【作者】 索琳； 杨淑桂； 李静；

【Author】 SUO lin;YANG shu-gui;LI jing;Dept.of Pharmacy,Meitan General Hospital;Dept.of Pharmacy,China-Japan Friendship Hospital;

【机构】 煤炭总医院药学部； 中日友好医院药学部；

【摘要】 性别对于科学进展与临床实践有着重要的意义。医学界已经开始意识到现今的医学是以男性为主的,基础诊断与治疗方法是以年轻的体重70kg的白种成年男性的特征为标准的。性别因素对于疾病的预防及进程是非常重要的。性别差异导致了机体解剖、生理、生化、疾病的发病机制、结局及治疗反应等方面的不同。药代动力学的差异要求不同的治疗药物监测。目前,性别差异对药动学及药效学参数的影响了解的还较少。生物学、精神因素、社会、经济地位与保健护理等因素均影响着男性及女性对药物的反应。本文将从性别因素对于药物依从性、医患关系、生物利用度及药物不良反应等方面的影响进行讨论。(1)性别对健康护理的影响:性别对于卫生保健是很重要的,比如关节置换手术、心血管疾病、肾脏疾病及结肠癌等疾病,男性与女性所接受的健康护理都是不同的。因此,性别差异对于健康保健与治疗的重要性不容忽视,否则将会导致男性与女性在健康保健上的不均等。(2)性别对用药依从性的影响:用药依从性对于达到治疗效果起到了一个强制性作用,大约有将近一半的慢性病患者没有按处方服药。依从性低导致了发病率、死亡率及经济负担的升高。女性与男性对于药品有着不同的行为特征。一些研究表明女性相比男性,对于药品有着更多的负性评价,依从性更低,这也许与女性的药物不良反应发生的更频繁与严重有关,因为药物不良反应的发生与擅自停药有着密切的关系。比如高血压、糖尿病、高血脂、抑郁症、哮喘、慢性阻塞性肺病、多发性硬化及骨质疏松等疾病的用药依从性都存在着性别差异,因此今后的用药依从性研究应纳入性别的研究。(3)性别对医患关系的影响:研究表明医患之间的性别因素会影响药物反应的许多方面,比如用药依从性及安慰剂效应。男性与女性医师有着不同的工作风格,同样男性与女性患者也有着不同的交流风格。一些研究表明女性医师会比男性医师在自己的患者身上花更多的时间,也有一些研究结果与其相反。因此提示预防性保健及健康促进方面应考虑医师与患者的性别因素。(4)性别对生物等效性的影响:性别因素对于药物代谢动力学有着重要的影响。男性与女性的生物等效性研究提示,男性与女性的浓度-时间曲线下面积或药物血浆浓度有显著差异。生物等效性研究应同时包括男性与女性,因为药物赋形剂会通过性别方式影响药物的生物利用度。(5)性别对药物不良反应的影响:在以往的临床实验中因缺乏女性受试者的数据,导致很难发掘药物不良反应发生率在性别上的差异,因此也可能造成女性相比于男性获得更多的不恰当的健康护理及用药安全性的降低。大量研究表明女性发生的药物不良反应的严重性更为显著,主要表现为与剂量相关的不良反应。减少女性药物不良反应发生的数量及降低严重性是当务之急,有助于增加卫生保健的持续发展。因此要通过临床前与临床研究充分了解药物不良反应的性别差异以减少女性的药物不良反应,并增加男性与女性的药物疗效。总之,男性与女性对于药物有着不同的反应。性别因素会影响流行病学、疾病的预防、治疗、结果及治疗等方面。在药物研究的过程中应考虑性别因素,在临床实践中重视性别差异将有助于男性与女性均获得最恰当的治疗。更多还原

【Abstract】 Sex and gender could have deleterious effects on scientific progress and clinical practice.Medicine is androcentric,basing diagnostic and therapeutic approaches on the characteristics of a young 70-kg Caucasian adult male at present.The studies suggest that being a woman or being a man significantly influences the prevention and course of disease.The variances of men and women lead to differences in anatomy,physiology,biochemistry,pathophysiology,outcome and therapeutic response.Sex-gender differences in pharmacokinetic parameters and pharmacodynamics,which are less known.Pharmacokinetic differences can require a different therapeutic drug monitoring.We discuss the influence of sex and gender on the access,emotional factors,including patients and care provider dyads,adherence and safety profile.(1) Access to care:sex-gender is important for access to healthcare,including treatments and individual use of the healthcare system.Such as joint arthroplasty,cardiovascular diseases,renal disease and heart disease have differences in quality of care in both the female and male population.In conclusion,the significance of sex-gender on access to care and treatment cannot be neglected avoid leading to inequality in the care of males and females.(2) Adherence:adherence to a prescribed regimen plays a mandatory role in reaching therapeutic efficacy,and approximately 50%of patients with chronic illness do not take their medications as prescribed.This poor adherence leads to elevated morbidity,mortality and costs.Women and men have different behaviors toward drugs.Several studies suggest that women have a more negative evaluation of drugs than men,and this outlook could be linked to adverse drug effects,which are more frequent and severe in women than in men,as experiencing an ADEs is strongly linked with primary discontinuation.In the future,adherence research should be conducted with a gender approach.(3) Dyads:the previous data demonstrate that the doctor-patient gender dyads affect many elements of drug response,such as adherence and the placebo response.Male and female care providers have different practice styles,and female and male patients also have different communication styles.Some studies show that female physicians spend more time with their patients than male physicians,but other studies contradict these results,indicating that preventive care and health promotion practices are comparable for male and female physicians.(4) Bioequivalence studies:pharmacokinetics is highly influenced by sex-gender.Bioequivalence studies performed in men and women revealed that when the AUC or peak plasma concentrations were considered,statistical variability was observed between men and women.In conclusion,bioequivalence studies should take sex and gender into consideration.(5) Adverse drug effects:the historical underrepresentation of women in clinical trials made the detection of sex-gender-related differences in the incidence of ADEs difficult due to the absence of adequate stratification by sex and inadequate sample sizes.This discrepancy may be responsible for the inappropriate care and adverse safety profiles in women compared with men.Numerous studies also indicate that the severity of ADEs can be more pronounced in women;additionally,women predominantly display dose-related ADEs.This goal can only be reached through preclinical and clinical research that is fully aware of sex-gender differences.The literature clearly suggests that men and women differ in their responses to drugs.Sex-gender should be included in the process of drug development and research because it significantly influences the epidemiology,prophylaxis,course,outcome and therapy of diseases.The inclusion of sex-gender determinant in all phase of the research,the clinical practice of sex-gender medicine could help in reaching the appropriate therapy for men and women.更多还原