PCOS : Long Term Sequelae BY Mohammad Emam Prof. OB& GYN Mansoura Faculty of Medicine Mansoura Integrated Fertility Center EGYPT 2009

PCOS : An Epidemic An epidemic in developing countries ( ED & PCOS !!!!). ( ED & PCOS !!!!). About 20% of reproductive age women demonstrate the ultrasound picture of polycystic ovaries. About % have clinical or biochemical signs of Anovulation and androgen excess. (These data were collected prior to Rotterdam diagnostic consensus).

PCOS : Cause  Complex interaction of genetic,epigenetic, metabolic, neurologic and environmental factors.  PCOS, starts in adolescence But not always diagnosed at that age.

Rationale women with PCOS cluster risky consequences leading to increased morbidity and mortality.

Rationale  Long term consequences of this syndrome are forgotten by clinicians.  Treatment is directed only for symptoms without digging into deeper

Aim  To heighlight to the different clinicians : ○ The long-term health consequences of PCOS ( other than infertility ). ○ How to minimize or prevent the development of these consequences.

Methods  Randomised controlled trials, systematic reviews and meta- analyses in: The Cochrane Library,RCOG,Medline and PubMed (between 1986 and January 2009).

Long term Consequences Of PCOS  Definite  Possible  Controversial

Definite Long term Consequences Of PCOS  Type 2 diabetes  Dyslipidemia  Endometrial cancer.

 Metabolic : Obesity &IR & Ms &Gall bladder disease  Cerbrovascular disease : Coronary & Cerbral & Hypertension  Depression & anxiety & loss of self esteem  Obstructive Sleep Apnea  Pregnancy complications: Gestational Diabetes Gestational Diabetes Gestaional hypertension Gestaional hypertension  Epilepsy?!!! Possible: Long term Consequences Of PCOS

Controversial Long term Consequences Of PCOS PIH PIH Miscarriage Miscarriage ovarian cancer ovarian cancer B Breast carcinoma

Long Term Risks Of PCOS PCOS CVD Gout Obesity pregnancy Infertility Endometrial Cancer Gallbladder Disease NIDDM

Prevalence Of MS In PCOS MS is present in 2/3 of the PCOS ( 2-fold higher than women in the general population).

Link between Metabolic S & PCOS PCOS MS MS IR

PCOSEpilepsy Epilepsy &PCOS ( what is the culprit?

Counseling  Women diagnosed with PCOS: ○ Should be informed of the possible long- term risks. ○ Should be advised regarding weight control and exercise (B).

Metabolic consequences of PCOS  Women presenting with PCOS: BMI >30 + age > 40 years + +ve Family history of diabetes.  Are at increased risk of type 2 diabetes and should be offered a glucose tolerance test. (B)

PCOS and obstructive sleep apnoea  Women diagnosed with PCOS should be asked (or their partners) about :  Snoring and daytime fatigue  Informed of the possible risks of sleep apnea

PCOS and cardiovascular risk  Hypertension should be treated.  Lipid-lowering drugs should only be prescribed by a specialist

PCOS &pregnancy  Women should be screened for gestational diabetes Before 20 weeks of gestation, with referral to a specialist if diabetes is detected ( B).  Metformin is currently not licensed for use in pregnancy in the UK !!!! and is not recommended for use in pregnancy ( D)………Contraversial

Cancer And PCOS  Amenorrhoeic or severely oligomenorrhoeic women with PCOS should have induced withdrawal bleedingat regular intervals to reduce the risk of developing endometrial hyperplasia(B).  There is no association with breast or ovarian cancer and no additional surveillanceis required (C).

Exercise and weight control  All overweight PCOS should be provided with dietary and lifestyle advice.

How to minimize or prevent long term consequences?

Concept  The genetic expression of PCOS can be optimized and modulated by prevention the interactions between genes and epigenetic factors.

1) Early Detection And treatment of PCOS during adolescence

Screening for PCOS in Adolescents  PCOS should be considered when an adolescent presents with:  Irregular menses, hirsutism, acne, alopecia, central adiposity, AN, and/or hyperinsulinemia

2)Prevention of peripupertal obesity

MORE THAN 1 IN 4 CHILDREN IS OVERWEIGHT or OBESE!!

Energy In Energy Out Peripupertal obesity Weight gain:

peripupertal obesity & PCOS PCOS Peripubertal obesity IR & ghrelin & Leptin

3)The Target Of ttt Should Be Causative Rather Than Symptomatic

Targets For ttt IR None IR Causative ttt +or- Adjunctive Symptomatic ttt : Anovulation, Acne, Hirsutism, Insulin sensitizers : Prevent Hyperandrogenemia – IR Vicious circle. PCOS

Targets for treatment PCOS

Conclusion Treating “the whole state” rather than “the disease” should be the principal on dealing with PCOS

Conclusion Infertility and oligohypomenorhea represent only the tip of ice-berg of PCOS, but late Sequelae are the hidden serious base

Conclusion  Management of PCOS should be started by prevention of obesity in peripupertal kids.

Conclusion  Screening for PCOS in adolescents is mandatory for early diagnosis and minimizing long term Sequelae

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