In May 2014, the National Institutes of Health (NIH) stated its intent to “require applicants to consider sex as a biological variable (SABV) in the design and analysis of NIH-funded research involving animals and cells.” Since then, proposed research plans that include animals routinely state that both sexes/genders will be used; however, in many instances, researchers and reviewers are at a loss about the issue of sex differences. Moreover, the terms sex and gender are used interchangeably by many researchers, further complicating the issue. In addition, the sex or gender of the researcher might influence study outcomes, especially those concerning behavioral studies, in both animals and humans. The act of observation may change the outcome (the “observer effect”) and any experimental manipulation, no matter how well-controlled, is subject to it. This is nowhere more applicable than in physiology and behavior. The sex of established cultured cell lines is another issue, in addition to aneuploidy; chromosomal numbers can change as cells are passaged. Additionally, culture medium contains steroids, growth hormone, and insulin that might influence expression of various genes. These issues often are not taken into account, determined, or even considered. Issues pertaining to the “sex” of cultured cells are beyond the scope of this Statement. However, we will discuss the factors that influence sex and gender in both basic research (that using animal models) and clinical research (that involving human subjects), as well as in some areas of science where sex differences are routinely studied. Sex differences in baseline physiology and associated mechanisms form the foundation for understanding sex differences in diseases pathology, treatments, and outcomes. The purpose of this Statement is to highlight lessons learned, caveats, and what to consider when evaluating data pertaining to sex differences, using 3 areas of research as examples; it is not intended to serve as a guideline for research design.

中文翻译：

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将性别视为基础和临床研究中的生物变量：内分泌学会的科学声明

2014 年 5 月，美国国立卫生研究院 (NIH) 表示其意图“要求申请人在 NIH 资助的涉及动物和细胞的研究的设计和分析中将性别视为一个生物变量 (SABV)”。从那时起，拟议的包括动物在内的研究计划通常表明将使用两种性别/性别；然而，在许多情况下，研究人员和评论者对性别差异问题感到困惑。此外，许多研究人员交替使用“性别”和“社会性别”这两个术语，这使得问题进一步复杂化。此外，研究人员的性别可能会影响研究结果，尤其是有关动物和人类行为研究的结果。观察行为可能会改变结果（“观察者效应”），任何实验操作，无论控制得多么好，都会受到它的影响。这在生理学和行为学中最适用。除了非整倍体之外，已建立的培养细胞系的性别也是另一个问题。染色体数量会随着细胞传代而改变。此外，培养基含有类固醇、生长激素和胰岛素，可能会影响各种基因的表达。这些问题往往没有被考虑、确定、甚至考虑。与培养细胞“性别”有关的问题超出了本声明的范围。然而，我们将讨论基础研究（使用动物模型）和临床研究（涉及人类受试者）以及一些常规研究性别差异的科学领域中影响性和性别的因素。基线生理学和相关机制的性别差异构成了理解疾病病理学、治疗和结果中性别差异的基础。本声明的目的是强调经验教训、注意事项以及在评估与性别差异相关的数据时应考虑的事项，并以 3 个研究领域为例；它无意作为研究设计的指南。