Gender medicine is a novel and rapidly evolving discipline of research. The present study shows how in the last 30 years, publications including sex and gender differences have progressively increased and more strikingly since the 1990s. Different medical disciplines incorporate this type of analysis in different manners, choosing distinct research approaches, experimental designs and cohort sizes; however, one feature common to all disciplines, but cardiology, is the dramatic underrepresentation of investigation of sex and gender differences in clinical management.
This particular aspect needs to be emphasized and critically evaluated. Research on clinical management, that is, diagnostic approaches, referral practices, invasive and non-invasive therapy choices, is essential in understanding, shaping and improving our everyday clinical practice. Lack of knowledge about gender differences and inadequacies in health care provision have led to significant and potentially fatal imbalances in outcomes. This has been demonstrated in the field of cardiology, where the numbers of women dying of heart infarction at a young age [15–17] significantly dropped after two decades of research and the dissemination of essential information about gender differences in clinical presentation, symptoms, diagnostic and therapeutic approaches [18, 19]. Examples from other disciplines are following [20, 21]; however, the information is still scarce and the benefits of this additional knowledge not yet widely accepted by the medical community.
Despite this critical lack of information we found a relevant increase in sex and gender-specific analysis over time, with publications markedly rising since the 1990s. This confirms early reports from the 1990s conducted on a limited set of medical journals [22, 23]. The phenomenon might be related to several factors. On the one side, the previously mentioned eye-opening reports about unexpectedly high numbers of female fatalities due to heart infarction  might have played a role, as well as the predominantly female fatalities related to torsade de pointes as a side effect of drug therapy [24, 25]. Both events have highlighted a previously ignored problem and created the momentum for the implementation of guidelines by the FDA  and NIH [11, 26]. Nonetheless, although the attention toward the topic is increasing, the publication numbers we are identifying are far from satisfactory.
This type of research might still be constrained by limited funds, as there are no specific funding agencies and still few calls for sex and gender-specific research. The difficulty in achieving publications in high impact journals might also play a role. While gender medicine is gaining attention in the scientific community, as demonstrated by the recent editorials in influential journals [10, 27–30], several editors do not consider the topic worthy of publication and refer authors to the few gender medicine journals. Some causes for this imbalance might also be inherent in the project design. Information about sex and gender specific analysis might be included only in the body of the article and thus not captured by our research strategy; however, this should account only for a minority of the publications. Furthermore, it should be clarified that gender specific analysis is not limited to the enumeration of the number of female and male subjects in the study cohort, but extends beyond that in the form of distinct subgroup analyses . This is not performed in many research publications and failure to do so may lead to incomplete or biased results leading to wrong conclusions and actions . Misleading and, at times, incorrect use of the terminology "sex" and "gender" also plays a role. Authors not familiar with the subject oftentimes use the words interchangeably or use the term "gender" for any distinction between subjects, even if this is related to purely biological differences. This represents a further hurdle to the systematic analysis of publications. If one wanted to clearly identify which articles analysed solely biological differences and which ones cultural and psychosocial distinctions, many publications identifying "gender differences" would have to be reclassified as "sex differences". This warrants further analysis in the future.
Our analysis also revealed how the percentage of basic research performed in animal models varies greatly among disciplines. This is an interesting finding and may reflect intrinsic differences in the use of animal models in different specialties. The importance of using both female and male animals in basic research for etiologic investigations or drug testing is being increasingly recognized . Sex differences in rodent and other animal models have been identified in wild type and congenic animals used in diverse disciplines. However, the variability of reaction in female animals due to their hormonal cycle and the potentially increased costs related to the need for larger numbers of animals to account for this variability during analysis still deters many investigators from doing so.
Last, a systematic collection of data is instrumental for research development and identification of needs and relevant questions. Diversity is the main focus of this area of research, but limited the possibility for comparison of strategies in the past. As we have seen, management research needs much attention if we strive to improve gender-sensitive health care, and although sex and gender-specific analyses are increasing, they are not increasing nearly as much as good research practice would lead us to expect. The present work represents a basic assessment of the status quo and will be used as basis for a public database, which will be made accessible to researchers in the field and open for input of their own research publications. We believe that this platform will encourage exchange among researchers interested in sex and gender-specific research and offer opportunities for fruitful cooperation to close some of the gaps identified in this analysis.