Lehmkuhl E, Regitz-Zagrosek V
Herz-Kreislauferkrankungen bei Frauen, Geschlechterforschung in der Medizin/GIM, Deutsches Herzzentrum Berlin und Charité/CCR, Berlin.
Ther Umsch. 2007 Jun;64(6):311-7. doi: 10.1024/0040-5930.64.6.311.
In cardiovascular diseases e.g. heart failure and coronary artery disease gender differences are evident in etiology, pathophysiology, clinical presentation, prognosis and response to treatment. Diabetes and hypertension are the major risk factors in women. Mechanisms leading to apparent diabetes or its clinical pre-stage are different in women and men and according to this result in different therapeutic implications. Diastolic heart failure is more frequent in women and effects and side effects of important groups of active pharmaceutical substances are, at least to some extent, different. Atrial fibrillation and ventricular arrhythmia differ in frequency of occurrence; drug induced tachycardia with QT interval prolongation is particularly frequent in women. Underlying pathomechanisms responsible for gender differences in pharmacotherapy are on the one hand differences in pharmacokinetic mechanisms. Particularly drugs which are metabolised via cytochrome P 450 CYP 3A pathway show different kinetics in women and men. In addition, important differences are evident in pharmocodynamics caused by effects of sex steroid hormones or products of X-chromosomal genes. The evidence of estrogen and testosterone receptors in cardiomyocytes and the vascular system, interaction of sex steroid hormones with cellular pathways and the role of X-chromosomal genes are the focus of basic research. Interactions of sex steroid hormone receptors with other nuclear receptors e.g. PPARs ("peroxisome proliferator-activated receptors") are another important underlying mechanism. The knowledge of different pharmacokinetic mechanisms has to be taken into consideration in pharmacotherapy of cardiovascular diseases, for example by adjustment of drug dosages in women, necessary in different groups of pharmaceutical substances or in the long run, gender differences in effects and side effects of drugs. In drug development both aspects have to be considered. There is more than one good reason to intensify basic and clinical research and research on health care on gender differences in cardiovascular diseases.
在心血管疾病(如心力衰竭和冠状动脉疾病)中,性别差异在病因、病理生理学、临床表现、预后及对治疗的反应方面都很明显。糖尿病和高血压是女性的主要危险因素。导致明显糖尿病或其临床前期的机制在女性和男性中有所不同,据此产生了不同的治疗意义。舒张性心力衰竭在女性中更为常见,并且重要类别的活性药物的作用和副作用至少在一定程度上存在差异。心房颤动和室性心律失常在发生率上有所不同;药物诱发的伴有QT间期延长的心动过速在女性中尤为常见。药物治疗中性别差异的潜在病理机制一方面是药代动力学机制的差异。特别是通过细胞色素P 450 CYP 3A途径代谢的药物在女性和男性中表现出不同的动力学。此外,由性甾体激素或X染色体基因产物的作用引起的药效学方面也存在明显差异。心肌细胞和血管系统中雌激素和睾酮受体的证据、性甾体激素与细胞途径的相互作用以及X染色体基因的作用是基础研究的重点。性甾体激素受体与其他核受体(如PPARs(“过氧化物酶体增殖物激活受体”))的相互作用是另一个重要的潜在机制。在心血管疾病的药物治疗中必须考虑不同的药代动力学机制,例如通过调整女性的药物剂量,这在不同类别的药物中是必要的,或者从长远来看,要考虑药物作用和副作用的性别差异。在药物研发中,这两个方面都必须加以考虑。有充分理由加强关于心血管疾病性别差异的基础和临床研究以及卫生保健研究。