Integrating the dimensions of sex and gender into basic life sciences research: methodologic and ethical issues.

Background: The research process -- from study design and selecting a species and its husbandry, through the experiment, analysis, peer review, and publication -- is rarely subject to questions about sex or gender differences in mainstream life sciences research. However, the impact of sex and gender on these processes is important in explaining biological variations and presentation of symptoms and diseases.

Objective: This review aims to challenge assumptions and to develop opportunities to mainstream sex and gender in basic scientific research.

Methods: Questions about the mechanisms of sex and gender effects were reviewed in relation to biological, environmental, social, and psychological interactions. Gender variations, in respect to aging, socializing, and reproduction, that are present in human populations but are rarely featured in laboratory research were considered to more effectively translate animal research into clinical health care.

Results: Methodologic approaches to address the present lack of a gender dimension in research include actively reducing variations through attention to physical factors, biological rhythms, and experimental design. In addition, through genomic and acute nongenomic activity, hormones may compound effects through multiple small sex differences that occur during the course of an acute pathologic event. Furthermore, the many exogenous sex steroid hormones and their congeners used in medicine (eg, in contraception and cancer therapies) may add to these effects.

Conclusions: The studies reviewed provide evidence that sex and gender are determinants of many outcomes in life science research. To embed the gender dimension into basic scientific research, a broad approach -- gender mainstreaming -- is warranted. One example is the use of review boards (eg, animal ethical review boards and journal peer-review boards) in which gender-related standardized questions can be asked about study design and analysis. A more fundamental approach is to question the relevance of present-day laboratory models to design methods to best represent the age-related changes, comorbidity, and variations experienced by each sex in clinical medicine.