Index

A Adrenal failure ACE inhibitors. See Angiotensin-converting breastfeeding, 346 enzyme (ACE) inhibitors dehydroepiandrosterone, 343 Acetaminophen, 416 fludrocortisone, 343 Acetylation or methylation, 81 hydrocortisone, 342 ACSs. See Acute coronary syndromes (ACSs) pregnancy, 344 Action potential duration (APD), 239, 240, Adverse drug effects (ADE), 270 245, 255 adverse allergic reactions in anesthesia, 270 action potential, 251 amenorrhea and infertility, 274 action potential prolongation, 253 nausea and vomiting, 271, 273 APD90, 245 opioid-induced endocrinopathy, 274 duration, ventricular action, 239–240 respiratory depression, 274 ventricular action potential, 240 sluggish feeling, 273 Activational effects, 72, 79 vomiting, 273 Acute coronary syndromes (ACSs), 184, 526 Adverse drug events (ADE), 109, 110, 112, 113 fibrinolysis, 525, 526 depression, 113 percutaneous coronary interventions, 526 doctors, 113 reperfusion therapies, 526 drug, 112 Addiction, 114 interactions, 110 alcohol, 114–116 polytherapy, 110 amphetamine, 114 social function, 113 cannabis derivates, 114 symptoms, 113 cigarette smoking, 116 Adverse effects, 212, 214, 219, 222, 226–229 cocaine, 114 postoperative nausea and vomiting, 276 deficits, 116 respiratory depression, 433 developmental alterations, 116 Age-and sex-specific differences, 153 ecstasy, 114 Aging, 110 ethanol, 115 decreased tolerability, 110 methamphetamine, 114 modifications, 110 nicotine, 114 Aldosterone, 227 opiates, 114 Aldosterone receptor antagonist tranquillizer, 114 eplerenone, 226, 227, 229 Addictive benzodiazepine tranquilisers, 152 spironolactone, 226–227 ADE. See Adverse drug effects (ADE); Alzheimer’s disease, 7, 14 Adverse drug events (ADE) Analgesics, 194 Adenoma Androgen receptor (AR), 551 colorectal, 456 Androgens, 415, 419, 545

V. Regitz-Zagrosek (ed.), Sex and Gender Differences in Pharmacology, 589 Handbook of Experimental Pharmacology 214, DOI 10.1007/978-3-642-30726-3, # Springer-Verlag Berlin Heidelberg 2012 590 Index

3b-Androstandiol, 562 Antipsychotics, 287 5-Androstenediol, 562 Antivirals Anesthesia acyclovir, 505, 507 atracurium, 270 adverse reactions, 504, 509 barbiturates, 270 alpha/ribavirin, 505 drug-induced absence of all perceptions, 270 antiretroviral therapies (ART), 504, 506 emergence time, 270 HAART, 505 epidural analgesia, 273 oseltamivir, 505, 511, 512 inhalatory, 270 pegylated interferon, 505 intravenous, 270 pegylated interferon alpha and neurosteroides, 270 ribavirin, 509 non-depolarizing neuroblocking toxicity, 513 agents, 265 zanamivir, 505, 511 nonsteroidal anti-inflammatory drugs, 274 APD. See Action potential duration (APD) opioid receptor agonists, 266 Apoptosis, 52–55, 57, 59–62 pain treatments, 266 apoptogenic factors, 53 propofol, 265 apoptotic cell death, 53, 57, 60 rocuronium, 269–270 apoptotic injury, 61 vecuronium, 270 apoptotic pathways, 53, 57 wake, 266 apoptotic response, 59 Ang II. See Angiotensin II (Ang II) driven cardiovascular pathology, 53 Angina pectoris, 184 initial apoptotic, 53 Angiotensin-converting enzyme (ACE) necrotic fate, 53 inhibitors, 164, 186–187, 189, 191, pro-and anti-apoptotic proteins, 59 212, 213, 221–224, 226, 228, 229 pro-apoptotic factors, 56, 57 Angiotensin II (Ang II), 213, 222–226 AR. See Androgen receptor (AR) Angiotensin II receptor blockers (ARBs), ARBs. See Angiotensin II receptor 187, 189 blockers (ARBs) Animal models, 23–42, 213–214, 217, 222 Aromatase inhibitor, 552 guinea pigs, 351, 352 Arrhythmias, 238–240, 242, 243, 245–253, rats, 352 255–256 sheep, 351 Andersen’s syndrome/LQT7, 248 Anthracyclin, 420 antiarrhythmic, 238, 239, 251–252 Antibiotics, 195 antiarrhythmic support, 250 Anti-cancer drugs, 422 antiarrhythmic therapy, 238, 246 Anticoagulation arousal-induced arrhythmias, 249 bivalirudin, 527, 531 arrhythmic risks, 240 factor Xa inhibitor, 531 atrial fibrillation (AF) episodes, 250 fondaparinux, 531 AV nodal reentrant tachyarrhythmia low-molecular-weight heparin, 527, 531 (AVNRT), 250 thrombin inhibitor, 527 Brugada patients, 254 unfractionated heparin, 527, 531 Brugada phenotype, 254 Anticonvulsants, 292 Brugada syndrome, 251, 253, 254 Antidepressants, 283–290 cardiac events, 242, 248 Antihypertensive agents, 191 inherited ventricular tachycardia Antihypertensive drug therapy, 191 syndrome, 251 Anti-inflammatory effects, 354–355 long QT syndrome (LQTS), 246–248, Anti-oestrogens, 552 253, 254 Antiplatelet treatment LQT1, 248 ADP receptor antagonist, 526 LQT1-13, 248 aspirin, 526 LQT2, 248, 249 clopidogrel, 526, 527 LQT3, 248 prasugrel, 527 LQT3, LQT1, 248 ticagrelor, 527 LQT2 mutations, 248 Index 591

LQT1 or LQT2, 248 B LQT3 patients, 248 Bazedoxifene, 567 reentrant arrhythmias, 241 Beers criteria, 154 reentry, 250 Behavioral teratogenicity, 282 sudden cardiac death, 241, 251 Benzodiazepine antagonists, 161 sudden death, 248 Benzodiazepines, 157–162, 195, 296 supra-ventricular tachyarrhythmia Beta-blockers, 162–163, 189 (tachycardia), SVT, 249–250 bisoprolol, 218 symptomatic long QT syndrome, 248 metoprolol, 218, 219 tachyarrhythmia, 250 propranolol, 218–219 torsades de pointes (TdPs), 240–242, 247, Bevacizumab, 425, 431–433 248, 253, 254, 256 Bicalutamide, 551, 575 torsades de pointes (TdP) Bleeding, 451, 531, 532 arrhythmias, 248 complications, 11, 14 torsades de pointes (TdP) risk, 248 major, 531 ventricular tachyarrhythmia, 251 minor, 533 Wolff–Parkinson–White (WPW) severe, 532 syndrome, 250 Blood pressure, 191, 213, 216–218, Asoprisnil, 558 221–226, 228 Aspirin, 188, 191, 416, 454 Breast cancer, 551, 552, 557 Atherosclerotic disease, 191 AT1 receptor antagonist candesartan, 224 C irbesartan, 217, 224 CAD. See Coronary artery disease (CAD) losartan, 224 Calcium-channel blockers, 189 valsartan, 224 amlodipine, 219, 221, 229 Atrial fibrillation, 7, 9, 11, 14, 16, 17, felodipine, 221 532–535 nifedipine, 219 Atypical antipsychotics, 288 verapamil, 219–221 Autoimmune, 76 Cancer Autoimmune diseases, 6, 13, 18 breast, 454 Autonomic regulation, 240 lung, 453, 457 autonomic blockade, 240, 242 Carboplatin, 419, 425, 427, 428 autonomic control, 249 Cardiac toxicity, 420 autonomic excision, 239 Cardiovascular diseases (CVD), 6, 8, 16–18, autonomic tone, 239, 244 24, 138 exercise capacity, 239 Cardiovascular events, 191 para-sympathetic tone, 249 Cardiovascular risk, 186, 193, 389 sympathetic nerves, 249 Cardiovascular secondary prevention, 184 Autophagy, 55–62 Cardiovascular system, 152 autophagic cytoprotection, 61 Catecholamines, 138 autophagic pathways, 57 Celecoxib, 457 autophagic response, 58 Cell-based therapies, 137 autophagic triggering, 57 Cell-mediated immune responses autophagic vacuoles, 57 T cells, 502, 503 autophagosome, 55–56 Cetuximab, 425, 432 cytoprotection pathway, 62 CHF. See Chronic heart failure (CHF) macro-autophagy, 55, 56 Cholesterol, 396 micro-autophagy, 55, 56 HDL-C, 389, 390, 395, 397 pathway, 56, 57, 59 LDL, 389, 395 process, 55 VLDL, 397 related genes (Atg), 55 Chromosome, 547 Average expenditure, 153 Chronic heart failure (CHF), 189 592 Index

Chronic obstructive pulmonary artery Cytokines disease, 7, 12 IL-1b, 448 Cisplatin, 417, 425, 427, 428, 434 IL-6, TNF-a and C-reactive protein, 448 Clinical studies, 111 TNF-a, 448 exclusion, 111 Cytostatic drugs, 413, 428, 434, 435 underrepresentation, 111 Clinical trials, 15–16, 18, 129, 179 Phase I, 130, 140 D Phase II, 130, 140 Damage Phase III, 130 mucosal, 455 Phase IV, 130 DBP. See Diastolic blood pressure (DBP) Clomiphene citrate, 571 DCM. See Dilated cardiomyopathy (DCM) Coagulation problems, 178 Declaration of Geneva, 131 Cognitive decline, 138 Declaration of Helsinki, 131 Colon carcinoma, 12 Defined daily doses (DDDs) volumes, 164 Comedication, 228 Depression, 194 Communication skills, 194, 198 DGK. See German Cardiac Society (DGK) Communication styles, 198, 201 DHT. See Dihydrotestosterone (DHT) Congenital adrenal hyperplasia, 346–351 Diabetes, 138–140, 188, 316–331 breastfeeding, 350 alpha-glucosidase inhibitors, 322 fludrocortisone, 348 glitazones, 323 glucocorticoid therapy, 347–348 incretin, 324–328 pregnancy, 348, 350 insulin, 328–330 Consulting rates, 173 metformin, 318–322 Contraception, 550, 557 sulfonylureas, 323–324 Contraceptives, 561 Diabetes mellitus, 7, 13–14, 190–193 Convergence hypothesis, 152 Diabetes processes of care, 191 Coronary artery disease (CAD), 6, 8, 9, 13, Diarylpropionitril, 563 16, 17 Diastolic blood pressure (DBP), 186 Corticosteroids, 138 Diastolic heart failure, 222 Cortisol, 420, 421, 428 Dienogest, 561 Coumestrol, 564 Diethylstilbestrol, 561 COX-1. See Cyclooxygenase (COX)-1 Digoxin, 212, 215, 228, 229 COX-2, 450 Dihydropyrimidine dehydrogenase, 426, 428 CSE inhibitors, 160 Dihydrotestosterone (DHT), 568, 574 Cultured cells, 136–137 Dilated cardiomyopathy (DCM), 11 CVD. See Cardiovascular diseases (CVD) Disability, 445 Cyclooxygenase (COX)-1, 450 Disease CYP. See Cytochrome P450 Parkinson, 457 mono-oxygenases (CYP) Diuretics, 189, 221–222, 226–229 Cyproterone acetate, 549, 574 DNA-binding domain, 545 Cytochrome P450 mono-oxygenases DNA-repair capacity, 413, 426 (CYP), 94, 96, 102, 103 Docetaxel, 417, 420, 421 CYP1A2, 94, 96, 98 Dosage regime, 413 CYP3A4, 94, 96, 98 Dose-related ADRs, 178 CYP2C9, 98 cytochrome P 450 activity, 179 CYP2C19, 98 difference in body weight, 179 CYP2D6, 94, 96, 98 renal clearance, 179 CYP2E1, 94, 96 smallest volumes of distribution, 178 Cytochromes, 215, 218, 220, 227, 228 Doxorubicin, 417, 420, 423, 428 Index 593

Drospirenone, 554 R and T waves, 240 Drug development, 15–16, 18 rate-corrected QT intervals, 238, 239, 249 Drug expenditure, 195 shorter PR/AH intervals Drug prescription, 199 (conduction time), 250 Drug-related problems, 177 ST elevation, 243 female gender was an independent ST-segment elevation, 251 predictor, 177 T-wave peak to T-wave end interval, Drugs, 239, 242, 245–248, 251–252, 254 240, 241, 256 anticoagulation, 250 virtual electrograms, 239 dofetilide, 245 wave interval and PQ or PR interval, 243 drug manufacturing, 246 Emotional learning, 354 E4031, 246 Endometriosis, 552, 553, 558 hERG blockade, 247 Endometrium, 550, 551, 553 ibutilide, 243 Endothelin, 216–218 nonprescription anti-inflammatory, 450 Endothelin receptor (ET) antagonist QT-prolonging drugs, 247 atrasentan, 218 survival, 461 bosentan, 218 Drugs “to avoid in the elderly”, 174 clazosentan, 218 women were more likely, 174 sitaxsentan, 218 Drug therapy, 201 Epidermal growth factor (EGF), 414, 415, Drug utilization studies, 156 429, 430, 432 DUTY registry, 191 Epigenetics, 79–82 Dyslipidemia, 187–188, 390 ERa. See Oestrogen receptor alpha (ERa) ERb. See Oestrogen receptor beta (ERb) ERE, 395 E ERs. See Estrogen receptors (ERs) E2. See Estradiol (E2) ESC. See European Cardiac Society (ESC) ECG. See Electrocardiograms (ECG) Estradiol (E2), 502, 504, 506, 510, 511 Educational level, 173 Estrogen, 214, 217, 219, 222, 223, 227, E2/ER, 36 414, 416, 426, 430, 431 EGF. See Epidermal growth factor (EGF) Estrogen (17b-estradiol; E2), 24, 25, 30–42 Eicosanoids, 397 significantly decreased infarct size, 35 Elderly patients, 194 Estrogen receptors (ERs), 24–25, 34–42, Elderly people, 156 389, 395 Electrocardiograms (ECG), 238–240 ERa, 25, 26, 31, 34–36, 38 AH interval, 243 ERb, 25, 26, 31–36, 38 baseline QTC intervals, 248 Estrogens, 399, 400, 448 HV interval, 243 17b-estradiol, 401 JT intervals, 240, 256 Ethisterone, 554 QT, 242, 243 Ethynyloestradiol, 544, 561 QT and JT, 241 European Cardiac Society (ESC), 17 QTC, 241 European Clinical Trials Directive QTC intervals, 240, 242, 243, 247, 248, 2001/20/EC, 134 254, 255 European Medicines Agency QTC prolongation, 254 EMEA, 133 QTC shortening, 243 European Medicines Agency (EMEA), 139 QTC values, 242 Events QT dispersion, 240, 241, 247, 256 adverse, 462 QT dispersion and T-wave peak to T-wave end, 241 QT intervals, 239–243, 245, 247, 249, 254 F QT or JT intervals, 241 Family responsibilities, 176 QT prolongation, 246, 248, 253 Fatty acid oxidation, 390 QT-prolonging drugs, 247 FCG. See Four core genotypes (FCG) 594 Index

FDA. See Food and Drug Administration Gene expression, 413–416, 428 (FDA) BCRP1, 353 Federal Food, Drug and Cosmetic Act, 129 CYP2B, 353 Female physicians, 201 mSULT2A, 353 Females, 109 NHE, 354 Fetal bovine serum, 137 Gene networks, 70 Fibrates, 390, 397, 398 General accounting office, 132 fenofibrate, 399 Genistein, 564 gemfibrozil, 399 German Cardiac Society (DGK), 17 Fibrinolytic therapy GH. See Growth hormone (GH) streptokinase, 531 Glucocorticoids, 545 5-Fluorouracil, 420, 422, 426–428 Glucose metabolism, 388, 390, 392 Flutamide, 575 Glucose tolerance, 392 Follicle-stimulating hormone (FSH), 550, 560 Glutathione S-transferase A (GST A), 416 Food and Drug Administration (FDA), 132 GnRH agonists. See Gonadotropin-releasing Foot examinations, 191 hormone (GnRH) agonists Four core genotypes (FCG), 74–79, 83 Gonadectomy, 137 FSH. See Follicle-stimulating hormone (FSH) Gonadotropin-releasing hormone (GnRH) Fulvestrant, 568 agonists, 553 Function Gpr 30. See G-protein-coupled receptor cognitive, 454 (Gpr) 30 G-protein-coupled receptor (Gpr) 30, 560 Growth hormone (GH), 414, 415, 419, 428 G GST A. See Glutathione S-transferase A Gemcitabine, 420 (GST A) Gender, 3–18, 50–52, 59, 108, 129, 447 Guidelines, 10, 16–18 associated, 61 Gut toxicity, 412 associated disease, 58 associated pathogenetic differences, 52 biased specific analyses, 57 H biased studies, 58 HbA1c, 191, 192, 200 cytology, 50, 51 Health Canada, 133 cytopathology derived, 51 Health outcomes research, 141–142 dependent, 54, 60 Heart failure, 6–11, 14–16, 139–140, 213–215, determinant, 51 218, 221, 222, 224, 226–229 differences, 52, 54, 55, 57, 58, 60, 61, 177 Heart failure with preserved ejection fraction disparity, 51, 54, 60, 62 (HFpEF), 139 dyad, 199 Heart rates, 238, 239, 250 environment, 108 sinus cycle length, 239 issue, 51 sinus node function, 239 perspective, 51, 52 Heat-shock proteins (hsp), 547 physiological, 108 Hemorrhage related differences, 54 lower gastrointestinal, 451 related mechanisms, 50 Hepatic enzymes, 218 specific information, 52 Hepatocellular carcinoma, 7, 12 tailored therapies, 61 Hepatocyte nuclear factor (HNF) 3beta, 414 Gender-related differences Heterochromatizing factors, 71 aggregation, 524, 525 Hispanic, 419 anticoagulation, 525 Histones, 79, 80 coagulation, 524, 525 HIV. See Human immunodeficiency virus platelet activation, 524 (HIV) platelet function, 524 HNF 3beta. See Hepatocyte nuclear factor reactivity, 524 (HNF) 3beta Index 595

Hodgkin lymphoma, 426, 429, 432 Innate immune responses Hormone replacement therapy, 215, 221, 400 dendritic cells (DCs), 502, 503 Hormones, 114 macrophages, 502 estrogens, 114 pattern recognition receptors, 502 oral contraceptives (OC), 115 proinflammatory cytokines, 510 pregnancy, 115, 116 type I interferon (IFN), 502 progesterone, 114 Insulin sensitivity, 392, 394 HREC, 134 International Code of Medical Ethics, 131 hsp. See Heat-shock proteins (hsp) International Conference on Harmonization Human immunodeficiency virus (HIV), 185 Guideline E4, 133 Human umbilical vein endothelial cells, 137 Guideline E8, 133 Humoral immune responses, 513 Guideline E18, 133 antibody, 502, 508, 509, 511 Guidelines E3, 133 Hydrocodone, 193 Guidelines M4E, 133 Hypercholesterolemia, 398 ICH, 133 Hyperlipidemia, 193 Intolerance, 462 Hypertension, 7, 8, 10, 12, 77–78, 139–140, Ion-channels, 212, 219, 244, 245, 253–255 186, 193, 216–219, 221, 223–228 cardiac delayed rectifier K+ channels, 248 Hyperthyroidism, 362–365 cardiac Na+ channel, 248, 251 breastfeeding, 365–369 human ether-a-go-go-related gene iodine, 368 (HERG), 245, 246, 254 lactation, 368 ICa,L, 255 lithium, 367–368 IKr channel, 248 pregnancy, 365–369 IKs, 255 radioiodine, 369 IKs and IKr, 255 thionamides, 363–367 IKs channel, 248 thyroid surgery, 367, 368 INa channel, 248 + Hypertriglyceridemia, 398 inwardly rectifying K current (IK1), 255 Hypnotics, 165 ion currents, 255 Hypoglycemia, 393 K+channel, 248 Hypogonadism, 549, 569 KCHIP2, 254 Hyponatremia, 178 KCNJ2, 248 Hypothalamus, 415 Kir2.3, 254 Hypothyroidism Kir6.2, 254 L-T4, 369 Na+ current, 251 pregnancy, 372–373 SCN5A, 251 selenium, 373–374 target—the hERG channel, 246 thyroxine (T4), 370 transient outward current (Ito), 255 transient outward (Ito) currents, 251, 254 + transient outward (Ito)K channel b-subunit I KChIP2, 254 IBS. See Irritable bowel syndrome (IBS) transient outward K+ current, 251 2+ Ifosfamide, 428 T-type Ca currents (ICa,T), 255 Impairment Irinotecan, 417, 427 renal, 453 Irritable bowel syndrome (IBS), 473–491 Inappropriate pain relievers, 176 antidepressants, 485–486 Inappropriate prescribing, 169–170 antidiarrheal agents, 483–484 Influenza, 138 antispasmodic agents, 482–483 Inflammation, 444 clinical implications, 489–491 Inflammatory bowel syndromes, 7, 12, 17 gender, 479–480 Inhibitors laxatives, 482 selective COX-2, 457 new drugs, 487–489 Injections, 195 pathophysiology, 475–477 596 Index

Irritable bowel syndrome (IBS) (cont.) Menopause, 549 plant extracts, 486 Menstrual cycle, 114, 214, 228, 239, probiotics, 486–487 242–243, 245, 246, 250, 253, prostaglandin derivatives, 483 254, 413 serotonergic agents, 484–485 early follicular phase, 239 sex differences, 475–477 follicular phase, 115, 245, 246, 254 sex hormones, 477–479 late follicular phase, 239, 243, 253 treatment, 480–489 luteal phases, 114, 239, 242, 243, 245, 246, 254 menopause, 243 K menstruation, 252 Kidney failure, 12–13 ovulation, 243 Kinin ovulatory, 239 bradykinin, 222 puberty, 242, 248, 253 KRAB zinc finger repressor, 416 Meperidine, 194 Metabolic disorders, 389 Metabolic enzymes, 419 L Metabolism, 212–215, 218–222, 226–229 LDL cholesterol. See Low-density Metabolites, 455 lipoprotein (LDL) cholesterol Methylation, 79 Leukotrienes, 446 Metoprolol, 164 Levonorgestrel, 554 MH. See Myocardial hypertrophy (MH) LH. See Luteinizing hormone (LH) Microalbuminuria, 186 Ligand-binding domain, 545 Mifepristone, 553, 554, 556 Lipid-lowering drugs, 191 Mineralocorticoids, 545 Lipid-lowering medication, 186–187 Mitochondrial biogenesis, 396 Lipid metabolism, 390, 392, 401 Monoclonal antibodies, 431–434 lipolysis, 388 Mood stabilisers, 291–292 b-oxidation, 388 Morphine, 194 Lipolysis, 397 Mortality, 165 Lipoproteins, 400 Multidrug-resistance gene 1A (MDR1A), 416 Lonaprisan, 554, 556, 558 Multiparous, 137 Loop diuretic Multiple sclerosis, 76, 138 furosemide, 227 Muscle/fat ratio, 413, 420, 434 torasemide, 227, 228 Myocardial hypertrophy (MH), 25, 27–36 Low-density lipoprotein (LDL) pathological cardiac hypertrophy, 39 cholesterol, 191 physiological, 27, 32–33, 38 Lung cancer, 427–430, 433 Myocardial infarction, 6–8, 10, 13, 15, 17, Luteinizing hormone (LH), 550, 560 157, 184 Lymphoma, 431, 432 N M National Institute of Health (NIH), 132 Mammary gland, 552 National Institutes of Health Revitalization MDR1A. See Multidrug-resistance gene 1A Act, 132 (MDR1A) Nausea, 421, 425, 428, 434 Mechanisms Necrosis, 55 molecular, 446 necrotic cells, 56 Medication addiction, 162 Neural tube closure, 77 Medication expenses, 153 Neuroleptic drugs, 152 Medication prescriptions, 153 NHRs. See Nuclear hormone receptors (NHRs) Medroxyprogesterone acetate, 554 Nilutamide, 575 Melanoma Nimesulide, 459 cutaneous, 456 Non-prescription drugs, 173 Index 597

Non-selective monoamine reuptake inhibitors P (NSMRIs), 161 P4. See Progesterone (P4) Nonsteroidal anti-inflammatory drugs Paclitaxel, 417, 420, 421, 426–428 (NSAIDs), 449 Pain, 118 NSAIDs. See Nonsteroidal anti-inflammatory sensitivity, 118 drugs (NSAIDs) Painkillers, 157 NSMRIs. See Non-selective monoamine Pain management, 193 reuptake inhibitors (NSMRIs) Parental imprint, 70 Nuclear hormone receptors (NHRs), 389, 392 Participatory decision making, 198 EERalpha, 396 Partnership, 198 EERbeta, 396 Patient-centered communication, 199, 201 N-COR, 390 Patterns p300, 391 different gender, 463 PGC1alpha, 391, 396 PCPs. See Primary care physicians (PCPs) PGC1beta, 391, 396 Perinatal, 282 p160/SRC, 391 Peroxisome proliferator-activated receptor g RIP140, 390 (PPAR g), 139 SMRT, 390 Peroxisome proliferator-activated receptors SRC1, 391, 396 (PPARs), 389–391 TIF2, 391, 396 Personalized medicine, 17–18 Nuremberg code, 131 Pethidine, 194 P-glycoprotein (P-gp), 218–221, 416, 419, 420, 426 P-gp. See P-glycoprotein (P-gp) O Pharmaceutical industry, 197 Obesity, 139–140, 196, 308–316 Pharmacodynamics, 97, 99, 101–103, 111, orlistat, 313–315 212, 213, 394 rimonabant, 310–312 long QT syndrome, 111 sibutramine, 312–313 Pharmacokinetics, 92–94, 97, 99, 101–103, Oestradiol, 562 111, 212, 213, 218, 220–222, 226–229, 17b-Oestradiol, 559 394, 413, 414, 420–432, 434, 435 Oestradiol, oestriol, 562 distribution volume, 111 Oestrogen, 545, 549, 550, 553 first passage, 115 Oestrogen receptor, 559–568 metabolism, 115 Oestrogen receptor alpha (ERa), 548, 560, 564 nicotine, 115 Oestrogen receptor beta (ERb), 396, 560, 564 plasma level, 111 Oestrone, 544 renal clearance, 111 Oestrous cycle, 560 Phase IV trials and registries, 179–180 Older drugs, 176 Physician gender, 185, 190, 193, 194, 196, Older women, 169 199, 201 Onapristone, 554, 557, 558 Physician–patient communication, 200 Opioid, 194 Physicians’ gender, 187 Oral anticoagulation Phytoestrogens, 138, 213, 214 apixaban, 534 Placebo, 117 dabigatran, 533, 534 benzodiazepine, 118 rivaroxaban, 534 conditioned stimuli, 118 vitamin K antagonist, 533–535 fibromyalgia, 119 warfarin, 533 opioid system, 119 Oral contraceptives, 219 pain/analgesia, 117 Oral mucositis, 424, 427, 435 psychosocial context, 118 Organizational effects, 72, 79 sex–gender, 117 Osteoporosis, 138, 185, 195–196, 393, 560, P450 monooxygenase, 415, 428 566, 567 Poly-ADP-ribose polymerase Ovulation, 550, 551 PARP1, 139 598 Index

Polymorphisms, 213–214, 217, 222, 223, Q 228, 394 Quality of life, 461 Polypharmacotherapy, 169 Polypharmacy, 170, 171, 177, 229 being female, 171 R large number of medications, 170 Raloxifene, 566, 567 potentially inappropriate medications RAS. See Renin-angiotensin system (RAS) (PIMs), 170 Reaction problem of evidence-based medicine and inflammatory, 449 medical progress, 171 Receptor risk factor, 170 angiotensin II type 1 receptor (AT1-R), Polyps 214, 217, 222–225 colorectal, 456 angiotensin II type 2 receptor (AT2-R), Postmenopausal women, 399 213, 214, 223–225 Postpubescent, 137 ETA receptor, 216–218 Potentially inappropriate medication, 154 ETB receptor, 216–218 PPARalpha, 389, 390, 397, 400, 401 Redox-system, 416, 427 PPARdelta, 389, 390 Regular monitoring, 178 PPARgamma, 389, 390, 392, 395, 396 Remission, 445 pro12Ala polymorphism, 394 Renal clearance, 227 pro12Ala variant, 394, 395 Renal insufficiency, 194 PPARs. See Peroxisome proliferator-activated Renin, 222–224, 226, 227 receptors (PPARs) Renin-angiotensin system (RAS), 213, PPREs, 390 222–226 PR antagonists, 553 Renin inhibitor Preclinical studies, 129, 135–138 aliskiren, 226 Pregnancies, 131, 132, 140, 141, 280, 445 Response Pregnenolone, 548 immune-inflammatory, 463 Prenylnaringenin, 564 poor, 461 Prescribed packages, 151 Retinoid acid receptors (RXRs), 389–391, 395 Prescribing physicians, 152 Rezulin (troglitazone), 139 Prescription volumes, 151 Rheumatoid arthritis, 444 Preventive therapies, 198 Risk factor, 174 Primary care physicians (PCPs), 186 Rituximab, 425, 431, 432, 434 PRISCUS, 175 Rosiglitazone, 139 PRISCUS list, 156 RXRs. See Retinoid acid receptors (RXRs) Proellex®, 557 Progenitor cells, 136–137 Progesterone (P4), 214, 220, 502, 504, 506, S 550, 551, 553 Safe medication therapy, 180 Progesterone receptor (PR), 550, 551 SBP. See Systolic blood pressure (SBP) Progestins, 545, 549, 550 Secondary data, 150 Progynon®, 549 Secondary prophylaxis, 162 Prophylactic folate treatment, 295 Sedative and antidepressant drugs, 176 Propranolol, 164 Selective oestrogen receptor modulators, 561 Prostaglandins, 397 Selective PR modulators (SPRMs), 552, 553 Prostate cancer, 551, 569–571 Serotonin reuptake inhibitors (SSRIs), 161 Protein expression, 353–354 Sex and gender, 265–274 Psychiatric disorders, 194 Sex bias, 176 Psychopharmacological treatment, 280 Sex chromosome effects, 72 Psychotropic drugs, 151, 175 Sex determination, 70–73 Public interest, 197 Sex-determining factors, 70 Pulmonary disease, 138 primary, 70, 71 Pure Food and Drug Act of 1906, 129–130 secondary, 70 Index 599

Sex differences, 23–42 Signal transducers and activators of Sexes, 3–18, 51, 52, 55, 61, 108, 129 transcription 5b (STAT5b), 413, 414 anatomical, 108 Skeletal muscle, 269 differences, 58 SLE. See Systemic lupus erythematosus (SLE) dimorphisms, 54 Smoking, 186 hormonal, 108 Social deprivation, 176 hormones, 54, 55, 57, 58 Somatostatin, 414 specific genetic architecture, 54 Spermatogenic cycle, 141 specific transcriptional regulation, 54 SPRMs. See Selective PR modulators (SPRMs) steroid hormone receptors, 54, 55 Sry, 71–74, 77, 78, 83 Sex-gender differences (SGD), 266–268 SSRIs. See Serotonin reuptake inhibitors body composition, 273 (SSRIs) clearance, 271 STAT5b. See Signal transducers and activators efficacy, 273 of transcription 5b (STAT5b) emergence, 271 Statins, 162–163, 398 hormonal variability, 266 Statutory health insurance fund, 150 metabolism, 267 Steroid, 413–415, 419, 420, 427, 428 physiological differences, 266–268 Stroke, 6, 7, 14, 16, 17, 138, 139, 157 progesterone, 270 Substitution hypothesis, 152 psychosocial factors, 273 Symptoms sexual hormones, 266 gastrointestinal, 451 transport proteins, 267 Systemic lupus erythematosus (SLE), 76 Sex hormones, 93–100, 102, 103, 214–215, Systolic blood pressure (SBP), 186 217, 219, 225, 228, 242, 244, 252, 254 androgens, 93, 96, 100, 242, 255 androgen therapy, 242 T 17b-estradiol (E2), 246 Tamoxifen, 551, 558, 564, 566–567 dihydrotestosterone, 245 Tanaproget, 559 E2, 246, 255 T2DM. See Type 2 diabetes mellitus (T2DM) estradiol, 95, 97, 101, 102, 242, 245 Temozolomide, 423, 427 estrogens, 94–98, 100–103, 238, 243, Teratogenicity, 282 245, 250, 254, 255 Testosterone (T), 214, 217, 227, 502, estrogen states, 239 549, 568–571 female hormones, 242, 243 Testosterone undecanoate, 573 ovarian hormones, 250 Thalidomide, 132, 133 ovarian steroids, 239, 242, 243, 250 Therapy problems, 156 progesterone, 94, 95, 102, 238, 243, 245, Thiazide diuretic 250, 253–255 hydrochlorothiazide (HCTZ), 224 progestins, 97, 98, 102, 103 Thiazolidinediones (TZDs), 390, 393, 396 sex hormonal regulation, 256 pioglitazone, 392–394 sex hormone receptor, 244 rosiglitazone, 392, 393 sex steroid hormone, 242 Thrombocyte aggregation inhibitors, 157 sex steroids, 238 Thromboembolic events testosterone, 94–97, 99, 101, 238, 239, adverse complications, 524 242, 245, 253–255 clinical outcomes, 524 Sexome, 70, 82 morbidity, 524 Sex-specific, 165 mortality, 524 Sex-specific considerations, 173 Thyroid hormone, therapy-related Sex-specific distribution differences, 157 antidepressive effects, 374–375 Sex steroid hormones, 243–245, 252, bile acid metabolism, 376 254–255, 513 cardiovascular effects, 376–377 Sexual differentiation, 70–73 energy metabolism, 375 Sexual maturity, 137 steroid metabolism, 376 Sf1, 74, 78 TNF-a inhibitors SGD. See Sex-gender differences (SGD) adalimumab, 460 600 Index

TNF-a inhibitors (cont.) HSV-2 gD vaccine, 505 certolizumab pegol, 460 recombinant gD-based HSV-2 vaccine, 507 etanercept, 460 trivalent inactivated vaccines (TIV), golimumab, 460 505, 511 infliximab, 460 Vasoconstriction, 216, 217, 219, 224–225 Torsades de pointes (TdPs), 138 Vasodilatation, 216, 225 Toxicity, 282 Vinca alkaloids, 417, 420, 426 Tranquilisers, 161 Vinorelbine, 426 Transgenic animal model, 213–214 Viral infections, 501, 513 Trials hepatitis, 508, 512 clinical, 458 hepatitis B virus (HBV), 501, 505 Triglycerides, 395, 397 hepatitis C virus (HCV), 501, 505, 508 Type 2 diabetes, 139, 184, 190, 193 herpes simplex virus, 501, 506, 508, Type 2 diabetes mellitus (T2DM), 388, 389, 512–513 392, 393 herpes simplex virus-type 2 (HSV-2), Typical antipsychotics, 287–288 505, 506 Tyrosine kinase inhibitors, 429, 430 HSV-type 1 (HSV-1), 506 TZDs. See Thiazolidinediones (TZDs) human, 501 human immunodeficiency virus (HIV), 503–506, 512 U immunodeficiency, 501 Ulcers influenza, 501, 505, 510–513 duodenal, 458 Vitamin D, 545 gastric, 458 Vomiting, 425, 428–429, 434, 435 gastroduodenal, 458 Vulnerability, 180 Ulipristal, 557 Undecanoate testosterone, 571 Underenrollment, 179 W Undertreatment, 16 Women, 110, 171, 172 United States Department of Health and higher risk for polypharmacy, 172 Human Services inappropriateness of care, 110 Code of Federal Regulations, 131 majority of old people, 173 United States Federal Drug “Women-are-expressive”-hypothesis, 152 Administration, 139 World Medical Association (WMA), 131 Unspecific complaints, 165 Urine albumin testing, 191 Uterine fibroids, 552, 556 X Uterine leiomyoma, 552 X-chromosome, 213, 223, 225 Xenobiotics, 413, 427 X-inactivation, 70, 73 V Vaccines, 509 adverse reactions, 513 Z HBV vaccine, 505 Z-drugs, 161