Drug Development in Endometriosis and Adenomyosis: It Takes More Than Just Good Science
Abstract
The pipelines of pharmaceutical companies are filled with thousands of promising new compounds for a plethora of indications. Yet, a close review of the drugs that have recently been in clinical trials quickly reveals that only a handful of drugs under evaluation in women with endometriosis can be genuinely qualified as truly innovative and breakthrough drugs. Why is there such an industry-wide lukewarm interest in drug research and development for endometriosis/adenomyosis? Why are pharmaceutical companies so reluctant to initiate programs or invest in academic research in endometriosis/adenomyosis? It is evident that a substantial part of the novel druggable targets originate from research in academia. However, only the pharmaceutical industry has the resources and expertise to bring drugs to patients. In other words, we are fully dependent on the pharmaceutical industry to bring new therapeutics to the market. The aim of this editorial is to make scientists from academia aware of the enormous complexity of the drug development process, the drivers that propel pharmaceutical companies to initiate new programs and to prioritize their portfolios, the value of intellectual property rights, and also about the importance of scientific rigor, predictive translational models, and biomarkers. At the same time, the pharmaceutical industry must be made aware of the enormous opportunity at hand, as the current patient population with endometriosis/adenomyosis is just the tip of the iceberg. We hope that the insights presented here will enable the endometriosis/adenomyosis research community to find ways to valorize their knowledge and attract the interest of the industry.
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All existing drugs for treating endometriosis are hormonal, with the aim of reducing estrogen production through induction of state of pseudo-pregnancy, pseudo-menopause, or chronic anovulation, thus creating an acyclic, hypoestrogenic environment.
“Currently, all existing drugs for treating endometriosis are hormonal74, with the aim of reducing estrogen production through induction of state of pseudo-pregnancy, pseudo-menopause, or chronic anovulation, thus creating an acyclic, hypoestrogenic environment75.”
From Platelets induce increased estrogen production through NF-κB and TGF-β1 signaling pathways in endometriotic stromal cells (2020) · cites this paper as [74]
Cites
Why Most Published Research Findings Are False
Ioannidis, J. P. A. (2005) · PLoS Medicine · doi:10.1371/journal.pmed.0020124 · Cited by 10,505 · see citing works
Why Most Published Research Findings Are False
Ioannidis, J. P. A. (2005) · CHANCE · doi:10.1080/09332480.2005.10722754 · Cited by 4,702 · see citing works
Can the pharmaceutical industry reduce attrition rates?
Kola, I., & Landis, J. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1470 · Cited by 4,167 · see citing works
Animal research: Reporting <i>in vivo</i> experiments: The ARRIVE guidelines
Kilkenny, C., Browne, W., Cuthill, I. C., Emerson, M., & Altman, D. G. (2010) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2010.00872.x · Cited by 3,625 · see citing works
How to improve R&D productivity: the pharmaceutical industry's grand challenge
Paul, S. M., Mytelka, D. S., Dunwiddie, C. T., Persinger, C. C., Munos, B. H., Lindborg, S. R., & Schacht, A. L. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3078 · Cited by 3,566 · see citing works
Giudice, L. C., & Kao, L. C. (2004) · The Lancet · doi:10.1016/s0140-6736(04)17403-5 · Cited by 3,166 · see citing works
Raise standards for preclinical cancer research
Begley, C. G., & Ellis, L. M. (2012) · Nature · doi:10.1038/483531a · Cited by 2,979 · see citing works
ESHRE guideline: management of women with endometriosis
Dunselman, G. A. J., Vermeulen, N., Becker, C., Calhaz-Jorge, C., D'Hooghe, T., De Bie, B., Heikinheimo, O., Horne, A. W., Kiesel, L., Nap, A., et al. (2014) · Human Reproduction · doi:10.1093/humrep/det457 · Cited by 2,211 · see citing works
Believe it or not: how much can we rely on published data on potential drug targets?
Prinz, F., Schlange, T., & Asadullah, K. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3439-c1 · Cited by 1,888 · see citing works
Eskenazi, B., & Warner, M. L. (1997) · Obstetrics and Gynecology Clinics of North America · doi:10.1016/s0889-8545(05)70302-8 · Cited by 1,617 · see citing works
Nnoaham, K. E., Hummelshoj, L., Webster, P., d’Hooghe, T., de Cicco Nardone, F., de Cicco Nardone, C., Jenkinson, C., Kennedy, S. H., & Zondervan, K. T. (2011) · Fertility and Sterility · doi:10.1016/j.fertnstert.2011.05.090 · Cited by 1,584 · see citing works
Lessons learned from the fate of AstraZeneca's drug pipeline: a five-dimensional framework
Cook, D., Brown, D., Alexander, R., March, R., Morgan, P., Satterthwaite, G., & Pangalos, M. N. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4309 · Cited by 1,344 · see citing works
Simoens, S., Dunselman, G., Dirksen, C., Hummelshoj, L., Bokor, A., Brandes, I., Brodszky, V., Canis, M., Colombo, G. L., DeLeire, T., et al. (2012) · Human Reproduction · doi:10.1093/humrep/des073 · Cited by 1,070 · see citing works
The social and psychological impact of endometriosis on women's lives: a critical narrative review
Culley, L. A., Law, C., Hudson, N., Denny, E., Mitchell, H., Baumgarten, M. N., & Raine‐Fenning, N. (2013) · Human Reproduction Update · doi:10.1093/humupd/dmt027 · Cited by 689 · see citing works
Cancer-associated mutations in endometriosis without cancer
Anglesio, M. S., Papadopoulos, N., Ayhan, A., Nazeran, T. M., Noë, M., Horlings, H. M., Lum, A., Jones, S., Senz, J., Seckin, T., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1614814 · Cited by 628 · see citing works
Treatment of Endometriosis-Associated Pain with Elagolix, an Oral GnRH Antagonist
Taylor, H. S., Giudice, L. C., Lessey, B. A., Abrao, M. S., Kotarski, J., Archer, D. F., Diamond, M. P., Surrey, E., Johnson, N. P., Watts, N. B., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1700089 · Cited by 511 · see citing works
De Graaff, A. A., D'Hooghe, T. M., Dunselman, G. A. J., Dirksen, C. D., Hummelshoj, L., WERF EndoCost Consortium, Simoens, S., Bokor, A., Brandes, I., Brodszky, V., et al. (2013) · Human Reproduction · doi:10.1093/humrep/det284 · Cited by 473 · see citing works
Pathophysiology and Immune Dysfunction in Endometriosis
Ahn, S. H., Monsanto, S. P., Miller, C. D., Singh, S. S., Thomas, R., & Tayade, C. (2015) · BioMed Research International · doi:10.1155/2015/795976 · Cited by 398 · see citing works
Pathology and physiopathology of adenomyosis
Bergeron, C., Amant, F., & Ferenczy, A. (2006) · Best Practice & Research Clinical Obstetrics & Gynaecology · doi:10.1016/j.bpobgyn.2006.01.016 · Cited by 359 · see citing works
The importance of new companies for drug discovery: origins of a decade of new drugs
KNELLER, R. W. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3251 · Cited by 347 · see citing works
Pathogenesis of adenomyosis, an update on molecular mechanisms
Vannuccini, S., Tosti, C., Carmona, F., Huang, S. J., Chapron, C., Guo, S.-W., & Petraglia, F. (2017) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2017.06.016 · Cited by 326 · see citing works
Self-citationChanging R&D models in research-based pharmaceutical companies
Schuhmacher, A., Gassmann, O., & Hinder, M. (2016) · Journal of Translational Medicine · doi:10.1186/s12967-016-0838-4 · Cited by 291 · see citing works
Clonogenic assay with established human tumour xenografts
Fiebig, H., Maier, A., & Burger, A. M. (2004) · European Journal of Cancer · doi:10.1016/j.ejca.2004.01.009 · Cited by 290 · see citing works
One mouse, one patient paradigm: New avatars of personalized cancer therapy
Malaney, P., Nicosia, S. V., & Davé, V. (2013) · Cancer Letters · doi:10.1016/j.canlet.2013.10.010 · Cited by 290 · see citing works
Fourquet, J., Báez, L., Figueroa, M., Iriarte, R. I., & Flores, I. (2011) · Fertility and Sterility · doi:10.1016/j.fertnstert.2011.04.095 · Cited by 262 · see citing works
Vitonis, A. F., Vincent, K., Rahmioglu, N., Fassbender, A., Buck Louis, G. M., Hummelshoj, L., Giudice, L. C., Stratton, P., Adamson, G. D., Becker, C. M., et al. (2014) · Fertility and Sterility · doi:10.1016/j.fertnstert.2014.07.1244 · Cited by 236 · see citing works
Self-citationTime to redefine endometriosis including its pro-fibrotic nature
Vigano, P., Candiani, M., Monno, A., Giacomini, E., Vercellini, P., & Somigliana, E. (2018) · Human Reproduction · doi:10.1093/humrep/dex354 · Cited by 235 · see citing works
Rahmioglu, N., Fassbender, A., Vitonis, A. F., Tworoger, S. S., Hummelshoj, L., D'Hooghe, T. M., Adamson, G. D., Giudice, L. C., Becker, C. M., Zondervan, K. T., et al. (2014) · Fertility and Sterility · doi:10.1016/j.fertnstert.2014.07.1208 · Cited by 227 · see citing works
Self-citationZhang, Q., Duan, J., Liu, X., & Guo, S.-W. (2016) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2016.03.015 · Cited by 211 · see citing works
Self-citationBecker, C. M., Laufer, M. R., Stratton, P., Hummelshoj, L., Missmer, S. A., Zondervan, K. T., Adamson, G. D., Adamson, G. D., Allaire, C., Anchan, R., et al. (2014) · Fertility and Sterility · doi:10.1016/j.fertnstert.2014.07.709 · Cited by 206 · see citing works
Self-citationEndometriosis-associated dyspareunia: the impact on women's lives
Denny, E., & Mann, C. H. (2007) · Journal of Family Planning and Reproductive Health Care · doi:10.1783/147118907781004831 · Cited by 190 · see citing works
Liu, X., Shen, M., Qi, Q., Zhang, H., & Guo, S.-W. (2016) · Human Reproduction · doi:10.1093/humrep/dew018 · Cited by 190 · see citing works
Self-citationThe pathophysiology of uterine adenomyosis: an update
Benagiano, G., Habiba, M. A., & Brosens, I. A. (2012) · Fertility and Sterility · doi:10.1016/j.fertnstert.2012.06.044 · Cited by 187 · see citing works
“Waiting for Godot”: a commonsense approach to the medical treatment of endometriosis
Vercellini, P., Crosignani, P., Somigliana, E., Vigano, P., Frattaruolo, M. P., & Fedele, L. (2011) · Human Reproduction · doi:10.1093/humrep/deq302 · Cited by 180 · see citing works
Medical and surgical management of adenomyosis
Farquhar, C. M., & Brosens, I. A. (2006) · Best Practice & Research Clinical Obstetrics & Gynaecology · doi:10.1016/j.bpobgyn.2006.01.012 · Cited by 171 · see citing works
Endometriosis—A disease because it is characterized by bleeding
Brosens, I. A. (1997) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(97)70482-4 · Cited by 169 · see citing works
Fassbender, A., Rahmioglu, N., Vitonis, A. F., Viganò, P., Giudice, L. C., D’Hooghe, T. M., Hummelshoj, L., Adamson, G. D., Becker, C. M., Missmer, S. A., et al. (2014) · Fertility and Sterility · doi:10.1016/j.fertnstert.2014.07.1209 · Cited by 162 · see citing works
Self-citationZhang, Q., Duan, J., Olson, M., Fazleabas, A., & Guo, S.-W. (2016) · Reproductive Sciences · doi:10.1177/1933719116641763 · Cited by 149 · see citing works
Self-citationAdenomyosis—A Result of Disordered Stromal Differentiation
Parrott, E. L., Butterworth, M., Green, A. R., White, I. N. H., & Greaves, P. (2001) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)61733-6 · Cited by 143 · see citing works
Adenomyosis: the pathophysiology of an oestrogen-dependent disease
Kitawaki, J. (2006) · Best Practice & Research Clinical Obstetrics & Gynaecology · doi:10.1016/j.bpobgyn.2006.01.010 · Cited by 143 · see citing works
Clinical relevance of the baboon as a model for the study of endometriosis
D’Hooghe, T. M. (1997) · Fertility and Sterility · doi:10.1016/s0015-0282(97)00277-x · Cited by 137 · see citing works
Vincent, K., Kennedy, S., & Stratton, P. (2010) · Fertility and Sterility · doi:10.1016/j.fertnstert.2008.09.056 · Cited by 132 · see citing works
First evidence of a menstruating rodent: the spiny mouse (Acomys cahirinus)
Bellofiore, N., Ellery, S. J., Mamrot, J., Walker, D. W., Temple-Smith, P. D., & Dickinson, H. (2016) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2016.07.041 · Cited by 129 · see citing works
Shen, M., Liu, X., Zhang, H., & Guo, S.-W. (2015) · Human Reproduction · doi:10.1093/humrep/dev314 · Cited by 124 · see citing works
Self-citationWhat is the societal burden of endometriosis-associated symptoms? A prospective Belgian study
Klein, S., D’Hooghe, T. M., Meuleman, C., Dirksen, C. D., Dunselman, G. A. J., & Simoens, S. (2013) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2013.09.020 · Cited by 100 · see citing works
Endometriosis Cost Assessment (the EndoCost Study): A Cost-of-Illness Study Protocol
Simoens, S., Hummelshøj, L., Dunselman, G. A. J., Brandes, I., Dirksen, C. D., & D’Hooghe, T. M. (2010) · Gynecologic and Obstetric Investigation · doi:10.1159/000316055 · Cited by 99 · see citing works
Bridging Translation by Improving Preclinical Study Design in AKI
deCaestecker, M. P., Humphreys, B. D., Liu, K. D., Fissell, W. H., Cerdá, J., Nolin, T. D., Askenazi, D. J., Mour, G. K., Harrell, F. E., Pullen, N., et al. (2015) · Journal of the American Society of Nephrology · doi:10.1681/asn.2015070832 · Cited by 98 · see citing works
Guo, S.-W., Ding, D., Shen, M., & Liu, X. (2015) · Reproductive Sciences · doi:10.1177/1933719115570907 · Cited by 86 · see citing works
Self-citationAltered genome-wide methylation in endometriosis
Naqvi, H., Ilagan, Y., Krikun, G., & Taylor, H. S. (2014) · Reproductive Sciences · doi:10.1177/1933719114532841 · Cited by 82 · see citing works
Zhang, Q., Liu, X., & Guo, S.-W. (2017) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2016.11.006 · Cited by 76 · see citing works
Self-citationAge-Related Differences in Quality of Life in Swedish Women with Endometriosis
Lövkvist, L., Boström, P., Edlund, M., & Olovsson, M. (2016) · Journal of Women s Health · doi:10.1089/jwh.2015.5403 · Cited by 73 · see citing works
Lesion kinetics in a non-human primate model of endometriosis
Harirchian, P., Gashaw, I., Lipskind, S. T., Braundmeier, A. G., Hastings, J. M., Olson, M. R., & Fazleabas, A. T. (2012) · Human Reproduction · doi:10.1093/humrep/des196 · Cited by 72 · see citing works
Leonardo-Pinto, J. P., Benetti-Pinto, C. L., Cursino, K., & Yela, D. A. (2017) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2017.02.015 · Cited by 72 · see citing works
What matters most in commercial success: first-in-class or best-in-class?
Schulze, U., & Ringel, M. S. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4035 · Cited by 61 · see citing works
An overview of the current status of clinical trials on endometriosis: issues and concerns
Guo, S. (2013) · Fertility and Sterility · doi:10.1016/j.fertnstert.2013.08.050 · Cited by 54 · see citing works
Self-citationAn analysis of original research contributions toward FDA-approved drugs
Patridge, E. V., Gareiss, P. C., Kinch, M. S., & Hoyer, D. (2015) · Drug Discovery Today · doi:10.1016/j.drudis.2015.06.006 · Cited by 45 · see citing works
Pullen, N., Birch, C. L., Douglas, G. J., Hussain, Q., Pruimboom-Brees, I., & Walley, R. J. (2011) · Human Reproduction Update · doi:10.1093/humupd/dmr030 · Cited by 42 · see citing works
Lack of Transparency of Clinical Trials on Endometriosis
Guo, S., & Evers, J. L. H. (2013) · Obstetrics and Gynecology · doi:10.1097/aog.0b013e318291f299 · Cited by 40 · see citing works
Self-citationMori, T., Kyokuwa, M., & Nagasawa, H. T. (1998) · PubMed · Cited by 26 · see citing works
Vallance, P. J., Williams, P. M., & Dollery, C. T. (2010) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2010.29 · Cited by 26 · see citing works
Non-health-care costs associated with endometriosis
Simoens, S., Meuleman, C., & D’Hooghe, T. M. (2011) · Human Reproduction · doi:10.1093/humrep/der215 · Cited by 23 · see citing works
Application of a Patient Derived Xenograft Model for Predicative Study of Uterine Fibroid Disease
Fritsch, M., Schmidt, N., Gröticke, I., Frisk, A.-L., Keator, C. S., Koch, M., & Slayden, O. D. (2015) · PLoS ONE · doi:10.1371/journal.pone.0142429 · Cited by 22 · see citing works
Drug Discovery and Development Technology in Transition
Emeritus, P. (2013) · Cited by 21 · see citing works
Otto, C., Schkoldow, J., Krahl, E., Fuchs, I., & Ulbrich, H. (2011) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2011.425 · Cited by 8 · see citing works
Rang, H. P., & Hill, R. (2013) · Drug Discovery and Development · doi:10.1016/b978-0-7020-4299-7.00005-6 · Cited by 1 · see citing works
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1 of the 66 references couldn’t be matched to a known paper.
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Dorning, A., Dhami, P., Panir, K., Hogg, C., Park, E., Ferguson, G. D., Hargrove, D. M., Karras, J. G., Horne, A. W., & Greaves, E. (2021) · Disease Models & Mechanisms · doi:10.1242/dmm.049070 · Cited by 45 · see citing works
Qi, Q., Liu, X., Zhang, Q., & Guo, S.-W. (2020) · Scientific Reports · doi:10.1038/s41598-020-57997-6 · Cited by 44 · see citing works
Self-citationBurla, L., Kalaitzopoulos, D. R., Metzler, J. M., Scheiner, D., & Imesch, P. (2021) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2021.05.040 · Cited by 36 · see citing works
Thurnherr, N., Burla, L., Metzler, J. M., File, B., & Imesch, P. (2023) · Human Reproduction · doi:10.1093/humrep/dead221 · Cited by 18 · see citing works
Bieske, L., Zinner, M., Dahlhausen, F., & Trübel, H. (2023) · Drug Discovery Today · doi:10.1016/j.drudis.2023.103734 · Cited by 15 · see citing works
D’Hooghe, T., Fassbender, A., O, D. F., & Vanhie, A. (2019) · Biology of Reproduction · doi:10.1093/biolre/ioz016 · Cited by 12 · see citing works
Burns, K. A., Peterse, D., Appleyard, C. B., Chandler, R. L., Guo, S., Pearson, A. M., Persoons, E., Anglesio, M. S., Rogers, M. S., Sharpe-Timms, K. L., et al. (2025) · Molecular Human Reproduction · doi:10.1093/molehr/gaaf021 · Cited by 9 · see citing works
Self-citationSaunders, P. T. K. (2020) · Advances in anatomy, embryology and cell biology · doi:10.1007/978-3-030-51856-1_6 · Cited by 7 · see citing works
Adenomyotic glands are highly related to endometrial glands
Maier, V., Höll, M., Dietze, R., Mecha, E. O., Omwandho, C. O. A., Tinneberg, H., Meinhold-Heerlein, I. M., & Konrad, L. (2019) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2019.11.007 · Cited by 5 · see citing works
Drug development for adenomyosis based on pathophysiology
Guo, S. (2025) · Journal of obstetrics and gynaecology research · doi:10.1111/jog.16322 · Cited by 4 · see citing works
Self-citationSanthamma, B., Chacon, J. A., Deemer, E. M., Stary, D., Hernandez, S. A., Subramani, R., Lakshmanaswamy, R., Nickisch, K. J., Batra, S., & Nair, H. B. B. (2026) · Cancer Letters · doi:10.1016/j.canlet.2026.218845 · Cited by 1 · see citing works
Peruzzo, C. D. S., Tiguman, G. M. B., & Aguiar, P. M. (2025) · Journal of Endometriosis and Pelvic Pain Disorders · doi:10.1177/22840265251340363
Exploring New Treatment Strategies for Endometriosis—Narrative Review
Błaszczak-Świątkiewicz, K., & Oettel, M. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27156750
- Authors
- Groothuis, P. G., & Guo, S.-W.
- Affiliations
- Synthon (Netherlands) (NL)
- Shanghai Medical College of Fudan University (CN)
- Corresponding author
- Groothuis, Patrick G.
- Venue
- Reproductive Sciences
- Published
- 2018-09
- Volume
- 25
- Issue
- 9
- Pages
- 1318-1329
- ISSN
- 1933-7191 (ISSN-L)
- 1933-7205
- OpenAlex
- W2810570322
- Cited by
- 13
- References
- 66
- Citations by year
- 2026: 2 · 2025: 3 · 2023: 2 · 2021: 2 · 2020: 2 · 2019: 2
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Reproductive Sciences (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Social Sciences › Economics, Econometrics and Finance › Economics and Econometrics › Pharmaceutical Economics and Policy
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmaceutical industry and healthcare
- Keywords
- endometriosis, adenomyosis, drug development, pharmaceutical industry, university-industry collaboration, intellectual property, therapeutic target, translational model, biomarkers, clinical trial pipeline
- MeSH terms
- Drug Industry, Endometriosis, Female, Humans, Research, Adenomyosis
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