The 100 most influential manuscripts in andrology: a bibliometric analysis

Background As the specialty of Andrology expands it is important to establish the most important studies that have shaped, and continue to shape, current research and clinical practice. Bibliometric analysis involving a citation rank list is an established means by which to identify the published material within a given field that has greatest intellectual influence. This bibliometric analysis sought to identify the 100 most influential manuscripts in Andrology, as well as the key research themes that have shaped contemporary understanding and management of andrological conditions. Methods The Thompson Reuters Web of Science citation indexing database was interrogated using a number of search terms chosen to reflect the full spectrum of andrological practice. Results were ranked according to citation number and further analysed according to subject, first and senior author, journal, year of publication, institution and country of origin. Results The Web of Science search returned a total of 24,128 manuscripts. Citation number of the top 100 articles ranged from 2819 to 218 (median 320). The most cited manuscript (by Feldman et al., The Journal of Urology 1994; 2819 citations) reported the prevalence and risk factors for erectile dysfunction (ED) in the Massachusetts Male Ageing Study. The Journal of Urology published the highest number of manuscripts (n = 11), followed by the New England Journal of Medicine (n = 10). The most common theme represented within the top 100 manuscripts was erectile dysfunction (n = 46), followed jointly by hypogonadism and male factor infertility (n = 24 respectively). Conclusion Erectile dysfunction should be considered the most widely researched, published and cited field within andrological practice. This study provides a list of the most influential manuscripts in andrology and serves as a reference of what comprises a ‘highly citable’ paper for both researchers and clinicians.


Background
Andrology is the medical specialty that focuses on many aspects of male health, comprising a wide range of conditions of the male reproductive system, as well as urological pathologies that are specific to men. Although the clinical science had been studied for many years, it was not until after the introduction of the term 'andrology' in 1951 that scientists and clinicians from a diverse range of backgrounds began to refer to themselves as 'andrologists' [1]. Since then the discipline has continued to evolve, with the introduction of national and international societies, recognised and accredited training courses and a number of high quality dedicated journals. In the present day, andrologists are involved in the management of a wide spectrum of diseases ranging from male factor infertility through to hypogonadism and penile cancer. As the specialty grows and the body of literature focusing on andrological topics expands it is important to establish the most important and influential manuscripts that have shaped, and continue to shape, current research and clinical practice.
The generation of a citation rank list is one method of identifying the published material within a given field that has greatest intellectual influence [2]. A citation refers to the referencing of an article by another peer-reviewed publication. It is therefore probable that articles which have the greatest impact on the scientific and clinical communities are cited many times more than those which have had little impact. Citation analysis is the process of ranking the most frequently cited articles in order to produce a citation rank list. In addition, citation numbers can be used to rank journals through calculation of their 'impact factor.' This is a measure of the average number of citations a manuscript published in a particular journal received during a specific timeframe and is often used a surrogate marker for journal quality.
A number of clinical disciplines have employed citation analysis to determine the most influential articles in their field. These include entire specialties such as general surgery [3], plastic surgery [4] and orthopaedic surgery [5], as well as subspecialties such as laparoscopic and emergency abdominal surgery [6,7]. Whilst citation analysis has been conducted within urology as a whole [8,9], and more specifically for male factor infertility [10], no study to date has been undertaken to determine the most influential manuscripts in andrology. This bibliometric analysis therefore aimed to identify the most influential articles in the field, as well as key research themes that have been instrumental in developing our contemporary understanding and management of andrological conditions.

Methods
The Thompson Reuters Web of Science citation indexing database was interrogated using the method  previously described by Ellul et al. [6]. As andrology is a broad subspecialty that draws from a range of other disciplines, it is probable that influential articles pertaining to relevant topics have been published in a wide array of journals, not just those specific to urology and sexual medicine. A number of title search terms were therefore selected and combined to ensure all relevant manuscripts were identified, as follows: 'andrology' , 'male infertility' , 'erectile dysfunction' , 'impotence' , 'penile deformity' , 'penile curvature' , 'peyronie's disease' , 'priapism' , 'penile fracture' , 'ejaculatory disorder' , 'male sexual dysfunction' , 'hypogonadism' , 'penile cancer' , 'squamous cell carcinoma' and 'penis'. Truncation using the asterisk function (*) was utilised for particular words with  multiple relevant variations, for example the term 'peni*' was used to capture both 'penis' and 'penile'. These search terms were chosen to reflect the core topics published in the European Academy of Andrology-European Society of Andrological Urology Joint Educational Curriculum for Clinical Andrology Training in Europe [11]. The search was conducted on 5th June 2018 and included all manuscripts published in the English language from 1900 onwards. Results were subsequently ranked by citation number. Final interrogation of the database was independently performed by two assessors (NB and TE). The 100 most cited articles were further evaluated according to subject, first and senior author, journal, year of publication, institution and country of origin. The 2016 impact factor of each journal was also identified from the Journal Citation Reports dataset [12]. In order to adjust for older articles accruing a higher number of citations over time the citation rate was calculated by dividing the number of citations by the number of years since publication. Articles were excluded if published prior to 1900, in languages other than English and/or if, after independent assessment by two researchers, it was agreed the main focus was not directly relevant to the field andrology. In cases of disagreement on the suitability for inclusion, the manuscript in question was discussed by both assessors and a consensus decision reached.

Results
The Web of Science search returned a total of 24,128 manuscripts. Table 1 lists the 100 most cited articles as ranked by citation number, following application of exclusion criteria. Where two articles had equal numbers of citations, further stratification was based on citation rate. The most cited article was that by Feldman et al. describing the prevalence of and risk factors for erectile dysfunction (ED) in the Massachusetts Male Ageing Study, published in The Journal of Urology in 1994 and has been cited 2819 times [13]. The 100 most cited manuscripts were published over a broad time period, with the greatest proportion between 2000 and 2009 (n = 41), as demonstrated in Fig. 1. The most historic article was that by Macleod and Gold reporting comparative semen analysis in both 'fertile' and 'infertile' men, published in The Journal of Urology in 1951 and cited 239 times [14]. The most recent manuscript was that published in 2010 in European Urology by Hatzimouratidis, et al. outlining the European Association of Urology guidelines on investigation and management of male sexual dysfunction, which has been cited 420 times [15]. Table 2 outlines the 43 journals in which the top 100 manuscripts were published. The Journal of Urology (impact factor 5.157) published the highest number (n = 11), including the most cited article by Feldman et al. [13], and accrued a total overall citation number of 6771. This was followed by The New England Journal of Medicine, which published 10 manuscripts and was also the journal with the highest impact factor (72.406).
The country with the greatest number of publications was the United States of America (n = 66), followed by the United Kingdom (n = 12) and Canada (n = 5). The Massachusetts General Hospital was the institution with the greatest number of manuscripts (n = 7), followed jointly by the Cleveland Clinic and New England Research Institute (n = 6 respectively), all of which are based in the USA. RC Rosen [16][17][18][19] and TF Lue [20][21][22] were the first authors with the highest number of manuscripts in the top 100, achieving 4 and 3 respectively. A number of senior authors published more than one manuscript, with JB McKinlay achieving the greatest (n = 5), including the most cited article [13,[23][24][25][26]. Figure 2 gives the top 100 manuscripts according to type. The majority were original research articles (n = 77, Fig. 2a), of which 59 (76.6%) reported clinical outcomes (based on either observational or interventional methodology) and 18 (23.4%) reported the findings of basic scientific work (Fig. 2b). The number of manuscripts pertaining to each of the main andrology themes are given in Fig. 3a. ED was the most common (n = 46), followed jointly by hypogonadism and male factor infertility (n = 24 respectively). Figure 3b demonstrates manuscript theme as strafitied by decade of publication. Hypogonadism was the most common theme prior to 1980 (n = 4), after which ED remained the most common up until 2010. Despite an overall trend of increasing numbers of manuscripts focussing on ED within the top 100 during this period, the relative proportion of manuscripts fell with each decade (66.7, 47.1 and 46.3% between 1980 and 89, 1990-99 and 2000-09 respectivelty). The citation rate of the top 10 manuscripts ranged from 118 to 45, as shown in Table 3. A number of articles from the top 10 remained the same when ranked by citation rate, although three were replaced by the more contemporary manuscripts by Wu, et al.

Discussion
This study is the first bibliometric analysis to identify and analyse the most influential manuscripts in the field of andrology. A range of topics were represented within the top 100, which reflects the spectrum of clinical andrological practice as well as the variation in the specialist backgrounds of andrological practitioners and researchers. Similarly, there is significant overlap with other medical specialties including, but not limited to, endocrinology. Despite this overlap, the most prevalent theme of publication was the assessment and/or treatment of patients with ED, constituting 46 papers within the top 100. This included the most cited article by Feldman, et al. [13] describing the prevalence of, and risk factors for, ED in the Massachusetts Male Ageing Study, published in The Journal of Urology in 1994 and cited 2819 times. The Massachusetts Male Aging Study was a community-based, observational survey of non-institutionalised men between 40 and 70 years old conducted between 1987 to 1989 in cities and towns near Boston, Massachusetts. The aim was to correlate a self-administered erectile function questionnaire with an assessment of patients' overall health. The authors noted a strong correlation with patients who had vascular, cardiac or smoking-related diseases and concluded that ED was associated with potentially reversible age-related changes.
The self-administered erectile function questionnaire reported in the Feldman, et al. study differed from the now more commonly used International Index of Erectile Function (IIEF), which was first described three years later in 1997 by Rosen,et al. [16]. This landmark publication constituted the second most cited article in this bibliometric analysis. Similarly, the fourth most cited article described an updated version of the IIEF questionnaire and was again published by Rosen, et al. [17]. The reason that these papers have been cited so frequently is most likely due to both the high overall prevalence of publications focussing on ED, and the fact that the IIEF-5 is widely used in clinical practice to measure the severity of ED and is hence frequently used in research studies as an 'objective' measurement of function, treatment efficacy or response.
Fourteen manuscripts in the top 100 focussed specifically on the treatment of ED. These ranged in age from the article by Brindley in 1983 examining the effects of intra-cavernosal alpha-blockade [29], to that by McVary, et al. in 2007 reporting the results of a randomised controlled trial investigating the effects of oral sildenafil on both ED and urinary symptoms [30]. This analysis demonstrates that there was a significant increase in the number of influential manuscripts focussing on the treatment of ED following publication of the landmark paper by  reporting the effectiveness of oral sildenafil [31]. This was the first paper to describe an oral treatment for ED and is the third most cited manuscript in the top 100. Prior to this time, treatments had been relatively intolerable for patients, including vacuum tumescence devices, intracavernosal injections of vasoactive agents, transurethral delivery of alprostadil, and invasive surgical procedures. The availability of oral treatments for ED subsequently resulted in a rapid increase in research being undertaken into all aspects of the condition, which is reflected in the numerous manuscripts published after 1998 that feature in the top 100 (Figs. 1 and 3b). Furthermore, it is probable that there was an increase in self-reporting of ED and a drive towards increased research funding and activity when a number of 'tolerable' treatments became available.
A significant majority of manuscripts were published by authors in the United States of America (n = 66), followed by the United Kingdom (n = 12) and Canada (n = 5). This disparity between the USA and other countries may reflect the subspecialisation that occurs in contemporary American Urological practice compared with other geographical regions [32]. This means that clinicians are more likely to be solely practicing andrology, with less emphasis on provision of 'core urological' services, therefore potentially allowing more time for academic pursuits. This geographical dominance has also been observed in other bibliometric analyses [7] and may also be explained by differences in academic focus in relation to clinical practice, with more funding provided to clinicians' academic work in the USA compared to elsewhere, which in turn appears to correlate with a higher quality of research [33].
It is important to note that only two manuscripts within the top 100 focus on the management of penile cancer (Maden, ranked 79 [34] and Daling, ranked 98 [35]). This is the only cancer that is commonly managed by andrologists and therefore one would expect to see a greater number of manuscripts related to its pathophysiology, treatment and follow-up within the top 100. However, it is likely that the low incidence of this condition makes it a relative 'Cinderella' subspecialty within the field and therefore papers focussed on penile cancer are less widely cited when compared to the much more commonly encountered conditions of ED and hypogonadism [36]. Moreover, due to the paucity of cases seen in routine practice it is difficult to establish a cohort of sufficient size for high quality observational or interventional research. This, coupled with the known difficulties in conducting high quality surgical trials [37], means that manuscripts are often of low levels of evidence, thus precluding them from publication in high impact factor journals.
The journals in which the top 100 manuscripts were published varied significantly both in theme and impact factor. The latter was particularly varied and ranged from 72.406 to 1.293 (median 5.5025). Interestingly, impact factor did not necessarily correlate with the most cited papers. For example, the second most cited paper by Rosen, et al. [16] was published in 'Urology' , which was the sixth-lowest ranked journal in terms of impact factor within this analysis (2.309). One explanation for this variation is the multidisciplinary nature of many conditions encountered under the umbrella of andrology. Furthermore, the subspecialised nature of many andrological conditions means that manuscripts pertaining to these topics are often not directly relevant to 'core' clinical practice and are therefore less likely to be published in higher impact factor journals that seek to meet the interests of a broad audience.
The main limitation of bibliometric analysis is the potential for a number of types of bias. Firstly, disproportionate citation may result from institutional bias, language biases, self-citation or powerful person bias. In addition, older manuscripts may receive more citations due to the length of time in which they are in the public domain. Although the use of citation rate attempts to control for this, it may take a number of years for influential manuscripts to accrue citations due to the publication lead-time for their citing manuscript. A further limitation is the inclusion of only first and senior authors, and the institution of the first author. It is possible that several first authors will have co-authored other papers in the top 100 and therefore be underrepresented in the current study. Finally, searching based on title means a small number of manuscripts that have key andrological themes without pertaining to these in their title may not have been identified.

Conclusion
This list of highly cited papers identifies the topics and authors that have made the most impact in the discipline of andrology over the last century. There is a clear predominance of manuscripts focusing on the treatment and pathophysiology of ED, which should therefore be considered the most widely researched, published and cited field within andrological practice. This study provides a reference of what may be considered as the most influential papers in andrology and serves as a inidcation of what comprises a 'highly citable' manuscript for both researchers and clinicians.