Objective: Fibrocystic breast disease (FBD) is a prevalent benign breast disorder primarily affecting women of reproductive age. Characterized by breast pain (mastalgia), cystic and solid breast lesions, and associated hormonal imbalances. Melatonin, a hormone produced by the pineal gland, exhibits potent antioxidant, anti-inflammatory, and has been shown to improve sleep quality and mental health in various clinical populations. These properties suggest that melatonin may be a promising therapeutic option for symptom management in women with FBD.

Methods: This randomized, double-blind, placebo-controlled trial enrolled 66 women aged 18-40 years with FBD, diagnosed according to American Cancer Society guidelines, at Beheshti Clinic, Kashan University of Medical Sciences. Participants were randomized to receive either melatonin (6 mg/day; n = 33) or placebo (n = 33) for 12 weeks. Primary outcomes included breast pain severity and high-sensitivity C-reactive protein (hs-CRP), while secondary outcomes assessed sleep quality, depression, anxiety, and biomarkers of oxidative stress and inflammation, including total antioxidant capacity (TAC), malondialdehyde (MDA).

Findings: After 12 weeks, melatonin supplementation resulted in a significant reduction in breast pain scores (P = 0.006) and improvement in sleep quality (P = 0.02) compared to placebo. Additionally, TAC was significantly increased in the melatonin group (P = 0.01). No significant differences were observed for depression, anxiety, serum hs-CRP, or MDA levels.

Conclusion: Twelve weeks of melatonin supplementation (6 mg/day) significantly alleviates breast pain, enhances sleep quality, and improves antioxidant status in women with FBD. These findings support the use of melatonin as a safe and effective adjunctive treatment for FBD symptom management.