Background: While cyclic mastalgia is a prevalent condition with varied treatment approaches, the effectiveness of phytoestrogens remains unclear. This systematic review aims to address this gap by evaluating the effectiveness of phytoestrogens in alleviating cyclic mastalgia based on the available evidence.
Materials and Methods: This systematic review and meta-analysis involved a comprehensive search of online databases (Scopus, Cochrane Central Register of Controlled Trials, EMBASE-Ovid, and Medline Complete) to identify randomized controlled trials and non-randomized prospective or retrospective clinical studies published up to August 2021. The search focused on studies evaluating the use of oral phytoestrogens for the treatment of cyclic mastalgia in women. Study selection was performed independently by two reviewers.
Results: This meta-analysis included eight studies. The results indicated that several interventions, including isoflavones, Nigella sativa, cinnamon chamomile tea, Vitex agnus-castus, and flax seeds, were associated with reduced mastalgia pain. Specifically, phytoestrogens (SMD: -1.40; 95% CI: -1.93 to -0.89), flaxseed (SMD: -1.48; 95% CI: -2.46 to -0.512), and Vitex agnus-castus (SMD: -1.78; 95% CI: -2.88 to -0.68; p < 0.001) demonstrated significant effectiveness in reducing the severity of cyclic mastalgia. However, the heterogeneity across all studies was high, ranging from moderate to substantial. Further, Nigella sativa, chamomile, red clover, and cinnamon were also found to significantly reduce the severity of cyclic mastalgia. 
Conclusion: While phytoestrogens like Isoflavones, Nigella sativa, Cinnamon Chamomile tea, Vitagnus, and Flax seeds show promise for relieving cyclic mastalgia, with Flaxseed and Vitex agnus-castus standing out, the evidence remains inconclusive due to variations and limitations in existing studies, highlighting the need for more research to confirm these benefits and guide optimal use.