Background: Severe dysmenorrhoea affects up to 30% of reproductive-age women (1). One of the most common causes of secondary dysmenorrhoea is adenomyosis. Pelvic imaging can now be used to diagnose adenomyosis with a high level of certainty (2). Whereas the general association of endometriosis and adenomyosis is well established (3), the complex clinical and molecular characteristics of patients with pelvic pain and adenomyosis is yet to be well defined.
Objective: To examine the presence of sonographic evidence of adenomyosis in a cohort of patients being surgically explored for endometriosis and to assess if there is an association between adenomyosis and endometriosis severity. Using gene expression analysis, we also aimed to determine if gene expression in eutopic endometrium differed in patients with and without adenomyosis.
Methods: Reproductive-age women who underwent laparoscopic surgery for investigation of pelvic pain were recruited between May 2012 and May 2016. Endometrial tissue, detailed patient questionnaires, pathology and surgical notes were collected for each participant. Sonographic data from tertiary ultrasounds performed up to 12 months before surgery was subsequently added (researchers blinded to surgical and pathological findings). Patients were divided to two groups according to presence or absence of sonographic evidence of adenomyosis (SEOA). Total RNA from endometrial tissue (n=59) was extracted and Illumina Human HT-12 Beadchips were performed to examine gene expression.
Results: 588 patients were recruited to the study, 234 patients (40%) had a tertiary pelvic scan and were included in this study. Average age of women was 30.6 years. 35% of patients were found to have SEOA. Patients with SEOA were 5.4 years older (p=0.02) and suffered period pain 2.5 years longer than patients without SEOA (p<0.001). Dyspareunia was also more prevalent in patients with SEOA (88% vs 77%, p=0.05). There was no significant difference in rates of endometriosis between groups, however, patients with SEOA were more likely to have stage 4 endometriosis (39% vs 15.1%, p<0.001). Patients with SEOA were also more likely to have other markers of severe endometriosis such as endometriomas and deep infiltrating endometriosis (p<0.001). No significant difference was observed in endometrial gene expression between adenomyosis cases and controls after adjusting for menstrual cycle phases.
Conclusion: Sonographic signs of adenomyosis are associated with severe dysmenorrhea and dyspareunia and can be used as a clinical marker to predict presence of severe endometriosis. Further research is needed to characterize uterine adenomyosis and to explore molecular pathways involved in its pathogenesis.