Available via license: CC BY 4.0
Content may be subject to copyright.
1
META-RESEARCH 1
The need for more research into reproductive health and disease 2
3
Natalie D Mercuri1, Brian J Cox1,2,* 4
1Department of Physiology, University of Toronto, Toronto, Canada 5
2Department of Obstetrics and Gynaecology, University of Toronto, Toronto, Canada 6
*Corresponding Author: b.cox@utoronto.ca
7
8
Abstract 9
Reproductive diseases have a significant impact on human health, especially on women’s health: 10
endometriosis affects 10% of all reproductive-aged women but is often undiagnosed for many 11
years, and preeclampsia claims over 70,000 maternal and 500,000 neonatal lives every year. 12
Infertility rates are also rising. However, relatively few new treatments or diagnostics for 13
reproductive diseases have emerged in recent decades. Here, based on analyses of PubMed, we 14
report that the number of research articles published on non-reproductive organs is 4.5 times 15
higher than the number published on reproductive organs. Moreover, for the two most-16
researched reproductive organs (breast and prostate), the focus is on non-reproductive diseases 17
such as cancer. Further, analyses of grant databases maintained by the Canadian Institutes of 18
Health Research and the National Institutes of Health in the United States show that the number 19
of grants for research on non-reproductive organs is 6–7 times higher than the number for 20
reproductive organs. Our results suggest that there are too few researchers working in the field of 21
reproductive health and disease, and that funders, educators and the research community must 22
take action to combat this longstanding disregard for reproductive science. 23
24
25
26
2
INTRODUCTION 27
It is difficult to overstate the impact of reproductive disease. Adverse pregnancy outcomes – 28
which include preterm delivery, low birth weight, hypertensive disorders, and gestational 29
diabetes –impact the acute and chronic health of the population1–3. About 20% of all pregnancies 30
require medical intervention4, and in lower resource settings, pregnancy and delivery 31
complications are a leading cause of maternal and neonatal death5. 32
In 1992, the Institute of Medicine in the United States published a report called 33
Strengthening Research in Academic OB-GYN Departments that outlined areas of research with 34
obstetrics and gynecology where improvements were needed, such as low-birth-weight infants, 35
fertility complications, and pregnancy-induced hypertension6. Three decades later, despite the 36
essential nature and impact of the reproductive system, these issues are still major challenges in 37
reproductive health. 38
Gender inequality and bias have been issues since the onset of biological and medical 39
research. For example, including women as subjects in clinical research was not standard 40
practice until after 19867. There has been progress in developing policies to increase the 41
representation of women (as both subjects and researchers) and in providing education on gender 42
inequality for all researchers, but women are still underrepresented in scientific and medical 43
research8. 44
There are a variety of stigmas and taboos surrounding any topic relating to reproductive 45
function. Menstruation is one function that has faced stigmatization that persists today9,10, with 46
women often feeling too embarrassed to talk about this natural process or even complete an 47
essential task, such as purchasing menstrual products at a local store. Political power highly 48
affects reproductive health care and rights over other biological processes. In many countries, 49
ongoing political and legal battles directly affect access to safe reproductive health care, 50
including contraception, safe abortion, and gender identity rights11. There are parallels between 51
the low level of research into reproductive diseases and the response to the AIDS epidemic in the 52
1980s. The long delay in recognizing AIDS as a significant health issue, and then implementing 53
research policies, perpetuated false ideas surrounding the lifestyles of those affected by the 54
disease and created a barrier to expanding sexual education and seeking healthcare, likely costing 55
many lives12. Despite great advances in AIDS research and treatment, including social 56
3
awareness, public health stigma still lingers in society13. Similar increases in advocacy and 57
public awareness are needed to overcome these barriers affecting reproductive health. 58
Reproductive pathologies are often challenging to diagnose and properly treat, which 59
increases the risk of comorbidity development. Moreover, a long-standing lack of research into 60
reproductive health and disease means that the acute and chronic healthcare burden caused by 61
reproductive pathologies is likely to continue increasing. This lack of research likely results from 62
historic and ongoing systemic biases against female-focused research, and from political and 63
legal challenges to female reproductive health14. In this exploratory analysis we seek to 64
understand the “research gap” between reproductive health and disease and other areas of 65
medical research, and to suggest ways of closing this gap. 66
67
68
RESULTS 69
Comparing numbers of publications 70
To benchmark research on reproductive health and disease, we used the PubMed database to 71
compare the number of articles published on seven reproductive organs and seven non-72
reproductive organs between 1966 and 2021 (Table 1). While the reproductive organs are not 73
essential to postnatal life, we posit that the placenta and the uterus are as essential to fetal 74
survival in utero as the lungs and the heart are to postnatal survival after birth. Our analysis 75
revealed that the average number of articles on non-reproductive organs was 4.5 times higher 76
than the number on reproductive organs (and ranged between about 2 and 20 in pairwise 77
comparisons). The reproductive organs with the most publications were the breast and prostate. 78
The research landscape can change over time and efforts to reduce gender bias in 79
research might have had an impact on the volume of reproductive research, so we plotted the 80
number of publications on the 14 organs as a function year between 1966 and 2021 (Figure 1A). 81
Breast and prostate were the only reproductive organs to increase in publication at a rate similar 82
to the kidney; the second least studied non-reproductive organ in our list. The intestine was the 83
only non-reproductive organ to show similar publication rates to the other five reproductive 84
organs. To investigate further, we compared disease-driven research versus research not related 85
to disease. 86
87
4
88
Comparing research related to disease and research not related to disease 89
In the 1970s, the National Institutes of Health (NIH) initiated a war on cancer, and the breast and 90
prostate are both associated with sex-specific cancers. We reassessed publication data with the 91
added search parameter "NOT cancer" to eliminate cancer-based research (Figure 1B). We 92
observed a reduction of approximately 20% for most non-reproductive organs; however, the 93
reduction for publication on the breast and prostate was about 80%, suggesting that most 94
research on these organs is driven by an interest in cancer research rather than reproductive 95
health and disease (Figure 1B). 96
Then, for each organ, we plotted the number of publications related to disease on the 97
vertical axis, and the number not related to disease on the horizontal axis, which revealed a high 98
degree of variation among the organs (Figure 2). For three non-reproductive organs (brain, heart, 99
and liver) the number of publications not related to disease was almost three times as high as the 100
number related to disease, and for two non-reproductive organs (kidney and lung) the numbers 101
were similar. For the breast and prostate, on the other hand, the number of publications related to 102
disease was three times as high as the number not related to disease. For the five remaining 103
reproductive organs, and also for the intestine and pancreas, the number of publications not 104
related to disease was about twice as high as the number related to disease (although the total 105
number of publications for these seven organs was about an order of magnitude lower than the 106
number for the other seven organs). 107
108
Research funding 109
Next we used databases belonging to the Canadian Institutes of Health Research (CIHR) and the 110
NIH to investigate funding trends for the different organs. The 14 keywords (brain, heart, liver, 111
lung, kidney, intestine, pancreas, breast, prostate, ovary, uterus, penis, testes, and placenta) were 112
entered into each database, and we extracted funding data for the period between 2013 and 2018. 113
These organs were chosen as keywords to investigate the funding related to a basic 114
understanding of the biology of these organs. Although grants that relate to pregnancy or fertility 115
may not be captured, these topics are much broader and would introduce subtopics outside of the 116
reproductive scope, similar to using keywords such as metabolism or behaviour. Table 2 gives 117
the number of projects for each keyword and the corresponding average funding amount per 118
5
grant for the CIHR, and the same for the NIH. Our analysis found that the mean grant amounts 119
for the CIHR and NIH are similar between different keyword research topics (CIHR: $ 370 000 120
± $ 50 000; NIH: $ 481 500 ± $ 50 000). The similar funding amounts between different organs 121
are encouraging and may result from standard funding guidelines for biomedical research. 122
However, our analysis found that the average number of funded projects is much higher for non-123
reproductive organs compared to reproductive organs for both the CIHR (800 vs. 115) and the 124
NIH (31 000 vs. 5 300). 125
126
DISCUSSION 127
Our analysis suggests a bias against research into reproductive health and disease, and it is 128
important that efforts are made to eliminate this bias so that research into reproductive medicine 129
does not fall further behind. The higher levels of research observed for some reproductive organs 130
(notably the breast and prostate) were driven by cancer-focused research, but this has not led to 131
an increase in the level of non-disease-related research on these organs (Figure 1B). Factors such 132
as Breast Cancer Awareness Month15 and screening programmes for prostate cancer16 likely led 133
to the increase in publications about these two reproductive organs. 134
While our analysis is suggestive that many reproductive organs achieve a good balance of 135
non-disease versus disease-related research, the paucity of research is highly problematic to the 136
field. An important consideration is that a lack of non-disease-related research on reproductive 137
organs may hinder progress in diagnosing and treating a wide range of pathologies (including 138
preeclampsia, polycystic ovary syndrome, and endometriosis). 139
In a competitive funding system, publications are correlated to successful grants and 140
dollar values awarded. Across research areas, we found that the mean grant dollar amounts per 141
project are similar. However, the numbers of funded research projects on non-reproductive 142
organs were higher than the numbers for reproductive organs by a factor of 6–7 (which is slightly 143
larger than the discrepancy seen in publication rates). An important consideration is that the part 144
of the NIH that supports reproductive research in the US, the National Institute of Child Health 145
and Development, is one of the lowest-funded institutes at the NIH and does not have the word 146
reproduction in its title. In Canada, the Human Development, Child and Youth Health Institute of 147
CIHR is a funder of most pregnancy and reproductive biology grants, typically awarded through 148
the Clinical Investigation – A panel, and it may be that the use of a clinical panel to fund this 149
6
area of research inhibits non-diseased focused research. This panel is well-funded relative to 150
other panels; however, some research areas (e.g., cardiovascular and neurological research) have 151
more than one panel. 152
A growing political and societal emphasis is placed on disease-related research, such as 153
cancer. This may arise from a view of basic research as ineffective or inefficient compared to 154
applied research17. Perhaps this is best seen in our analysis by the high percentage of research 155
publications on the prostate and breast that are due to cancer research, whereas most research on 156
the other reproductive organs we studied was not disease-related. While the placenta and uterus 157
are widely viewed as causal organs for reproductive complications that claim large numbers of 158
maternal and neonatal lives, and treatments cost tens of billions of US dollars every year, there is 159
relatively little disease-related research into these organs. The investigation of cancer biology 160
within a reproductive organ can rely on knowledge of cancer in other organ systems. However, 161
the low levels of research into reproductive organs relative to other organs means that there is 162
much less foundational knowledge to rely on when seeking to develop treatments for diseases of 163
these organs. Moreover, there are fewer researchers who are experienced on working with these 164
organs. 165
There are several limitations to our approach. One important limitation is that the number 166
of unfunded grant applications is not accessible, so we could not determine if the lower numbers 167
of grants for research on reproductive health and disease were due to proportionally lower total 168
application numbers, or to a bias against reproductive research. Funding bodies should conduct 169
internal analyses to determine appropriate action. The use of keywords to distinguish between 170
non-disease and disease-related research is a limitation, and the relatively low numbers of 171
publications on reproductive organs can also present challenges when making comparisons. 172
However, the differences we observe between research into reproductive and non-reproductive 173
organs (as measured by numbers of publications and levels of funding) are large and are unlikely 174
to result from missing search terms. 175
176
CONCLUSIONS 177
How can we address the research gap and enable the field of reproductive health and disease to 178
catch up with other areas of research? Based on our analysis, we need to increase the number of 179
researchers working on reproductive organs and related pathologies. Recent efforts by the NIH, 180
7
such as the Human Placenta Project18, indicate a recognition of the need to increase research 181
capacity in reproductive sciences, and may lead to further increases in both interest and research 182
capacity in the longer term. 183
New researchers may avoid the reproductive field due to social and political factors and 184
the research gap (ie, the low levels of grant funding and publications), and this in turn may 185
discourage students and trainees, which will make it even more difficult to increase the size of 186
the research base. While continued advocacy, education, and political lobbying may help to 187
overcome many of the social and political factors, closing the research gap will require other 188
approaches. 189
To increase researchers and research output, we may learn lessons from the examples of 190
breast and prostate cancer. In both cases, research increased dramatically from a historically low 191
level. While public campaigns played a prominent role in these increases, the existence of a large 192
pool of researchers and trainees already working on other types of cancers was probably more 193
important (as it was these researchers, rather than those doing non-disease-related research on 194
these organs, do did most of the work on breast and prostate cancer). However, this is unlikely to 195
work for preeclampsia and other reproductive pathologies as there are no large pools of existing 196
researchers available to switch the focus of their work. 197
Therefore, to increase research capacity, we should promote collaborations between 198
researchers working on reproductive health and disease and those working in other areas of 199
physiology and medicine, especially other areas with much higher research capacities. There are 200
plenty of examples that show the benefit of such an integrated approach. For instance, female sex 201
hormones protect against many aging diseases, such as cardiovascular and neurological diseases, 202
leading to the prescription of hormone replacement therapies after menopause in some women19. 203
Links to immunology, cardiology and other systems can be used to increase research 204
capacity. During pregnancy, there are dramatic changes in maternal physiology, including 205
metabolism, the immune system, and cardio-pulmonary systems, and consequently, these are the 206
same systems affected by reproductive pathologies. Preeclampsia predisposes the mother to a 207
long-term cardiovascular risk of developing peripheral artery disease, coronary artery disease, 208
and congestive heart failure20. Additionally, complications of the liver and kidney are associated 209
with preeclampsia. Polycystic ovary syndrome and endometriosis are related to metabolism 210
8
problems and the risk of cancer development. Children born from pregnancies affected by 211
preeclampsia or fetal growth restriction are at a 2.5 times higher risk of developing hypertension 212
and require anti-hypertensive medications as adults21,22. 213
The pathological interaction of reproductive with non-reproductive systems and organs 214
should attract investigators from nephrology, hepatology and cardiovascular research, where the 215
total number of researchers is 10–20 times as high as the number in reproductive health and 216
disease. If just 1% of the researchers in the cardiovascular field were to refocus on pregnancy-217
related cardiovascular adaptation and pathologies, this would increase reproductive research by 218
10%. 219
Our neglect of the placenta and reproductive biology impedes other biomedical research 220
areas. In cancer research, the methylation patterns of tumours look most like those found in the 221
placenta, but why placenta methylation patterns are so unlike all other organs is not known23 24. 222
In regenerative medicine, the immune-modulating genes used by the placenta25 are repurposed to 223
generate universally transplantable stem cells and tissues26. A poor understanding of 224
reproductive biology is dangerous, considering emerging diseases that affect pregnancy and fetal 225
development, such as the recent Zika virus outbreak27,28. There are likely many other broad 226
benefits to better understanding reproductive biology. The time to act is now, as waiting longer 227
will not improve the situation. 228
229
METHODS 230
Publication rates 231
Published research manuscripts were searched in NCBI’s PubMed database 232
(https://pubmed.ncbi.nlm.nih.gov/) between and including the years 1966 and 2021. Keywords 233
for each search pertained to a specific organ or disease and were limited to the title/abstract of 234
the manuscripts (Available in supplementary zip file). The organs used for these analyses were 235
the brain, heart, liver, lung, kidney, intestine, pancreas, breast, prostate, ovary, uterus, penis, 236
testes, and placenta. We restricted the organ publication timelines to the years 1966–2021 and 237
extracted the annual article count (Available in supplementary zip file). The organ publication 238
timeline was reconducted with the addition of the search parameter "NOT cancer". 239
240
9
Funding rates 241
Grant funding data was obtained from the CIHR funding database (https://webapps.cihr-242
irsc.gc.ca/funding/Search?p_language=E&p_version=CIHR) and the NIH reporter tool 243
(https://reporter.nih.gov) by searching keywords in the title and abstracts/summary. Keywords 244
used for these searches were brain, heart, liver, lung, kidney, intestine, pancreas, breast, prostate, 245
ovary, uterus, penis, testes, and placenta (Available in supplementary zip file). The years were 246
restricted to 2013–2018. The total number of projects pertaining to each search term during this 247
period was extracted, and the total amount of funding for those projects was averaged. 248
249
Graphing 250
All graphs were produced using R (version 4.0.2) in R Studio (version 1.3.1073). R packages 251
used were ggplot2, tidyverse, formattable, gridExtra, RColorBrewer, ggrepel. 252
253
ACKNOWLEDGEMENTS 254
We thank the University of Toronto and the Department of Physiology for providing the 255
opportunity and supporting the completion of this review. We also thank the librarians who 256
offered expert advice on keyword searches of databases. 257
258
DATA AVAILABILITY 259
All data were obtained from public databases (PubMed/NCBI, NIH and CIHR). 260
261
262
263
10
REFERENCES 264
1. Barker, D.J. (1997). The fetal origins of coronary heart disease. Acta Paediatr Suppl 422, 265
78–82. 266
2. Williams, D. (2011). Long-term complications of preeclampsia. Semin Nephrol 31, 111–267
122. 10.1016/j.semnephrol.2010.10.010. 268
3. Lewis, R.M., Cleal, J.K., and Hanson, M. a (2011). Review: Placenta, evolution and 269
lifelong health. Placenta 33 Suppl, 1–5. 10.1016/j.placenta.2011.12.003. 270
4. Murray, C.J.L., Lopez, A.D., Organization, W.H., and others (1998). Health dimensions 271
of sex and reproduction: the global burden of sexually transmitted diseases, HIV, maternal 272
conditions, perinatal disorders, and congenital anomalies/edited by Christopher JL 273
Murray, Alan D. Lopez. In Health dimensions of sex and reproduction: the global burden 274
of sexually transmitted diseases, HIV, maternal conditions, perinatal disorders, and 275
congenital anomalies/edited by Christopher JL Murray, Alan D. Lopez. 276
5. WHO (2019). Trends in maternal mortality 2000 to 2017: estimates by WHO, UNICEF, 277
UNFPA, World Bank Group and the United Nations Population Division: executive 278
summary (World Health Organization). 279
6. Staff, I. of Medicine., and Townsend, Jessica. (1992). Strengthening Research in 280
Academic OB-GYN Departments. (National Academies Press). 281
7. Liu, K.A., and DiPietro Mager, N.A. (2016). Women’s involvement in clinical trials: 282
historical perspective and future implications. Pharm Pract (Granada) 14. 283
10.18549/PharmPract.2016.01.708. 284
8. Huang, J., Gates, A.J., Sinatra, R., Aszí O Barabási, A.-L.´, and Barabási, B. (2020). 285
Historical comparison of gender inequality in scientific careers across countries and 286
disciplines. PNAS 117, 4609–4616. 10.1073/pnas.1914221117/-/DCSupplemental.y. 287
9. Litman, J. (2018). Menstruation Stigma Must Stop. Period. The Public Health Advocate. 288
Berkeley. 289
10. Pickering, K. (2019). The taboo around menstruation and menopause doesn’t only hurt 290
women. The Guardian. 291
11. Pugh, S. (2019). Politics, power, and sexual and reproductive health and rights: impacts 292
and opportunities. Sex Reprod Health Matters 27. 10.1080/26410397.2019.1662616. 293
12. Francis, D.P. (2012). Deadly AIDS policy failure by the highest levels of the US 294
government: A personal look back 30 years later for lessons to respond better to future 295
epidemics. J Public Health Policy 33. 10.1057/jphp.2012.14. 296
13. Turan, B., Budhwani, H., Fazeli, P.L., Browning, W.R., Raper, J.L., Mugavero, M.J., and 297
Turan, J.M. (2017). How Does Stigma Affect People Living with HIV? The Mediating 298
Roles of Internalized and Anticipated HIV Stigma in the Effects of Perceived Community 299
Stigma on Health and Psychosocial Outcomes. AIDS Behav 21, 283–291. 300
10.1007/s10461-016-1451-5. 301
14. Coen-Sanchez, K., Ebenso, B., El-Mowafi, I.M., Berghs, M., Idriss-Wheeler, D., and 302
Yaya, S. (2022). Repercussions of overturning Roe v. Wade for women across systems 303
and beyond borders. Reprod Health 19, 1–5. 10.1186/s12978-022-01490-y. 304
15. Jacobsen, G.D., and Jacobsen, K.H. (2011). Health awareness campaigns and diagnosis 305
rates: Evidence from National Breast Cancer Awareness Month. J Health Econ 30, 55–61. 306
10.1016/j.jhealeco.2010.11.005. 307
11
16. Dickinson, J., Shane, A., Tonelli, M., Gorber, S.C., Joffres, M., Singh, H., and Bell, N. 308
(2016). Trends in prostate cancer incidence and mortality in Canada during the era of 309
prostate-specific antigen screening. CMAJ Open 4, E73–E79. 10.9778/cmajo.20140079. 310
17. Lee, C. (2019). Not So Basic Research: the unrecognized importance of fundamental 311
scientific discoveries. Science in the News. 312
18. Guttmacher, A.E., Maddox, Y.T., and Spong, C.Y. (2014). The Human Placenta Project: 313
Placental structure, development, and function in real time. Placenta 35, 12–13. 314
10.1016/j.placenta.2014.02.012. 315
19. Paciuc, J. (2020). Hormone Therapy in Menopause. In Hormonal Pathology of the 316
Uterus., L. Deligdisch-Schor and A. Mareş Miceli, eds. (Springer, Cham). 10.1007/978-3-317
030-38474-6_6. 318
20. Rana, S., Lemoine, E., Granger, J., and Karumanchi, S.A. (2019). Preeclampsia: 319
Pathophysiology, Challenges, and Perspectives. Circ Res 124, 1094–1112. 320
10.1161/CIRCRESAHA.118.313276. 321
21. Ferreira, I., Peeters, L.L., and Stehouwer, C. da (2009). Preeclampsia and increased blood 322
pressure in the offspring: meta-analysis and critical review of the evidence. J Hypertens 323 27. 10.1097/HJH.0b013e328331b8c6. 324
22. Fox, R., Kitt, J., Leeson, P., Aye, C.Y.L., and Lewandowski, A.J. (2019). Preeclampsia: 325
Risk Factors, Diagnosis, Management, and the Cardiovascular Impact on the Offspring. J 326
Clin Med 8. 10.3390/jcm8101625. 327
23. smith, Z.D., shi, J., Gu, H., Donaghey, J., Clement, K., Cacchiarelli, D., Gnirke, A., 328
michor, F., and meissner, A. (2017). Epigenetic restriction of extraembryonic lineages 329
mirrors the somatic transition to cancer. 10.1038/nature23891. 330
24. Rousseaux, S., Debernardi, A., Jacquiau, B., Vitte, A.L., Vesin, A., Nagy-Mignotte, H., 331
Moro-Sibilot, D., Brichon, P.Y., Lantuejoul, S., Hainaut, P., et al. (2013). Ectopic 332
activation of germline and placental genes identifies aggressive metastasis-prone lung 333
cancers. Sci Transl Med 5. 10.1126/scitranslmed.3005723. 334
25. Szekeres-Bartho, J. (2002). Immunological relationship between the mother and the fetus. 335
Int Rev Immunol 21, 471–495. 10.1080/08830180215017. 336
26. Han, X., Wang, M., Duan, S., Franco, P.J., Kenty, J.H.R., Hedrick, P., Xia, Y., Allen, A., 337
Ferreira, L.M.R., Strominger, J.L., et al. (2019). Generation of hypoimmunogenic human 338
pluripotent stem cells. Proc Natl Acad Sci U S A 116, 10441–10446. 339
10.1073/pnas.1902566116. 340
27. Schuler-Faccini, L., Ribeiro, E.M., Feitosa, I.M.L., Horovitz, D.D.G., Cavalcanti, D.P., 341
Pessoa, A., Doriqui, M.J.R., Neri, J.I., Neto, J.M. de P., Wanderley, H.Y.C., et al. (2016). 342
Possible Association Between Zika Virus Infection and Microcephaly - Brazil, 2015. 343
MMWR Morb Mortal Wkly Rep 65, 59–62. 10.15585/mmwr.mm6503e2. 344
28. Calvet, G., Aguiar, R.S., Melo, A.S.O., Sampaio, S.A., de Filippis, I., Fabri, A., Araujo, 345
E.S.M., de Sequeira, P.C., de Mendonça, M.C.L., de Oliveira, L., et al. (2016). Detection 346
and sequencing of Zika virus from amniotic fluid of fetuses with microcephaly in Brazil: a 347
case study. Lancet Infect Dis. 10.1016/S1473-3099(16)00095-5. 348
349
350
12
FIGURE CAPTIONS 351
352
353
354
Figure 1: Number of articles published every year on seven reproductive organs and seven 355
non-reproductive organs. 356
A) The number of articles published on most of the non-reproductive organs (including the brain, 357
heart, lung and liver) has increased more rapidly than the number of articles published on the 358
reproductive organs. B) Removing articles that contain the keyword cancer has relatively little 359
effect on the number of articles for non-reproductive organs (with the exception of the lung), but 360
has a significant impact on the number of articles for the two reproductive organs with the most 361
articles: the breast and prostate. Data extracted from PubMed using organ-specific keyword 362
searches for the period 1966–2021. 363
364
365
AB
Figure 1
Annual Article Count
Annual Article Count
13
366
367
Figure 2: Comparing research related to disease and research not related to disease for 368
reproductive and non-reproductive organs 369
For each organ (colored circles) the vertical axis shows the number of publications for the period 370
1966–2021 related to disease, and the horizontal axis shows the number not related to disease: 371
the area of the circle is proportional to the total number of publications. The straight blue line 372
corresponds to equal numbers of disease-related and non-disease-related publications, so organs 373
to the right of this line (notably non-reproductive organs such as the brain, heart and liver) tend 374
to be the subject of more basic or non-disease-related research, whereas organs to the left of this 375
line (notably reproductive organs such as the breast and prostate) tend to be the subject of 376
disease-related research. The lung is the only non-reproductive organ in our sample to the left of 377
the blue line. 378
379
380
381
382
Figure 2
14
TABLES 383
Table 1 384
Total number of matching articles from PubMed for seven non-reproductive keywords and 385
seven reproductive keywords for the period 1966–2021. 386
387
388
389
390
391
392
393
394
395
396
397
398
399
400
401
402
403
404
405
406
Keyword Total Matching
Articles
Non-Reproductive Keywords
Brain 1,058,995
Heart 851,955
Liver 834,006
Lung 652,797
Kidney 451,177
Intestine 120,034
Pancreas 99,772
Reproductive Keywords
Breast 464,629
Prostate 197,736
Ovary 83,971
Placenta 57,076
Uterus 55,971
Testes 32,344
Penis 15,019
15
Table 2 407
Total number of projects funded and average grant (in Canadian or US dollars) for the 408
Canadian Institutes of Health Research (columns 2 and 3) and the US National Institutes of 409
Health (columns 4 and 5) for the years 2013–2018 for seven non-reproductive keywords 410
and seven reproductive keywords (column 1). 411
412
Keyword
Number
of
projects
(CIHR)
Average
grant
funded
(CAD)
Number
of
projects
(NIH)
Average
grant
funded
(USD)
Non-Reproductive Keywords
Brain 1686 $391,023 81666 $441,149
Heart 1214 $369,665 43833 $491,993
Liver 1597 $314,473 22072 $454,276
Lung 526 $371,154 34492 $525,631
Kidney 347 $424,360 21176 $508,853
Intestine 128 $444,490 5800 $371,727
Pancreas 96 $491,274 8649 $482,901
Reproductive Keywords
Breast 459 $336,734 19132 $525,134
Prostate 143 $299,034 8960 $514,638
Ovary 42 $379,349 4814 $520,804
Placenta 105 $369,825 2169 $526,147
Uterus 45 $324,690 1356 $509,250
Testes 10 $372,110 340 $500,160
Penis 1 $304,676 323 $369,434
413
414
