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PCO Over 40PCO Over 40
The Lost AreaThe Lost Area
Hesham Al-Inany, PhDHesham Al-Inany, PhD
Kaainih@yahoo.comKaainih@yahoo.com
An international consensusAn international consensus
 Defines PCOS as the presence of at leastDefines PCOS as the presence of at least
12 follicles measuring 212 follicles measuring 2--9 mm in diameter9 mm in diameter
and/or an ovarian volume in excess of 10and/or an ovarian volume in excess of 10
mLmL
The Rotterdam ESHRE/ASRM , 2004The Rotterdam ESHRE/ASRM , 2004
AgeAge
 Most women present in their thirtiesMost women present in their thirties
Kahsar-Miller , 2001Kahsar-Miller , 2001
Complaining ofComplaining of
irregular menstrual cycles,irregular menstrual cycles,
scanty or absent menses,scanty or absent menses,
hirsutismhirsutism
infertilityinfertility
Recent interestRecent interest
 Adolescent PCOAdolescent PCO
 More recently, PCO over FortyMore recently, PCO over Forty
Lost AreaLost Area
 PCOS is the most common endocrinePCOS is the most common endocrine
abnormality ofabnormality of reproductive-agedreproductive-aged
womenwomen
 >40 = fading reproduction>40 = fading reproduction
Lost Area IILost Area II
 The main difficulty lies in the absence ofThe main difficulty lies in the absence of
prospective studies in women over 40 ysprospective studies in women over 40 ys
• Loverro GLoverro G. , 2004. , 2004
E
V
I
D
E
N
C
E
The Evidence PyramidThe Evidence Pyramid
ProspectiveProspective
RetrospectiveRetrospective
Observational StudiesObservational Studies
ExposureExposure
Study DirectionStudy Direction
OutcomeOutcome
ExposureExposure OutcomeOutcome
Cohort Study
Case Control Study
OutcomeOutcome
ExposureExposure
Cross Sectional
Study
Cohort StudyCohort Study
 Advantages:Advantages:

Ethically safeEthically safe

Can establish causality (temporalCan establish causality (temporal
relationship)relationship)

Allow studying multiple outcomes for 1Allow studying multiple outcomes for 1
exposureexposure
PCO over FortyPCO over Forty
 Why such an interestWhy such an interest
 There is some evidence that women withThere is some evidence that women with
PCOS are at increased risk of developingPCOS are at increased risk of developing
 type 2 diabetestype 2 diabetes
 cardiovascular disorderscardiovascular disorders
 endometrial hyperplasia and, later,endometrial hyperplasia and, later,
endometrial carcinoma.endometrial carcinoma.
ART:ART: New problemNew problem
Pregnancies after 40yPregnancies after 40y
 PIHPIH
 DiabetesDiabetes
 Miscarriage rateMiscarriage rate
 Low birth weightLow birth weight
How patient would presentHow patient would present
 Classic PCO caseClassic PCO case
Seeking conceptionSeeking conception
Menstrual troubleMenstrual trouble
HirsutismHirsutism
 Pregnant after assisted conceptionPregnant after assisted conception
 Long term consequences of PCOLong term consequences of PCO
(probably will not be you)(probably will not be you)
Most Important ManagementMost Important Management
 Prevention of Long term consequencesPrevention of Long term consequences
 Increase awarenessIncrease awareness
 Spot your potential casesSpot your potential cases
Infertility TreatmentInfertility Treatment
 Ovulation induction by anti-oestrogenOvulation induction by anti-oestrogen
(Clomiphene citrate or Tamoxifen) is not a(Clomiphene citrate or Tamoxifen) is not a
valid optionvalid option
 Risk of OHSS is remoteRisk of OHSS is remote
 Gonadotrophins can be usedGonadotrophins can be used
(Al-Inany, 2005)(Al-Inany, 2005)
Infertility TreatmentInfertility Treatment
 IVF vs OI + IUIIVF vs OI + IUI
 IVF is the optimum solutionIVF is the optimum solution
HirsutismHirsutism
 No hormonal therapy (OC, Dian, etc..)No hormonal therapy (OC, Dian, etc..)
Long term HazardsLong term Hazards
 It is a premenopausal endocrino-metabolicIt is a premenopausal endocrino-metabolic
disorderdisorder
 As a consequence of insulin-resistance,As a consequence of insulin-resistance,
women affected by PCOS often presentwomen affected by PCOS often present
abnormalities of glucose metabolism andabnormalities of glucose metabolism and
lipid profile .lipid profile .
Another FactorAnother Factor
 Besides insulin-resistance, it has beenBesides insulin-resistance, it has been
demonstrated that some of these womendemonstrated that some of these women
also have alterations in beta-cell-function.also have alterations in beta-cell-function.
Both disorders (insulin-resistance andBoth disorders (insulin-resistance and
beta-cell-dysfunction) are recognized asbeta-cell-dysfunction) are recognized as
major risk factors for the development ofmajor risk factors for the development of
type 2 diabetes.type 2 diabetes.
clear evidenceclear evidence
 women with PCOS are at increased (3–7women with PCOS are at increased (3–7
times) risk of developing type 2 diabetestimes) risk of developing type 2 diabetes
(Legro(Legro et alet al., 1999 ; Wild., 1999 ; Wild et alet al., 2000 )., 2000 )
AccordinglyAccordingly
 Obese women with PCOS should beObese women with PCOS should be
screened for the metabolic syndrome,screened for the metabolic syndrome,
including glucose intolerance with an oralincluding glucose intolerance with an oral
glucose tolerance test.glucose tolerance test.
CVSCVS
 No clear evidence of increase incidence ofNo clear evidence of increase incidence of
death from CVS events in women withdeath from CVS events in women with
PCOS,PCOS,
 Evidence of significant associationEvidence of significant association
between PCOS and IHD, due tobetween PCOS and IHD, due to
dyslipidaemia (Legrodyslipidaemia (Legro et alet al., 2001 ) and., 2001 ) and
markers of abnormal vascular functionmarkers of abnormal vascular function
(Christian(Christian et alet al., 2003 ).., 2003 ).
PCOS and cancer riskPCOS and cancer risk
 ovarian cancer: Limited dataovarian cancer: Limited data
 Women with PCOS are also thought to beWomen with PCOS are also thought to be
at increased risk for endometrial cancerat increased risk for endometrial cancer
through chronic anovulation withthrough chronic anovulation with
unopposed estrogen exposure of theunopposed estrogen exposure of the
endometrium. However, epidemiologicalendometrium. However, epidemiological
evidence to support this hypothesis isevidence to support this hypothesis is
limited (Hardimanlimited (Hardiman et alet al., 2003 ).., 2003 ).
Why such limited EvidenceWhy such limited Evidence
 Well designed cohort studies are still notWell designed cohort studies are still not
availableavailable
 Only retrospective studies and someOnly retrospective studies and some
Cross sectional studies are availableCross sectional studies are available
ConclusionConclusion
 insulin sensitizers, and modifying life styleinsulin sensitizers, and modifying life style
are the key for managementare the key for management
 Long-term prospective trials are neededLong-term prospective trials are needed
to better delineate the nature andto better delineate the nature and
magnitude of disease risks associatedmagnitude of disease risks associated
with PCOSwith PCOS

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PCOS over 40YRS

  • 1. PCO Over 40PCO Over 40 The Lost AreaThe Lost Area Hesham Al-Inany, PhDHesham Al-Inany, PhD Kaainih@yahoo.comKaainih@yahoo.com
  • 2. An international consensusAn international consensus  Defines PCOS as the presence of at leastDefines PCOS as the presence of at least 12 follicles measuring 212 follicles measuring 2--9 mm in diameter9 mm in diameter and/or an ovarian volume in excess of 10and/or an ovarian volume in excess of 10 mLmL The Rotterdam ESHRE/ASRM , 2004The Rotterdam ESHRE/ASRM , 2004
  • 3. AgeAge  Most women present in their thirtiesMost women present in their thirties Kahsar-Miller , 2001Kahsar-Miller , 2001 Complaining ofComplaining of irregular menstrual cycles,irregular menstrual cycles, scanty or absent menses,scanty or absent menses, hirsutismhirsutism infertilityinfertility
  • 4. Recent interestRecent interest  Adolescent PCOAdolescent PCO  More recently, PCO over FortyMore recently, PCO over Forty
  • 5. Lost AreaLost Area  PCOS is the most common endocrinePCOS is the most common endocrine abnormality ofabnormality of reproductive-agedreproductive-aged womenwomen  >40 = fading reproduction>40 = fading reproduction
  • 6. Lost Area IILost Area II  The main difficulty lies in the absence ofThe main difficulty lies in the absence of prospective studies in women over 40 ysprospective studies in women over 40 ys • Loverro GLoverro G. , 2004. , 2004
  • 8. ProspectiveProspective RetrospectiveRetrospective Observational StudiesObservational Studies ExposureExposure Study DirectionStudy Direction OutcomeOutcome ExposureExposure OutcomeOutcome Cohort Study Case Control Study OutcomeOutcome ExposureExposure Cross Sectional Study
  • 9. Cohort StudyCohort Study  Advantages:Advantages:  Ethically safeEthically safe  Can establish causality (temporalCan establish causality (temporal relationship)relationship)  Allow studying multiple outcomes for 1Allow studying multiple outcomes for 1 exposureexposure
  • 10. PCO over FortyPCO over Forty  Why such an interestWhy such an interest  There is some evidence that women withThere is some evidence that women with PCOS are at increased risk of developingPCOS are at increased risk of developing  type 2 diabetestype 2 diabetes  cardiovascular disorderscardiovascular disorders  endometrial hyperplasia and, later,endometrial hyperplasia and, later, endometrial carcinoma.endometrial carcinoma.
  • 11. ART:ART: New problemNew problem Pregnancies after 40yPregnancies after 40y  PIHPIH  DiabetesDiabetes  Miscarriage rateMiscarriage rate  Low birth weightLow birth weight
  • 12. How patient would presentHow patient would present  Classic PCO caseClassic PCO case Seeking conceptionSeeking conception Menstrual troubleMenstrual trouble HirsutismHirsutism  Pregnant after assisted conceptionPregnant after assisted conception  Long term consequences of PCOLong term consequences of PCO (probably will not be you)(probably will not be you)
  • 13. Most Important ManagementMost Important Management  Prevention of Long term consequencesPrevention of Long term consequences  Increase awarenessIncrease awareness  Spot your potential casesSpot your potential cases
  • 14. Infertility TreatmentInfertility Treatment  Ovulation induction by anti-oestrogenOvulation induction by anti-oestrogen (Clomiphene citrate or Tamoxifen) is not a(Clomiphene citrate or Tamoxifen) is not a valid optionvalid option  Risk of OHSS is remoteRisk of OHSS is remote  Gonadotrophins can be usedGonadotrophins can be used (Al-Inany, 2005)(Al-Inany, 2005)
  • 15. Infertility TreatmentInfertility Treatment  IVF vs OI + IUIIVF vs OI + IUI  IVF is the optimum solutionIVF is the optimum solution
  • 16. HirsutismHirsutism  No hormonal therapy (OC, Dian, etc..)No hormonal therapy (OC, Dian, etc..)
  • 17. Long term HazardsLong term Hazards  It is a premenopausal endocrino-metabolicIt is a premenopausal endocrino-metabolic disorderdisorder  As a consequence of insulin-resistance,As a consequence of insulin-resistance, women affected by PCOS often presentwomen affected by PCOS often present abnormalities of glucose metabolism andabnormalities of glucose metabolism and lipid profile .lipid profile .
  • 18. Another FactorAnother Factor  Besides insulin-resistance, it has beenBesides insulin-resistance, it has been demonstrated that some of these womendemonstrated that some of these women also have alterations in beta-cell-function.also have alterations in beta-cell-function. Both disorders (insulin-resistance andBoth disorders (insulin-resistance and beta-cell-dysfunction) are recognized asbeta-cell-dysfunction) are recognized as major risk factors for the development ofmajor risk factors for the development of type 2 diabetes.type 2 diabetes.
  • 19. clear evidenceclear evidence  women with PCOS are at increased (3–7women with PCOS are at increased (3–7 times) risk of developing type 2 diabetestimes) risk of developing type 2 diabetes (Legro(Legro et alet al., 1999 ; Wild., 1999 ; Wild et alet al., 2000 )., 2000 )
  • 20. AccordinglyAccordingly  Obese women with PCOS should beObese women with PCOS should be screened for the metabolic syndrome,screened for the metabolic syndrome, including glucose intolerance with an oralincluding glucose intolerance with an oral glucose tolerance test.glucose tolerance test.
  • 21. CVSCVS  No clear evidence of increase incidence ofNo clear evidence of increase incidence of death from CVS events in women withdeath from CVS events in women with PCOS,PCOS,  Evidence of significant associationEvidence of significant association between PCOS and IHD, due tobetween PCOS and IHD, due to dyslipidaemia (Legrodyslipidaemia (Legro et alet al., 2001 ) and., 2001 ) and markers of abnormal vascular functionmarkers of abnormal vascular function (Christian(Christian et alet al., 2003 ).., 2003 ).
  • 22. PCOS and cancer riskPCOS and cancer risk  ovarian cancer: Limited dataovarian cancer: Limited data  Women with PCOS are also thought to beWomen with PCOS are also thought to be at increased risk for endometrial cancerat increased risk for endometrial cancer through chronic anovulation withthrough chronic anovulation with unopposed estrogen exposure of theunopposed estrogen exposure of the endometrium. However, epidemiologicalendometrium. However, epidemiological evidence to support this hypothesis isevidence to support this hypothesis is limited (Hardimanlimited (Hardiman et alet al., 2003 ).., 2003 ).
  • 23. Why such limited EvidenceWhy such limited Evidence  Well designed cohort studies are still notWell designed cohort studies are still not availableavailable  Only retrospective studies and someOnly retrospective studies and some Cross sectional studies are availableCross sectional studies are available
  • 24. ConclusionConclusion  insulin sensitizers, and modifying life styleinsulin sensitizers, and modifying life style are the key for managementare the key for management  Long-term prospective trials are neededLong-term prospective trials are needed to better delineate the nature andto better delineate the nature and magnitude of disease risks associatedmagnitude of disease risks associated with PCOSwith PCOS