Cinsiyet Hormonlarının İlaç Farmakolojisi Üzerine Etkileri

Mahmut  Özdemir

doi:10.37609/akya.3743

Yazarlar

Mahmut Özdemir

https://orcid.org/0000-0003-1124-6957

DOI: https://doi.org/10.37609/akya.3743.c7741

Özet

Referanslar

Yang Y, Carlin AS, Faustino PJ,et al. Participation of women in clinical trials for new molecular entities (NMEs) approved by FDA in 2000–2002. AAPS Annual Meeting. Abstract: 2008. 002330.

Oertelt-Prigione S, Regitz-Zagrosek V. Gender aspects in cardiovascular pharmacology. Journal of Cardiovascular Translational Research. 2009; 2: 258–266.

Bigos KL, Pollock BG, Stankevich BA, et al. Sex differences in the pharmacokinetics and pharmacodynamics of antidepressants: an updated review.Gender Medicine.2009; 6 (4): 522–543.

Fillingim RB, King CD, Ribeiro-Dasilva MC, et al. 2009. Sex, gender, and pain: a review of recent clinical and experimental findings. Journal of Pain; 2009; 10(5): 447–485.

Nicolas JM, Espie P, Molimard M. Gender and interindividual variability in pharmacokinetics. Drug Metabolism Reviews. 2009; 41: 408–421

Freire AC, Basit AW, Choudhary R, et al. Does sex matter? The influence of gender on gastrointestinal physiology and drug delivery. International Journal Pharmaceutics, 2011; 415: 15-28.

Ibekwe VC, Fadda HM, McConnell EL, et al. Interplay between intestinal pH, transit time and feed status on the in vivo performance of pH responsive ileo-colonic release systems. Pharmaceutical Research.2008; 25:1828–1835.

Prewett EJ, Smith JTL, Nwokolo CU, et al. Twenty four hour intragastric acidity and plasma gastrin concentration in female and male subjects. Clinical Science. 1991; 80: 616–624.

Feldman M, Richardson CT, Walsh JH. Sex-related differences in gastrin release and parietal cell sensitivity to gastrin in healthy human beings. Journal of Clinical Investigations. 1983;715–720.

Tuo BG, Wen GR, Wei JQ, et al. Gender differences in duodenal bicarbonate secretion cause gender differences in human duodenal ulcer. Gastroenterology. 2008; 134: A137–A1137.

Nicolas JM, Espie P, Molimard M. Gender and interindividual variability in pharmacokinetics. Drug Metabolism Reviews.2009; 41 (3) : 408–421, https://doi.org/ 10.1080/10837450902891485.

Sadik R, Abrahamsson H, Stotzer PO. Gender differences in gut transit shown with a newly developed radiological procedure. Scandinavian Journal of Gastroenterology. 2003; 38: 36–42.

Jung HK, Kim DY, Moon IH. 2003. Effects of gender and menstrual cycle on colonic transit time in healthy subjects. Korean Journal of International Medicine. 2003; 18: 181–186.

Senek M, Nyholm D, Nielsen EI. Population pharmacokinetics of levodopa/carbidopa microtablets in healthy subjects and Parkinson’s disease patients. European Journal of Clinical Pharmacology. 2018; 74 (10): 1299–1307. https://doi.org/ 10. 1007/s00228-018-2497-2.

Zimmermann T, Laufen H, Yeates R, et al., The pharmacokinetics of extended-release formulations of calcium antagonists and of amlodipine in subjects with different gastrointestinal transit times, Journal of Clinical Pharmacology.1999; 39 (10): 1021–1031,

Nicolson TJ, Mellor HR, Roberts RRA. Gender differences in drug toxicity. Trends in Pharmacological Sciences.2010; 31: 108–114.

Spaanderman ME, Van Beek E, Ekhart TH, et al. Changes in hemodynamic parameters and volüme homeostasis with the menstrual cycle among women with a history of preeclampsia. American Journal of Obstetrics and Gynecology. 2000; 182: 1127–1134.

Regitz-Zagrosek V, Seeland U. Sex and gender differences in clinical medicine, Handbook Experimental Pharmacology. 2012; 3–22. https://doi.org/10.1007/ 978-3-642-30726-3_1.

Gandhi M, Aweeka F, Greenblatt RM, et al. Sex differences in pharmacokinetics and pharmacodynamics. Annual Review of Pharmacology and Toxicology. 2004; 44: 499–523

Cirrincione LR, Huang KJ. Sex and gender differences in clinical pharmacology: implications for transgender medicine. Clinical Pharmacology & Therapeutics. 2021;110(4):897–908. doi: 10. 1002/cpt.223436

Veering B, Burm A, Souverijn J, et al. The effect of age on serum concentrations of albumin and alpha 1-acid glycoprotein. British Journal of Clinical Pharmacology. 1990; 29(2): 201–206. doi: 10.1111/j.1365-2125.1990

Christie KN. Is dosage adjustment for olanzapine really necessary? Open Journal of Psychiatry. 2023;13(3):187–206. doi: 10.4236/ ojpsych.2023. 133016

Schwartz, JB. The influence of sex on pharmacokinetics. Clinical Pharmacokinetics. 2003; 42: 107–121.

Schwartz JB. The current state of knowledge on age, sex, and their interactions on clinical pharmacology. Clinical Pharmacology & Therapeutics. 2007; 82: 87–96.

Schuetz EG, Furuya KN, Schuetz JD. Interindividual variation in expression of P-glycoprotein in normal human liver and secondary hepatic neoplasms. Journal of Pharmacology &. Experimental Therapeutics. 1995; 275: 1011–1018.

Woldbold R, Klein K, Burk O, et al. Sex is a major determinant of CYP3A4 expression in human liver. Hepatology 2003; 38: 978–988.

Hagg S, Spigset O, Dahlqvist R. Influence of gender and oral contraceptives on CYP2D6 and CYP2C19 activity in healthy volunteers. British Journal of Clinical Pharmacology. 2001; 51: 169–173.

Tang Y, Mao P, Li F, et al. Gender, age, smoking behaviour and plasma clozapine concentrations in 193 Chinese inpatients with schizophrenia. British Journal of Clinical Pharmacology. 2007;64(1):49–56. doi: 10. 1111/j.1365-2125.2007.02852.x41

Pollock BG, Wylie M, Stack JA, et al. Inhibition of caffeine metabolism by estrogen replacement therapy in postmenopausal women. The Journal of Clinical Pharmacology.2013; 39 (9): 936-940.

Brand BA, Haveman YRA, de Beer F, et al. Antipsychotic medication for women with schizophrenia spectrum disorders. Psychological Medicine. 2022; 52(4): 649–663. doi: 10.1017/ S00 3329172100459147 .

González-Rodríguez A, Seeman MV. The association between hormones and antipsychotic use: a focus on postpartum and menopausal women. Therapeutic Advances in Psychopharmacology. 2019; Jul 3: 9: 204512531985997. doi: 10. 1177/204512531985997349

Choi S-Y, Koh KH, Jeong H. Isoform-specific regulation of cytochromes p450 expression by estradiol and progesterone. Drug Metabolism and Disposition. 2013; 41(2): 263–269. doi: 10.1124/ dmd.112.046276• A work on the influence of estradiol and progesterone on the expression of several CYP isoforms.

Mwinyi J, Cavaco I, Pedersen RS, et al. Regulation of CYP2C19 expression by estrogen receptor α: implications for estrogen-dependent inhibition of drug metabolism. Molecular Pharma-cology. 2010;78(5):886–894. doi: 10.1124/mol.110 .065540

Greenblatt DJ, von Moltke LL. Gender has a small but statistically significant effect on clearance of CYP3A substrate drugs. The Journal of Clinical Pharmacology. 2008;48(11):1350–1355. doi: 10.1177/ 0091270008323754

Scandlyn MJ, Stuart EC, Rosengren RJ. Sex-specific differences in CYP450 isoforms in humans. Expert Opinion on Drug Metabolism & Toxicology. 2008;4(4):413–424. doi: 10.1517/ 17425255.4.4.413• A review covering the sex-dependent activity of several CYP isoforms.

Mai Y, Dou L, Yao Z, et al. Quantification of p-glycoprotein in the gastrointestinal tract of humans and rodents: methodology, gut region, sex, and species matter. Molecular Pharmacology. 2021; 18(5):1895–1904. doi: 10.1021/acs.molpharmaceut.0c00574

Canaparo R, Finnstrom N, Serpe L, et al. Expression of CYP3A isoforms and P-glycoprotein in human stomach, jejunum and ileum. Clinical Experimental Pharmacology and Physiology. 2007a; 34: 1138–1144.

Canaparo R, Nordmark A, Finnstrom N, et al. Expression of cytochromes P450 3A and P-glycoprotein in human large intestine in paired tumour and normal samples. Basic & Clinical Pharmacology &. Toxicology. 2007b;100: 240–248.

Paine MF, Ludington SS, Chen ML, et al. Do men and women differ in proximal small intestinal CYP3A or Pglycoprotein expression? Drug Metabolism and Disposition.2005; 33: 426–433.

Castberg I, Westin AA, Skogvoll E, et al. Effects of age and gender on the serum levels of clozapine, olanzapine, risperidone, and quetiapine. Acta Psychiatrica Scandinavica. 2017;136(5):455–464. doi: 10. 1111/acps.12794

Choi SY, Koh KH, Jeong H. Isoform-specific regulation of cytochromes p450 expression by estradiol and progesterone. Drug Metabolism and Disposition 2013;41(2):263–269. doi: 10.1124/ dmd.112.046276• A work on the influence of estradiol and progesterone on the expression of several CYP isoforms.

Tsuchiya Y, Nakajima M, Kyo S, et al. Human CYP1B1 is regu-lated by estradiol via estrogen receptor. Cancer Research. 2004; 64:3119–3125. https://doi.org/10.1158/0008-5472.can-04-0166.

Suzuki T, Zhao YL, Nadai M, et al. Gender-related differences in expression and function of hepatic P-glycoprotein and multidrug resistance-associated protein (Mrp2) in rats. Life Scinces. 2006; 79: 455-461.

Cummins CL, Wu CY, Benet LZ. Sex-related differences in the clearance of cytochrome P450 3A4 substrates may be caused by P-glycoprotein. Clinical Pharmacology & Therapeutics. 2002; 72: 474-489.

Bebawy M, Chetty M. Gender differences in p-glycoprotein expression and function: effects on drug disposition and outcome. Current Drug Metabolism. 2009; 10: 322-328.

Kim WY, Benet LZ. P-glycoprotein (P-gp/MDR1)-mediated efflux of sex steroid hormones and modulation of P-gp expression in vitro. Pharmacological Research. 2005; 21: 1284–1293.

Mineiro R, Santos C, Gonçalves I, et al. Regulation of ABC transporters by sex steroids may explain differences in drug resistance between sexes. Journal of Physiology & Biochemistry. 2023;79(3):467–487. doi: 10. 1007/s13105-023-00957-1

Frohlich M, Albermann N, Sauer A, et al. In vitro and ex vivo evidence for modulation of P-glycoprotein activity by progestins. Biochemical Pharmacology. 2004; 68: 2409–2416.

Klein SL, Roberts CW. Sex and gender differences in infection and treatments for infectious diseases, Springer, 2015. DOI: 10.1007/978-3-319-16438-0.

Clark RA, Bessinger R. Clinical manifestations and predictors of survival in older women infected with HIV. Journal of Acquired Immune Deficiency Syndromes & Human Retrovirology.. 1997;15: 341–345

Rathore SS, Wang Y, Krumholz HM. 2002. Sex-based differences in the effect of digoxin for the treatment of heart failure. New England Journal of Medicine.2002; 347: 1403–1411.

Krecic-Shepard ME, Barnas CR, Slimko J, et al. Faster clearance of sustained release verapamil in men versus women: continuing observations on sex-specific differences after oral administration of verapamil. Clinical Pharmacology & Therapeutics. 2000; 68: 286–292.

Gorski JC, Jones DR, Haehner-Daniels BD, et al. The contribution of intestinal and hepatic CYP3A to the interaction between midazolam and clarithromycin. Clinical Pharmacology & Therapeutics. 1998, 64: 133–143.

Seaber EJ, Peck RW, D.A. Smith DA, et al. The absolute bioavailability and effect of food on the pharmacokinetics of zolmitriptan in healthy volunteers, British Journal of Clinical Pharmacology. 1998;46: 433–439. https://doi.org/10.1046/j.1365-2125.1998.00809.x.

Meech R, Hu DG, McKinnon RA, et al. The udp-glycosyltransferase (UGT) superfamily: new members, new functions, and novel paradigms. Physiological Reviews. 2019;99(2):1153–1222. doi: 10.1152/phys rev.00058.2017 .

Gallagher CJ, Balliet RM, Sun D, et al. Sex differences in udp-glucuronosyltransferase 2B17 expression and activity. Drug Metabolism & Disposition. 2010;38(12):2204–2209. doi: 10.1124/ dmd.110. 035345

Chen H, Yang K, Choi S, et al. Up-regulation of udp-glucuronosyltransferase (UGT) 1A4 by 17β-estradiol: a potential mechanism of increased lamotrigine elimination in pregnancy. Drug Metabolism & Disposition. 2009;37(9):1841–1847. doi: 10.1124/dmd.109. 026609

Di Pietro G, Magno LA, Rios-Santos F. Glutathione S-transferases: an overview in cancer research. Expert Opinion Drug Metabolism &. Toxicology. 2010; 6: 153–170.

Hoensch H, Morgenstern I, Petereit G, et al. Influence of clinical factors, diet, and drugs on the human upper gastrointestinal glutathione system. Gut.2002; 50: 235–240.

Hoensch H, Peters WH, Roelofs HM, et al. Expression of the glutathione enzyme system of human colon mucosa by localisation, gender and age. Currrent Medical Research & Opinion. 2006;22:1075–1083. doi: 10.1185/030079906X112480.

Mulder TP, Court DA, Peters WH. Variability of glutathione S-transferase alpha in human liver and plasma. Clinical Chemistry. 1999; 45: 355–359.

Temellini A, Castiglioni M, Giuliani L, et al. Glutathione conjuga-tion with 1-chloro-2,4-dinitrobenzene (CDNB): interindividual variability in human liver,lung, kidney and intestine. Internatinal Journal of Clinical Pharmacology and Therapeutics.1995; 33: 498–503

Peters WH, Roelofs HM, Hectors MP, et al. Glutathione and glutathione S-transferases in Barrett’s epithelium. British Journal of Cancer.1993; 67: 1413–1417.

Hayes JD, Pulford DJ. 1995The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Critical Reviews in Biochemistry and Molecular Biology. 1995; 30: 445–600.

Tapaninen T, Neuvonen PJ, Niemi M. Grapefruit juice greatly reduces the plasma concentrations of the OATP2B1 and CYP3A4 substrate aliskiren. Clinical Pharmacology and Therapeutics 2010; 88: 339–342.

Frezza M, Di Padova C, Pozzato G, et al. High blood alcohol levels in women. The role of decreased gastric alcohol dehydrogenase activity and first-pass metabolism. The New England Journal of Medicine. 1990; 322: 95–99.

Jones BM, Jones MK. Alcohol effects in women during the menstrual cycle. Annals of the New York Academy of Sciences.1976; 273: 576–587.

Fenton A, Montgomery E, Nightingale P, et al. Glomerular filtration rate: new age- and gender- specific reference ranges and thresholds for living kidney donation. BMC Nephrology. 2018;19(1):336. doi: 10.1186/s12882-018-1126-8

Berg UB. Differences in decline in GFR with age between males and females. Reference data on clearances of inulin and PAH in potential kidney donors. Nephrology Dialysis Transplantation. 2006;21(9):2577–2582. doi: 10.1093/ndt/gfl22799

Madla CM, Gavins FKH, Merchant HA, et al. Let’s talk about sex: differences in drug therapy in males and females. Advanced Drug Delivery Reviews 2021;175:113804. doi: 10.1016/j.addr.2021.05. 014 •• A review examining the impact of sex on pharmacokinetic responses.

Waas T, Schulz A, Lotz J, et al. Distribution of estimated glomerular filtration rate and determinants of its age dependent loss in a German population-based study. Scientific Reports. 2021;11(1):10165. doi: 10.1038/s41598-021-89442-796.

Kanado Y, Tsurudome Y, Omata Y, et al. Estradiol regulation of P-glycoprotein expression in mouse kidney and human tubular epithelial cells, implication for renal clearance of drugs. Biochemical and Biophysical Research Communications. 2019; 519(3):613–619. doi: 10.1016/j.bbrc

Joseph S, Nicolson TJ, Hammons G, et al. Expression of drug transporters in human kidney: impact of sex, age, and ethnicity. Biology of Sex Difference. 2015;6(1):4. doi: 10.1186/s13293-015-0020-

Regitz-Zagrosek V. Sex and Gender Differences in Pharmacology, Springer Science & Business Media, 2012.

Soldin OP, Mattison DR. Sex differences in pharmacokinetics and pharmacodynamics, Clinical Pharmacokinetics. 2009; 48: 143–157. https://doi. org/10.2165/00003088-200948030-00001.

Jochmann N, Stangl K, Garbe E et al. Female-specific aspects in the pharmacotherapy of chronic cardiovascular diseases. The European Heart Journal. 2005; 26:1585–1595 (Jochmann ve ark. 2005).

Ostadal B, Netuka I, Maly J et al. Gender differences in cardiac ischemic injury and protection–experimental aspects. Experimental biology and medicine (Maywood, N.J.). 2009; 234: 1011–1019.

Malorni W, Campesi I, Straface E et al. Redox features of the cell: a gender perspective. Antioxidants & Redox Signaling.2007; 9: 1779–1801.

De Silva TM, Broughton BR, Drummond GR et al. Gender influences cerebral vascular responses to angiotensin II through Nox2-derived reactive oxygen species. Stroke, 2009; 40:1091–1097

Arias-Loza PA, Hu K, Dienesch C et al. Both estrogen receptor subtypes, alpha and beta, attenuate cardiovascular remodeling in aldosterone salt-treated rats. Hypertension. 2007; 50:432–438

Malorni W, Straface E, Matarrese P et al. Redox state and gender differences in vascular smooth muscle cells. FEBS Letters. 2008; 582:635–642

Fischer M, Baessler A, Schunkert H. Renin angiotensin system and gender differences in the cardiovascular system. Cardiovascular Research. 2002; 53:672–677

Makkar RR, Fromm BS, Steinman RT, et al. Female gender as a risk factor for torsades de pointes associated with cardiovascular drugs, Journal of the American Medical Association. 1993; 270: 2590–2597. https://doi.org/ 10.1001/jama.270.21.2590. .

A. Parekh A, Fadiran EO, Uhl K, et al. Adverse effects in women:implications for drug development and regulatory policies, Expert Review of Clinical Pharmacology. 2011; 4 (4): 453–466. https://doi.org/10.1586/ecp.11.29.

Arya A, Gender-related differences in ventricular repolarization: beyond gonadal steroids. The Journal of Cardiovascular Electrophysiology. 2005; 16:525–527, https:// doi.org/10.1111/j. 1540-8167.2005.40845.x. (245).

Vierhapper H, Nowotny P, Waldhäusl W. Sex-specific differences in cortisol production rates in humans, Metabolism. 1998; 48: 974–976, https://doi.org/10.1016/s0026-0495(98)90353-5.

Lew KH, Ludwig EA, Milad MA,et al. Gender-based effects on methylprednisolone pharmacokinetics and pharmacodynamics, Journal of Clinical Pharmacology and Therapeutics. 1993; 54: 402–414.

Gan TJ, Glass PS, Sigl J,et al. Women emerge from general anesthesia with propofol/alfentanil/nitrous oxide faster than men, Anesthesiology. 1999; 50: 1283–1287, https://doi.org/10.1097/ 00000542-199905000-00010247

Eugene AR, Masiak J. A pharmacodynamic modelling and simulation study identifying gender differences of daily olanzapine dose and dopamine D2-receptor occupancy, Nordic Journal of Psychiatry.2017; 71: 417–424, https://doi.org/ 10. 1080/ 08039488, 2017. 1314011.

Bigos KL, Pollock BG, Coley KC, et al. Sex, race, and smoking impact olanzapine exposure, The Journal of Clinical Pharmacolog. 2008; 48: 157–165. https://doi.org/10.1177/009127 0007310385.248-249.

Cataldi M, Muscogiuri G, Savastano S, et al. Gender‐related issues in the pharmacology of new anti‐obesity drugs. Obesity Reviews. 2019;20(3):375‐384.

Juul KW. Klein BM, Sandström R, et al. Gender difference in antidiuretic response to desmopressin, The American Journal of Physiology-Renal Physiology. 2011; 300: F1116–1122,https://doi. org/10.1152/ ajprenal.00741.2010.

Schroeder MK, Juul KW, Mahler B, et al, Desmopressin use in pediatric nocturnal enuresis patients: is there a sex difference in prescription patterns?, The European Journal of Pediatrics. 2018; 177: 389–394, https://doi.org/ 10.1007/s00431-017-3074-x

Shen Q, Lin Y, Handa T, et al. 2006. Modulation of intestinal P-glycoprotein function by polyethylene glycols and their derivatives by in vitro transport and in situ absorption studies. International Journal of Pharmaceutics. 2006; 56 (313): n1-2, 49-56,

Zhang XX, Pan WS, Gan L, et al. 2008. Effects of breast cancer resistance protein inhibitors and pharmaceutical excipients on decreasing gastrointestinal toxicity of camptothecin analogs. Acta Pharmacologica Sinica.2008; 29: 1391–1398.

Mokhtar M, Gosselin P, Hildgen P. 2009. PEG-grafted-PLA nanoparticles as bioavailability enhancer for orally administrated drugs. In: The American Association of Pharmaceutical Scientists, 2009, LA (AAPS2009-001358).

Schulze JD, Waddington WA, Eli PJ, et al. Concentration-dependent effects of polyethylene glycol 400 on gastrointestinal transit and drug absorption, Journal of Pharmaceutical Research. 2003; 20: 1984–1988, https://doi.org/10.1023/ b:pham. 00000080 46.64409.d.

Basit AW, Podczeck F, Newton JM, et al. Influence of polyethylene glycol 400 on the gastrointestinal absorption of ranitidine, Journal of Pharmaceutical Research. 2002; 19: 1368–1374, https://doi.org/10.1023/a:1020315228237.

Basit AW, Podczeck F, Newton JM, et al. 2004. The use of formulation technology to assess regional gastrointestinal drug absorption in humans European Journal of Pharmaceutical Sciences. 2004; 21: 179–189

Abad-Santos F, Carcas AJ, Guerra P, et al. Evaluation of sex differences in the pharmacokinetics of ranitidine in humans. The Journal of Clinical Pharmacology. 1996; 36: 748–751.

Ashiru DA, Patel R, Basit AW. Polyethylene glycol 400 enhances the bioavailability of a BCS class III drug (ranitidine) in male subjects but not females. Pharmacological Research . 2008; 25: 2327–2333.

Ashiru DA, Patel R, Basit AW. Gender differences in the bioavailability of cimetidine in the presence of an excipient. In: AAPS Annual Meeting and Exposition, 2009. Los Angeles (AAPS2009-003792).

Mai Y, Ashiru-Oredope DAI, Yao Z, et al. Boosting drug bioavailability in men but not women through the action of an excipient, International Journal of Pharmacology. 2020; 25: 587: 119678. https://doi.org/10.1016/j.ijpharm.2020.119678 119678.

Mitchell SC, Smith RL, Waring RH, The menstrual cycle and drug metabolism, Current Drug Metabolism. 2009;10: 499–507, https://doi.org/10.2174/ 138920009788897966.

Rael B, Romero-Parra N, Alfaro-Magallanes VM, et al. Body Composition Over the Menstrual and Oral Contraceptive Cycle in Trained Females, International Journal of Sports Physiology and Performance. 2020; 16: 375–381, https://doi.org/ 10.1123/ijspp.2020- 0038.

Rodriguez I, Kilborn MJ, Liu XK, et al. Drug-induced QT prolongation in women during the menstrual cycle, Journal of the American Medical Association. 2001; 285: 1322–1326, https:// doi.org/10.1001/jama.285.10.1322.

Hara M, Danilo Jr P, Rosen MR, Effects of gonadal steroids on ventricular repolarization and on the response to E4031, The Journal of Pharmacology and Experimental Therapeutics. 1998; 285: 1068–1072.

Kornstein SG, Schatzberg AF, Thase ME, et al. Gender Differences in Treatment Response to Sertraline Versus Imipramine in Chronic Depression, The American Journal of Psychiatry 2000: 157: 1445–1452, https://doi.org/10.1176/appi. ajp.157.9.1445.

Pae CU, Mandelli l, Kim TS, et al. Effectiveness of antidepressant treatments in pre-menopausal versus post-menopausal women: a pilot study on differential effects of sex hormones on antidepressant effects, Biomedicine & pharmacotherapy. 2009; 228–235, https://doi.org/10.1016/j. Bio pha.2008.03.010.

Barth C, Villringer A, Sacher J. Sex hormones affect neurotransmitters and shape the adult female brain during hormonal transition periods, Frontiers in Neuroscience. 2015; 9:37, https://doi.org/10.3389/fnins.2015.00037.

Matthaei J, Tzvetkov MV, Strube J, et al. Heritability of caffeine metabolism: Environmental effects masking genetic effects on CYP1A2 activity but not on NAT2, Clinical Pharmacology & Therapeutics.2016; 100: 606– 616, https://doi. org/ 10.1002/cpt.444.

H. Whitley, W. Lindsey, Sex-based differences in drug activity, Am. Fam.Physician. 80 (2009) 1254–1258.

Pirmohamed M, James S, Meakin S, et al. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18 820 patients, British Medical Journal. 2004;329: 15–19, https:// doi.org/10.1136/bmj.329.7456.15.

Patel H, Bell D, Molokhia M, et al. Trends in hospital admissions for adverse drug reactions in England:analysis of national hospital episode statistics 1998–2005, BMC Clinical Pharmacology. 2007; 7. https://doi.org/10.1186/1472-6904-7-9 9.

Ekhart C, van Hunsel F, Scholl J, et al.Sex differences in reported adverse drug reactions of selective serotonin reuptake inhibitors. Drug Safety. 2018; 41(7): 677‐683.

Vries ST, Denig P, Ekhart C, et al. Sex differences in adverse drug reactions reported to the National Pharmacovigilance Centre in the Netherlands: An explorative observational study. British Journal of Clinical Pharmacology. 2019;85(7):1507‐1515.

Aubrun F. Salvi N, Coriat P, et al. Sex- and age-related differences in morphine requirements for postoperative pain relief, Anesthesiology. 2005; 103: 156–160, https://doi.org/10.1097/ 000 00542- 00507000-00023.

Craft RM. Sex differences in drug-and non-drug-induced analgesia, Life Sciences. 2003; 72: 2675–2688. https://doi.org/10. 1016/ s0024 3205(03)00178-4.

Pieretti S, Di Giannuario A, Di Giovannandrea R,et al. Gender differences in pain and its relief, Annali dell'Istituto superiore di sanità. 2016; 52: 184–189. https://doi.org/10.4415/ ANN_16_02_09.

James AF, Choisy SC, Hancox JC. Recent advances in understanding sex differences in cardiac repolarization. Progress in Biophysics and Molecular Biology. 2007;94:265–319. doi: 10.1016/j.pbiomolbio.2005.05.010.

Nakagawa M, Ooie T, Takahashi N, et al. Influence of menstrual cycle on QT interval dynamics. Pacing and Clinical Electrophysiology. 2006;29:607–613. doi: 10.1111/j.1540-8159. 2006.00407.x.