PCO Over 40PCO Over 40The Lost AreaThe Lost Area

Hesham Al-Inany, PhDHesham Al-Inany, PhDKaainih@yahoo.comKaainih@yahoo.com

An international consensusAn international consensus

Defines PCOS as the presence of at least Defines PCOS as the presence of at least 12 follicles measuring 212 follicles measuring 2--9 mm in diameter 9 mm in diameter and/or an ovarian volume in excess of 10and/or an ovarian volume in excess of 10 mL mL

The Rotterdam ESHRE/ASRM , 2004The Rotterdam ESHRE/ASRM , 2004

AgeAge Most women present in their thirties Most 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, hirsutismhirsutisminfertility infertility

Recent interestRecent interest Adolescent PCOAdolescent PCO More recently, PCO over FortyMore recently, PCO over Forty

Lost AreaLost Area

PCOS is the most common endocrine PCOS is the most common endocrine abnormality of abnormality of reproductive-agedreproductive-aged women women

>40 = fading reproduction>40 = fading reproduction

Lost Area IILost Area II

The main difficulty lies in the absence of The 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

EVIDENCE

The Evidence PyramidThe Evidence Pyramid

ProspectiveProspective

RetrospectiveRetrospective

Observational StudiesObservational Studies

ExposureExposure

Study DirectionStudy Direction

OutcomeOutcome

ExposureExposure OutcomeOutcome

Cohort Study

Case Control Study

OutcomeOutcome

ExposureExposureCross

Sectional Study

Cohort StudyCohort Study

Advantages: Advantages: Ethically safeEthically safe Can establish causality (temporal Can establish causality (temporal

relationship)relationship) Allow studying multiple outcomes for 1 Allow studying multiple outcomes for 1

exposureexposure

PCO over FortyPCO over Forty Why such an interestWhy such an interest There is some evidence that women with There is some evidence that women with

PCOS are at increased risk of developingPCOS are at increased risk of developing type 2 diabetes type 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 rate Miscarriage rate Low birth weightLow birth weight

How patient would presentHow patient would present

Classic PCO caseClassic PCO caseSeeking conceptionSeeking conceptionMenstrual troubleMenstrual troubleHirsutismHirsutism

Pregnant after assisted conceptionPregnant after assisted conception Long term consequences of PCO Long 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 awareness Increase awareness Spot your potential casesSpot your potential cases

Infertility TreatmentInfertility Treatment

Ovulation induction by anti-oestrogen Ovulation 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 used Gonadotrophins can be used

(Al-Inany, 2005)(Al-Inany, 2005)

Infertility TreatmentInfertility Treatment

IVF vs OI + IUIIVF vs OI + IUI IVF is the optimum solution IVF 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-metabolic It is a premenopausal endocrino-metabolic

disorderdisorder As a consequence of insulin-resistance, As a consequence of insulin-resistance,

women affected by PCOS often present women affected by PCOS often present abnormalities of glucose metabolism and abnormalities of glucose metabolism and lipid profile . lipid profile .

Another FactorAnother Factor

Besides insulin-resistance, it has been Besides insulin-resistance, it has been demonstrated that some of these women demonstrated that some of these women also have alterations in beta-cell-function. also have alterations in beta-cell-function. Both disorders (insulin-resistance and Both disorders (insulin-resistance and beta-cell-dysfunction) are recognized as beta-cell-dysfunction) are recognized as major risk factors for the development of major risk factors for the development of type 2 diabetes. type 2 diabetes.

clear evidenceclear evidence

women with PCOS are at increased (3–7 women with PCOS are at increased (3–7 times) risk of developing type 2 diabetes times) risk of developing type 2 diabetes (Legro(Legro et al et al., 1999 ; Wild., 1999 ; Wild et al et al., 2000 ) ., 2000 )

AccordinglyAccordingly

Obese women with PCOS should be Obese women with PCOS should be screened for the metabolic syndrome, screened for the metabolic syndrome, including glucose intolerance with an oral including glucose intolerance with an oral glucose tolerance test. glucose tolerance test.

CVSCVS

No clear evidence of increase incidence of No clear evidence of increase incidence of death from CVS events in women with death from CVS events in women with PCOS, PCOS,

Evidence of significant association Evidence of significant association between PCOS and IHD, due to between PCOS and IHD, due to dyslipidaemia (Legrodyslipidaemia (Legro et al et al., 2001 ) and ., 2001 ) and markers of abnormal vascular function markers of abnormal vascular function (Christian(Christian et al et al., 2003 ). ., 2003 ).

PCOS and cancer risk PCOS and cancer risk

ovarian cancer: Limited dataovarian cancer: Limited data Women with PCOS are also thought to be Women with PCOS are also thought to be

at increased risk for endometrial cancer at increased risk for endometrial cancer through chronic anovulation with through chronic anovulation with unopposed estrogen exposure of the unopposed estrogen exposure of the endometrium. However, epidemiological endometrium. However, epidemiological evidence to support this hypothesis is evidence to support this hypothesis is limited (Hardimanlimited (Hardiman et al et al., 2003 ). ., 2003 ).

Why such limited EvidenceWhy such limited Evidence

Well designed cohort studies are still not Well designed cohort studies are still not availableavailable

Only retrospective studies and some Only retrospective studies and some Cross sectional studies are availableCross sectional studies are available

ConclusionConclusion

insulin sensitizers, and modifying life style insulin sensitizers, and modifying life style are the key for managementare the key for management

Long-term prospective trials are needed Long-term prospective trials are needed to better delineate the nature and to better delineate the nature and magnitude of disease risks associated with magnitude of disease risks associated with PCOS PCOS