pcos dr rabi

PCOS AN OVER VIEW

DR. RABI NARAYAN SATAPATHYASST.PROFESSORDEPT. OF OBST.& GYNAECOLOGYSCB MEDICAL COLLEGE, CUTTACKMOB-09861281510EMAIL-drrabisatpathy@gmail.com

“ Young married peasant woman, moderately obese and infertile, with two larger than normal ovaries, bumpy, shiny and whitish, just like pigeon eggs.” - A. Vallisneri, 1721

Cited in Insler, V. and Lunenfeld, B.; Gynec. Endocrinology 4 (1990)

.

Nineteenth Century

Recognition and description of sclero-cystic changes

in the ovary

Chereau A, 1844

.

1935 Stein and Leventhal

First presented their paper on seven women with

amenorrhoea, hirsutism and enlarged ovaries with multiple cysts

and thickened tunica at the Central Association of Obstetricians and Gynecologists.

.

Most Common

Endocrine Disorder

in WOMENwith

multi-system involvement

Homburg, R ; Human Reprodn. 11 : 1996 Kovacs, GT ; Polycystic ovary syndrome ( Cambridge Univ. Press ) : 2000 Marx, TL & Mehta, AE ; Cleveland Clinic J. of Medicine : January 2003

Diagnosis

Any two of the following

(i) Oligo- and/or anovulation

(ii) Clinical and/or biochemical signs of Hyperandrogenism

(iii) Polycystic ovary morphology on USG scan [defined as presence of 12 or more fiollicles in each ovary measuring 2-9 mm in diameter and/or

icreased ovarian volume, > 10 mm3]

The Rotterdam ESHRE/ASRM - sponsored PCOS Work shop Group 2004

PCOS associated with

Metabolic syndrome • Hypertension : 130/85 or higher

• TG Levels : 150 mg/dl Or higher

• HDL-C levels : Less than 50 mg/dl

• Abd. Obesity : Waist circumference > 35”

• Fasting Glucose : 110mg/dl or higher

Chronic anovulation due to

spectrum of etiologies

and clinical manifestations which now include Insulin Resistance

and Hyperinsulinemia and

Hyperandrogeism

Pathogenesis

Combination of genetic and environmental factors

contribute with potential etiological factors including Insulin resistance,

Ovarian dysfunction, Hyperandrogenism and

Hypothalamic-pituitary dysfunction.

It is multi-factorial. .

Genetic disorder with Autosomal dominant mode of inheritance

: Genes involved : Steroid hormone synthesis, Carbohydrate

metabolism, Gonadotrophin action & Major histocompatibility region

: Candidates : CYP11A, CYP17, CYP21, Androgen receptor gene,

SHBG gene, Insulin gene, IR gene, IRS gene, Capain10, FSH β -subunit gene, Dopamine

receptor gene & Follistatin gene

[D19S884 at 19p13.3] located 2 mega bases centromeric from the IR gene

DR. RABI NARAYAN SATAPATHYASST.PROFESSORDEPT. OF OBST.& GYNAECOLOGYSCB MEDICAL COLLEGE, CUTTACKMOB-09861281510EMAIL-drrabisatpathy@gmail.com

HYPERANDROGENISM

HYPOTHALAMUS

ADRENALS

PANCREAS

OVARIES

.

LH FSH

INSULIN

GnRH

DHEA-S, ANDROSTENEDION TESTOSTERONE & ESTRONE

zPITUITARY

GENETIC ENVIRONMENT

HYPOTHALAMUS PITUITARY

GENETIC PREDISPOSITION

OVARY Theca cell hyperplasia

Impaired folliculogenesis

INSULIN RESISTANCE Compensatory hyperinsulinemia

OBESITY

LIVER

SHBG

IGFBP-I

LH GH

IGF-I

HYPERANDROGENISM

.

‘diabete a femmes de barbe’

Achard & Thiers, 1921[ Bull Acad. Natl. Med.( Paris ) ]

Kahn et al, 1976 [ N Engl J Med ]

There was description of several women with insulin resistance ,

severe hyperandrogenism and acanthosis nigrans; most of these

women were noted to have bilaterally multicystic ovaries.

TODAYInsulin Resistance and PCOS

Strong association both in obese and non-obese

Central to Pathophysiology relationship

South Asian Women With PCOS more

likely to suffer from Insulin Resistance and to have Low

SHBG

Wijeyaratne et al .; Clin. Endocrinol.. : 2002

IR With INSULIN

TYR-PO4 TYR-PO4RAS

MAP Kinase

SHC

SOC

MITOGENESIS METABOLIC ACTIONS

IRS-1/2

Inactive PI-3

Kinase

Active PI-3 Kinase

PIP PIP 3

GLUT-4 PDH

Glycogen Synthase

DCI-IPG

G-Pr.

INSULIN RESISTANCE

Hyperinsulinaemia ENDOCRINE MANIFESTATIONS

Theca cell hyperplasiaOvary

Liver Adrenal glandPituitary

LH FSH

IGFBP-I

IGF-I

SHBG

Hyperandrogenism

Anovulation

CLINICAL PRESENTATION

Infertility Menstrual disorder Hirsuitism

Clinical Presentation [ Wide variety of presentation]

Menstrual disturbances Anovulation Infertility

Recurrent miscarriage

Hirsutism Acne Alopecia

Metabolic symptomatology - Obesity -

Long Term Risks

[ Abnormal GT and DM,

Dyslipidaemia,

Hypertension,

Coronary arterial disease and

Cancer of Endometrium / Breast / Ovary ]

AT PRESENT NO SIMPLE SOLUTION TO A

COMPLEX PROBLEM

Treatment

Life style modification Insulin sensitisers Menstrual disorder Anovulation/Infertility Hirsutism

Long term follow up

.