Sci Rep. 2026 Jul 16. doi: 10.1038/s41598-026-62548-6. Online ahead of print.
ABSTRACT
Endometriosis is a chronic, estrogen-dependent inflammatory disease that causes debilitating pain and significantly impairs quality of life. Due to its anti-inflammatory and immunomodulatory properties, vitamin D has been proposed as a potential therapeutic agent, but clinical evidence remains inconsistent. This study aimed to evaluate the effect of vitamin D supplementation on pain symptoms and quality of life in women with endometriosis. This randomized, double-blind, placebo-controlled clinical trial was conducted on 66 women with symptomatic endometriosis and vitamin D levels below 30 ng/mL. Participants were randomly assigned to either the intervention group (n = 33), receiving 4000 IU of vitamin D every other day, or the control group (n = 33), receiving a matching placebo for eight weeks. Crucially, all participants in both groups continued their standard dienogest (Verogest) therapy. The primary outcomes were pain severity, assessed using the Visual Analogue Scale (VAS) and the ENDOPAIN-4D questionnaire, and quality of life as secondary outcome, assessed with the Endometriosis Health Profile-30 (EHP-30). Outcomes were measured at baseline and after the eight-week intervention. All 66 participants completed the trial. Despite baseline imbalances in socio-demographic characteristics (quantified via standardized mean differences), adjusting for these variables as covariates did not yield significant differences between groups. Regarding the ENDOPAIN-4D scores, for the “usual level of pain,” the post-intervention mean score was 38.8 (SD = 6.5) in the vitamin D group compared to 50.1 (SD = 7.4) in the placebo group (adjusted mean difference [AMD]: -11.3; 95% Confidence Interval [CI]: -26.2 to 3.5; P = 0.136). For the “worst level of pain,” the post-intervention mean score was 23.6 (SD = 3.1) in the vitamin D group and 25.6 (SD = 3.5) in the placebo group (AMD: -2.0; 95% CI: -9.0 to 4.9; P = 0.492). The adjusted mean post-intervention VAS score was 5.8 (SD = 0.3) in the vitamin D group versus 6.2 (SD = 0.4) in the placebo group (AMD: -0.3; 95% CI: -1.3 to 0.5; P = 0.113). No significant differences were observed in the ENDOPAIN-4D scores or in any of the five domains of the EHP-30 questionnaire (all P > 0.05). In women under hormonal suppression with dienogest, eight weeks of adjunctive vitamin D did not yield statistically or clinically significant improvements in pain or quality of life. These null findings likely reflect a “floor effect” from the baseline hormonal therapy and are limited by the lack of biochemical confirmation of repletion. These findings are specific to adjunctive use and may not reflect the potential of vitamin D as a monotherapy.Trial registration: Iranian Registry of Clinical Trials (IRCT) IRCT20120718010324N78. Date of first registration 2023-05-25. URL https//irct.behdasht.gov.ir/trial/68131.
PMID:42463771 | DOI:10.1038/s41598-026-62548-6
