11/12/2013 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 amenorrhea, and signs of androgen excess like hirsutism and acne • In most patients, the ovaries contain multiple cysts 1 11/12/2013 Rotterdam 2010 Definition PCOS • Oligo – ovulation / anovulation – 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 oligomenorrhea or amenorrhea • AdAndrogen excess increas ing ri iksk o f metabolic syndrome and causing hirsutism 2 11/12/2013 PCOS – A Bear Of A Problem Signs and Symptoms 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 endometrium 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 Endometrial Hyperplasia and Cancer • Endometrial cancer arises from the inner layer (endometrium) of the uterus • The endometrium gets thick in response to estrogen stimulation 3 11/12/2013 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 4 11/12/2013 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 5 11/12/2013 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 6 11/12/2013 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 equa ltl to • Greater than or equal to 100 mg / dL 150 mg / dL – Decreased HDL cholesterol level • Less than or equal to 50 mg / dL 7 11/12/2013 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 8 11/12/2013 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 9 11/12/2013 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