Brenda Sánchez-Ramírez

Women with endometriosis experience chronic cyclic pelvic pain (CCPP) or chronic persistent pelvic pain (CPPP), both of which may be incapacitating even after treatment. Emotional dysregulation in endometriosis impedes patient recovery. This study evaluated the relationships among emotional state, pain perception, and inflammatory biomarkers (IL-1β, IL-6, and TNF-α) in women with endometriosis presenting with CCPP or CPPP. An exploratory, observational, descriptive, cross-sectional, comparative with repeated sampling study was conducted with 52 women diagnosed with endometriosis and experiencing either CPPP or CCPP. Participants completed a psychometric battery including the State-Trait Anxiety Inventory (STAI), Beck Depression Inventory (BDI-II), Goldberg General Health Questionnaire (GHQ-30), Hospital Anxiety and Depression Scale (HADS), and Mini-Mental State Examination (MMSE). Pain perception was assessed using the Wong–Baker Pain Rating Scale (FACES). Saliva samples were collected at baseline, during stressor and recovery phases, and concentrations of IL-1β, IL-6, and TNF-α were determined by ELISA. Fifty-two women with endometriosis were included (CPPP: n = 33; CCPP: n = 19). No significant between group differences were observed in emotional state (HADS: p = 0.682; BDI: p = 0.842), anxiety (STAI-State: p = 0.086; STAI-Trait: p = 0.615), general distress (GHQ-30: p = 0.730), or pain intensity (FACES: p = 0.705). The prevalence of depressive symptoms did not differ between groups (CPPP: 69.7% vs. CCPP: 73.7%; χ² = 0.093, p = 0.760). Salivary cytokine levels (IL-1β, IL-6, TNF-α) were comparable between groups across all measurement conditions. Spearman correlations revealed uncorrected significance between TNF-α and emotional distress: basal TNF-α correlated inversely with HADS (ρ = −0.292, p = 0.031) and BDI (ρ = −0.278, p = 0.041); TNF-α under stress correlated with HADS (ρ = −0.329, p = 0.014) and GHQ-30 (ρ = −0.271, p = 0.046); and TNF-α during recovery correlated with GHQ-30 (ρ = −0.363, p = 0.006). These findings indicate that CPPP and CCPP were not associated with statistically significant differences in emotional states or salivary cytokine profiles at the group level. Exploratory pos hoc analyses suggested that pain pattern may moderate the association between TNF-α and psychological burden, particularly in the CCPP subgroup; however, these findings require confirmation in larger studies with prespecified analyses. Exploratory analyses suggested patterns between salivary inflammation and psychological burden; however, these findings should be interpreted cautiously because of the small subgroup size, multiple comparisons, and lack of a matched healthy control group.

Endometriosis affects an estimated 5–10% of women of reproductive age and presents with substantial clinical and biological heterogeneity. Recent clinical guidelines have shifted toward symptom-guided diagnosis supported by expert imaging, moving away from mandatory diagnostic laparoscopy and redefining the evidentiary standards for evaluating new diagnostic technologies. Advances across omics domains, including genomics, epigenomics, transcriptomics, proteomics, metabolomics, extracellular vesicle profiling, microbiome research, and multi-omics integration, have deepened understanding of lesion biology, immune dysregulation, metabolic alterations, and progesterone resistance. However, translation of these molecular insights into clinically actionable tools remains limited. Most candidate biomarkers remain at discovery or internal/developer-led validation stages, constrained by small sample sizes, heterogeneous analytical platforms, incomplete control of confounding variables, and limited independent multicenter validation. In this review, we apply a four-tier evidence-maturity framework, spanning discovery, internal or developer-led validation, independent external validation, and demonstrated clinical utility, to classify omics-based diagnostic, prognostic, and treatment-response applications in endometriosis. We also distinguish potential clinical roles, including triage, adjunctive testing, and replacement-test evaluation, each requiring different validation standards and performance thresholds. Salivary microRNA currently represents the most clinically advanced diagnostic omics candidate, but the available evidence remains developer-led and is best classified as advanced Tier 2/Tier 2+ rather than independent Tier 3 validation. Prognostic and treatment-response applications are less mature and remain discovery-stage because prospective patient-level longitudinal validation and biomarker-stratified treatment trials are lacking. Overall, no omics-derived biomarker has yet achieved independent Tier 3 validation or Tier 4 readiness for routine clinical implementation. At present, omics approaches should be regarded primarily as research and translational prioritization tools rather than determinants of routine clinical decision-making.

Endometriosis is a disorder characterized by the presence of endometrial tissue outside the uterus, leading to dyspareunia, chronic pelvic pain, dysuria, and infertility. The latter has been related to implantation failure associated with alterations in decidualization, a process regulated by sex hormones such as progesterone. Membrane progesterone receptor β (mPRβ) exhibits a lower expression in endometriotic tissues than in normal endometrial ones. However, the role of mPRβ in decidualization is unknown. This work aimed to investigate whether mPRβ plays a role in the decidualization of endometrial stromal cells (ESCs) derived from women with and without endometriosis. The mPR agonist OrgOD-2 induced the gene expression of key decidualization markers (insulin-like growth factor binding protein 1, prolactin, transcription factor heart and neural crest derivatives-expressed transcript 2, and fork-head transcription factor) in healthy ESCs, eutopic (uterine cavity), and ectopic (outside of the uterine cavity) ESCs from women with endometriosis. Notably, the expression of the decidualization markers was lower in endometriotic cells than in healthy endometrial ones. An siRNA mediated knockdown of mPRβ reduced the expression of decidualization-associated genes in ESCs treated with a decidualization stimuli, regardless of whether cells were derived from healthy women or those with endometriosis. Our data suggest that progesterone, through mPRβ activation, regulates the decidualization process in endometrial stromal cells from women with and without endometriosis.

Background and Objectives: Postoperative shoulder pain is a common issue after total laparoscopic hysterectomy (TLH). This study evaluated the impact of a shoulder movement routine on postoperative shoulder pain in women undergoing uncomplicated TLH. Materials and Methods: An open-label randomized clinical trial included women without prior shoulder pain undergoing TLH between 20 January and 20 March 2024. Participants were randomized into two groups: Group 1 (n = 36) received a shoulder movement routine, while Group 2 (control, n = 39) performed a hand movement routine. Shoulder pain was assessed using the visual analog scale (VAS) at 6 h, 24 h, and 7 days postoperatively. Results: Seventy-five women participated. No significant differences were found between the groups regarding demographic variables, surgery duration, or hospital stay. Shoulder pain scores (VAS) at three time points (6 h, 24 h, and 7 days) showed no significant differences between groups (p = 0.57, p = 0.69, and p = 0.91, respectively). Similarly, there were no significant differences in incisional or abdominal pain. Conclusions: The shoulder movement routine did not significantly reduce postoperative shoulder pain in women undergoing uncomplicated TLH.