CENTRAL
(LH ) 55 %

I.R OVARY
69 % 64 %

HYPER
ANDROGEN*

OLIGO /
PCO
AN OVUL

* DUE TO h-p-o Axis, not the other etiologies


INSULIN RESISTANCE PCOs
(69 %)

Obesity 70 % Insulin Resistance

PCOs 69 % Insulin Resistance

PCOs 50 % Obese
Obesity Insulin Resistance
Insulin Resistance - PCOs

Insulin HYPERANDROGEN
Resistance
OBESITY - I.R - PCOs
OBESITY
LEPTIN INSULIN

-INTERNEURON
THECA FREE
(MCH,NO) IGF BP-1 SHBG
-NPY CELL IGF I&II

GnRH TESTOSTERON

ANDRO-
RATIO STENEDION
LH E1
FSH (PERIPHERY) -MUSCLE FREE FREE E2
-FAT TESTOSTERON PERIPHERY

E2 . DISTURB
INTRA . FOLICULO-
GENESIS
HIRSUTISME
FOLICEL
-DUB
-MALIGNANCY RISK
ANOVULATION -ENDOMET.(5X)
-BREAST (2X)
PCOs - INFERTILITY
PCOs

OLIGO/ AN
HYPERANDROGEN
OVULATION

SERUM ESTROGEN INCREASES

INCREASED LH

ALTERED OMI

INFERTILITY OOCYTE QUALITY DECREASES

CONCEPTION RATE DECREASES


&
INCREASE ABTORTION RATE
PCOs : CLINICAL SIGN & CLINICAL IMPACT
HYPOTHALAMUS

GnRH

PITUITARY

FSH QUALITY OF
OBESITY LEPTIN OOCYTE
LH

OVARY DISTURB
64% FOLICULO- OLIGO
I.R GENESIS ANOVUL.
LEAN
69%
HYPER
ESTROGEN
ANDROGEN
PERIPHERY
PCO ABORTION
-NID DM RATE
-DISLIPIDEMIA HIRSUTISM DUB
-HYPERTENSION
ENDOMETRIAL CA
-CVD BREAST CA INFERTILITY
IGF-1 ACTIVITY

THECA CELLS
LH R
R IGFBP-1
+
INSULLIN R
(INSUL.RESIST)
+ ANDROGEN
IGF-1 FROM
CIRCULATION

IGBP-1 ? R
PROD.
- FSH

HYPER + INSULLIN
ANDROGENISM AROMATASE R (INSUL.RESIST)

E2 DEFECTIVE
FOLLICULAR
GRANULOSA CELLS MATURATION

JOURNAL OF ENDOCRINOLOGY (1996)161, 1-13