The effect of antioxidant supplementation on dysmenorrhea and endometriosis-associated painful symptoms: a systematic review and meta-analysis of randomized clinical trials

Abstract

This study aimed to review randomized controlled trials (RCTs) investigating the effects of dietary antioxidant supplements on the severity of endometriosis-related pain symptoms. The PubMed/Medline, Scopus, and Web of Science databases were searched until April 2022. Additionally, we manually searched the reference lists. Endpoints were summarized as standardized mean difference (SMD) with 95% confidence intervals (CIs) in a random-effects model. The I2 statistic was used to assess heterogeneity. Ten RCTs were included in this meta-analysis. Overall, 10 studies were related to dysmenorrhea, four to dyspareunia, and four to pelvic pain. Antioxidants significantly reduced dysmenorrhea (SMD, -0.48; 95% CI, -0.82 to -0.13; I2=75.14%). In a subgroup analysis, a significant reduction of dysmenorrhea was observed only in a subset of trials that administered vitamin D (SMD, -0.59; 95% CI, -1.13 to -0.06; I2=69.59%) and melatonin (SMD, -1.40; 95% CI, -2.47 to -0.32; I2=79.15%). Meta-analysis results also suggested that antioxidant supplementation significantly improved pelvic pain (SMD, -1.51; 95% CI, -2.74 to -0.29; I2=93.96%), although they seem not to have a significant beneficial impact on the severity of dyspareunia. Dietary antioxidant supplementation seems to beneficially impact the severity of endometriosis-related dysmenorrhea (with an emphasis on vitamin D and melatonin) and pelvic pain. However, due to the relatively small sample size and high heterogeneity, the findings should be interpreted cautiously, and the importance of further well-designed clinical studies cannot be overstated.

Keywords: Antioxidant; Dysmenorrhea; Dyspareunia; Endometriosis; Pelvic pain.

Fig. 1

The flow diagram of literature search and selection of studies. RCT, randomized controlled trials.

Fig. 2

The summary of risk of bias assessments.

Fig. 3

Forest plot of the effect of antioxidants on dysmenorrhea pain. N, number; SD, standard deviation; CI, confidence interval; FA, fatty acid.

Fig. 4

Subgroup forest plot of the effect of antioxidants on dysmenorrhea pain. N, number; SD, standard deviation; CI, confidence interval.

Fig. 5

Forest plot of the effect of antioxidants on dyspareunia pain. N, number; SD, standard deviation; CI, confidence interval.

Fig. 6

Forest plot of the effect of antioxidants on pelvic pain. N, number; SD, standard deviation; CI, confidence interval; REML, restricted maximum likelihood.