{"paper_id":"f7bb07d3-3eba-4ee0-8d27-1987b1eaf59d","body_text":"R E S E A R C H A R T I C L E Open Access\nEndometriosis and its global research\narchitecture: an in-depth density-equalizing\nmapping analysis\nDörthe Brüggmann 1,2*, Alexandra Elizabeth-Martinez 2, Doris Klingelhöfer 2, David Quarcoo 2, Jenny M. Jaque 1\nand David A. Groneberg 2\nAbstract\nBackground: Endometriosis is one of the most common gynecological diseases. It is still a chameleon in many\naspects and urges intense research activities in the fields of diagnosis, therapy and prevention. Despite the need to\nfoster research in this area, no in-depth analysis of the global architecture of endometriosis research exists yet.\nMethods: We here used the NewQIS platform to conduct a density equalizing mapping study, using the Web of\nScience as database with endometriosis related entries between 1900 and 2009. Density equalizing maps of global\nendometriosis research encompassing country-specific publication activities, and semi-qualitative indices such as\ncountry specific citations, citation rates, h-Indices were created.\nResults: In total, 11,056 entries related to endometriosis were found. The USA was leading the field with 3705\npublications followed by the United Kingdom (952) and Japan (846). Concerning overall citations and country-specific\nh-Indices, the USA again was the leading nation with 74,592 citations and a modified h-Index of 103, followed by the\nUK with 15,175 citations (h-Index 57). Regarding the citation rate, Sweden and Belgium were at top positions with rates\nof 22.46 and 22.26, respectively. Concerning collaborative studies, there was a steep increase in numbers present;\nanalysis of the chronological evolution indicated a strong increase in international collaborations in the past 10 years.\nConclusions: This study is the first analysis that illustrates the global endometriosis research architecture. It shows that\nendometriosis research is constantly gaining importance but also underlines the need for further efforts and\ninvestments to foster research and ultimately improve endometriosis management on a global scale.\nKeywords: Endometriosis, Density equalizing, Mapping, Research architecture\nBackground\nEndometriosis is one of the most common benign\ngynecological diseases affecting 1 in 10 women of child-\nbearing age; its management constitutes a daily routine\nin the practice of obstetrician/gynecologists [1 –3]. In the\nUnited States (USA), it represents the third leading\ncause of gynecologic hospitalization, limits workforce\nparticipation and impacts both a woman ’s physical and\nmental well being [4]. Hence, endometriosis poses a tre-\nmendous burden on individual and community health: In\nthe USA alone, the related total societal costs were pro-\njected at $70 billion in 2009 [5].\nEndometriosis is an estrogen-dependent condition char-\nacterized by endometrial glands and stroma located out-\nside the uterine cavity [6 –9]. Implants are found in the\nperitoneum, the ovaries and the rectovaginal septum\nconstituting three different disease entities [10]. Endo-\nmetriosis is a commonly underdiagnosed condition: Its\nepidemiologic assessment is hampered by a high num-\nber of obscure cases in the general population and the\nlack of non-invasive diagnostic tools [11, 12]. However,\nendometriosis is estimated to have a prevalence of up to\n5 % in fertile and 25 –40 % in infertile women [8].\n* Correspondence: doerthe.brueggmann@med.usc.edu\n1Department of Obstetrics and Gynecology, Keck School of Medicine,\nUniversity of Southern California, 2020 Zonal Ave, IRD 509, Los Angeles\n90089-9300, CA, USA\n2Institute of Occupational Medicine, Social Medicine and Environmental\nMedicine, Goethe-University, Theodor-Stern Kai 7, 60590 Frankfurt, Germany\n© 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0\nInternational License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and\nreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to\nthe Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver\n(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.\nBrüggmann et al. BMC Women's Health  (2016) 16:64 \nDOI 10.1186/s12905-016-0336-0\n\nAdditionally to debilitating symptoms such as dysmen-\norrhea, chronic pelvic pain and infertility, 8 –30 % of\npatients will develop endometriosis-associated ovarian\ncancer during their lifetime [13 –1 5 ] .C u r r e n t l y ,t h e r ei s\nno cure for endometriosis but several treatment proto-\ncols exist for the management of associated sequelae\n[8, 16, 17].\nAlthough substantial progress has been achieved\ninvestigating the pathogen esis and pathophysiology of\nthe disease, endometriosis still belongs to the most\nenigmatic and complex conditions in the field of ob-\nstetrics and gynecology (OB/GYN). Further multidis-\nciplinary, translational and clinical research is needed\n[4, 11, 18] to define disease origins, to develop non-\ninvasive diagnostic tools and in-vitro models aiming\nto evaluate the process of malignant transition as well\nas novel treatment approaches [6, 12, 19, 20]. In this\nrespect, it is commonly accepted that further random-\nized clinical trials, which focus on proposed etio-\npathogenic mechanisms and therapeutic innovation,\nare necessary to identify more conclusive, evidence-\nbased answers [8].\nBesides posing a scientific challenge, endometriosis\nconstitutes a major burden on female health worldwide.\nHence, we deduce that research and public health ef-\nforts have to be strengthened to ensure future suc-\ncesses. To plan these research endeavors accordingly so\nthey meet identified shortcomings and to supply deci-\nsion makers with information concerning funding strat-\negies, it is the objective of the study to assess the\npresent scientific performance in the field. The ‘New\nQuality and Quantity Indices in Science ’ (NewQIS) pro-\nject [21, 22] combines scientometric tools and advanced\ndensity equalizing mapping procedures [23] to depict\nthe global research architecture and to evaluate\ncountry-specific productivity in the framework of the\nscientific landscape. We also aim to guide individual\nscholarship and the publication of own research by pre-\nsenting the 10 most cited articles and the most prolifer-\native journals in the field of endometriosis research.\nMethods\nNewQIS protocol\nWe employed the previou sly established NewQIS\nplatform to conduct this study [21, 22]. The method\nencompasses the use of advanced visualization algo-\nrithms such as Gastner and Newman ’s density equal-\nizing calculations and scientometric tools in order to\nevaluate and visualize endo metriosis-associated re-\nsearch activity [21, 22].\nData source\nAs described previously [24, 25], the database Web of\nScience (WoS, Thomson Scientific) was used for data\ncollection. We based this study on this particular re-\nsource because WoS provides the unique opportunity\nto analyze the global public ation activity and to per-\nform an in-depth citation analysis, which includes the\ncalculation of combined semi-qualitative country- and\nendometriosis-specific indices such as the modified h-\nindices or average citation rates.\nSearch strategy\nIn the presented approach, we identified endometriosis-\nspecific publications by the use of the specific search term\n‘(endometrios*)’. The operator * was applied to identify\nboth singular and plural cases in title, abstract and key\nwords of all eligible publications listed in the WoS.\nTimeframe\nThe search was performed in 2010; the analyzed time-\nframe covered the years between 1900 (01-01) and 2009\n(31-12). As discussed in previous studies, results from\n2010 onwards were not considered due to incomplete\ndata acquisition (i.e. citation rate) in order not to ham-\nper the global citation analyses.\nData analysis and categorization\nAll endometriosis-related publications issued in the\ntimeframe of 110 years were analyzed using our stan-\ndardized protocol and categorized with respect to publi-\ncation date, country of origin, source title, and authors\n[26]. Also, the numbers of citations were retrieved for\neach publication and the average citation per item (CR,\ncitation rate) were calculated as previously described.\nAfter transfer the raw data to excel charts, the findings\nwere illustrated in diagrams and visualized by density-\nequalizing mapping projections (DEMP) [26]. The current\nDEMP analysis was based on the algorithm of Gastner\nand Newman [23], so the territories of the different coun-\ntries publishing endometriosis research were resized in\nproportion to our selected variables. In the present con-\ntext, we used these visualization algorithms to draw a\nsketch of worldwide endometriosis-related research activ-\nities illustrating the global distribution of country-specific\nnumbers of published items and related citation rates.\nAnalysis of research cooperations\nTo investigate endometriosis-related research collabora-\ntions between the different countries, the affiliations of\nthe endometriosis-related publications were screened as\nearlier described for other diseases [24, 26]. If at least\ntwo authors, attributed to different countries, contrib-\nuted to an endometriosis article, this relationship was\ndefined as a collaborative publication.\nBrüggmann et al. BMC Women's Health  (2016) 16:64 Page 2 of 12\n\nJournal analysis\nWe evaluated journals publishing endometriosis research\nby analyzing quantitative and qualitative aspects, e.g.\nnumber of published endometriosis-specific articles as\nwell as citations these items received (CR).\nResults\nGlobal endometriosis research activity\nIn total, 11,056 endometriosis-related publications were\nidentified. These items were published in 20 different lan-\nguages: 93.0 % were written in English, 3.4 % in German,\n2.3 % in French, and 0.5 % in Spanish, respectively.\nOut of 11,056 publications, 10,881 were attributed to\none or more originating countries and issued by authors\nfrom 88 nations. The USA was most productive with\n3705 publications (p). It was followed by the United\nKingdom (UK, p: 952), Japan (p: 846), Italy (p: 720),\nGermany (p: 715), France (p: 497), Belgium (p: 378),\nCanada (p: 375), Australia (p: 270) and Spain (p: 213). In\nthe DEMP-analysis (Fig. 1a), major parts of Asia in-\ncluding Russia and China (with the exception of Japan),\nAfrica and South America (except Brazil), appear mini-\nmized. The DEMP visualizes that North America\nclearly constitutes the scientific center of endometriosis\nresearch, followed by Western Europe.\nIn the analysis of the chronological evolution of endo-\nmetriosis research (Fig. 1b), a significant increase in an-\nnual publication numbers was visible from 1980 onwards.\nThe steep increase after 1990 can be explained by the fact\nthat the WoS started to include abstracts of the publica-\ntions in the database, which increased the likelihood to\nidentify endometriosis-related items by topic search. Cor-\nrespondingly, a larger number of publications and related\ncitations could be identified in our search. The years with\nthe highest publication activities included 2007 (746 an-\nnual publications), 2009 (739 annual publications) and\n2008 (726 annual publications). The highest growth in\npublication output was present between 2002 and 2003\nwith an increase from 428 to 618 %. In the last 10 years of\nour analysis spanning 110 years of endometriosis research,\n6221 publications were published (equals 56 % of all).\nCitation analysis\nIn the country-specific citation analysis (Fig. 2a), again,\nthe USA was found to be the leading nation with a total\nof 74,592 citations, followed by the UK with 15,175 cita-\ntions, Japan with 11,704 citations and Italy with 10,147\ncitations. DEMP results of total citations resembled the\naforementioned DEMP analysis of total publications\nnumbers with some minor exceptions, i.e. Belgium was\nranked 5 th with 8489 citations (Fig. 2a). In Additional file\n1, we compiled the 10 most cited articles in the field.\nThe calculation of the country-specific citation rate\n(citations per endometriosis publication of a country,\nwith a threshold of 30 publications per country) was\nused as a semi-qualitative measure (Fig. 2b). It pointed\nto a high average citation of Belgian endometriosis pub-\nlications with a citation rate (CR) of 22.46 citations per\nsingle endometriosis publication. Sweden was located in\nthe second position with a rate of 22.26 followed by\nFinland (CR 20.77), the USA (CR 20.13), Norway (CR\n19.42), the Netherlands (CR 17.19), Canada (CR 16.69)\nand the UK (CR 15.94).\nThe country- and endometriosis-specific h-Index cal-\nculation (Fig. 2c) demonstrated a leading position of the\nUSA with 103 endometriosis-related publications cited\nat least 103 times. The USA is followed by the UK with\na country-specific h-Index (HI) of 57, Belgium (HI 49),\nItaly and Japan (HI both 47), France (HI 42) and Canada\n(HI 41). Again, countries from Asia (with the exception\nof Japan), Africa, Eastern Europe, or Latin America were\ncharacterized by very low citation rates.\nCooperation articles\nIn the period between 1900 an d 2009, 902 of all publica-\ntions were based on international collaborative efforts. This\nequaled a rather low percentage of 8.15 %. 771 of these\nitems were issued by bilateral collaborations (85.5 %,\nFig. 3a), followed by trilateral (101 publications) and collab-\norations between four countries (20 publications). Analysis\nof the chronological evolution indicated a strong increase\nin international collaborations in the past 10 years (Fig. 3b).\nOverall, the USA dominated the category of collaborative\nefforts in the field of endometriosis research; 493 publica-\ntions could be attributed to international cooperations. It\nwas followed by the UK (197 papers based on international\ncollaborations out of 952 items in total), Germany (130 pa-\npers based on international collaborations out of 715 items\nin total), Belgium (129 papers based on international col-\nlaborations out of 378 items in total), and Italy (121 papers\nbased on international collaborations out of 720 items in\ntotal). The USA established 75 bilateral collaborations with\nCanada, 61 with Germany and 61 with the UK. Other fruit-\nful collaborations were identified between Belgium and the\nUK (39 items), Japan and the USA (38 items), Belgium and\nKenya (34 items), Italy with the UK (34 items) and Italy\nwith the USA (32 items, Fig. 4a). Among the ten countries\nhaving issued the most cooperation articles in the field, the\npercentage of publications based on international collab-\norative efforts were the lowest in Japan (9 %) and the USA\n(13 %). Belgium and Sweden constituted notable excep-\ntions. These countries published more than a third of their\ntotal research output on endometriosis within the frame-\nwork of international cooperations (Fig. 4b).\nSubject area analysis\nMost endometriosis publications were assigned to one\n(6151) or two (4592) subject areas (Fig. 5a). We\nBrüggmann et al. BMC Women's Health  (2016) 16:64 Page 3 of 12\n\nidentified ‘Obstetrics and Gynecology ’ as the most fre-\nquently applied subject category with 6634 assignments\nfollowed by ‘Reproductive Biology ’ with 3410 assign-\nments. Then, separated by a large gap, ‘Medicine, Gen-\neral & Internal ’ was found (806 assignments), followed\nby ‘Surgery’ (588 assignments), ‘Pathology’ (532 assign-\nments) and ‘Endocrinology & Metabolism ’ (512 assign-\nments) (Fig. 5b). The most frequent combination of two\nassigned subject areas was ‘Obstetrics & Gynecology ’ with\n‘Reproductive Biology ’ attributable to 3014 publications.\nWhen focusing on differences in subject areas between\nthe 15 most productive countries in endometriosis re-\nsearch, no large differences were found.\nJournal analysis\nThe 15 most prolific journals in endometriosis re-\nsearch were identified and illustrated in Fig. 6. “Fertility\nand Sterility” was leading the field (1837 articles), followed\nby “Human Reproduction” (721 articles) and the “American\nJournal of Obstetrics and Gynecology ” (501 articles). The\nFig. 1 a Density-equalizing map of total endometriosis publications in each country. The area of each country was scaled in proportion to its total\nnumber of publications. Different colors encode numbers of endometriosis publications. This DEMP figure was generated by the authors as\ndescribed in the methods section. b Chronological evolution of endometriosis-related publications. The red dotted line indicates the steep\nincrease in publication activity visible after 1990\nBrüggmann et al. BMC Women's Health  (2016) 16:64 Page 4 of 12\n\nhighest citation rate was achieved by the “Journal of\nClinical Endocrinology and Metabolism ” (104 articles,\nCR = 48.66).\nDiscussion\nAs elegantly described by Kvaskoff et al., the etiology of\nendometriosis remains poorly understood despite an es-\ntimated prevalence of 10 % in women [9]. The authors\nstress the fact that many unsolved questions still exist\nsince endometriosis has been associated with an in-\ncreased risk of several debilitating and chronic condi-\ntions, such as ovarian cancer, asthma, autoimmune,\natopic and cardiovascular diseases [9]. Therefore, it is\ncommonly accepted that a deeper understanding of\nthese associations is needed as they may provide novel\ninsights into the etiology or clinical implications of the\nFig. 2 a Density-equalizing map of country total citations of endometriosis publications. The area of each country was scaled in proportion to its\ntotal number of citations. Colors encode numbers of citations. b Density-equalizing map of country citation rate of endometriosis publications.\nThe area of each country was scaled in proportion to its citation rate. Colors encode numbers of citations. These DEMP figures were generated\nby the authors as described in the methods section\nBrüggmann et al. BMC Women's Health  (2016) 16:64 Page 5 of 12\n\ncondition [9]. Thus, research in this field needs a strong\nboost with new and profound funding programs to be\ninitiated by agencies around the world. Since these en-\ndeavors require a sound underlying basis, we identified\nthe need for an all-encompassing depiction of the exist-\ning global research landscape and conducted the first de-\ntailed analysis of worldwide endometriosis research. So\nfar, only a few other OB/GYN topics including breast\ncancer [7, 27] and smoking and pregnancy [28] were\nsubjected to a similar in-depth analysis using the New-\nQIS platform.\nGlobal endometriosis research is dominated by a small\nnumber of scientific power players: These include the\nUSA and the UK holding the leading positions in\nregards to publication quantity, country-specific citation\nnumbers and h-Indices. Our data align with other stud-\nies evaluating the scientific productivity in the biomedical\nfield. Groneberg-Kloft et al. analyzed over 5.5 million\nFig. 3 a International collaborations from 1983 to 2009. b Number of co-authors\nBrüggmann et al. BMC Women's Health  (2016) 16:64 Page 6 of 12\n\npublications related to 22 organ systems and identified the\nUSA in the top position regarding overall research output\n[29]. Comparing our results with other investigations in\nthe areas of Internal Medicine or OB/GYN in particular\nleads to a similar picture: When scientific productivity\nwas evaluated in regards to “tuberculosis”, bacterial men-\ningitis”, “influenza” as well as “smoking in pregnancy ” or\n“breast cancer ”, the USA and the UK were once again\ndominating the field [28, 30 –32]. This pattern might point\nto the fact that both countries dedicate major financial re-\nsources towards biomedical research creating a supportive\nscientific infrastructure, e.g. as indicated by the worldwide\nhighest number of endometriosis research institutions (n:\n1293) located in the USA. Also, both nations established\nnumerous fruitful collaborations facilitating high quality\nresearch. Furthermore, we identified Belgium and Japan as\nprominent scientific forces within the endometriosis com-\nmunity. Japan’s strong interest in the field might be based\nFig. 4 a Number of collaborative items published in a joint effort between two countries dedicated to research in the field of endometriosis.\nThe figure depicts only cooperations of countries with more than 20 collaborative publications b Proportions of international collaborative efforts\namong all publications of the ten most proliferative countries in endometriosis research\nBrüggmann et al. BMC Women's Health  (2016) 16:64 Page 7 of 12\n\non the fact that prevalences of endometriosis and asso-\nciated clear-cell ovarian cancers are estimated to be\nthe worldwide highest among Asian - and particularly\nJapanese - women [33, 34]. Therefore, the nation prior-\nitizes related research with the aim to alleviate the as-\nsociated disease burden for its inhabitants. For many\nyears, Belgian scientists (e.g. at the University of Leuven)\nhave been focusing on endometriosis research. Their\nefforts translated into numerous highly regarded publica-\ntions as documented by the highest country-specific cit-\nation rate this nation received in our analysis. Concerning\ncountry-specific citation rates, we also found three Scandi-\nnavian countries (Sweden, Finland and Norway) among\nthe five leading nations indicating the outstanding quality\nand high recognition of their publications. This finding\nmight be linked to the vast data resources these countries\nFig. 5 a Distribution of subject area assignments per endometriosis publication. b Most frequently assigned subject areas\nBrüggmann et al. BMC Women's Health  (2016) 16:64 Page 8 of 12\n\nestablished (e.g. The Swedish National Patient Register),\nwhich enable researchers to conduct meaningful and\nhighly cited key studies in the field.\nThe need for an assessment of the worldwide endomet-\nriosis research architecture becomes even more pressing\nwhen the limited number of studies with a global perspec-\ntive on endometriosis is compared with the fact that this\nenigmatic disease heavily affects female health in a global\ncontext - ranging from high income to low income coun-\ntries and all ethnicities. In this respect, Nnoaham et al.\nstressed that little is known about the impact of endomet-\nriosis across the world [35]. Therefore, they initiated inte-\ngrated multicenter studies to collect prospective,\nstandardized, epidemiological data, to 1) examine the glo-\nbal impact of endometriosis and relative effect of risk-\nfactors, and 2) develop a symptom-based diagnostic tool\n[35]. Their studies encompassed 19 hospitals in 13 coun-\ntries [36, 37]. In one study, the authors assessed the im-\npact of endometriosis on mental, physical and social well\nbeing and concluded that endometriosis impairs health-\nrelated quality of life and work productivity significantly\nacross countries and ethnicities, yet women continue to\nexperience diagnostic delays in primary care [37]. These\nfindings stress the need for further multinational ap-\nproaches, especially also with the participation of low\nincome countries in which millions of women suffer\nfrom undiagnosed and insufficiently treated endometri-\nosis. This claim is substant iated by our presented data:\nA closer look into the global endometriosis research\narchitecture exemplifies that a large gap of research ac-\ntivity exists in a multitude of countries in which – under\nconservative estimations – tens of millions of affected\nwomen live, e.g. in China, India (BRIC countries – nations\nat a similar stage of newly advanced economic develop-\nment - with established research infrastructures that could\nbe instantly used for endometriosis research) and African\ncountries. These numbers are mirrored by an extremely\nlow number of endometriosis publications originating\nfrom these countries. This disparity verifies that research\nin this field is simply not a priority in developing or under-\ndeveloped countries. Overall, research on the endometri-\nosis in low resource countries is extremely scarce. Kyama\net al. reflected on the problem of endometriosis in women\nliving on the African continent and concluded in 2007\nthat research programs have to be developed and estab-\nlished to tackle the local unique challenges the condition\ncreates [38]. The authors point out that rates of endomet-\nriosis are reported to be lower in African women com-\npared with females in industrialized countries. They\nattributed this finding to an epidemiological under-\nestimation since the locally perceived need for accurate\nstudies is low, to under-diagnosis due to limited awareness\nNumber of Articles \nCitation Rate \nJournal \nNumber of Articles Citation Rates \nFig. 6 The 15 most prolific journals in endometriosis research with number of articles, number of citations and citation rate\nBrüggmann et al. BMC Women's Health  (2016) 16:64 Page 9 of 12\n\nof both patients and doctors, restricted access to health-\ncare and surgical resources as well as a protective lifestyle\n(e.g. earlier childbearing, high parity). Our study further\nverifies the clear lack of research activity in countries of\nlow-resources and reinforces Kyama ’s call to action in\nparticular. Hence, it would be key to extent the world-\nwide increasing collaborative efforts and involve these\nunderserved nations with the aim to share data, resources\nand knowledge. In this context, we have to mention one\nexception, Kenya, showcasing successful international col-\nlaborative endeavors: This African nation has established\n41 co-operations with other countries (e.g. with Belgium).\nAs early as 1968, spontaneous endometriosis was reported\nin baboons [39, 40]. Since then, these monkeys, which are\nhoused in the “Institute of Primate Research ” in Nairobi\n(http://www.primateresearch.org), serve as an invaluable\nanimal model in the field of endometriosis research lead-\ning to many milestone publications in the field [41 –49].\nSeveral methodological issues need to be discussed\nwhen interpreting the present data: 1) As an important\nstrength of this study, the NewQIS platform constitutes\nan established protocol to assess basic and clinical sci-\nences benchmarks in a standardized and verified way. So\nfar, it was primarily used i.e. within the areas of public\nhealth [29, 50 –53] and internal medicine [32, 54]. Now,\nit has been extended to OB/GYN; in this field, many dis-\neases are treated that pose a major thread on female and\npediatric well-being and have large public health impli-\ncations. 2) Our platform is configurated to access the\nWoS database instead of PubMed. Therefore, differences\nin the overall number of identified endometriosis publi-\ncations can be expected. This finding can be explained\nby the differing set of journals enlisted in both databases.\nHowever, we prefer to work with WoS as the primary\ndatabase since it enables the user to integrate a concise\ncitations analysis. This unique feature allowed us to\nperform valuable multifaceted semi-qualitative ap-\nproaches, i.e. by calculating endometriosis-specific,\ncountry-specific h-indices or average citation rates. 3)\nA language bias constitutes a mentionable weakness of the\npresented NewQIS analysis: Clearly, the WoS - but also\nthe PubMed - does not automatically index every Non-\nEnglish scientific journal. By contrast, other databases\nsuch as Scopus include them. Since the majority of jour-\nnals included in the WoS - and therefore analyzed in our\nsearch - are written in English an underrepresentation of\nnon-English publications can be assumed. Especially in\nthe area of public health and epidemiology, which are\noften focused on country-specific, national issues, there\nmay be non-English endometriosis studies that are not\ntraceable in the WoS. However, we consider this language\nbias as limited because data of outstanding interest and\nquality will be published in WoS-listed scientific journals\nand therefore included in our search.\nConclusion\nThis is the first study to delineate a picture of the global\nresearch landscape of one of the most enigmatic diseases\npresent in OB/GYN. In this area of medicine, the USA\nplays the leading role for the advancement of science. It\nis the country with the highest number of highly cited\nendometriosis publications and it shares the highest num-\nber of collaborations with other countries. It is also note-\nworthy that small Northern European countries such as\nBelgium, Finland and Sweden, seem to dedicate many re-\nsources in relation to their low numbers of inhabitants.\nAn intensification of research efforts is needed to battle\npressing challenges on a global scale such as the malignant\ntransition of endometriosis or the development of novel\nnon-invasive diagnostic tests and treatment approaches in\norder to improve disease management for millions of af-\nfected women in industrialized and developing countries.\nIn this context, it should be a priority of supranational in-\nstitutions such as the WHO or private funding organiza-\ntions to provide the much needed monetary support.\nAdditional file\nAdditional file 1: Most cited articles in endometriosis research. The\ntable depicts the ten most cited articles in the area of endometriosis\nresearch are displayed including their title, publication year, country of\norigin, citation count and journal. (DOCX 113 kb)\nAbbreviations\nCR: Citation report; DEMP: Density Equalizing Map Projections; HI: Hirsch-\nIndex; NewQIS: New Quality and Quantity Indices in Science; OB/\nGYN: Obstetrics and Gynecology; UK: United Kingdom; USA: United States of\nAmerica; WoS: Web of Science\nAcknowledgements\nWe thank Gabriele Volante for expert editorial help. This study is part of a\nthesis project (AEM).\nFunding\nWe did not receive any funding to conduct this study.\nAvailability of data and materials\nThe datasets supporting the conclusions of this article are available upon\nrequest.\nAuthors’ contributions\nDB, AEM and DAG conceived of the study and designed the experiments,\nAEM and DK performed the technical conduction of the experiments, DB,\nAEM, DK, DQ, JJ and DAG analyzed and discussed the results, and drafted\nthe manuscript. All authors read and approved the final manuscript.\nCompeting interests\nThe authors declare that they have no competing interests.\nConsent for publication\nNot applicable.\nEthics approval and consent to participate\nNot applicable, because this study did not involve human participants,\nhuman data or human tissue.\nReceived: 1 June 2015 Accepted: 10 June 2016\nBrüggmann et al. BMC Women's Health  (2016) 16:64 Page 10 of 12\n\nReferences\n1. Nezhat C, Nezhat F, Nezhat C. Endometriosis: ancient disease, ancient\ntreatments. Fertil Steril. 2012;98:S1 –S62.\n2. Mitri F, Casper RF. Endometriosis and mild bleeding disorders. Fertil Steril.\n2015;103:886–7. e881.\n3. Koninckx PR, Ussia A, Adamyan L, Wattiez A, Donnez J. Deep endometriosis:\ndefinition, diagnosis, and treatment. Fertil Steril. 2012;98:564 –71.\n4. McLeod BS, Retzloff MG. Epidemiology of endometriosis: an assessment of\nrisk factors. Clin Obstet Gynecol. 2010;53:389 –96.\n5. Simoens S, Dunselman G, Dirksen C, Hummelshoj L, Bokor A, Brandes I,\nBrodszky V, Canis M, Colombo GL, DeLeire T, et al. The burden of\nendometriosis: costs and quality of life of women with endometriosis and\ntreated in referral centres. Hum Reprod. 2012;27:1292 –9.\n6. Burney RO, Giudice LC. Pathogenesis and pathophysiology of\nendometriosis. Fertil Steril. 2012;98:511 –9.\n7. Healy NA, Glynn RW, Scutaru C, Groneberg D, Kerin MJ, Sweeney KJ. The h\nindex and the identification of global benchmarks for breast cancer\nresearch output. Breast Cancer Res Treat. 2011;127:845 –51.\n8. Ozkan S, Murk W, Arici A. Endometriosis and infertility: epidemiology and\nevidence-based treatments. Ann N Y Acad Sci. 2008;1127:92 –100.\n9. Kvaskoff M, Mu F, Terry KL, Harris HR, Poole EM, Farland L, Missmer SA.\nEndometriosis: a high-risk population for major chronic diseases? Hum\nReprod Update. 2015;21(4):500 –16.\n10. Nisolle M, Donnez J. Peritoneal endometriosis, ovarian endometriosis, and\nadenomyotic nodules of the rectovaginal septum are three different\nentities. Fertil Steril. 1997;68:585 –96.\n11. Missmer SA, Cramer DW. The epidemiology of endometriosis. Obstet\nGynecol Clin North Am. 2003;30:1 –19. vii.\n12. Eskenazi B, Warner ML. Epidemiology of endometriosis. Obstet Gynecol Clin\nNorth Am. 1997;24:235 –58.\n13. Ogawa S, Kaku T, Amada S, Kobayashi H, Hirakawa T, Ariyoshi K, Kamura T,\nNakano H. Ovarian endometriosis associated with ovarian carcinoma: a\nclinicopathological and immunohistochemical study. Gynecol Oncol. 2000;\n77:298–304.\n14. Pearce CL, Templeman C, Rossing MA, Lee A, Near AM, Webb PM,\nNagle CM, Doherty JA, Cushing-Haugen KL, Wicklund KG, et al.\nAssociation between endometriosis and risk of histological subtypes of\novarian cancer: a pooled analysis of case-control studies. Lancet Oncol.\n2012;13:385 –94.\n15. Wu AH, Pearce CL, Tseng CC, Templeman C, Pike MC. Markers of inflammation\nand risk of ovarian cancer in Los Angeles County. Int J Cancer. 2009;124:1409–15.\n16. Guo SW. An overview of the current status of clinical trials on\nendometriosis: issues and concerns. Fertil Steril. 2014;101:183 –90. e184.\n17. Kobayashi H. Ovarian cancer in endometriosis: epidemiology, natural history,\nand clinical diagnosis. Int J Clin Oncol. 2009;14:378 –82.\n18. Fassbender A, Vodolazkaia A, Saunders P, Lebovic D, Waelkens E, De Moor\nB, D’Hooghe T. Biomarkers of endometriosis. Fertil Steril. 2013;99:1135 –45.\n19. Lawrenson K, Lee N, Torres HA, Lee JM, Brueggmann D, Rao PN,\nNoushmehr H, Gayther SA. Src as a novel therapeutic target for\nendometriosis. Gynecol Oncol. 2014;135:100 –7.\n20. Brueggmann D, Templeman C, Starzinski-Powitz A, Rao NP, Gayther SA,\nLawrenson K. Novel three-dimensional in vitro models of ovarian\nendometriosis. J Ovarian Res. 2014;7:17.\n21. Groneberg-Kloft B, Quarcoo D, Scutaru C. Quality and quantity indices in\nscience: use of visualization tools. EMBO Rep. 2009;10:800 –3.\n22. Groneberg-Kloft B, Fischer TC, Quarcoo D, Scutaru C. New quality and\nquantity indices in science (NewQIS): the study protocol of an international\nproject. J Occup Med Toxicol. 2009;4:16.\n23. Gastner MT, Newman ME. Diffusion-based method for producing density-\nequalizing maps. Proc Natl Acad Sci U S A. 2004;101:7499 –504.\n24. Gerber A, Klingelhoefer D, Groneberg DA, Bundschuh M. Silicosis:\ngeographic changes in research: an analysis employing density-equalizing\nmapping. J Occup Med Toxicol. 2014;9:2.\n25. Gerber A, Groneberg DA, Klingelhofer D, Bundschuh M. Gout: a critical\nanalysis of scientific development. Rheumatol Int. 2013;33:2743 –50.\n26. Bundschuh M, Groneberg DA, Klingelhoefer D, Gerber A. Yellow fever\ndisease: density equalizing mapping and gender analysis of international\nresearch output. Parasit Vectors. 2013;6:331.\n27. Glynn RW, Scutaru C, Kerin MJ, Sweeney KJ. Breast cancer research output,\n1945–2008: a bibliometric and density-equalizing analysis. Breast Cancer Res.\n2010;12:R108.\n28. Mund M, Kloft B, Bundschuh M, Klingelhoefer D, Groneberg DA, Gerber A.\nGlobal research on smoking and pregnancy-a scientometric and gender\nanalysis. Int J Environ Res Public Health. 2014;11:5792 –806.\n29. Groneberg-Kloft B, Scutaru C, Kreiter C, Kolzow S, Fischer A, Quarcoo D.\nInstitutional operating figures in basic and applied sciences: scientometric\nanalysis of quantitative output benchmarking. Health Res Policy Syst. 2008;6:6.\n30. Fricke R, Uibel S, Klingelhoefer D, Groneberg DA. Influenza: a scientometric\nand density-equalizing analysis. BMC Infect Dis. 2013;13:454.\n31. Groneberg DA, Weber E, Gerber A, Fischer A, Klingelhoefer D, Brueggmann\nD. Density equalizing mapping of the global tuberculosis research\narchitecture. Tuberculosis (Edinb). 2015;95:515 –22.\n32. Pleger N, Kloft B, Quarcoo D, Zitnik S, Mache S, Klingelhoefer D, Groneberg\nDA. Bacterial meningitis: a density-equalizing mapping analysis of the global\nresearch architecture. Int J Environ Res Public Health. 2014;11:10202 –14.\n33. Jacoby VL, Fujimoto VY, Giudice LC, Kuppermann M, Washington AE. Racial\nand ethnic disparities in benign gynecologic conditions and associated\nsurgeries. Am J Obstet Gynecol. 2010;202:514 –21.\n34. Miyazawa K. Incidence of endometriosis among Japanese women. Obstet\nGynecol. 1976;48:407 –9.\n35. Nnoaham KE, Sivananthan S, Hummelshoj L, Jenkinson C, Webster P,\nKennedy SH, Zondervan KT. Multi-centre studies of the global impact of\nendometriosis and the predictive value of associated symptoms.\nJ Endometr. 2009;1:36 –45.\n36. Nnoaham KE, Hummelshoj L, Kennedy SH, Jenkinson C, Zondervan KT.\nDeveloping symptom-based predictive models of endometriosis as a\nclinical screening tool: results from a multicenter study. Fertil Steril. 2012;98:\n692–701. e695.\n37. Nnoaham KE, Hummelshoj L, Webster P, d ’Hooghe T, de Cicco NF, de Cicco\nNC, Jenkinson C, Kennedy SH, Zondervan KT. Impact of endometriosis on\nquality of life and work productivity: a multicenter study across ten\ncountries. Fertil Steril. 2011;96:366 –73. e368.\n38. Kyama CM, Mwenda JM, Machoki J, Mihalyi A, Simsa P, Chai DC, D ’Hooghe\nTM. Endometriosis in African women. Womens Health (Lond Engl). 2007;3:\n629–35.\n39. Binhazim AA, Tarara RP, Suleman MA. Spontaneous external endometriosis\nin a De Brazza ’s monkey. J Comp Pathol. 1989;101:471 –4.\n40. Merrill JA. Spontaneous endometriosis in the Kenya baboon (Papio\ndoguera). Am J Obstet Gynecol. 1968;101:569 –70.\n41. Cornillie FJ, D ’Hooghe TM, Bambra CS, Lauweryns JM, Isahakia M, Koninckx\nPR. Morphological characteristics of spontaneous endometriosis in the\nbaboon (Papio anubis and Papio cynocephalus). Gynecol Obstet Invest.\n1992;34:225–8.\n42. D ’Hooghe TM, Bambra CS, De Jonge I, Machai PN, Korir R, Koninckx PR.\nA serial section study of visually normal posterior pelvic peritoneum from\nbaboons (Papio cynocephalus, Papio anubis) with and without spontaneous\nminimal endometriosis. Fertil Steril. 1995;63:1322 –5.\n43. D ’Hooghe TM, Bambra CS, Isahakia M, Koninckx PR. Evolution of\nspontaneous endometriosis in the baboon (Papio anubis, Papio\ncynocephalus) over a 12-month period. Fertil Steril. 1992;58:409 –12.\n44. D ’Hooghe TM, Bambra CS, Kazungu J, Koninckx PR. Peritoneal fluid volume\nand steroid hormone concentrations in baboons with and without either\nspontaneous minimal/mild endometriosis or the luteinized unruptured\nfollicle syndrome. Arch Gynecol Obstet. 1995;256:17 –22.\n45. D ’Hooghe TM, Bambra CS, Raeymaekers BM, De Jonge I, Hill JA, Koninckx\nPR. The effects of immunosuppression on development and progression of\nendometriosis in baboons (Papio anubis). Fertil Steril. 1995;64:172 –8.\n46. D ’Hooghe TM, Bambra CS, Raeymaekers BM, De Jonge I, Lauweryns JM,\nKoninckx PR. Intrapelvic injection of menstrual endometrium causes\nendometriosis in baboons (Papio cynocephalus and Papio anubis). Am J\nObstet Gynecol. 1995;173:125 –34.\n47. D ’Hooghe TM, Bambra CS, Raeymaekers BM, Koninckx PR. Serial\nlaparoscopies over 30 months show that endometriosis in captive baboons\n(Papio anubis, Papio cynocephalus) is a progressive disease. Fertil Steril.\n1996;65:645–9.\n48. D ’Hooghe TM, Bambra CS, Suleman MA, Dunselman GA, Evers HL, Koninckx\nPR. Development of a model of retrograde menstruation in baboons (Papio\nanubis). Fertil Steril. 1994;62:635 –8.\n49. D ’Hooghe TM, Scheerlinck JP, Koninckx PR, Hill JA, Bambra CS. Anti-\nendometrial lymphocytotoxicity and natural killer cell activity in baboons\n(Papio anubis and Papio cynocephalus) with endometriosis. Hum Reprod.\n1995;10:558–62.\nBrüggmann et al. BMC Women's Health  (2016) 16:64 Page 11 of 12\n\n50. Groneberg DA, Schilling U, Scutaru C, Uibel S, Zitnik S, Mueller D,\nKlingelhoefer D, Kloft B. Drowning –a scientometric analysis and data\nacquisition of a constant global problem employing density equalizing\nmapping and scientometric benchmarking procedures. Int J Health Geogr.\n2011;10:55.\n51. Groneberg-Kloft B, Klingelhoefer D, Zitnik SE, Scutaru C. Traffic medicine-\nrelated research: a scientometric analysis. BMC Public Health. 2013;13:541.\n52. Borger JA, Neye N, Scutaru C, Kreiter C, Puk C, Fischer TC, Groneberg-Kloft B.\nModels of asthma: density-equalizing mapping and output benchmarking.\nJ Occup Med Toxicol. 2008;3 Suppl 1:S7.\n53. Groneberg-Kloft B, Scutaru C, Fischer A, Welte T, Kreiter C, Quarcoo D.\nAnalysis of research output parameters: density equalizing mapping and\ncitation trend analysis. BMC Health Serv Res. 2009;9:16.\n54. Schmidt S, Bundschuh M, Scutaru C, Klingelhoefer D, Groneberg DA, Gerber\nA. Hepatitis B: global scientific development from a critical point of view.\nJ Viral Hepat. 2014;21(11):786 –93.\n•  We accept pre-submission inquiries \n  Our selector tool helps you to find the most relevant journal\n  We provide round the clock customer support \n  Convenient online submission\n  Thorough peer review\n  Inclusion in PubMed and all major indexing services \n  Maximum visibility for your research\nSubmit your manuscript at\nwww.biomedcentral.com/submit\nSubmit your next manuscript to BioMed Central \nand we will help you at every step:\nBrüggmann et al. BMC Women's Health  (2016) 16:64 Page 12 of 12","source_license":"CC0","license_restricted":false}