Introduction

The term gender dysphoria (GD) was first introduced as a medical term by Fisk, in 1974,¹ to describe discomfort with an individual's biological sex and the willingness to undergo medical intervention for gender reassignment. Research in gender development and gender dysphoria has been growing over the years as a sign of the intention to understand and characterize the causative relationships between the psychological sphere, genetic alterations, hormone conditions, and sociocultural factors. In addition, the will to describe variants in psychosexual differentiation and possible treatments, like surgical and hormone, for gender affirmation have led to find a wide range of different types of studies describing and exploring this condition.^2-5

The issues currently under discussion abound, taking into account the multifactorial origin of this condition and the controversy concerning especially the social and phycological aspects.⁶ Despite the abundance of published literature, there is a significant level of discordance in many aspects of this subject, but, above all, a lack of literature with appropriate evidence that allows decisions to be made in clinical practice with a scientific basis.

There are multiple theories that explain the etiology of the gender dysphoric behavior. No biological anomalies have been found that may be associated with GD;⁷ however, it is suggested that the etiology could be explained by hormonal influences and genetic factors rather than environmental and behavioral factors.⁸ There are also several descriptions of neural basis and sexual orientation variability in GD^7,9 This rapidly evolving topic has allowed us to understand how to approach individuals and offer support and management. The published literature has also tried to keep up with these rapid changes. Nonetheless, the current management of individuals with GD include gender-affirming surgery, which is technically challenging and should only be performed by specialized multidisciplinary teams. Our aim is to perform a bibliometric analysis of the literature, looking for the quality of the published literature that supports the current management as well as to make a critical review of the literature on the most discussed topics and to propose future trends in the field of GD.

Methods

Results

A total of 1,239 manuscripts were identified. After the screening process and final review 1,041 manuscripts were selected. The average number of citation counts per year per manuscript was 1.84 (interquartile range [IQR] 0-2.33). The average impact index was 47.8 (IQR 20-111.6). The median for total citations per manuscript was 3 (IQR 0-33.1), and the highest number of citations per manuscript was 484, corresponding to the term consensus statement on 6 of intersex disorders, which also had the highest average per year, with 37.2 citations.¹¹ The results of elements and citations published every year are shown in Figure 1. The year with the highest number of publications was 2017, with 197. The Archives of Sexual Behavior was the journal with the highest number of publications, with 118 during the study period. Publication trends have shown a steady increase in the amount of publications per year (Fig. 1).

Figura 1 Elements published and citations every year. 

Most publications focus on the psychological aspects of GD, and there is a significant number of manuscripts related to social and anthropological issues (the percentage of articles and their main topics are presented in (Table 1). Regarding the trends of recent years, in the last 5 years, 215 (31.3%) articles were written related to the psychiatric and psychological aspects of the condition. Publications about surgical management amounted to 62 (9%), and those discussing endocrinology totaled 63 (9.2%).

Table 1 Distribution of main topic discussed per manuscript 

We also noted that most articles have a low level of scientific evidence. Of the 1,041 articles evaluated, we found that 256 (27%) were cross sectional studies, 255 (26.9%) were topic reviews, 73 (7.7%) were case reports, 72 (7.6%) were prospective cohorts, 63 (6.6%) were cases and controls, 49 (5.2%) were retrospective cohorts, 42 (4.4%) were systematic reviews, 35 (3.7%) were case series, 16 (1.7%) were letters to the editor, 5 (0.5%) were qualitative studies, 2 (0.2%) were clinical trials, and 80 (8.4%) were classified as others, among which are chronicles, essays, and opinion articles, among others.

Figures 2 and 3 were created using the VOSviewer term co-occurrence network. In these figures, each circle represents a term. The size of a circle indicates the number of publications that have the corresponding term in their title or abstract. Terms that co-occur a lot tend to be located close to each other in the visualization. In Figure 2,the main cluster corresponds to the word dysphoria and its associations with other terms. It demonstrates a close relationship with terms such as psychiatry, concept, respect, implication, and a considerable distance from terms such as hormonal treatment, surgical treatment, and practice care. The colors indicate that towards the blue area are terms related to childhood and adolescence; red corresponds to human or social study areas, such as literature and history, but also it also includes terms such as psychiatry and guideline; in the green area, there are terms related to endocrinology, like hormonal treatment, testosterone, and transsexual; and, finally, in the yellow area, there are various terms that are related and overlap transversely to other clusters, such as man, woman, symptoms, and analysis.

Fig. 2 Co-occurrence network figures by term. 

In Figure 3 we clustered results around the topic "surgical treatment" and found that there is poor publishing correlation to other topics.

Figura 3 Co-occurrence network figures using the term: "surgery". 

Discussion

Historically, the first reference to GD was made in 1966, and it was in a book written by Harry Benjamin,¹² who was the first widely known physician (endocrinologist and sexologist) recognized for his work on transgender people. In this book, multiple topics related to etiology, physiology, general management, and hormonal and surgical treatments were addressed. At that point in time, the definition of dysphoria has not been used, but later, during the early 70's, the term gender dysphoria syndrome was used to describe transsexualism in addition to other gender identity disorders.¹ This terminology continues to be valid to date. Nonetheless, from a psychiatric perspective, there have been great advances since the update of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) to the last DSM-V, in which it was decided to stop using the term gender identity disorder and only use gender dysphoria, thus emphasizing that it is not in itself a mental disorder.^13,14 We found that 35.4% of the total articles reviewed correspond to the psychiatry/psychology category. Our results show that the topic that had been assessed in greater depth in most of the publications is psychiatry and its relation to the changes in terminology.

These individuals are known to carry a high emotional burden due to external factors (discrimination, value judgments, isolation), which puts them at risk of developing psychiatric illness; ^15,16 many adults face these challenges with social support, but it is known that social and family support is very limited in childhood and adolescence.¹² A higher rate of psychopathology has been found among groups of trans individuals compared to their cis counter-parts.¹⁷ Some studies recognize the high prevalence of suicide among transgender individuals, and a higher risk or life-threatening behavior has been observed in the youth population.^18,19 Gender dysphoria groups showed elevated levels of depressive distress compared to non-gender minority respondents, and this behavior was also seen when evaluating symptoms of anxiety.²⁰ These individuals, in addition to having a greater chance of presenting these conditions, also have a greater possibility of being diagnosed but not being adequately treated or having unmet needs of mental health care.²¹ Other psychiatric disturbances, such as eating disorders, are prevalent in these communities. Standard screening for these symptoms should be considered.^19,22

More recently, there has been an increasing interest in publications about gender-affirmation procedures and therapies.^23-25 An increment trend of publications about gender-affirmation surgery have been identified over recent years. The first surgical technique for gender-affirmation surgery in an individual with GD was described in 1948 by Harold Gillies and RJ Harrison.²⁶ The goals of surgical male-to-female genital surgery have been reported with general successful outcomes by the minimization of complications and the creation of a functional and aesthetically perineo-genital complex, feminine in appearance and functional to allow regular sexual inter-course and to achieve orgasm.²⁷ Nonetheless, our results put in evidence that the current surgical techniques lack good quality research, and they are supported with low-quality literature in this field. The published literature also lacks long-terbm follow-up for the relatively recent proposed surgical techniques. This needs to be acknowledged by surgeons involved in GD surgery. For female-to-male genital affirming surgery, the operative procedures are usually performed in different stages, including hysterectomy-ovariectomy and genital transformation that includes a vaginectomy, scrotoplasty, penile reconstruction and testicular prosthesis delayed implantation.²⁸ Based on our bibliometric analysis, there is a limited amount of literature evaluating the physiologic implications of these procedures.

The average number of citations per year per manuscript was 1.84 (IQR 0-2.33), which indicates how small the target of these publications is, compared to other subjects. Considering the prevalence of this condition in the general population, it is clear when comparing the scientific evidence in other research categories,²⁹ that there is an absence of interest in the replication of this information in scientific fields.

There is an overwhelming amount of literature regarding GD; however, in the medical field, it is only from the 1970s on that studies began to be published, making GD a very recent topic. Previous approaches are made from a social and human perspective, but not with the intention of understanding this condition physiologically. Also, there is confusion in the literature about the current terminology used by GD individuals and how this spectrum needs to be taken into consideration at the moment of surgical intervention. The medical field has delayed the study of this condition and, therefore, of the optimal treatment of these individuals. This is why the scientific study of this condition and its treatments are still in an early exploration phase. It is hard to believe that 50 years after the start of literary publications on this topic, we still experience a lack of evidence. This situation might be rare in relation to other medical conditions, which leads us to wonder if this is indeed because of an inherent difficulty due to the complexity of this condition or a lack of interest in the subject and limited investments in this type of research; finally, this explains the evident lack of agreement in the medical management of this condition that persists through the years.

Conclusion

It is essential to be aware of the lack of thoroughness and rigor in the literature regarding GD, which prevents the acceleration of knowledge about this entity, knowing results of high methodological quality on which medical practice in this field could be based. The present study results show that the quality of evidence of most of the studies is low. About 16.1% are case reports and case series and 26.9% correspond to topic reviews.

Concerning gender-affirmation procedures, there is a gap in high-quality literary evidence that supports the emerging expansion of medical practices and the monitoring of their possible complications in the long term. Furthermore, there is also a need to acknowledge the differences between patients, knowing their history, and making case-by-case decisions based on long-term evidence that mitigates adverse events.