Key takeaways:
- Neuroproliferative vestibulodynia offers a potential treatment model for neuroproliferative dyspareunia, but targeted therapies will require first characterizing the upstream molecular drivers of nerve growth in endometriosis lesions.
- Serum nerve growth factor levels are a logical candidate biomarker for non-surgical identification of the neuroproliferative dyspareunia subtype, with intraoperative histologic identification remaining clinically useful for guiding future treatment decisions.
- The most immediate clinical application is in patient counseling: clinicians can now explain to patients with deep dyspareunia that differential nerve growth around lesions—driven by individual differences in cellular signaling and genetics—may be a contributing biological mechanism.
As the concept of neuroproliferative dyspareunia gains traction as a distinct subtype of endometriosis-associated pain, the most immediate clinical application may not be a new treatment—but a new conversation, according to Mahfuza Sreya, BMLSc, a PhD student at the University of British Columbia whose prospective registry findings were reported in a prior installment.1
With the core study data and the proposed subtype framework already covered, Sreya turned to what the findings mean for how clinicians counsel patients, how the field might develop diagnostic tools, and what therapeutic directions are worth pursuing.
On treatment, Sreya identified neuroproliferative vestibulodynia as a relevant model.
"It is a possibility that we can start to guide treatments based on what we see in neuroproliferative vestibulodynia, because we do see common overlap between mechanisms in both," she said. However, she emphasized that translating that parallel into targeted therapy for endometriosis-associated deep dyspareunia will first require a clearer understanding of the upstream molecular drivers of nerve growth in endometriosis lesions. Developing those targeted treatments, she said, is a future project.
The study's finding that nerve bundle density was associated specifically with deep dyspareunia—and not with superficial dyspareunia, dysmenorrhea, dyschezia, or chronic pelvic pain—raises the possibility of using nerve proliferation as a phenotyping tool. Sreya was careful not to overstate what can be concluded from the current cohort of approximately 170 patients.
"It may be too early to definitively say that there's no correlation between nerve growth and other pain types," she acknowledged, adding that co-existing central sensitization or inflammatory mechanisms may cloud phenotypic distinctions in individual patients. Definitive clinical phenotyping will depend on a deeper mechanistic understanding of nerve growth in endometriosis.
Future diagnostic tools may not require surgical tissue at all. Sreya identified serum NGF levels as a logical next biomarker investigation, given the established correlation between NGF expression and peripheral nerve bundle density in the tissue data.
"It would be interesting to see whether serum levels of nerve growth factor correlate to our findings," she said. Importantly, she noted that histologic identification of neuroproliferative dyspareunia at the time of surgery is not necessarily a disadvantage—particularly as drug targets for nerve proliferation are developed, knowing a patient's neuroproliferative status postoperatively could directly inform management of recurring pain.
For now, the most actionable implication is in counseling.
"The message we'd like to drive home is that there is a potential biological cause for deep dyspareunia in endometriosis," Sreya said. "We're hoping that clinicians can use these findings to counsel their patients that some may have more nerve growth around their endometriosis lesions than others due to differences in cellular signaling, genetics, and other factors that may be contributing to their experience."
Reference:
1. Sreya M, Williams C, Tucker DR, et al. Neuroproliferative dyspareunia in endometriosis: Validation of a novel subtype of endometriosis-associated sexual pain. Presented at: International Society for the Study of Women's Sexual Health Annual Meeting. February 12-15, 2026. Long Beach, California. Accessed April 21, 2026. Abstract 013
