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Melatonin Supplementation Improves Pain, Sleep Quality, and Total Plasma Antioxidant Capacity in Women with Fibrocystic Breast Disease: A Randomized, Double-blind, Placebo-controlled Trial

Published on Friday, 24 April 2026

Abstract

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.

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About this publication.

The Di Bella's Method: Use of Melatonin, Retinoids (40mg per day Beta-Carotene, 10mg per day ATRA and 10mg per day Axerophthol palmitate), Estrogen therapy (Anastrozole 1 mg tab per day), pseudo-Metronomic Chemotherapy Cyclophosphamide and/or Hydroxyurea, Somatostatin/Octreotide analogues and/or derivatives with Cabergoline and/or Bromocriptine (together with others chemical compounds) in Breast Cancer:

- A retrospective observational clinical study of triple negative breast cancer cases treated with Di Bella Method: A preliminary data;

- The Synergism of Somatostatin, Melatonin, Vitamins Prolactin and Estrogen Inhibitors Increased Survival, Objective Response and Performance Status In 297 Cases of Breast Cancer;

- Complete objective response, stable for 5 years, with the Di Bella Method, of multiple-metastatic carcinoma of the breast;

- Evaluation of the safety and efficacy of the first-line treatment with somatostatin combined with melatonin, retinoids, vitamin D3, and low doses of cyclophosphamide in 20 cases of breast cancer: a preliminary report;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 122 cases of breast cancer;

- Complete objective response to biological therapy of plurifocal breast carcinoma;

- The Di Bella Method (A Fixed Part - Melatonin tablets. From 30-40mg/day up to 200mg/day and more orally in patients with advanced stage of cancer disease and/or patients without respond to traditional treatments);

- Melatonin use in cancer patients have started in 1974, when melatonin prepared according to Prof. Di Bella’s formulation [...]. For 11 days was administered to the patient, admitted to the general medical ward at the Maggiore-Pizzardi Hospital in Bologna, very slowly (over approx. 8 hours) and intravenously administered 1000 mg of melatonin for 11 days. During the course of each day, the patient was intravenously administered 4 saline drips of 500 ml, each containing ten 25 mg bottles of freeze-dried melatonin, lasting 2 hours, totaling 1000 mg per day. No other drug of any kind was administered in order to ascertain the effect of the MLT without interference [...]. From Melatonin with adenosine solubilized in water and stabilized with glycine for oncological treatment - technical preparation, effectivity and clinical findings;

- About Melatonin - In vitro, review and in vivo publications;

- Publication: Melatonin anticancer effects: Review (from Di Bella's Foundation);

- Publication: Key aspects of melatonin physiology: 30 years of research (from Di Bella's Foundation);

- The Di Bella Method (A Fixed Part - Alpha tocopheryl acetate/Vitamin E, approximately 20 grams per day orally);

- Cancer and Vitamin E (analogues and/or derivatives) and cancer - In vitro, review and in vivo publications;

- Solution of retinoids in vitamin E in the Di Bella Method biological multitherapy;

- The Di Bella Method (A Fixed Part - All-Trans Retinoic Acid, Analogues and/or Derivatives - Approximately 60mg per day orally: 40mg per day Beta-Carotene/β-Carotene, 10mg per day ATRA and 10mg per day Axerophthol palmitate);

- All-Trans-Retinoic Acid (ATRA - analogues and/or derivatives) - In vitro, review and in vivo publications;

- The Di Bella Method (A Fixed Part - Somatostatin, Octreotide, Sandostatin LAR, analogues and/or derivatives since 1977);

- Somatostatin in oncology, the overlooked evidences - In vitro, review and in vivo publications;

- Publication, 2018 Jul: Over-Expression of GH/GHR in Breast Cancer and Oncosuppressor Role of Somatostatin as a Physiological Inhibitor (from Di Bella's Foundation);

- Publication, 2018 Sep: The over-expression of GH/GHR in tumour tissues with respect to healthy ones confirms its oncogenic role and the consequent oncosuppressor role of its physiological inhibitor, somatostatin: a review of the literature (from Di Bella's Foundation);