Efficacy of Zinc Supplementation in the Management of Primary Dysmenorrhea: A Systematic Review and Meta-Analysis

Abstract

Background/objectives: Primary dysmenorrhea (PD) is a common condition affecting up to 90% of menstruating women, which often results in significant pain without an underlying pathology. Zinc, recognized for its anti-inflammatory and antioxidant effects through inhibiting prostaglandin production and superoxide dismutase 1 (SOD1) upregulation, alleviates menstrual pain by preventing uterine spasms and enhancing microcirculation in the endometrium, suggesting its potential as an alternative treatment for primary dysmenorrhea. The goal of this systematic review and meta-analysis was to assess the efficacy and safety of zinc supplementation in reducing pain severity among women with PD and to explore the influence of dosage and treatment duration.

Methods: Following the PRISMA 2020 guidelines, we conducted an extensive search across databases such as PubMed, Embase, Cochrane Library, Web of Science, and Google Scholar, up to May 2024. Randomized controlled trials assessing the effects of zinc supplementation on pain severity in women with PD were included. Pain severity was evaluated with established tools, such as the Visual Analog Scale (VAS). Risk of bias was assessed using the Cochrane Risk of Bias 2 (RoB2) tool. Two reviewers independently performed the data extraction, and a random-effects model was used for meta-analysis. Meta-regressions were conducted to examine the influence of zinc dosage and treatment duration on pain reduction. Adverse events were also analyzed.

Results: Six RCTs involving 739 participants met the inclusion criteria. Zinc supplementation significantly reduced pain severity compared to placebo (Hedges's g = -1.541; 95% CI: -2.268 to -0.814; p < 0.001), representing a clinically meaningful reduction in pain. Meta-regression indicated that longer treatment durations (≥8 weeks) were associated with greater pain reduction (p = 0.003). While higher zinc doses provided additional pain relief, the incremental benefit per additional milligram was modest (regression coefficient = -0.02 per mg; p = 0.005). Adverse event rates did not differ significantly between the zinc and placebo groups (odds ratio = 2.54; 95% CI: 0.78 to 8.26; p = 0.122), suggesting good tolerability.

Conclusions: Zinc supplementation is an effective and well-tolerated option for reducing pain severity in women with primary dysmenorrhea. Doses as low as 7 mg/day of elemental zinc are sufficient to achieve significant pain relief, with longer durations (≥8 weeks) enhancing efficacy. The favorable safety profile and ease of use support the consideration of zinc supplementation as a practical approach to managing primary dysmenorrhea.

Keywords: anti-inflammatory; menstrual pain; meta-analysis; nutritional supplements; pain relief; primary dysmenorrhea; randomized controlled trials; women’s health; zinc supplementation.

Figure 1

PRISMA 2020 diagram summarizing the study selection process for this meta-analysis.

Figure 2

Quality assessment summary for studies included in the meta-analysis, evaluated using the Cochrane Risk of Bias 2 tool.

Figure 3

Forest plot showing the overall effect of zinc supplementation on pain severity using the longest follow-up data [12,13,23,24,25,26].

Figure 4

Forest plot for the subgroup analysis using the follow-up duration as the moderator, including one, two, and three months. The directions of association between zinc supplementation and pain scale assessment were consistent across all follow-up durations, with overlapping 95% confidence intervals (CIs), indicating similar trends in pain reduction over time despite varying levels of statistical significance and heterogeneity [12,13,23,24,25,26].

Figure 5

Meta-regression of Hedges’s g versus treatment duration (month). The coefficient was −0.452 with a p value < 0.001.

Figure 6

Meta-regression of Hedges’s g against daily dose (mg/day). Coefficient = −0.02; p = 0.005.

Figure 7

Sensitivity analysis using the one-study removal method. The primary outcome remained consistent after excluding each individual trial. Zinc supplementation consistently showed significant pain reduction [12,13,23,24,25,26].

Figure 8

Funnel plot of included studies displaying asymmetrical distribution, suggesting potential publication bias.

Figure 9

Forest plot of adverse event rates associated with treatment. No significant difference was observed between the two groups (p = 0.122) [12,13,23].