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FacultyFaculty

Deborah Davis, CRNP PCOS: Nurse Practitioner Senior A “Bear” of a Problem Alabama Department of Public Health

Satellite Conference and Live Webcast Friday, November 15, 2013 9:00 – 11:00 a.m. Central Time

Produced by the Alabama Department of Public Health Video Communications and Distance Learning Division

Objectives Objectives • At the conclusion of this • Explain and review the clinical presentation the learner should be significance of PCOS and Metabolic able to: Syndrome – Define PCOS and Metabolic • Describe the management of PCOS Syndrome and Metabolic Syndrome and relate – Identify the risk factors and to PHD protocol guidelines implications associated with diagnosis of PCOS and Metabolic Syndrome

Definition of PCOS • Polycystic ovarian syndrome is a clinical syndrome characterized by obesity, irregular menses or , and signs of androgen excess like hirsutism and acne • In most patients, the ovaries contain multiple cysts

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Rotterdam 2010 Definition PCOS • Oligo – ovulation / – Menstrual irregularity • Hyperandrogenism – Clinical or biochemical • Polycystic ovaries – Greater than 10 – 12 follicles per ovary detected by pelvis ultrasonography, resembling “string of pearls”

PCOSPCOS Change in Cycles • The most common cause of infertility in the United States

PCOS – A Bear Of A Problem • Anovulation or ovulatory dysfunction – Causing or amenorrhea • AdAndrogen excess increasi ng ri iksk of metabolic syndrome and causing hirsutism

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PCOS – A Bear Of A Problem PCOS • Hyperinsulinemia due to insulin resistance and may contribute to increased ovarian production of androgens – Becomes vicious cycle • Over time, androgen excess increases risk of cardiovascular disorders, such as HTN

Menstrual Changes In PCOS Menstrual Changes In PCOS • With anovulation: • Thickened may – Chronic follicular phase occurs become unstable and fragile secondary to constant estrogen eventually rupturing thus causing stimulation irregular and prolonged bleeding in anovulatory women – Endometrial proliferation or build up and vascularization of the endometrium results

Change in Cycles and Cancer • arises from the inner layer (endometrium) of the • The endometrium gets thick in response to estrogen stimulation

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Endometrial Hyperplasia Types of Endometrial Hyperplasia and Cancer • Simple hyperplasia • Chronic lack of progesterone causes • Complex hyperplasia unregulated growth of the endometrium or hyperplasia • Simple atypical hyperplasia – A precursor to endometrial cancer • Complex atypical hyperplasia

Endometrial Hyperplasia Endometrial Hyperplasia • Simple hyperplasia • Complex hyperplasia without atypia – Thickening of the endometrium – Thicker than simple hyperplasia and increase number glands and demonstrates some abnormal – No atypia and treated with architecture of the glands progesterone supplementation – Without treatment approximately • Less than 1% chance 10% can progress to endometrial progression to cancer cancer

Endometrial Hyperplasia Endometrial Hyperplasia – Treated usually with progesterone • Complex hyperplasia with atypia or if patient has completed – Similar abnormalities as complex childbearing may opt for hyperplasia without atypia, but the hysterectomy cells have bizarre appearance and can progress to endometrial cancer

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Endometrial Hyperplasia Endometrial Cancer – Increased risk of invasive • Most common gynecologic endometrial cancer and is malignancy in the United States imperative the patient receive – Estimated 41,000 women surgical staging by gynecologic diagnosed this year with the oncologist disease • Overall survival rate is excellent if disease confined to the uterus

Risk Factors: Symptoms of Endometrial Cancer Endometrial Cancer • Obesity • Irregular, unusual or heavy vaginal • Chronic anovulation bleeding • Early menarche or late menopause • ANY amount of bleedinggpg or spotting after menopause • Hypertension • Pain with intercourse • Exogenous estrogen use • Pain with urination – No progestin • Lower abdominal or pelvic pain

PCOS Signs and Symptoms • Premature adrenarche – Characterized by excess dehydroepiandrosterone sulfate (()DHEAS) – Early growth of axillary hair, body odor, and microcomedonal acne

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PCOS Signs and Symptoms PCOS Signs and Symptoms • Typical symptoms – Acne – Obesity – Balding – Hirsutism – Acanthosis nigricans of axillae, • Body hair growth on upper lip, neck, and skin folds, knuckles, chin, around nipples, and the elbows linea alba of lower abdomen • Secondary to high insulin levels – Irregular menses or amenorrhea –Insulin resistance

Diagnosis of PCOS Diagnosis PCOS (Biochemical) (Rotterdam 2010) • Some physicians may want: • Oligo – ovulation / anovulation – Serum testosterone causing menstrual irregularity • Serum free testosterone • Clinical or biochemical evidence of hyperandrogenism –Better but more difficult to measure • Presence of polycystic ovaries • Total testosterone – 10-12 follicles noted on pelvic u / s –Usually normal to mildly elevated

Diagnosis PCOS (Biochemical) Best Lab Information • Follicle - stimulating hormone (FSH) • Prolactin level – Normal to mildly decreased – Greater than 20 ng / ml = hyperprolactinemia • Thyroid-stimulating hormone (TSH) – Normal level = 0.5 – 4.5 mlU / L

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To Rule Out Other – To Rule Out Other – Some MDs May Want Some MDs May Want • Evaluate serum cortisol levels to • Rule out Metabolic Syndrome exclude Cushing’s syndrome – Evaluate BP and serum glucose • Earlyyg morning serum levels and lipppppid profile 17 - hydroxyprogesterone to evaluate congenital adrenal hyperplasia • Serum DHEAS – If abnormal evaluate for amenorrhea

Definition of Metabolic Syndrome • Metabolic syndrome is characterized by a group of risk factors for cardiovascular disease, dyslipidemia, and Type 2 Diabetes Mellitus • Clinically patients may have: – Excess intra - abdominal fat • Waist size greater than or equal to 35” in women, 40” in men

Definition of Metabolic Syndrome Definition of Metabolic Syndrome – Insulin resistance – HTN • Acne,hirsutism,androgenic • 130 / 85 mmHg alopecia, acanthosis nigricans – Elevated fasting glucose – Elevated serum triglyceride levels • GtthGreater than or equal lt to • Greater than or equal to 100 mg / dL 150 mg / dL – Decreased HDL cholesterol level • Less than or equal to 50 mg / dL

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Metabolic Syndrome Metabolic Syndrome • Insulin resistance has been reported • Dyslipidemia with elevated LDL, in about 50 - 75% of the women with elevated cholesterol, and decreased PCOS HDL, is usually associated with – Regardless of BMI PCOS • The risk for insulin resistance is – Can be correlated with the level of higher in women who have chronic insulin resistance anovulation, polycystic ovaries, hirsutism, and family history

Clinical Significance • Insulin resistance – The body is resistant to the effects of insulin resulting in hyperglycemic state • Pancreas overcompensates by producing more insulin, causing the ovaries to produce more androgens – Hirsutism, acne, oligo-ovulation / anovulation

Clinical Significance Cardiovascular Disease Risk • Hyperglycemic state secondary to • Low serum sex hormone - binding increased insulin production = globulin (SHBG) found in most Type 2 Diabetes Mellitus women with PCOS is linked to decreased levels of serum high- ditlitihltldensity lipoprotein cholesterol (HDL – C) – The most cardio protective lipid in the body

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Cardiovascular Disease Risk Additional Factors • Decreased levels of HDL – C are • Elevated C - Reactive Protein (CRP) associated with increased risk for levels cardiovascular disease – Directly linked to coronary • Increased serum - free testosterone inflammation and other is associated with elevated systolic cardiovascular related risks are and diastolic blood pressure levels elevated in PCOS leading to hypertension – Increases the risks of cardiovascular disease

Dyslipidemia Dyslipidemia • Atherothrombotic cardiovascular – Ischemic stroke disease is the leading cause of death • Risk factors include: in men and women and is the – Elevated levels of atherogenic underlying reason for: lipoproteins – LDL – Angina – Elevated trigycerides – Unstable angina – Low levels of HDL – Acute myocardial infarction – Sudden cardiac death

Cardiovascular Disease Cardiovascular Disease • Accounts for approximately • More women die from cardiovascular $448 billion of direct and indirect disease than from cancer, stroke, health care costs annually chronic lung disease, Alzheimers • More women die from cardiovascular disease, unintentional injuries, disease than men diabetes, and influenza pneumonia combined – Framington Heart Study

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Total Cholesterol Low - Density • A large meta - analysis study has Lipoprotein Cholesterol shown that a total cholesterol level • Increasing levels of LDL - C are greater than 240mg / dL confers associated with increased risk of almost a two and one - half increased cardiovascular disease risk for cardiovascular disease in – Per the American Diabetes women less than 65 years of age Association (ADA) and the National Cholesterol Education Program (NCEP) Third Adult Treatment Panel (ATP III)

Low - Density Additional Factors Lipoprotein Cholesterol • CVD is the primary clinical outcome of • LDL - pattern B phenotype often metabolic syndrome – American Heart Association accompanies insulin resistance and • Diabetes is the major risk factor for other features of metabolic development of CVD (ATP III) syndrome, and are implicated in cardiovascular disease • Excess abdominal fat leads to increased free fatty acids in the portal vein, increasing fat accumulation in the liver

Additional Factors More Risk Factors – Fatty liver - cirrhosis • Prolonged anovulatory cycles leads to endometrial hyperplasia and • Prothrombic state with increased increased risk of uterine cancer levels of fibrinogen and plasminogen activator inhibitor - 1 and • Increased serum uric acid levels, inflammatory process = increased resulting in chronic renal disease risk for thrombosis • Lipoprotein (a) is an independent risk factor for coronary heart disease

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Possible PCOS? Treatment Guidelines • Per ACOG recommendation: – Healthy diet and exercise • Weight loss – UfUse of MtfMetform in • Decreases body’s resistance to insulin, decreases blood sugar and circulating androgens

Treatment Guidelines Combined Hormonal – In combination with clomid to Contraception improve ovulation for those • If not seeking pregnancy: seeking pregnancy – Combination low - dose hormonal – Management of cardiovascular risk contraceptives recommended by factorsfactors ACOG for management of menstrual disorders if not contraindicated by other health concerns • BMI greater than 34, smoking, migraines, HTN, etc.

Progestin Contraceptives Progestin Contraceptives • If combined hormonal contraception • No studies address the long term use is contraindicated, ACOG of DepoProvera or oral Provera use recommends – Progestin only contraceptives – Progestin containing intrauterine devices as an alternative for endometrial protection from uterine hyperplasia

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Treatment Options – Treatment Options – Public Health Public Health • Public Health – page 66 Clinic • Phone consult REQUIRED to initiate Protocol Manual under Family and annual consult thereafter to Planning Contraceptive Management continue progestin only of Patients with Risk Factors: – Phone consult REQUIRED to initiate and annual consult thereafter for combined method use

Health Department Protocol Health Department Protocol • Menstrual history compatible with • Metabolic Syndrome pre - disposes suspected PCOS necessitates to cardiovascular disease, stroke, endometrial assessment and Type 2 Diabetes Mellitus evaluation to rule out endometrial – Therefore patient needs medical hyperplasia PRIOR to initiating work - up and ongoing medical hormonal methods management

Conclusion Conclusion • PCOS and Metabolic Syndrome is a • Current health risks associated with “bear of a problem” PCOS and Metabolic Syndrome need • We see more patients who are assessment and treatment to prevent overweight or obese with irregular significant FUTURE health menstrual cycles and conditions hyperandrogenic characteristics – Important in Family Planning

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Take Home Message Going To Be A Bear • PCOS is significant because it is • In this life I am a woman associated with: • In my next life I would like to come – Infertility back as a bear – Uterine cancer • When you are a bear, you get to – Insulin Resistance/Metabolic hibernate Syndrome/Diabetes • You do nothing but sleep for six – Dyslipidemia/Cardiovascular Disease months – I could deal with that

Going To Be A Bear Going To Be A Bear • Before you hibernate, you are • If you are a mama bear, everyone supposed to eat yourself stupid knows you mean business – I could deal with that • You swat anyone who bothers your • When you are a girl bear, you birth cubs your children (who are the size of • If your cubs get out of line, you swat walnuts) while you are sleeping and them too wake to partially grown cute, cuddly – I could deal with that cubs – I could definitely deal with that

Going To Be A Bear • If you are a bear, your mate EXPECTS you to wake up growling • He EXPECTS that you will have hairy legs and excess body fat – Yup, going to be a bear!

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