Vitamin D deficiency and pain severity in endometriosis: a phenotype-based retrospective observational study

To evaluate the association between serum 25-hydroxyvitamin D [25(OH)D] levels and pain severity in women with surgically and histopathologically confirmed endometriosis, and to assess whether this association differs between ovarian endometrioma (OE) and deep infiltrating endometriosis (DIE) phenotypes.

This retrospective observational analytical study included 427 women with surgically confirmed endometriosis. Patients were classified according to dominant phenotype as OE (n=231) or DIE (n=196). Serum 25(OH)D levels were categorized as deficient (<20 ng/mL), insufficient (20-30 ng/mL), and sufficient (≥30 ng/mL). Pain severity-including dysmenorrhea, chronic pelvic pain, and dyspareunia-was assessed using the Visual Analog Scale (VAS). Multivariable linear regression analyses were performed to examine the association between vitamin D levels and pain scores, adjusting for age, body mass index, and seasonal variation.

Serum 25(OH)D levels were inversely associated with all pain parameters (p<0.001). Patients with vitamin D deficiency had higher median VAS scores compared to those with sufficient levels [7.0 (6.0-8.0) vs 4.0 (3.0-5.0), p<0.001]. In multivariable analyses, lower 25(OH)D levels remained significantly associated with higher pain severity (β = -0.28, p<0.001). A significant interaction between vitamin D levels and disease phenotype was observed (interaction p=0.004), suggesting that the association between lower vitamin D levels and higher pain scores was more pronounced in patients with the DIE phenotype compared to those with OE. A threshold value of 18.5 ng/mL demonstrated 74% sensitivity for identifying patients with severe pain (VAS ≥7).

Lower serum vitamin D levels are significantly associated with greater pain severity in women with endometriosis, with a stronger association observed in the DIE phenotype. However, given the retrospective and cross-sectional nature of the analysis, causality cannot be inferred. Prospective studies are needed to further clarify these associations and their potential clinical implications.