Spoletini Ilaria, Vitale Cristiana, Malorni Walter, Rosano Giuseppe M C
Department of Medical Sciences, IRCCS San Raffaele Pisana, via della Pisana, Rome, Italy.
Handb Exp Pharmacol. 2012(214):91-105. doi: 10.1007/978-3-642-30726-3_5.
In recent years, it has become clear that women and men may differ for drug response. Also, there is an increasing recognition on the role of sex hormones on pharmacokinetics and pharmacodynamics as mechanism accounting for sex differences in drug effects.In women, the phases of menstrual cycle, of reproductive life and fluctuations in the concentrations of sexual steroids on pharmacokinetics and pharmacodynamics must be considered. Furthermore, the use of oral contraceptives or hormonal replacement therapy, the sex hormone-related changes in total body water or in the amount of fat influence the overall effect of drugs.On the contrary, the influence of androgens on drug effects is minimal because of the even plasma levels of these hormones in adult males.Nevertheless, since women have been scarcely included in the early phases of clinical trials, the results obtained in men have been often translated to women and their exact response to drugs is still not well known.The available evidence suggests that sex hormones influence drug absorption, distribution, metabolism, pharmacodynamics, and adverse effects. For instance, many cardiovascular drugs are metabolized by enzymes of the cytochrome P450 mono-oxygenases system, which is more expressed in females than in males, showing sex differences in drug response.Upcoming pharmacological research should aim to further clarify the influence of sex hormones on drug effects and, for this purpose, to increase the number of women enrolled in all phases of clinical trials. An evidence-based pharmacotherapy in women is therefore auspicable for women's health.
近年来，女性和男性对药物的反应可能存在差异这一点已变得清晰。此外，人们越来越认识到性激素在药代动力学和药效学方面的作用，将其视为药物效应性别差异的机制。对于女性，必须考虑月经周期阶段、生殖生活阶段以及性类固醇浓度波动对药代动力学和药效学的影响。此外，口服避孕药或激素替代疗法的使用、与性激素相关的全身水含量或脂肪量变化会影响药物的总体效果。相反，由于成年男性体内雄激素水平较为平稳，雄激素对药物效应的影响极小。然而，由于女性很少被纳入临床试验的早期阶段，男性试验获得的结果常常被应用于女性，而女性对药物的确切反应仍不为人所知。现有证据表明，性激素会影响药物的吸收、分布、代谢、药效学及不良反应。例如，许多心血管药物由细胞色素P450单加氧酶系统的酶代谢，该系统在女性中比在男性中表达更丰富，这显示出药物反应的性别差异。未来的药理学研究应旨在进一步阐明性激素对药物效应的影响，为此，要增加参与临床试验各阶段的女性人数。因此，基于证据的女性药物治疗对女性健康有益。
