pcos dr rabi
TRANSCRIPT
PCOS AN OVER VIEW
DR. RABI NARAYAN SATAPATHYASST.PROFESSORDEPT. OF OBST.& GYNAECOLOGYSCB MEDICAL COLLEGE, [email protected]
“ 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, [email protected]
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
.