Analysis of sex and gender-specific research reveals a common increase in publications and marked differences between disciplines

Abstract

Background: The incorporation of sex and gender-specific analysis in medical research is increasing due to pressure from public agencies, funding bodies, and the clinical and research community. However, generations of knowledge and publication trends in this discipline are currently spread over distinct specialties and are difficult to analyze comparatively.

Methods: Using a text-mining approach, we have analysed sex and gender aspects in research within nine clinical subspecialties--Cardiology, Pulmonology, Nephrology, Endocrinology, Gastroenterology, Haematology, Oncology, Rheumatology, Neurology--using six paradigmatic diseases in each one. Articles have been classified into five pre-determined research categories--Epidemiology, Pathophysiology, Clinical research, Management and Outcomes. Additional information has been collected on the type of study (human/animal) and the number of subjects included. Of the 8,836 articles initially retrieved, 3,466 (39%) included sex and gender-specific research and have been further analysed.

Results: Literature incorporating sex/gender analysis increased over time and displays a stronger trend if compared to overall publication increase. All disciplines, but cardiology (22%), demonstrated an underrepresentation of research about gender differences in management, which ranges from 3 to 14%. While the use of animal models for identification of sex differences in basic research varies greatly among disciplines, studies involving human subjects are frequently conducted in large cohorts with more than 1,000 patients (24% of all human studies).

Conclusions: Heterogeneity characterizes sex and gender-specific research. Although large cohorts are often analysed, sex and gender differences in clinical management are insufficiently investigated leading to potential inequalities in health provision and outcomes.

Figure 1

Comparison of publication trends for general and gender-specific literature. (A) Absolute numbers of gender-related yearly publications within the nine disciplines analysed are presented (n = 3,466). Publications are limited between 1975 and 1989, while they increase more markedly thereafter. (B) Publications trends in the field of Myocardial infarction (MI) and Asthma between 1976 to 1977 and 2008. Black squares indicate the total yearly number of publications within the field; black dots represent the number of sex/gender-specific publications within the field; red squares indicate the log(2) ratio between sex/gender literature and general literature. The noted increase after 1990 is recapitulated by these single diseases. Publications increase more in the field of gender medicine compared to overall trends (as expressed by the ratio between the trends).

Figure 2

Analysis of gender-related publications. (A) Literature was classified into five research categories: Epidemiology, Pathophysiology, Clinical research, Management, and Outcomes. Research categories within the nine disciplines studied are illustrated. Equal distribution of research efforts would lead to a similar number of publications within each category. However, the categories of Pathophysiology and Epidemiology appear to be the most intensively investigated areas in most specialties. (B) The percentage of studies conducted on humans or animals was investigated. As all animal studies have been classified as "Pathophysiology" research, the relative percentages of animal model use can be derived by the ratio between the "Pathophysiology" data and the "Animal Study" data. Animal models are frequently used for basic research about sex differences; however, significant differences can be observed between specialties.

Figure 3

Size of clinical studies in gender medicine. Pie chart showing the numbers of enrolled individuals in research projects involving human subjects. 60% of the studies included 100 or more subjects. 24% of all analyses were conducted in studies involving more than 1,000 participants.

Figure 4

Studies on clinical management appear underrepresented in gender medicine. The bar graphs represent the total number of gender-related publication in each of the nine fields. Studies on clinical management are highlighted in red. The percentage of studies about management with respect to the overall number of gender-specific studies for each category is also reported as the percentage. The number of publications on clinical management within single diseases is shown below the bar graph. All disciplines, but Cardiology (22%), display low percentages of research conducted on gender differences in management.