http://repub.eur.nl/res/aut/26023/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/37359/ 2012-09-19T00:00:00Z In the early sixties, a prominent professor in Clinical Pharmacology at the University College in London, D.R. Laurence, stated: “There are no clinically important sex differences in drug action, except, of course, to sex steroid hormones, but the subject is poorly documented. Women are said to be more liable to become excited by morphine than are men; in this respect they resemble cats.” It was thought that study results in men could easily be extrapolated to women, and women were excluded from clinical studies for simplicity and protection from harmful drug effects to them and their fetuses. Fortunately, the following decades, this insight changed and sex differences in clinical pharmacology have gained more attention. Unfortunately, however, still not enough, as will be demonstrated in this thesis. Sex and gender both refer to the differentiation in men and women. Sex refers to the biological differences; gender to the behavioral and psychological perception of sexual identity. Besides the well-known sex differences in the reproductive system and physical and psychological features,4 men and women differ from more perspectives, such as physiology, anatomy and pathophysiology and disease treatment. This variety also leads to differences in drug response. http://repub.eur.nl/res/pub/33328/ 2011-08-15T00:00:00Z In this issue of the Journal, Zhang et al. (Am J Epidemiol. 2011;174(4):403-411) make a substantial contribution to research in the area of hormonal influences on cardiac repolarization by demonstrating an inverse association between testosterone levels and the Bazett's adjusted QT interval (QTc) and RR-adjusted QT interval in men but not in postmenopausal women. They suggest that testosterone levels might explain the difference in QTc-interval duration between men and women and could contribute to population variability in QTc-interval duration among men. In this commentary, the gender difference and the role of testosterone in human cardiac repolarization are addressed. In addition, the gender differences in the congenital long-QT syndrome, drug-induced ventricular arrhythmias, and sudden cardiac death are discussed. http://repub.eur.nl/res/pub/33888/ 2011-01-01T00:00:00Z AIM Adverse drug reactions (ADRs) are a major burden in health care, regularly leading to hospital admission, morbidity or death. Women tend to have a higher risk of adverse drug reactions with a 1.5 to 1.7-fold greater risk than men. Our primary aim was to study differences in ADR-related hospitalizations between the sexes.METHODS We conducted a nationwide study of all ADR-related hospitalizations in the period between 2000 and 2005 in the Netherlands, which were selected from all 9 287 162 hospital admissions in this period. ADR-drug group combinations with at least 50 admissions in one of the sexes were selected. Relative risks and confidence intervals were calculated with respect to total admissions and total prescriptions with men as reference.RESULTS In total, 0.41% of the 4 236 368 admissions in men (95% CI 0.40, 0.42%) and 0.47% of the 5 050 794 admissions in women (95% CI 0.46, 0.48%) were attributed to an ADR by medical specialists (57% of all ADR-related admissions were in women). Differences between the sexes in risk for ADR-related hospitalization were found for antineoplastic and immunosuppressive drugs, antirheumatics, anticoagulants and salicylates, cardiovascular and neurological drugs, steroids and antibiotics. In certain drug categories, risks for hospitalization changed after taking into account total drug prescriptions.CONCLUSION In all different drug classes, significant differences exist between the sexes in ADR-related hospital admissions. Cardiovascular drugs account for the most pronounced differences between men and women. More research is needed to explain the clear sex differences in ADR-related hospital admissions. © 2010 The Authors. British Journal of Clinical Pharmacology http://repub.eur.nl/res/pub/21171/ 2010-09-01T00:00:00Z Introduction: In Caucasians, basal cell carcinoma (BCC) is among the most frequently diagnosed cancers and its incidence is increasing. Known risk factors for the development of BCC are age, sun exposure, and certain skin characteristics. Despite photosensitizing abilities of diuretic agents, little is known about a possible association with BCC. Methods: Data were obtained from the Rotterdam Study; a large prospective population-based follow-up study with coverage of prescription-only drugs from pharmacies. The diagnoses of BCC were obtained through general practitioners, and by linkage with a registry of histo- and cytopathology. Cumulative use of diuretics at the date of diagnosis was categorized into quartiles for users of high-ceiling diuretics, potassium sparing agents and thiazides. The association between these drugs and BCC was assessed by Cox proportional hazard modeling with adjustment for age, gender and potential confounders. Effect modification was tested with interaction terms. Results: Use of high-ceiling diuretics in the highest quartile (>3.7 years cumulative exposure) was associated with an increased hazard of BCC of 62% compared to no use (HR 1.6; 95% CI 1.1-2.4). Patients who used high-ceiling diuretics and had a high tendency of getting sunburned had a higher risk of diagnosis than non-users who do not easily get sunburned. Neither the use of potassium sparing agents, nor the use of thiazides was associated with BCC. Conclusion: In our study, cumulative use of high-ceiling diuretics was associated with an increased risk of diagnosis of BCC. This effect is stronger in patients who easily get sunburned.