I am familiar with polycystic I am familiar with polycystic ovary syndrome. ovary syndrome. 25% 25% 25% 25% Polycystic Ovary Syndrome: Polycystic Ovary Syndrome: 1. 1. Strongly disagree Strongly disagree Pharmacologic Considerations Pharmacologic Considerations 2. 2. Disagree Disagree 3. Agree 3. Agree Susan M. Sirmans, Pharm.D., BCPS Susan M. Sirmans, Pharm.D., BCPS 4. Strongly agree 4. Strongly agree Associate Professor Associate Professor College of Pharmacy College of Pharmacy . e e e . e e University of Louisiana at Monroe University of Louisiana at Monroe . e g r r r a g g g s a A a i s d i y D l y g l n g n o o r t r S S t 60 Answer Now Countdown Countdown I know someone with polycystic I know someone with polycystic PCOS PCOS ovary syndrome. ovary syndrome. 33% 33% 33% 1. Disagree 1. Disagree 2. Agree 2. Agree 3. Not sure 3. Not sure e e e e e r r r u g g s a A t s o i N D 60 Answer Now Countdown Countdown PCOS PCOS PCOS PCOS http://www.implementingdesignism.org/posteranne.html http://www.implementingdesignism.org/posterjames.html 1
PCOS PCOS PCOS PCOS http://www.implementingdesignism.org/posteridriss.html http://www.implementingdesignism.org/posterchristi.html Pathophysiology Pathophysiology Polycystic Ovary Syndrome (PCOS) Polycystic Ovary Syndrome (PCOS) • Stein • Primary defect unknown Stein Leventhal Leventhal Syndrome Syndrome Primary defect unknown • Inappropriate LH secretion • Affects 5 Inappropriate LH secretion – – 30 30- -90% 90% Affects 5- -10 % of pre 10 % of pre- -menopausal women menopausal women – Increased LH Increased LH • Affects 28% of overweight or obese Affects 28% of overweight or obese g – Increased LH:FSH Increased LH:FSH - Increased LH:FSH Increased LH:FSH - >2 >2 >2 3:1 >2-3:1 3:1 3:1 • Varying number and degree of signs and Varying number and degree of signs and • Hyperandrogenism Hyperandrogenism symptoms symptoms – Increased testosterone Increased testosterone – – ovarian origin ovarian origin – Menstrual disturbances Menstrual disturbances – Increased Increased dihydroepiandrosterone dihydroepiandrosterone sulfate sulfate - - adrenal adrenal • Hyperinsulinemia – Hormonal abnormalities Hormonal abnormalities- - hyperandrogenic hyperandrogenic Hyperinsulinemia → → decreased decreased SHBG SHBG – Polycystic ovaries Polycystic ovaries I know someone with polycystic I know someone with polycystic Diagnostic criteria Diagnostic criteria ovary syndrome. ovary syndrome. 33% 33% 33% • Androgen Excess Society Criteria Androgen Excess Society Criteria 1. Disagree 1. Disagree • Rotterdam Criteria Rotterdam Criteria 2. Agree 2. Agree • NIH criteria NIH criteria 3. 3. Not sure • Features considered Not sure Features considered – Oligo Oligo- - or or anovulation anovulation – Clinical and/or biochemical signs of Clinical and/or biochemical signs of hyperandrogenism hyperandrogenism e e e e e r – Polycystic ovaries Polycystic ovaries u r r g g s a A t s o i D N 60 Answer Now Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Fertil Steril. 2004;81:19-25 Countdown Countdown 2
PCOS affects ______ percent of PCOS affects ______ percent of All women with polycystic All women with polycystic women. women. ovaries have PCOS. ovaries have PCOS. 25% 25% 25% 25% 50% 50% 1. 1. 5- -10 10 1. True 1. True 2. 20 2. 2. 2. False 2. False 2. 20- -30 30 False False 3. 3. 40 40- -50 50 4. > 50 4. > 50 0 0 0 0 1 3 5 5 e 5 ‐ 0 ‐ 0 ‐ > e u s 2 4 r a l 60 T 60 F Answer Now Answer Now Countdown Countdown Countdown Countdown Ovulatory Ovulatory disorders disorders Hyperandrogenic Hyperandrogenic • Menstrual abnormalities Menstrual abnormalities • Ovarian or adrenal gland abnormalities Ovarian or adrenal gland abnormalities – Inconsistent Inconsistent • Clinical picture Clinical picture – Oligomenorrhea Oligomenorrhea – Hirsutism Hirsutism Hirsutism Hirsutism – 70 % 70 % 70 % 70 % – Amenorrhea Amenorrhea – Acne Acne – 20 20- -30 % 30 % - - normal menses normal menses • 25 25- -35% 35% – 5 5- -15% polymenorrhea, menorrhagia 15% polymenorrhea, menorrhagia • Severe acne Severe acne – – high incidence of PCOS high incidence of PCOS • Decreased fertility Decreased fertility – Alopecia Alopecia – – 10 % 10 % • Endometrial cancer Endometrial cancer Hyperandrogenic Hyperandrogenic Hirsutism Hirsutism http://www.endotext.org/female/female4/figures/figure4.jpg http://img.webmd.com/dtmcms/live/webmd/consumer_assets/site_images/articles/health_tools/weight_gain_shockers_slideshow/PRinc_rm_photo_of_hirsutism.jpg 3
Modified Modified Ferriman Ferriman Galwey Galwey Score Score Polycystic Ovaries Polycystic Ovaries www.advancedfertility.com/pics/singlefollicle... www.advancedfertility.com/pics/pco.jpg Polycystic Ovary Normal Ovary Yildiz BO (2008) Assessment, diagnosis and treatment of a patient with hirsutism. Single Follicle Nat Clin Pract Endocrinol Metab doi:10.1038/ncpendmet0789 Insulin resistance Insulin resistance Insulin resistance detection Insulin resistance detection • 50 • No clear agreement on preferred 50- -70% 70% No clear agreement on preferred • Obese and non diagnostic criteria diagnostic criteria Obese and non- -obese women obese women • Hyperinsulinemia Hyperinsulinemia • Clinical picture of metabolic syndrome Clinical picture of metabolic syndrome Clinical picture of metabolic syndrome Clinical picture of metabolic syndrome • Increased androgen secretion Increased androgen secretion – Blood pressure ≥ 130/85 Blood pressure ≥ 130/85 • Inappropriate LH secretion Inappropriate LH secretion – Waist circumference ≥ 35 inches Waist circumference ≥ 35 inches • Impaired glucose tolerance, diabetes Impaired glucose tolerance, diabetes – Fasting glucose ≥ 100 mg/ Fasting glucose ≥ 100 mg/dL dL • Dyslipidemia Dyslipidemia – HDL HDL- -C ≤ 50 mg/ C ≤ 50 mg/dL dL – Triglycerides ≥ 150 mg/ Triglycerides ≥ 150 mg/dL dL http://www.nhlbi.nih.gov/guidelines/cholesterol/atp3full.pdf Acanthosis Acanthosis Nigricans Nigricans Endocrine consequences Endocrine consequences • Reproductive and cosmetic consequences Reproductive and cosmetic consequences – Infertility Infertility – Hirsutism Hirsutism – Acne Acne http://www.nlm.nih.gov/medlineplus/ency/images/ency/fullsize/2353.jpg 4
Cardiometabolic Consequences Cardiometabolic Consequences Subclinical Atherosclerosis Subclinical Atherosclerosis • Insulin resistance • Coronary artery calcification Insulin resistance – – 50 50- -70% 70% Coronary artery calcification • Obesity • Aortic calcification Obesity – – 30 30- -60% 60% Aortic calcification • Impaired glucose tolerance • Impaired glucose tolerance • Increased carotid • Increased carotid Impaired glucose tolerance Impaired glucose tolerance – 35% 35% 35% 35% Increased carotid intima Increased carotid intima intima media wall intima-media wall media wall media wall • Diabetes thickness thickness Diabetes – – 7.5 7.5- -10% 10% • Dyslipidemia • Increased left ventricular mass Dyslipidemia – – 70% 70% Increased left ventricular mass • Hypertension • Left ventricular diastolic dysfunction Hypertension – – 28% 28% Left ventricular diastolic dysfunction • Metabolic syndrome Metabolic syndrome – – 43% 43% Atherosclerotic events Atherosclerotic events Treatment goals Treatment goals • Maintain normal Maintain normal endometrium endometrium • Clinical features of PCOS Clinical features of PCOS • Block androgen effects on targets Block androgen effects on targets – 3.3 fold greater risk of cardiovascular death 3.3 fold greater risk of cardiovascular death • Reduce insulin resistance Reduce insulin resistance and myocardial infarction and myocardial infarction • Correct Correct anovulation anovulation l l • Irregular menses Irregular menses – – relative risk of CAD relative risk of CAD • Improve infertility Improve infertility 1.34 vs. those with normal menses 1.34 vs. those with normal menses • Weight reduction Weight reduction • Prevent long Prevent long- -term complications term complications – AGGRESSIVE MANAGEMENT OF CV RISK AGGRESSIVE MANAGEMENT OF CV RISK Shaw LJ, Bairey Merz CN, Azziz R, et al . J Clin Endocrinol Metab . 2008;93(4): 1276-84. FACTORS FACTORS Solomon CG, Hu FB, Dunaif A, et al. J Clin Endocrinol Metab. 2002;87(5):2013-17 . Not wishing to conceive Not wishing to conceive Weight reduction Weight reduction – – 5 5- -10% 10% • Menstrual disorders • Decreases insulin concentration/resistance Menstrual disorders Decreases insulin concentration/resistance – COC COC • Reduces Reduces hirsutism hirsutism – Insulin sensitizers Insulin sensitizers • Reduces acne • Reduces acne Reduces acne Reduces acne • Hirsutism Hirsutism • Reduces androgens Reduces androgens – Antiandrogens Antiandrogens • Improves ovulation, fertility – Nonpharmacologic Nonpharmacologic Improves ovulation, fertility • Cardiovascular risk factors Cardiovascular risk factors – Insulin sensitizers Insulin sensitizers – Statins Statins 5
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