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Polycystic Ovarian Syndrome A Hidden Epidemic

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Title: Polycystic Ovarian Syndrome A Hidden Epidemic


1
Polycystic Ovarian SyndromeA Hidden Epidemic
  • Gad Lavy, M.D.
  • New England Fertility Institute
  • Lifeline Cryogenics

2
PCOS-Taking points
  • A common condition recognized for decades and
    familiar to all Ob/Gyns and general
    practitioners.
  • Fertility and esthetic concerns often bring it to
    attention.
  • New information suggests it to be a more serious
    medical condition and a significant public
    health problem.
  • Treatment is focused on the metabolic defect.
  • A team approach to therapy is essential.

3
Stein-Leventhal Syndrome 1935
  • Amenorrhea associated with bilateral polycystic
    ovaries Stein I.F. and Leventhal M.L. (1935). Am.
    J. Obstet. Gynecol. 29181-189.
  • Wedge Resection restored normal menses

4
Stein-Leventhal Syndrome
  • Stein-Leventhal Syndrome The Triad
  • Amenorrhea
  • Obesity
  • Hirsutism
  • Many cases do not conform to the classic
    description.
  • The polycystic ovaries are not the primary cause
    but one of the manifestation of the underlying
    endocrine disorder which results in anovulation.

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6
320,000 Google pages.
5000 publications (2000 since 2002).
7
PCOS in the Limelight
  • PCOS no longer a primarily gynecological
    disorder.
  • Associated with cardiovascular disease and
    diabetes, the most significant cause of morbidity
    and mortality in women.

8
Origins
  • Genetic disorder Potential present at birth.
  • Manifests often at puberty.
  • Ovarian function is necessary.
  • A history of PCOS carries major long term
    consequences of cardiovascular disease even after
    menopause.

9
PCOS Prevalence
  • Affects 6-10 of women in childbearing age (4-5
    million women).
  • Most common cause of anovulatory infertility
    (50-60).
  • Most common endocrine disorder in young women.
  • It is one of the major and unrecognized public
    health problems in this country

10
PCOS
  • Insulin resistance is a prominent feature.
  • Hyperandrogenism secondary to high insulin
  • Chronic anovulation A result of both

11
The Faces of PCOS
12
When to Suspect PCOS
  • Irregular or infrequent menses.
  • Increased androgens causing hirsutism and acne.
  • Polycystic ovaries by ultrasound.
  • Exclusion of other endocrine disorders (thyroid,
    adrenal, ovary).

13
When to Suspect PCOSAdditional clues
  • Infertility or pregnancy loss
  • Problems maintaining normal weight
  • Family history of PCOS, infertility of irregular
    cycles
  • Family history of diabetes or CVD
  • Hyper or hypoglycemia
  • Hypertension
  • Dark skin patches in skin fold
  • Scalp hair loss
  • High LDL, TG and low HDL
  • Sleep apnea, Depression and anxiety

14
PCOS Diagnostic Criteria
  • Anatomical
  • Biochemical
  • Clinical

15
PCOS Diagnostic Criteria
  • Anatomical
  • Ultrasound
  • Surgery
  • Pathology
  • Biochemical
  • Altered androgens
  • Reverse in LH/FSH
  • Altered fasting/stimulated glucose/insulin
  • Clinical
  • Ovulatory dysfunction
  • Body weightgt110 of ideal
  • Hyperandrogenism

16
Anatomy of PCOS
17
PCOS Diagnostic Criteria
  • Anatomical
  • Ultrasound
  • Surgery
  • Pathology
  • Biochemical
  • Altered androgens
  • Reverse in LH/FSH
  • Altered fasting/stimulated glucose/insulin
  • Clinical
  • Ovulatory dysfunction
  • Body weightgt110 of ideal
  • Hyperandrogenism

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PCOS Diagnostic Criteria
  • Anatomical
  • Ultrasound
  • Surgery
  • Pathology
  • Biochemical
  • Altered androgens
  • Reverse in LH/FSH
  • Altered fasting/stimulated glucose/insulin
  • Clinical
  • Ovulatory dysfunction
  • Body weightgt110 of ideal
  • Hyperandrogenism

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21
Hyperandrogenism Hyperinsulinemia
22
Diagnosis of PCOS
  • Ovarian/menstrual dysfunction (stein-Leventhal
    1935)
  • Clinical/biochemical evidence of increased
    androgens (1990 NIH conference of PCOS)
  • Ultrasound Showing polycystic ovaries (2003
    consensus conference)
  • Insulin resistance and metabolic syndrome
    glucose tolerance test

23
PathophysiologyInsulin Resistance and PCOS
  • Hyper-insulinemic insulin resistance is a
    universal feature of PCOS
  • PCOS is associated with a unique form of insulin
    resistance.
  • Hyper-insulinemic insulin resistance is present
    in obese and non-obese PCOS women

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25
Insulin Resistance in Women with PCOS
Insulin Sensitivity decreases
Insulin release and circulating levels increase
Normal glucose tolerance
Compensatory Hyperinsulinemic Insulin Resistance
26
Hyperinsulinemia and Hyperandrogenism
Hyper-insulinemia
Disordered LH/FSH release
Ovarian androgen production
SHBG production
Anovulation
Hyperandrogenism
PCOS
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Impact of PCOS
  • Gynecological ovulatory dysfunction
  • Cosmetic Hyperandrogenism
  • Metabolic Insulin resistance and
    hyperandrogenism

29
Impact of PCOS
  • Gynecological ovulatory dysfunction
  • Infertility
  • Endometrial cancer
  • Cosmetic Hyperandrogenism
  • Hirsutism
  • Acne
  • Metabolic Insulin resistance and
    hyperandrogenism
  • Type 2 Diabetes
  • Dyslipedemia
  • Cardiovascular disease
  • Hypertension

30
PCOS and Infertility
  • Ovulatory dysfunction
  • Hyper-insulinemia
  • Hyper-androgenism
  • Ovulation Induction therapy
  • Pregnancy loss
  • Pregnancy complications

31
PCOS Ovulation Induction
  • Poor response to standard ovulation drugs
  • Multiple pregnancy
  • Ovarian Hyper-stimulation
  • Once pregnant
  • Pregnancy Loss
  • Gestational Diabetes

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Metformin and Ovulation
  • Ovulation Rate
  • 3.9 fold increase (plt0.00001)
  • 46 with metformin compared to 24 with placebo
  • NNT4.4
  • Clinical Pregnancy
  • 2.8 fold increase (p0.09)

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35
Metformin and Clomiphene
  • Ovulation rate
  • 4.4 fold increase
  • 76 with metformineclomid vs. 42 with clomid
    alone
  • NNT3.0 (1.5 for clomid resistant women)
  • Clinical Pregnancy Rate
  • 4.4 fold increase

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37
PCOS and Pregnancy Loss
  • Women with PCOS have a very high incidence of
    pregnancy loss (30-50)
  • Insulin resistance underlies the pregnancy loss
    (glycodelins endometrial proteins).
  • Insulin sensitizers reduce the risk of pregnancy
    loss.
  • No evidence that IS should be continued past the
    first trimester.

38
Impact of PCOS
  • Gynecological ovulatory dysfunction
  • Infertility
  • Endometrial cancer
  • Cosmetic Hyperandrogenism
  • Hirsutism
  • Acne
  • Metabolic Insulin resistance and
    hyperandrogenism
  • Type 2 Diabetes
  • Dislipedemia
  • Cardiovascular disease
  • Hypertension

39
Skin Manifestations of PCOS
  • Acne
  • Hirsutism
  • Alopecia
  • Acanthosis Nigricans

Hyperandrogenism
Hyperinsulinemia
40
Treatment of Skin Manifestations of PCOS
  • Drug therapy
  • Cosmetic therapy
  • Skin care
  • Hair removal

41
PCOS Treatment of Hyperandrogenism
  • Inhibit ovarian/adrenal androgen production
  • Block androgen receptor
  • Block 5 alpha reductase in the hair follicle

42
Drug therapy for hyperandrogenism
  • Flutamide
  • Spironolactone
  • Cyprotarome Acetate (in OCP)
  • Thiazolidinediones (TZDs)
  • OCP
  • Metformin
  • Finestimide

43
Impact of PCOS
  • Gynecological ovulatory dysfunction
  • Infertility
  • Endometrial cancer
  • Cosmetic Hyperandrogenism
  • Hirsutism
  • Acne
  • Metabolic Insulin resistance and
    hyperandrogenism
  • Type 2 Diabetes
  • Dislipedemia
  • Cardiovascular disease
  • Hypertension

44
Metabolic Impact of PCOS Syndrome X
Insulin Resistance and Hyper-insulinemia
Diabetes
PCOS
hypertension
Dyslipidemia
Atherosclerosis
45
Metabolic Syndrome(NHANES III criteria)- three
of five needed for dx
  • Increased waist circumference (gt36 in)
  • Elevated TGs (gt149 mg/dl)
  • Decreased HDL cholesterol (lt50 mg/dl)
  • High blood pressure gt130/85
  • Fasting glucose gt 100 mg/dl

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47
PCOS and Type 2 Diabetes
  • 30-50 of obese women with PCOS develop IGT or
    DM2 by age 30
  • 25-28 of pre-menopausal women with DM2 have
    PCOS (often undiagnosed).
  • 82 of pre-menopausal women with DM2 have
    anatomically polycystic ovaries.

48
Cardiovascular Risks Factorsand PCOS
  • Obesity
  • Hypertension
  • Vascular dysfunction
  • Decreased HDL
  • Increased TG
  • Increased CRP, Endothelin-1 and PAI-1

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51
PCOS and Cardiovascular Risk
  • Retrospective study of Swedish women who had
    ovarian wedge resection RR for MI of 7.4 (acta
    Obstet Gynecol 1992, 71599)
  • Association between PCOs and extent of CAD in
    women undergoing cardiac cath (Ann Intern
    Med.12632)

52
PCOS and Cardiovascular Disease
  • Nurses Health Study
  • 82,439 women followed for 14 years
  • Women with irregular menses
  • RR for CHD1.5
  • RR for fatal MI1.9 (JCEM 2002 872013)

53
PCOS Cardiovascular Risk Factors
  • Postmenopausal women with history of irregular
    cycles are at a higher risk of MI

54
Evaluation of Women with PCOSGeneral Health
Issues
  • Glucose Tolerance Test (2 hour OGTT)
  • Monitor BP Hypertension
  • Check lipid profile Dyslipidemia
  • Assess risk factors for heart disease

55
Impact of PCOS
Goal of Therapy
  • Gynecological
  • Infertility
  • Endometrial cancer
  • Cosmetic
  • Hirsutism
  • Acne
  • Metabolic
  • Type 2 Diabetes
  • Dislipedemia
  • Cardiovascular disease
  • Hypertension
  • Gynecological
  • Improve reproductive function
  • Reduce risk of endometrial cancer
  • Reduce serum androgens
  • Metabolic Ameliorate complications due to IR
  • Glucose intolerance
  • Dyslipidemia
  • Atherogenesis
  • Hypertension

56
PCOS Drug Therapy
  • Anti-androgens
  • OCP
  • Insulin Sensitizers

57
OCP and Insulin Sensitizers
  • OCP
  • Worsen insulin resistance
  • Induce glucose intolerance
  • Increase serum TG
  • Increase risk of DM2
  • Increase risk of CVD
  • Reduce ovarian androgens (acne, hirsutism)
  • Reduce risk of endometrial carcinoma
  • Insulin Sensitizers
  • Improve insulin sensitivity
  • Improve Glucose tolerance
  • Reduce serum TG
  • Reduce CRP, Endothelin-1 and PAI-1 (and risk of
    CVD)
  • No effect on androgens (acne, hirsutism)
  • No reduction in endometrial cancer risk

58
PCOS Surgical Therapy
  • Wedge resection
  • Ovarian drilling
  • Bariatric surgery

59
Team Approach to PCOS A coordinated approach
Fertility
Metabolic Disorder
Risk of Endometrial cancer
Hirsutism and Acne
60
Team Approach to PCOS A coordinated approach
Psychological counseling
Drug Therapy
Cosmetic therapy
Nutritional counseling
Exercise
61
The PCOS ClinicA Team Approach
  • Eight week treatment and education program
  • Intended for all women with PCOS (regardless of
    desire to conceive)
  • Initial assessment medical, Psychological and
    Fitness
  • Weekly group Education and support

62
PCOS ClinicEducational Component
  • The science of PCOS
  • Women and heart disease
  • Nutrition and low glycemic index diets
  • Intervention for hirsutism and Acne
  • Stress reduction

63
PCOS ClinicPsychological Support
  • Individual weekly assessment
  • Weekly support groups
  • Couples week (get your partner involved)

64
PCOS ClinicFitness
  • Individual assessment and recommendations
  • Group education and instruction

65
Summary
  • Insulin resistance prominent feature of PCOS in
    obese and non-obese women.
  • Increases risk of DM2 and CVD.
  • Plays a pathogenic role in the development of PCOS

66
Summary Insulin Sensitizers
  • Administration of insulin sensitizers
  • Decreases circuiting androgens
  • Improves ovulation and fertility

67
Summary PCOS and general Health Issue
  • OCP may worsen risk of DM2 and CVD
  • Insulin sensitizers may reduce risk of DM2 and CVD

68
PCOS Summary
  • A combination of drug therapy, counseling, and
    cosmetic procedures is needed
  • Dramatic Lifestyle change are needed
  • A team approach to PCOS will maximize results

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