PCOSPCOSPolycystic Ovary Polycystic Ovary

SyndromeSyndrome

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ObjectivesObjectives

Know the clinical definition of PCOSKnow the clinical definition of PCOS

Know the typical physical and Know the typical physical and laboratory findings associated with laboratory findings associated with PCOSPCOS

Be familiar with the current Be familiar with the current management optionsmanagement options

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DefinitionDefinition

Polycystic ovary syndrome is a Polycystic ovary syndrome is a clinical diagnosisclinical diagnosis

2 or more of the following features:2 or more of the following features: Chronic oligo-ovulation or anovulationChronic oligo-ovulation or anovulation Androgen excessAndrogen excess Polycystic ovariesPolycystic ovaries

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EpidemiologyEpidemiology

Affects 5-10% of women of Affects 5-10% of women of childbearing agechildbearing age

Most common cause of anovulatory Most common cause of anovulatory infertility in developed countriesinfertility in developed countries

Prevalence of the metabolic syndrome Prevalence of the metabolic syndrome is 2-3x higher among women with is 2-3x higher among women with PCOSPCOS

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Theories to Etiology of Theories to Etiology of PCOSPCOS

Genetic predisposition Genetic predisposition Most likely although no gene isolatedMost likely although no gene isolated

Premature adrenarche (<8 y/o)Premature adrenarche (<8 y/o)

Heterozygosity for congenital adrenal Heterozygosity for congenital adrenal hyperplasia (CAH)hyperplasia (CAH)

Intrauterine Growth Retardation (IUGR)Intrauterine Growth Retardation (IUGR)

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PathophysiologyPathophysiology Majority of women with PCOS Majority of women with PCOS

(regardless of weight), have insulin (regardless of weight), have insulin resistanceresistance Association with: type 2 diabetes, Association with: type 2 diabetes,

dyslipidemia, and hypertensiondyslipidemia, and hypertension Effects of hyperinsulinemiaEffects of hyperinsulinemia

Ovaries remain sensitive to insulin (maybe Ovaries remain sensitive to insulin (maybe hypersensitive) hypersensitive) Androgen excess Androgen excess

Inhibits hepatic production of sex hormone binding Inhibits hepatic production of sex hormone binding globulin globulin increases circulating free testosterone increases circulating free testosterone

Impedes ovulationImpedes ovulation

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Nestler J. N Engl J Med 2008;358:47-54

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Pituitary gland

heightened to GnRH

Exaggerated pulsatile

LH release

LH/FSH ratio

elevated

androgens

Cascade Cascade leading to leading to

excess excess androgensandrogens

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Augment pituitary

sensitivity to GnRH

LH

ovaries overproduce

androstenedione and

testosterone

Androgens converted to estrone

and estradiol

Vicious Cycle of PCOS

CYCLE STARTS

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Clinical FindingsClinical Findings

Anovulation Anovulation amenorrhea & infertility amenorrhea & infertility HirsuitismHirsuitism Acne VulgarisAcne Vulgaris Male pattern baldness/thinningMale pattern baldness/thinning Obesity- android-type with Obesity- android-type with waist-hip waist-hip

ratiosratios Cancer- endometrialCancer- endometrial

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Evaluation: Differential Evaluation: Differential DxDx

PregnancyPregnancy PCOPCO HypothyroidismHypothyroidism Ovarian tumorOvarian tumor Pituitary tumorPituitary tumor

CAHCAH Female Athlete Female Athlete

Triad Triad (hypothalamic (hypothalamic amenorrhea)amenorrhea)

Turner’s syndromeTurner’s syndrome Testicular Testicular

FeminizationFeminization

MORE LIKELY LESS LIKELY

Knowing all of this, Knowing all of this, what laboratory what laboratory tests would you tests would you

order for a patient order for a patient you are suspecting you are suspecting

of PCOS?of PCOS?

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Laboratory Tests to Laboratory Tests to Consider in Evaluation Consider in Evaluation

ProcessProcess B-HCGB-HCG ThyroidThyroid LH/FSHLH/FSH Prolactin Prolactin Free/total Free/total

testosteronetestosterone Fasting 17-OPH Fasting 17-OPH

and cortisoland cortisol

Fasting glucoseFasting glucose Fasting Insulin Fasting Insulin

levellevel Fasting Lipid Fasting Lipid

profileprofile Androstenedione Androstenedione DHEASDHEAS KaryotypeKaryotypeRED - those tests most critical to diagnosis of PCOS

GREEN – consider these tests as associated problems with PCOS

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Ultrasound FindingsUltrasound Findings

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Problems associated with high Problems associated with high levels of sex hormones:levels of sex hormones:

Insulin resistanceInsulin resistance

HyperinsulinemiaHyperinsulinemia

DiabetesDiabetes

Cardiovascular Cardiovascular diseasedisease

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Management: Non-Management: Non-medicalmedical

Weight controlWeight control

Low carb dietsLow carb diets

Exercise Exercise reduce weight and CV reduce weight and CV

risk factorsrisk factors Increase insulin Increase insulin

sensitivitysensitivity

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Management: MedicalManagement: Medical OCP’s: OCP’s:

suppress LH suppress LH androgensandrogens SHBG SHBG free testosteronefree testosterone adrenal production of androgenadrenal production of androgen 5alpha-reductase5alpha-reductase

SpironolactoneSpironolactone

Cyclic progestinsCyclic progestins

GnRH agonistsGnRH agonists

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Management: Management: MetforminMetformin

Reduces hyperinsulinemiaReduces hyperinsulinemia Decreases risk factors for CHDDecreases risk factors for CHD Improved weight-lossImproved weight-loss Normalization of circulating Normalization of circulating

androgensandrogens Resumption of normal ovulatory Resumption of normal ovulatory

menses and therefore reversal of menses and therefore reversal of infertilityinfertility

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