In this first article, I will provide you with the basic contextual information on endometriosis research so that you can understand how it has developed over time. First, I will present you with the “long-run” side of the story: the historical developments linked to the (somewhat) scientific study of endometriosis from the distant past onwards. Then, I will detail the evolution of modern endometriosis research from the early 20th century to our days.
Graphs may not be fully visible on cell phones. Using a computer is recommended for the best reading experience. The titles can be clicked to get a fullscreen version of the graphs.
“Inventing” endometriosis: science in the long-run
Defining science is a tricky enterprise (some philosophers literally spend their entire career trying to distinguish science from “non-science”, an issue which is called the “demarcation problem”1https://plato.stanford.edu/entries/pseudo-science/). Our views and expectations of what counts as science tend to evolve. For instance, science can nowadays be defined as the activity of a specific class of persons (“scientists”). These persons carry out a series of tasks (e.g., defining topics and hypotheses, conducting experiments, drafting papers, sending them to journals, getting stuck in endless arguments about trivial details or major methodological issues, etc.). They hold specialized diplomas, such as PhDs. They work in specific institutions (universities, research centers…). It is evident that these modern criteria are meaningless to understand how endometriosis was seen and studied in the distant past when the social organization of research was very different.
Moreover, endometriosis is also particularly difficult to define and to distinguish from other diseases, adding a further layer of difficulty. For this article, I will circumvent these issues by focusing on the evolution of the medical understanding of the disease over time, i.e., by providing an overview of its significant developments. It leaves out the non-medical research, but there is evidence that these aspects have only emerged relatively recently in scientific research (see next article for further information on the scientific disciplines that investigate endometriosis).
For the long history of endometriosis, I will mainly draw information from a 2012 paper written by Nezhat and colleagues2https://pubmed.ncbi.nlm.nih.gov/23084567/. Conventional medical history typically considers that the modern identification of endometriosis started with Rokitansky, who provided a microscopic description of the illness in 1860. Another canonical figure that medical doctors strongly emphasize in their hagiography is Sampson. He proposed a first description of the (likely) causes of the disease in the 1920s. The diagnosis of endometriosis as such and its visibility are thus relatively recent by historical standards. In that regard, it can be argued that endometriosis is an “invention”. Obviously, it does not imply that the illness is not “real”, but rather that it was identified, defined and conceptualized in a specific social, spatial and historical context based on exchanges of people, practices and techniques3https://journals.openedition.org/rac/6867#ftn2.
However, it is clear that endometriosis “existed” in the distant past, even though it was not named, understood and identified as such. A method to prove this is to look for ancient descriptions of medical problems with symptoms that are consistent with what we call today “endometriosis”. In practice, it means focusing on old reports of pelvic pain, menstrual disorders… Of course, this approach has multiple issues, including how descriptions were made (or not) in different periods, the diversity of experienced symptoms, etc. Still, the authors of the 2012 paper highlight several historical medical diagnoses and theories that could actually correspond to endometriosis. It ranges from the wandering womb in Classical Antiquity (i.e., the idea that the uterus could move within a woman’s body and cause symptoms) to demonic possessions, hysteria and psychiatric disorders. Treatment ideas were often derived from the “causes” identified in these theories. From the 19th century onwards, theories that closely resemble what we now consider scientific began to emerge. I mean that more rigorous standards of proof gradually appeared, with their fair share of debates, controversies and mistakes on the nature of endometriosis and potential treatments.
A central claim of the 2012 paper is that the authors believe that most historical cases of “hysteria” were actually endometriosis. I do not really buy it because hysteria was often a blanket diagnosis for psychiatric illnesses in the past (e.g., bipolar disorder or schizophrenia). More research performed by historians of medicine would probably be necessary to uncover additional elements. However, it is evident that the psychologization of endometriosis was (and still is) a significant issue, leading to wrong diagnoses and delayed care. It also tends to influence medical practitioners, leading to patient-blaming and “advice” linked to traditional gender roles (e.g., having children)4See https://www.routledge.com/The-Makings-of-a-Modern-Epidemic-Endometriosis-Gender-and-Politics/Seear/p/book/9780367078027 & https://www.tandfonline.com/doi/abs/10.1080/00497878.2015.1078212?journalCode=gwst20. Psychologization has also likely hindered scientific advances.
The rise of endometriosis research
Having this long-run picture in mind, I will now move to the original section of this blog article, namely the description of “modern” scientific research dedicated to endometriosis, i.e., from the 1920s onwards. As you can see in the following figure, there is a clear upward trend in the number of scientific publications dedicated to endometriosis.
Note: Graph based on the full dataset of 36,929 endometriosis-related publications obtained from Dimensions.
More precisely, distinctive periods are visible. Few publications focused on endometriosis were released at the beginning of the 20th century. It can stem from the relatively low scientific activity at this period and, to some extent, from gaps in the data. Between the 1950s and the 1970s, the number of endometriosis-related publications tended to oscillate around 100 per year at the global level. Then, the first period of notable growth occurred in the 1980s, with the number of publications increasing by 8.3% yearly during this decade. It led to an output of about 500 endometriosis-related publications per year in the 1990s. Since the early 2000s, another period of explosive growth has occurred. Average yearly growth rates have reached 7.8% in the 2000s, 5% in the 2010s. This dynamism has allowed a jump from 556 annual publications in 2000 to 2000 in 2019.
However, these figures must be contextualized. Is 2000 publications each year a lot? Is the growth since the early 2000s special? Or is it the mere “natural” course of things? Indeed, research has boomed on quantitative terms since this period for all topics. To truly understand the magnitude of the effort dedicated to endometriosis, it thus ought to be compared to scientific research in general. Thankfully, it is possible to retrieve the number of scientific publications for all topics from the Dimensions database. The following graph tracks the number of scientific publications for endometriosis and all subjects over time. Of course, the output for all publications is much greater since it encapsulates all types of things (mathematics, medicine, sociology…). To compare with endometriosis research, the numbers are thus standardized. An index of 100 is the baseline for the year 2000. As a result, the curves can show whether the number of scientific publications evolves differently for endometriosis and all scientific topics.
Note: Graph based on the full dataset of 36,929 endometriosis-related publications obtained from Dimensions and the full Dimensions database
This graph shows that the number of publications dedicated to endometriosis has increased at a similar pace or faster than all scientific topics in recent years. Indeed, the number of endometriosis-related publications has been multiplied by 3.6 between 2000 and 2019, compared to 3.2 for all scientific subjects. Before the mid-1980s, it seems that endometriosis-related research was instead experiencing slower growth as compared to other scientific topics. Data for the very early years could be much less reliable, so interpretations are trickier. Overall, these patterns suggest that the effort dedicated to endometriosis research has progressed more or less in parallel with the rest of scientific advances (with a slight recent advantage). Moreover, there seems to be an acceleration linked to political activism for endometriosis research in the 2020s. For instance, the US Congress approved in 2020 the doubling of funding for such research through the National Institutes of Health5https://www.endofound.org/congress-approves-doubling-funding-for-endometriosis-research-blossom.
The only color that matters is green…
Having the “right” levels of funding is paramount to scientific advances in the realm of endometriosis, as in other topics. The monetary amounts dedicated to the disease are notoriously difficult to estimate. This uneasy situation stems from the diversity of funding sources (in the different countries, but also within countries, e.g., various funding agencies), problems to categorize expenditures (what “counts” as endometriosis R&D or not) and lower attention than for other diseases. In particular, the private sector has tended to neglect endometriosis historically, compared to other areas of investigation (e.g., cancer, cardiovascular diseases…). However, it is likely that funding for endometriosis research has substantially progressed in recent years. How do we know that? Well, it is not 100% sure, but several hints point towards this direction. Firstly, the number of endometriosis publications has strongly risen since the 2000s, so the natural expectation is that funding has experienced the same trend. Secondly, the increased attention towards the disease has led major R&D agencies and funders to secure additional financing for endometriosis (e.g., the case of the US NIH, as previously mentioned). Thirdly, there is evidence that private companies, which are significant contributors to biomedical research in general, have recently decided to boost their endometriosis activities6See for instance https://www.statista.com/statistics/1242547/companies-conducting-endometriosis-clinical-trials-worldwide/
With the assumption of the correlation between funding and the number of published articles, the database produced for this project can yield a rough “guesstimate” of global R&D endometriosis spending. The result should be taken with a grain of salt, but the order of magnitude should be informative.
Note: The guesstimate for global R&D spending dedicated to endometriosis is obtained through the following formula: Endometriosis R&D Spendingworld = GDPworld x (total R&D spendingworld / GDPworld) x (Endometriosis scientific publications / Total scientific publications) x (1/3). World GDP is obtained from the World Bank in USD7https://data.worldbank.org/indicator/NY.GDP.MKTP.KD.The share of global GDP dedicated to R&D is extracted from the UNESCO database8http://data.uis.unesco.org/Index.aspx?DataSetCode=SCN_DS&lang=en. The number of scientific publications is collected from Dimensions. A corrective factor of one third is applied to the result to take into account the fact that for the vast majority of the considered period, the bulk of endometriosis research is public, and in most countries, about one-third of the R&D effort is public9See for instance https://epthinktank.eu/2018/11/22/research-and-innovation-in-the-eu-evolution-achievements-challenges/gross-domestic-expenditure-on-rd-by-sector-2016/. The results are expressed in millions of current USD. They are converted to EUR using the average exchange rates from OFX10https://www.ofx.com/en-au/forex-news/historical-exchange-rates/yearly-average-rates/. Amounts are converted to real 2020 euros to consider inflation, using the ratios from indexes from Inflationtool11https://www.inflationtool.com/euro
These results seem consistent with some partial evidence on endometriosis R&D spending (such as the fact that US NIH spending is about 10 million USD a year in the 2010s). Keeping in mind the limitations of this guesstimate, it is clear that the funding dedicated to endometriosis R&D has progressed in the last years, reaching about 150 million of 2020 euros in 2018. This is a significant improvement, about a doubling from the mid-1990s. Obviously, it does not encapsulate spending for endometriosis care (e.g., hospitalization costs, drugs…), which are much higher.
Despite this progress, resources dedicated to endometriosis R&D at a global level remain (very) limited. Arguably, regarding the prevalence of endometriosis, it is still too low. This becomes clear if we contextualize this amount by comparing it to other spending examples.
Note: Graph based on own elaboration for the guesstimate of global endometriosis R&D spending (see previously). Economic data are extracted from the World Bank dataset on GDP12https://data.worldbank.org/indicator/NY.GDP.MKTP.KD. Medical R&D spending data (US-NIH spending only) are obtained from the NIH13https://report.nih.gov/funding/categorical-spending#/. Military spending data is extracted from the SIPRI database14https://www.sipri.org/databases/milex. All financial data are converted to real 2020 euros based on exchange rates from OFX15https://www.ofx.com/en-au/forex-news/historical-exchange-rates/yearly-average-rates/ and price indexes from Inflationtool16https://www.inflationtool.com/euro. All data from 2018.
Indeed, as seen on this graph, global spending for endometriosis R&D is comparable to the total economic output of small island nations such as Nauru or Kiribati, or smaller than the military budget of developing countries like Senegal. Compared to other budgets for medical R&D, global endometriosis R&D spending is meager. It is between what the National Institutes of Health dedicate to depression or prostate cancer R&D in the US alone! These diseases are also very prevalent (depression is one of the most common psychiatric disorders, prostate cancer is one of the most common cancers in males), yet the gap is clear. Further progress will require addressing this under-financing of endometriosis R&D.