SEX BIAS IN ANIMAL RESEARCH: BIOETHICAL AND SCIENTIFIC IMPLICATIONS FOR HEALTH EQUITY

Abstract

Preclinical research exhibits a systematic sex bias, characterized by the predominance of male animals, omission of sex as a biological variable, and limited use of stratified analyses. This bias compromises scientific validity, reproducibility, and clinical translation, while reinforcing health inequalities. This integrative review aimed to identify the bioethical implications of sex bias in animal research, synthesizing methodological practices and their consequences for the applicability of findings and health equity. A literature search was conducted in PubMed, ScienceDirect, SciELO, and Google Scholar, including studies published between 2010 and 2025 in English and Portuguese. Data were organized into three analytical axes: methodological approaches to sex in experimental design; ethical implications based on the 3Rs principles; and impacts on the quality and generalizability of results. Findings indicate that male bias is endemic across fields such as neuroscience, cardiology, surgery, and parasitology, expressed through both exclusive use of males and failure to report sex. Even when both sexes are included, analytical limitations persist, particularly the pooling of data without testing for interaction effects. The exclusion of females, historically justified by estrous cycle variability, has been refuted. Misinterpretation of the Reduction principle also contributes to biological surplus and compromised animal welfare. Sex bias in preclinical research constitutes a bioethical issue requiring cultural change, statistical literacy, and stronger oversight by Animal Ethics Committees to ensure scientific validity and health equity.