Nerve Bundles and Deep Dyspareunia in Endometriosis

Abstract

The etiology of deep dyspareunia in endometriosis is unclear. Our objective was to determine whether nerve bundle density in the cul-de-sac/uterosacrals (zone II) is associated with deep dyspareunia in women with endometriosis. We conducted a blinded retrospective immunohistochemistry study (n = 58) at a tertiary referral center (2011-2013). Patients were stringently phenotyped into a study group and 2 control groups. The study group (tender endometriosis, n = 29) consisted of patients with deep dyspareunia, a tender zone II on examination, and an endometriosis lesion in zone II excised at surgery. Control group 1 (nontender endometriosis, n = 17) consisted of patients without deep dyspareunia, a nontender zone II on examination, and an endometriosis lesion in zone II excised at surgery. Control group 2 (tender nonendometriosis, n = 12) consisted of patients with deep dyspareunia, a tender zone II on examination, and a nonendometriosis lesion (eg, normal histology) in zone II excised at surgery. Protein gene product 9.5 (PGP9.5) immunohistochemistry was performed to identify nerve bundles (nerve fibers surrounded by perineurium) in the excised zone II lesion. PGP9.5 nerve bundle density (bundles/high powered field [HPF]) was then scored by a pathologist blinded to the group. We found a significant difference in PGP9.5 nerve bundle density between the 3 groups (analysis of variance, F2,55 = 6.39, P = .003). Mean PGP9.5 nerve bundle density was significantly higher in the study group (1.16 ± 0.56 bundles/HPF [±standard deviation]) compared to control group 1 (0.65 ± 0.36, Tukey test, P = .005) and control group 2 (0.72 ± 0.56, Tukey test, P = .044). This study provides evidence that neurogenesis in the cul-de-sac/uterosacrals may be an etiological factor for deep dyspareunia in endometriosis.

Anatomic Sites and Associated Clinical Factors for Deep Dyspareunia

“… 10 , 11 , 32 Tenderness of the cul-de-sac or uterosacral ligaments in endometriosis can arise from local neuroinflammation, 33 and in previous work we found that local nerve density correlates to deep dyspareunia severity in cul-de-sac or uterosacral endometriosis. 15 However, we also found that tenderness of the bladder, pelvic floor, and cervix and uterus was similarly present in women with and without endometriosis. This could account for why women with the same type and location of endometriosis can have wide variability in deep dyspareunia symptoms.…”

“…The sample size of this cohort is 548. Based on data from a previous retrospective dataset, 15 for the association between pelvic floor tenderness and severity of deep dyspareunia (with power = 0.99, α = 0.05, SD = 2.57, mean difference = 1.15, and incidence of pelvic floor tenderness = 33%), a sample size of 480 would be required. 30 …”

“…This was demonstrated in a study of women with cul-de-sac or uterosacral endometriosis: although cul-de-sac or uterosacral endometriosis increases the risk for deep dyspareunia, there was still wide variability in severity of deep dyspareunia reported by this population of women. 15 …”

The clinical anatomy of dyspareunia: A review

“…Endometriosis is a well‐known and key cause of deep dyspareunia in women of reproductive age (Howard et al, ; De Sousa et al, ; William et al, ; Yong et al, ). It can be defined as the presence of ectopic endometrial tissue outside of the uterus (De Sousa et al, ; Yong et al, ).…”

“…The prevalence of endometriosis in women of reproductive age is approximately 10%, with about half of these having deep dyspareunia (Yong et al, ). One study observed an increase density of nociceptive nerve bundles in the uterosacral ligaments of women with endometriosis proposing local neurogenesis as a cause of deep dyspareunia in patients with this disorder (William et al, ). However, the severity of the dyspareunia varies among women with laparoscopic evidence of endometriosis.…”