Slide1 l.jpg
This presentation is the property of its rightful owner.
Sponsored Links
1 / 81

PCOS, dyslipidemia and CVD Nelly Pitteloud, MD Reproductive Endocrine Unit Massachusetts General Hospital COI: Repros Consultant PowerPoint PPT Presentation


  • 129 Views
  • Uploaded on
  • Presentation posted in: General

PCOS, dyslipidemia and CVD Nelly Pitteloud, MD Reproductive Endocrine Unit Massachusetts General Hospital COI: Repros Consultant. Objectives. PCOS Definition Pathophysiology Metabolic features. 22 yo woman with oligomenorrhea. 22 yo with 9 months oligoamenorrhea

Download Presentation

PCOS, dyslipidemia and CVD Nelly Pitteloud, MD Reproductive Endocrine Unit Massachusetts General Hospital COI: Repros Consultant

An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -

Presentation Transcript


Slide1 l.jpg

PCOS, dyslipidemia and CVDNelly Pitteloud, MD Reproductive Endocrine UnitMassachusettsGeneral HospitalCOI: Repros Consultant


Objectives l.jpg

Objectives

  • PCOS

    • Definition

    • Pathophysiology

    • Metabolic features


22 yo woman with oligomenorrhea l.jpg

22 yo woman with oligomenorrhea

  • 22 yo with 9 months oligoamenorrhea

  • Menarche age 11 yrs, cycles approx 45 days

  • Slightly overweight since elementary school

  • Acne with menses

  • Waxes upper lip, chin weekly for one year

  • Family history of type 2 diabetes


Examination l.jpg

Examination

  • Weight 178, height 5’5”, BMI 29 kg/m2

  • Terminal hair on face

  • Acanthosis nigricans

  • Work-up: Neg hCG, FSH 5.2 IU/L, Prl 10 ng/ml, TSH 2.0 uU/ml, T 90 ng/dL

Diagnosis?

Further work-up?


Slide5 l.jpg

Hypothalamic-Pituitary-Gonadal Axis

Hypothalamus

GnRH

Pituitary

LH

E2

FSH

Ovary


Polycystic ovarian syndrome definition 1990 nih workshop l.jpg

POLYCYSTIC OVARIAN SYNDROMEDefinition 1990 NIH Workshop

  • CHRONIC OLIGO/ANOVULATION

  • HYPERANDROGENISM

in the absence of other known causes of androgen excess

(tumor, CAH, hyperprolactinemia)


Polycystic ovarian syndrome 2003 rotterdam workshop l.jpg

POLYCYSTIC OVARIAN SYNDROME2003 Rotterdam Workshop

  • 2 of 3:

  • CHRONIC OLIGO/ANOVULATION

  • HYPERANDROGENISM

  • POLYCYSTIC OVARIAN MORPHOLOGY

in the absence of other known causes of androgen excess


Polycystic ovarian syndrome l.jpg

Polycystic Ovarian Syndrome

  • Affects 6-10% of women of childbearing age (3.2 to 5.4 million women in the U.S.)

  • Chronic anovulation and hyperandrogenism

  • Most common cause of female infertility (approximately 50-60%)

    • Anovulation

    • Early miscarriage

  • Most common endocrinopathy in young women

  • Insulin resistance is a prominent feature


Slide9 l.jpg

The Polycystic Ovary


Slide10 l.jpg

  • Normal ovary

  • Few follicles

  • Random distribution

  • No increased stroma

  • Polycystic ovary (PCO)

  • Ovarian vol >10 ml or

  • >12 small follicles (2-8 mm)

  • Peripheral distribution

  • Increased stromal vol

    • (Jonard et al, 2003)


Slide11 l.jpg

Proportion of Anovulatory PCOS Subjects

0 20 40 60 80 100%


Slide12 l.jpg

POLYCYSTIC OVARY SYNDROME: Clinical concerns

  • Menstrual cycle irregularity/Chronic unopposed estrogen exposure

  • Hyperandrogenic symptoms (hirsutism, acne, alopecia)

  • Anovulatory infertility (but risk of intermittent ovulation)

  • Metabolic risks


Slide13 l.jpg

Neuro-

endocrine

Androgens

Insulin

Pathophysiology of PCOS

Menstrual

Irregularity

+

Hyperandrogenism


Slide14 l.jpg

Pathophysiology of PCOS

Hyperandrogenism

ovary

1o or 2o

morphology

adrenal


Slide15 l.jpg

PCOS

PCOS

Normal

Normal

Taylor et al, 1994


Slide16 l.jpg

Pathophysiology of PCOS

Neuroendocrine

abnormalities

1o or 2o?

LH

FSH

Hypothalamus

Pituitary


Gonadotropin abnormalities in pcos l.jpg

100

LH IU/L

50

PCOS

25

FSH IU/L

20

10

Yen et al, 1970

Gonadotropin Abnormalities in PCOS

Normalized transiently after ovulatory cycle or progestin


Slide18 l.jpg

Obesity results in decreased serum LH

LH

LH


Slide19 l.jpg

Pathophysiology of PCOS

Hyperinsulinemia

 insulin

signaling

SHBG


Slide20 l.jpg

Insulin Resistance and PCOS

  • Insulin resistance is a very common feature of women with PCOS (60-75%)

  • Insulin resistance occurs in both obese and non-obese women with PCOS

  • Anomalies in insulin Receptor mediated transduction

  • Obesity has a synergystic effect on glucose metabolism and IR

Palomba S, Endocrine Review, 2009


Slide21 l.jpg

WHO 2006 Criteria to define hyperglycemia

2-h glucose/OGTT

    NGT<140 mg/dl (7.8 mmol/liter)

IGT >140 mg/dl (7.8 mmol/liter) and < 200 mg/dl (11.1 mmol/L)

DM= or > 200 mg (11.1 mmol/liter

Fasting glucose

Normal FG<110 mg/dl (6.1 mmol/liter)

IGT110 mg/dl (6.1 mmol/liter) to 125 mg/dl (6.9 mmol/L)

Diabetes = or > 126 mg/dl (7.0 mmol/liter)


Slide22 l.jpg

*

*

*

*

*

*

200

LEAN

200

*

PCOS

*

150

PCOS

150

100

NL

100

50

NL

0

50

0

20

40

60

80

100

120

0

200

0

20

40

60

80

100

120

*

200

*

*

*

PCOS

PCOS

150

150

100

NL

NL

100

50

50

0

120

0

20

40

60

80

100

0

0

20

40

60

80

100

120

Insulin and Glucose Responses in PCOS

OBESE

INSULIN

GLUCOSE

MINUTES

Dunaif A et al, 1987


Slide23 l.jpg

IR is present in both lean and obese PCOS compared to

their BMI and age matched counterpart

Insulin Sensitivity

Nl

Lean

Nl

Obese

PCOS

Lean

PCOS

Obese

Dunaif A et al, 1987


Slide24 l.jpg

PCOS and Obesity

  • 60% of US women with PCOS are obese

  • Distribution of fat: visceral adiposity (Android pattern)

    • Known to be metabolically active

    • Highly associated with hyperinsulinemia

    • Central obesity correlates with  CV risk.

  • 70% of lean PCOS women have an android pattern of fat distribution.

    • Is obesity an intrinsic clinical sign of PCOS or promoting environmental factor?

    • Nelson SM, 2007


Slide25 l.jpg

Prevalence of Glucose intolerance and

Diabetes in PCOS


Prevalence of igt by ogtt in 254 women with pcos 14 44 yr old l.jpg

Prevalence of IGT (by OGTT ) in 254 womenwith PCOS 14-44 yr old

61,3%

31.1%

7.5%

NGT

IGT

Type II DM

Legro et al, JCEM, 1999


Slide27 l.jpg

Conversion rate to IGT and type II DM

  • Controlled Study

  • Baseline OGTT

  • 71 PCOS and 23 normal

  • F/U 2-3 yr

  • PCOS:

    • 37% IGT and 10% DM2 at baseline

    • 16% conversion/year from NGT to IGT

    • 2% conversion/year from IGT to DM2

    • The conversion from IGT to frank diabetes is substantiallyenhanced in women with PCOS

      • Legro et al, JCEM, 2005


Slide28 l.jpg

Development of Gestational DM

  • Meta-analysis

  • 720 women with PCOS and 4505 controls

  • RR 2.94 (CI 1.70-5.08) of developing GDM than controlwomen

  • Besides converting to IGT or type 2 DM, women with PCOS arealso at high risk for developing gestational DM

    • Boomsma et al, Hum Reprod Update, 2006


Slide29 l.jpg

PCOS and Type II diabetes

  • Nurses’ Health Study II (NHSII): 101.073 women

    • Women followed for 8 years

    • Conversion rate to DMII was 2-fold higher in oligo-

    • menorrheic women, independent of weight

    • By age 30, 30-50% of obese PCOS developed IGT or DM

    • 3-7x increase as compared to the general population

      • Legro et al, JCEM, 1999


Slide30 l.jpg

Mechanisms of Predisposition to the development

Type II DM in PCOS

  • Women with PCOS are insulin resistant independent of obesity

    • Defects in insulinreceptor or post-receptor signal transduction

    • Alteredadipocyte lipolysis

    • Decrease GLUT-4 expression in the adipocytes

    • Many PCOS women exhibit β-Cell dysfunction

  • Ek I et al JCEM 1997

  • Ek I et al, Diabetes 2002

  • Kelsey ES, JCEM 2007


Slide31 l.jpg

PCOS and Metabolic Syndrome


Slide32 l.jpg

Metabolic Syndrome NCEP 2001 ATP III

> 3 of the following for women:

Triglycerides>150 mg/dL

HDL Cholesterol (F)< 50 mg/dL

Blood Pressure>130/85 mm/Hg

Waist> 88 cm

Glucose (fasting)> 100 mg/dL


Slide33 l.jpg

Prevalence of Metabolic syndrome in PCOS

  • 33.4% of obese PCOS

  • (Ehrmann et al, 2006)

  • 24% of PCOS (BMI

  • = 31 kg/m2)

  • (Welt et al, 2007)

  • 37% of adolescent

  • girls

  • (Coviello et al 2006)

Apridonidze T eta al JCEM 2005


Slide34 l.jpg

Prevalence of Metabolic syndrome in PCOS

compared to NHANES women

Age GroupBMI (kg/m2)

<2525–30>30

20–29 yr (n = 29)

    PCOS (%)175845

    U.S. females (%)0.88.327

30–39 yr (n = 49)

    PCOS (%)234062

    U.S. females (%)11443

Apridonidze T eta al JCEM 2005


Slide35 l.jpg

PCOS and CVD


Slide36 l.jpg

CV Risk Factor in PCOS

  • Surrogate endpoints suggest increased CV risk:

    • Hypertension, Obesity,  WHI, Insulin resistanc, HDL

    • TG , Chronic inflammation, C-reactive protein & PAI-1

    •  Likely due to both:

    • Hyperandrogenism

    • Impaired insulin sensitivity


Slide37 l.jpg

Distribution of CHD risk factors in premenopausal

women PCOS vs. control

PCOS (n=36)

NL (n=71)

Pvalue

Variable

  • Age (yr)38.5 39.0 0.40

  • BMI (kg/m2)31.431.2 0.26

  • Waist (cm)94.75 94.5 0.14

  • Ferriman-Gallwey 16.0 4.0 0.0001

  • Systolic BP (mm Hg)116 116 0.73

  • Diastolic BP (mm Hg)74.8 71.5 0.03

  • Smoking status8.3%11.4%

  • Fasting insulin (µIU/ml)7.65 6.3 0.11

  • Fasting glucose (mg/dl)90.5 93.0 0.43

  • IGT36.1%23.2%0.18

  • Cholesterol (mg/dl)190 174 0.008

  • HDL (mg/dl)48 48 0.49

  • LDL (mg/dl)111 99 0.04

  • TG (mg/dl) 125 118 0.33

  • SHBG (nmol/liter31.7 38.5 0.04

  • Total T (ng/dl)47.5 34 <0.0001

  • Free T (ng/dl)0.19 0.12 <0.0001

Christian RC, JCEM, 2003


Slide38 l.jpg

PCOS AND CARDIOVASCULAR DISEASE

  • Retrospective study of Swedish women who had ovarian

  • wedge resection in 1950s’:

  • RR for MI of 7.4

  • Acta Obstet Gynecol Scand, 1992;71;599

  • Death certificates from women with PCOS in the UK showed no

  • Increase in MI above expected number

  • J. Clin. Epidemiol 1998; 51;581


Slide39 l.jpg

PCOS AND CARDIOVASCULAR DISEASE

  • Nurse Health Study: 82.439 women followed for 14 years.

  • In women with very irregular menses:

  • RR for CHD was 1.5 (CI 1.3-1.9)

  • RR for fatal MI was 1.9 (CI 1.3-2.7)

  • JCEM, 2002; 87;2013

Prospective controlled studies on CVD morbidity and mortality

in PCOS are LACKING


Slide40 l.jpg

Evaluation of metabolic anomalies

In PCOS patients


Slide41 l.jpg

Evaluation of Women with PCOS: Metabolic issues

  • Check for :

    • Glucose intolerance (OGTT)

    • Position of the Androgen Excess Society (2008)

    • Women with PCOS regardless of their weight should be

    • Screened for IGT and DMII by an OGTT at presentation

    • And every 2 yrs.

    • HTA

    • Dyslipidemia

    • Risk factors for heart disease


Slide42 l.jpg

Traditional and novel therapy for

PCOS patients


Slide43 l.jpg

Traditional and Novel Goals of Therapy in PCOS

  • Improve reproductive function/fertility

  • Decrease risk of endometrial cancer

  • Treatment of acne and hirsutism

  • Ameliorate complications putatively due to insulin resistance

    • Prevent IGT and DM

    • Prevent ATS and acute cardiac events


Slide44 l.jpg

PCOS: Management

  • Menstrual cycle irregularity/Chronic unopposed estrogen exposure:

    Oral contraceptives (avoid levonorgestrel)

    Cyclic progestin therapy

  • medroxyprogesterone acetate 10mg x10d every other month

  • Natural progesterone 200mg x 12d every month

    Metformin? (need for monitoring)


Pcos management l.jpg

PCOS: Management

  • Hirsutism

  • Oral contraceptives

  • Oral contraceptives + antiandrogen (spironolactone)

  • Insulin lowering agents ineffective

  • Direct hair removal (laser and electrolysis)

  • Topical agents (eflornithine)

    Martin et al. JCEM 2008


Pcos management46 l.jpg

PCOS: Management

Infertility

  • Weight loss!

  • Ovulation induction (metformin vs clomiphene)


Pcos management47 l.jpg

PCOS: Management

Prevention of IGT and Type II diabetes


Slide48 l.jpg

Prevention of type II DM in non-PCOS Population

  • Diabetes Prevention Program Research Group 2002 (DPP)

    • Large placebo controlled RCT on 3234 subjects in the US with high risk of developing DM

      • Gestational DM

      • Presence of IGT

      • First degree relative with DM

    • Subjects were randomized to

      • Standard management

      • Intensive life style intervention

      • Metformin

      • Troglitazone (discontinued after 18 M– hepatic dysfct)

      • DPP Group, NEJM, 2002


Slide49 l.jpg

Prevention of DMII in non-PCOS Population (DPP)

Mean F/U of 2.8 yr

  • Intensive life style intervention  incidence of new type II DM by 58%

  • Metformin  incidence of new type II DM by 31%

Improvement in insulin sensitivity either through intensive life

Style modification ++ or metformin reduces the risk of developing DM in

High risk population

DPP Group, NEJM, 2002


Slide50 l.jpg

Metformin and Prevention of IGT in PCOS

  • Limited data on the long-term beneficial effect of Metformin on the

  • risk for type II DM in women with PCOS.

  • One retrospective study of PCOS women treated with metformin for an

  • average of 43 M

  • At baseline: 78% had NGT & 22% had IGT

  • At F/U: No woman developed DM

  • IGT group: 45% continued IGT

  • 55% revert to NGT

  • NGT group: 5% converted to IGT

  • 95% continued NGT

  •  11-fold decrease in the annual conversion rate from NGT to IGT

  • with 55% of IGT patients reverting to NGT

Sharma et al End. Pract, 2007


Slide51 l.jpg

Metformin and Prevention of IGT in PCOS

  • Meta-analysis (Salpeter et al, Am J Med. 2008)

  • Goals:To assess the effect of metformin on metabolic risk in patients at

  • high risk for DM

  • Inclusions: 31 clinical trials (n= 4570) including 620 PCOS subjects

  • F/U: Average 2 yrs

  • Results: Fasting glucose Reduction - 4.5 mg/dL; 95% CI -6 to -3

  • Fasting insulin Reduction - 14.4 IU/L 95% CI -19 to -9

  • PCOS vs non-PCOS & obese vs nonobese -- p value NS

  • New onset DM40% decrease p< 0.01

  • Absolute risk of DM6% decrease 95% CI 4 to 8

  • No data on subgroups.

Sharma et al End. Pract, 2007


Slide52 l.jpg

PCOS: Management

Metabolic Abnormalities

  • INTENSIVE LIFE STYLE CHANGES

    • Diet low in CH

    • Exercise

    • ? Surgery for morbid obesity

  • Medication to enhance insulin sensitivity

    • Metformin

    • Thiazolidinedione (rosiglitazone, pioglitazone)


Slide53 l.jpg

Insulin Sensitizing Drug in PCOS

  • Insulin sensitizing drug in PCOS

    • Improves insulin sensitivity

    • Improve glucose tolerance

    • May reduce serum TG

    • Reduce plasma PAI-1 & CRP

  • Insulin sensitizing drug in IGT or GDM

    • Prevent progression to DM2

    • May decrease CV disease


Slide54 l.jpg

Summary

  • PCOS is a GENERAL HEALTH ISSUE

    • Evaluation should include screen for :

    • IGT

    • Dyslipidemia

    • HTA

    • CV risk factors

  • Novel Goals of Therapy

    • Decrease risk for type II DM

    • Decrease risk for early CV disease

    • Life style modification

    • Insuline sensitizing agents


Return to patient l.jpg

Return to patient

  • Irregular menses

  • Hyperandrogenism (acne and hirsutism, high serum T)

  • Nl Prolactin, not pregnant

    = PCOS

    High BMI, acanthosis nigricans, FH of type II diabetes

    BP normal, Waist 89 cm

    Fasting glucose : normal

    OGTT: 2h glucose was 190 mg/dL

    Lipid profile: Cholesterol 210, HDL 53, TG 160, LDL 126


Slide58 l.jpg

Insulin Signaling Pathways in PCOS – Differential Effects

IRS1/2 mediation of PI3 kinase

 glucose transport & carbohydrate metabolism

MAP kinase mitogenesis


Polycystic ovarian syndrome 2000 nih workshop l.jpg

PCO

Morphology

Idiopathic Hirsutism

Hyperandrogenism

PCOS

PCOS

Hypothalamic

Amenorrhea

Irregular cycles

POLYCYSTIC OVARIAN SYNDROME2000 NIH Workshop


Implications of rotterdam criteria l.jpg

Implications of Rotterdam Criteria

  • Ovulatory vs anovulatory bleeding

  • PCOS vs hypothalamic amenorrhea

    • Estrogen status

    • LH/FSH ratio

  • Is insulin resistance present in all patients?

    • Risk for diabetes

    • OGTT

  • What are the cardiovascular implications?

    • Lipids, hypertension


Polycystic ovarian syndrome 2003 rotterdam workshop61 l.jpg

PCO

Morphology

Idiopathic Hirsutism

PCOS

PCOS

PCOS

Hypothalamic

Amenorrhea

Irregular cycles

POLYCYSTIC OVARIAN SYNDROME2003 Rotterdam Workshop

Less obese

Less hyperandrogenic

No increase in LH

No IR

Less obese

Increased LH

Mild IR (1 of 3 studies)

No hyperandrogenism


What is the role of genetics in pcos l.jpg

  • familial clustering of PCOS

  • not every obese woman develops PCOS, not all women with PCO morphology develop PCOS

  • in vitro

    • theca cells from PCOS ovaries are more efficient at synthesizing androgens from precursors

    • insulin stimulates androgen production by ovaries of PCOS women, but not by ovaries of normal women

  • complex multigenic disorder

    • candidate genes -

      • steroid pathways – CYP11a (P450scc) (Waterworth et al, 1997); HSD17B5 SNP-71G (Qin et al 2006)

      • ~D19S884 (chromosome 19p13.2) (Urbanek et al 2005)

WHAT IS THE ROLE OF GENETICS IN PCOS?


Slide63 l.jpg

What is the Role of Genetics in PCOS?

  • association studies

    • marker ~D19S884 (chromosome 19p13.2) near the insulin receptor

      • Tucci S, JCEM 2001p=0.006, corrected p=0.042

      • Urbanek M, JCEM 2005, 2006

        • linkage and association now confirmed in 3 independent data sets

        • fine mapping of insulin receptor region, including an intragenic marker: no other positive associations

        • marker is within fibrillin 3

        • evidence of regulatory regions near D19S884


Polycystic ovarian syndrome principles of management l.jpg

POLYCYSTIC OVARIAN SYNDROME:PRINCIPLES OF MANAGEMENT

  • MENSTRUAL CYCLE IRREGULARITY/

    ENDOMETRIAL PROTECTION

  • HYPERANDROGENIC SYMPTOMS

  • CONTRACEPTION / INFERTILITY

  • METABOLIC RISK


Slide65 l.jpg

140

120

Before

After

100

80

60

40

20

0

Fast.

Insulin

pmol/L

SHBG

nmol/L

Free T

pmol/L

Effect of Metformin on Lean PCOS

  • Improvement in:

  • menstrual pattern

  • fertility +/- clomid

Nestler, JCEM, 1997


Menstrual cycle irregularity endometrial protection l.jpg

MENSTRUAL CYCLE IRREGULARITY/ENDOMETRIAL PROTECTION

WEIGHT LOSS

WITHDRAWAL BLEEDING IF CYCLES > 60 DAYS

cyclic medroxyprogesterone 5 to 10 mg/day x 10-14 days

cyclic micronized progesterone 200 mg/day x 10-14 days

oral contraceptives


Hyperandrogenic symptoms l.jpg

Cosmetic Approaches

- electrolysis, laser

Oral Contraceptives

Anti-androgens

Insulin Sensitizing Agents

Inhibitors of Steroidogenesis

Direct inhibitors of hair growth

Glucocorticoids

GnRH Analogs

HYPERANDROGENIC SYMPTOMS

No primary treatment established

Combination treatments better than single-agent approaches


Oral contraceptives androgenic potential l.jpg

LevonorgestrolNordette, Triphasil

Ethynodiol DiacetateDemulen

NorethindroneBrevicon, Modicon

DesogestrelDesogen, Ortho-Cept

NorgestimateOrtho-Cyclen, Ortho Tri-Cyclen

DrospirenoneYasmin

ORAL CONTRACEPTIVES: Androgenic Potential

Androgenic Potential


Antiandrogens l.jpg

spironolactone (off label use)

aldosterone antagonist, competitive inhibitor of DHT, 5-a reductase inhibitor, inhibits p450 enzymes, decreases androgens

cyproterone acetate

competitive inhibitor of DHT, 5-a reductase inhibitor, decreased LH

flutamide (off label use)

non-steroidal anti-androgen, competitive inhibitor of DHT, inhibits p450 enzymes

ANTIANDROGENS


Treatment of hirsutism l.jpg

Vaniqa

TREATMENT OF HIRSUTISM

  • anhydrous eflornithine hydrochloride

  • irreversibly inhibits ornithine decarboxalase activity in the skin  inhibits cell division and synthetic functions  decreases hair growth

  • apply bid, improvement expected in 4 to 6 weeks

  • can use in conjunction with other hair removal techniques


Contraception l.jpg

CONTRACEPTION

OLIGO/OVULATORY STATUS

BARRIER METHODS WITH USE OF PROVERA

FOR ENDOMETRIAL PROTECTION


Infertility l.jpg

INFERTILITY

WEIGHT LOSS

obesity - infertility and obstetrical risks

OVULATION INDUCTION

clomiphine +/- metformin

controversial

aromatase inhibitors – more data needed

low dose gonadotropins

PCOM – generally responds like PCOS

WEDGE RESECTION / LASER SURGERY

8-34% incidence of pelvic adhesions

ovulatory status - 60% ovulatory, 30% oligo/ovulatory

ASSISTED REPRODUCTIVE TECHNOLOGIES

high # of follicles and oocytes retrieved

fertilization, cleavage rate low

risk of ovarian hyperstimulation


Slide73 l.jpg

METABOLIC RISK

35 to 50% of obese women with PCOS develop either impaired glucose tolerance or type 2 diabetes by the age of 30!

Legro RS 1999; Dahlgren E 1992;

Dunaif A1995;Ehrmann DA, 1995.

PCOS women are at risk for IGT and DM II at all weightsdetection is markedly improved by the use of post-challenge glucose values


Slide74 l.jpg

METABOLIC RISK

  • HEART DISEASE

  • no prospective studies have documented an increased risk

  • increased prevalence of subclinical atherosclerosis

  • surrogate endpoints suggest increased risk

    • hypertension, obesity, increased WHR, insulin resistance, lipids (~70%)

  • METABOLIC SYNDROME

  • 33.4% of adults with PCOS (Ehrmann et al, 2006)

    • waist circ 80%, HDL 66%, TG 32%, BP 21%, FBS 5%

  • 37% of adolescent girls (Coviello et al 2006)


Slide75 l.jpg

METABOLIC RISK

Screen for -

GLUCOSE INTOLERANCE

HYPERTENSION

DYSLIPIDEMIA

RISK FACTORS FOR HEART DISEASE


Slide76 l.jpg

Therapeutic Options

  • weight loss

  • diet

  • surgery

  • diet modification

  • exercise

  • medication to enhance insulin sensitivity

  • metformin

DPP: importance of lifestyle interventions and metformin in preventing DM in IGT

insufficient data to warrant prophylactic use of metformin in all women with PCOS


Slide77 l.jpg

Metformin: Meta-analysis of RTC in PCOS (n=13)Lord, Flight, Norman BMJ 2003

  • Ovulation

    • metformin alone vs placebo OR 3.88

    • metformin + clomid vs clomid OR 4.41

    • endometrial surveillance if used alone

  • Pregnancy*

    • metformin + clomid OR 4.41

  • * no teratogenecity in in vitro models, no teratogenecity when administered during pregnancy - limited data; may decrease miscarriage

  • Metabolic Syndrome

    • positive effect on fasting insulin, BP, LDL

    • no effect on weight loss


Slide78 l.jpg

FreeT

SHBG

pg/mL

Ug/dL

*

20

*

1.0

15

0.8

10

0

0.6

After

Baseline

Baseline

After

* = P<0.05

Effect of 1000 Kcal diet for 7 months in 13 women

with PCOS (< 5 % weight loss, mean 12%)

Improvement in - menstrual pattern 11/13

- 5 conceived

- hirsutism (40%)

Kiddy, Clin Endo, 1992


Therapeutic options metabolic risk l.jpg

Therapeutic Options – Metabolic Risk

  • weight loss

  • diet

  • surgery

  • diet modification

  • exercise

  • medication to enhance insulin sensitivity

  • metformin

DPP: importance of lifestyle interventions and metformin in preventing DM in IGT

insufficient data to warrant prophylactic use of metformin in all women with PCOS


Slide80 l.jpg

Hirsutism

  • Defined as presence of terminal (coarse) hair in male pattern

  • Interaction between circulating androgens and sensitivity of the hair follicle

  • Majority of women with hirsutism have underlying endocrine disorder

  • --75-80% have PCOS (Azziz,Carmina)

    --Nonclassic CYP21A2 deficiency

    --Androgen-secreting tumors


Slide81 l.jpg

LH

Cholestrol

b

Androstenedione

Testosterone

a

Insulin

IGF

Androstenedione

Testosterone

FSH

Estrone

Estradiol

aromatase

Theca Cell

Granulosa Cell


  • Login