Case Questions. Polycystic Ovarian Syndrome: Treatment Goals and Options. Differential Diagnosis of Hyperandrogenic Anovulation

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1 Polycystic Ovarian Syndrome: Treatment Goals and Options Marc Cornier, MD Division of Endocrinology, Metabolism and Diabetes Colorado Center for Health and Wellness University of Colorado School of Medicine Denver Health Medical Center Case Questions Is this PCOS? How do we think about amenorrhea? What is the definition of PCOS? What is hirsutism? What do we consider normal levels of androgens? Differential Diagnosis of Hyperandrogenic Anovulation Polycystic Ovarian Syndrome Obesity-induced Hyperandrogenic Anovulation Congenital adrenal hyperplasia Ovarian or adrenal tumor Other: exogenous androgen administration, Cushing s syndrome, prolactinoma Idiopathic hirsuitism

2 Polycystic Ovary Syndrome Clinical and/or biochemical signs of hyperandrogenism (after exclusion of other etiologies) Chronic oligo- and/or anovulation Polycystic ovaries Not in definition: Overweight, Metabolic Syndrome, LH/FSH ratios Revised 2003 consensus on diagnostic criteria and long-term health risks related to PCOS, Hum Reprod 2004;19(1):41-47 Pathogenesis of PCOS GnRH abnormalities LH Insulin resistance insulin, IGF extraovarian androgens Ovarian steroidogenesis block Enzyme defect Hyperandrogenemia Follicular Atresia Metabolic Disorders in PCOS Obesity (central) Insulin Resistance: 31-35% of women with PCOS have IGT % of women with PCOS have T2DM vs 1.6 and 2.2% in similarly aged women Progression to T2DM is also faster. Risk of GDM is higher. Metabolic Dyslipidemia NAFLD OSA Increased CVD?

3 History Onset and pace of hirsutism Prior menstrual history** Weight history: ie timing with weight gain Stress Medications Family history of endocrine disorders, hirsuitisms Acne, balding, headaches, breast discharge Physical Exam Evidence and pattern of acne and hirsutism, male pattern balding Evidence of acanthosis nigricans Body habitus, body fat distribution Cushingoid features Thyroid Galactorrhea Pelvic exam for anatomy, clitoromegaly Visual field testing? Laboratory Evaluation ß-HCG, TSH, Prolactin, CMP Follicular Phase (progesterone withdrawal): Testosterone (total +/- freet) Dehydroepiandosterone sulfate (DHEA-S) LH, FSH, Estradiol If appropriate: 17OH-Progesterone (30min after Cosyntropin 250ug stimulation) Urinary free cortisol or LDDST

4 Laboratory/Diagnostic Evaluation Evaluate for Metabolic Disorders: Fasting Blood Glucose and/or A1c Fasting Lipid Panel Liver function tests (r/u NAFLD) Evaluate for Endometrial Hyperplasia GYN exam, etc Ovarian ultrasound not necessary Case: Case: Labs Follicular phase: LH 10 miu/ml ( ) FSH 4 miu/ml (2-10) E2 40 pg/ml (<70-12 from LH peak; from LH peak) Total T 72 ng/ml (14-76) DHEA-S 274 ( ug/ml) 17OHP 25 ng/dl (<200 in EFP) other Hormones ß-HCG neg TSH and Prolactin WNL Fasting Lipids LDL 107 Tg 89 HDL 64 TC 188 Basic metabolic panel Electrolytes, LFTs WNL Glucose 88, A1C 5.7

5 PCOS: What are the goals of therapy? Depends on stage of life what is bothering you the most? Androgen Excess (Dermatologic issues) Irregular menstrual periods (endometrial protection) Fertility Metabolic disorders Androgen Excess (Dermatologic issues): OCPs (androgenicity): Levonorgestrol (++) Norethindrone (+) Norgestimate-Desogestrel (+/-) Cyproterone actetate (0) Drospirenone (0) Spironolactone Finasteride Metformin? Direct hair removal Mechanical (laser, electrolysis, shaving) Topical Flornithine Comparison of Metformin vs OCP on Total Testosterone Costello M F et al. Hum. Reprod. 2007;22:

6 Comparison of Metformin vs OCP On Hirsutism Costello M F et al. Hum. Reprod. 2007;22: Irregular menstrual periods and endometrial protection: OCPs Intermittent progestin therapy medroxyprogesterone (10 mg) for 7 to 10 days every one to three months Continuous progesterone Fertility: Weight Loss Metformin Clomiphene Metformin + Clomiphene Others? Aromatase Inhibitors Gonadotropin Therapy Fertility Expert

7 Fertility: Metformin vs Clomiphene vs Both in Women with PCOS Legro RS et al. N Engl J Med 2007;356: Metabolic disorders: Lifestyle Modification and Weight Loss Insulin Sensitizers Metformin TZDs? Incretin based therapies? Other Cardiac Risk Factors Antihypertensives Lipid-lowering therapy PCOS: What are the goals of therapy? Androgen Excess (Dermatologic issues): OCPs ± Spironolactone direct hair removal Irregular menstrual periods (endometrial protection): OCPs Fertility: not an issue at this time but may be in the future Metabolic disorders: Not an issue currently but will screen on a regular basis Promote lifestyle modification

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