Subject Index. Bariatric surgery, obesity management 134

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1 Subject Index Acromegaly, PCOS differential diagnosis 149, 150, 154, 155 Adipokines, see specific adipokines Adiponectin, metabolic syndrome role Adolescents, PCOS diagnosis 16, 17 Adrenal hyperplasia, see Congenital adrenal hyperplasia, Non-classic adrenal hyperplasia Advanced glycation end products, PCOS role 19 Aldosterone, cardiovascular disease risk in PCOS 69, 70 AMP-dependent protein kinase, metformin effects Androgen receptor, sensitivity in PCOS 35 Androgens, see Hyperandrogenism Anovulation anti-müllerian hormone in pathophysiology 26 etiology 36, 130 metformin benefits ovulation inducers aromatase inhibitors 135, 136 clomiphene citrate 134, 135 follicle-stimulating hormone 137 gonadotropin-releasing hormone analogs 137, 138 laparoscopic ovarian drilling 138 letrozole 135, 136 metformin 136, 137 tamoxifen 135 phenotypes in PCOS 9, 10 Anti-Müllerian hormone, anovulation pathophysiology 26 Aromatase, inhibitors for ovulation induction 135, 136 Atherosclerosis, see Cardiovascular disease Bariatric surgery, obesity management 134 Cardiovascular disease arterial stiffness 76, 77 dyslipidemia, see Dyslipidemia endothelial dysfunction epidemiology in PCOS 65, 66 metabolic syndrome, see Metabolic syndrome non-classic adrenal hyperplasia risk factors insulin resistance 166, 167 obesity 166 overview 165 oral contraceptives and risks general population PCOS oxidative stress, see Oxidative stress risk factors in PCOS aldosterone 69, 70 dyslipidemia 69 hypertension 68, 69 insulin resistance 67, 68 obstructive sleep apnea 70, 71 overview 66, 67 phenotypes in PCOS and risk differences risk modification in PCOS drospirenone 79 glucagon-like peptide-1 agonists 79, 80 lifestyle modification 77 metformin 78 thiazolidinediones 78, 79 subclinical disease evaluation electron-beam computed tomography 72, 77 flow-mediated dilation

2 intima-media thickness 72, 75, 76 magnetic resonance imaging 72 pulse wave velocity 72, 76 β-cell, dysfunction in PCOS candidate gene studies 33 etiology 32 Chemerin, metabolic syndrome role 41, 44 Cholesterol, see Dyslipidemia, PCOS Classification, see Phenotypes, PCOS Clomiphene citrate, ovulation induction 134, 135 Congenital adrenal hyperplasia forms 163, 164 genetics 163 Cushing syndrome, PCOS differential diagnosis 14, 15, 148, 149, 153, 154 CYP11A, variants in PCOS 33, 34 CYP19, variants in PCOS 37 CYP21 congenital adrenal hyperplasia defects 163 heterozygotic carriers in PCOS 164, 165 non-classic adrenal hyperplasia defects 160 Cytoproterone acetate, hirsutism management 111 Definitions, PCOS 2 4, 129 Diabetes differential diagnosis , 155 gestational diabetes 151 type 1 disease 151 type 2 disease 150, 151 Diagnosis, PCOS adolescents 16, 17 secondary causes of PCOS signs 129 Differential diagnosis, PCOS acromegaly 149, 150, 154, 155 adrenal and ovarian androgen-producing tumors , 160, 161 adrenal-ovarian steroidogenic defects 146, 147 Cushing syndrome 14, 15, 148, 149, 153, 154 glucocorticoid metabolism alterations 147, 148 resistance 147 hyperinsulinemia and insulin resistance hyperprolactinemia 149 medication side effects 152, 153 non-classic adrenal hyperplasia 14 16, 153, 161, 162 overview thyroid dysfunction 149 Drospirenone cardiovascular risk modification 79 hirsutism management 112 Dyslipidemia, PCOS cardiovascular disease risks 69 HDL-cholesterol 54, 55 LDL-cholesterol 53, 54 pathophysiology aging and body composition 52, 53 hyperandrogenism 53 insulin resistance 53 prevalence 52 therapeutic targeting 60, 61 total cholesterol 3, 54 triglycerides 55 Electron-beam computed tomography, atherosclerosis diagnosis 72, 77 Finasteride, hirsutism management 111 Flow-mediated dilation, atherosclerosis diagnosis 72 Flutamide, hirsutism management 112 Follicle-stimulating hormone local inhibition 25 secretion in PCOS 23 Follicle-stimulating hormone, ovulation induction therapy 137 Folliculogenesis, PCOS candidate gene studies 36 excessive early growth 24 follicle-stimulating hormone local inhibition 25 secretion 23 follicular arrest 24 FTO, variants in PCOS 31, 37 Genetics, PCOS candidate gene studies androgen receptor sensitivity 35 β-cell dysfunction 32, 33 folliculogenesis 36 hyperandrogenism 33, 34 obesity and insulin resistance 31, 32 genome-wide association studies 36, 37 limitations of studies etiology lack of knowledge 29 Subject Index 173

3 gene effect size 30 heterogeneity of disease 29 inheritance mode 30 retrospective diagnosis difficulty 29 sub-fertility in disease 30 Genome-wide association studies, PCOS 36, 37 Glucagon-like peptide-1, agonists for cardiovascular risk modification 79, 80 Gonadotropin-releasing hormone, analogs for ovulation induction 137, 138 Hirsutism, see also Hyperandrogenism clinical evaluation differential diagnosis , 145 etiology 104 laboratory evaluation 108, 109 non-classic adrenal hyperplasia 160 oral contraceptive benefits 122 pathophysiology 104, 105 phenotypes in PCOS 8, 9 treatment Hyperandrogenism, see also Hirsutism adipokine response 48 adrenal and ovarian androgen-producing tumors , 160, 161 candidate gene studies 34 cardiovascular disease risk in PCOS 68, 69 dyslipidemia pathophysiology 53 etiology 33 metformin benefits 89 oral contraceptive benefits 122 pathophysiology 23, 24 phenotypes in PCOS 6 8 Hyperprolactinemia, PCOS differential diagnosis 149 Infertility, see also Anovulation assisted reproduction 138 etiology in PCOS 130, 131 lifestyle interventions behavior modification 133 diet 132 exercise 132, 133 overview 131, 132 non-classic adrenal hyperplasia 167 obesity management bariatric surgery 134 pharmacotherapy 133, 134 ovulation inducers aromatase inhibitors 135, 136 clomiphene citrate 134, 135 follicle-stimulating hormone 137 gonadotropin-releasing hormone analogs 137, 138 laparoscopic ovarian drilling 138 letrozole 135, 136 metformin 136, 137 tamoxifen 135 Insulin receptor, variants in PCOS 32 Insulin resistance, see also Metabolic syndrome candidate gene studies 31, 32 cardiovascular disease risk in PCOS 67, 68 differential diagnosis , 155 dyslipidemia pathophysiology 53 etiology 31 hyperglycemia and oxidative stress 56, 57, 59 non-classic adrenal hyperplasia 166, 167 oral contraceptives and risks general population 121 PCOS 124, 125 sensitizers, see Metformin, Thiazolidinediones Intima-media thickness, atherosclerosis diagnosis 72, 75, 76 Laparoscopic ovarian drilling, infertility management 138 Leptin, metabolic syndrome role 41, 42 Letrozole, ovulation induction 135, 136 α-lipoic acid, dyslipidemia management 61 Lipodystrophy, PCOS differential diagnosis 152 Luteinizing hormone ectopic secretion 150 elevation in PCOS 23, 143 phenotype differences in PCOS 12 Magnetic resonance imaging, atherosclerosis diagnosis 72 Metabolic syndrome, see also Insulin resistance, Obesity adipokines androgen effects in PCOS 48 general population PCOS metabolic profile phenotypes in PCOS 12, 13 metformin benefits 89, Subject Index

4 Metformin cardiovascular risk modification 78 clinical benefits anovulation and pregnancy hirsutism 113 hyperandrogenism 89 metabolic syndrome 89, 90 obesity 89, 90 dose dependence 92, 93 mechanism of action overview 84, 85 ovulation induction 136, 137 pharmacokinetics response prediction 93, 94 side effects 90 thiazolidinedione comparison 98 N-Acetylcysteine, PCOS management 61 Nitric oxide endothelial dysfunction in PCOS 73, 74 PCOS production 57, 58 Non-classic adrenal hyperplasia adrenal androgens and PCOS 160, 161 cardiovascular disease risks insulin resistance 166, 167 obesity 166 overview 165 CYP21 defects 160 epidemiology 160 hirsutism 107, 108 infertility 167 PCOS differential diagnosis 14 16, 153, 161, 162 Nonalcoholic fatty liver disease, PCOS association 61 Obesity infertility association 131 insulin resistance 151, 152 management bariatric surgery 134 pharmacotherapy 133, 134 non-classic adrenal hyperplasia 166 PCOS candidate gene studies 31, 32 etiology 31 metformin benefits 89, 90 Obstructive sleep apnea, cardiovascular disease risk in PCOS 70, 71 Omentin, metabolic syndrome role 41, 44 Oral contraceptives administration 117 benefits in PCOS 121, 122 cardiovascular risks general population PCOS composition 116 contraindications 117 hirsutism management 110, 111 metabolic risks general population 121 PCOS 124, 125 Organic cation transporter-1 metformin response prediction 94 metformin as substrate 91 Oxidative stress cardiovascular risk 51, 52 consequences in PCOS endogenous defenses 58, 59 free radical sources in PCOS adipose tissue 56 enzymatic sources 57 fatty acid oxidation 56 hyperglycemia 56, 57 mitochondrial dysfunction 58 nitric oxide 57, 58 insulin resistance pathophysiology 59 overview 55, 56 therapeutic targeting 60, 61 Peroxisome proliferator-activated receptor-γ activators, see Thiazolidinediones variants in PCOS 32 Peroxynitrite, PCOS production 58 Phenotypes, PCOS cardiovascular risk differences life cycle differences 5 limitations in classification anovulation 9, 10 hirsutism 8, 9 hyperandrogenism 6 8 polycystic ovarian morphology 10, 11 luteinizing hormone differences 12 management specificity 17, 18 metabolic profile differences 12, 13 nutrition role 18, 19 overview 2, 3, 129, 130 prevalence 4, 5 Polycystic ovarian morphology, phenotypes in PCOS 10, 11 Subject Index 175

5 Prevalence, phenotypes of PCOS 4, 5 Prolactin, see Hyperprolactinemia Pulse wave velocity, atherosclerosis diagnosis 72, 76 Reactive oxygen species, see Oxidative stress Resistin, metabolic syndrome role 41, 43 Retinol-binding protein-4, metabolic syndrome role 41, 44, 45 Sibutramine, obesity management 134 Sleep apnea, see Obstructive sleep apnea Spironolactone, hirsutism management 112 Statins, dyslipidemia management 60, 61 Tamoxifen, ovulation induction 135 Thiazolidinediones benefits in PCOS 97, 98 cardiovascular risk modification 78, 79 mechanism of action metformin comparison 98 overview 84, 85, 95 severe insulin resistance management Thyroid dysfunction, PCOS differential diagnosis 149 Triglycerides, see Dyslipidemia, PCOS Vaspin, metabolic syndrome role 41, 43 Visfatin, metabolic syndrome role 41, Subject Index

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