Utility of exogenous melatonin in patients with breast cancer: A systematic review

Abstract

Fatigue, sleep disturbance, menopausal symptoms and impaired quality of life remain common and poorly controlled in breast cancer. Exogenous melatonin is an inexpensive, plausible supportive-care option that has not yet been systematically appraised. PubMed, Web of Science and the Cochrane Library were searched to May 15, 2026 for controlled studies of oral melatonin in patients with breast cancer or survivors (full-text English only). Screening, extraction, and Cochrane Risk of Bias 2 assessment were performed in duplicate; results were synthesized narratively (Synthesis Without Meta-analysis), stratified by daily dose, with post hoc sensitivity analyses. Eleven trials (849 participants) were included, spanning chemotherapy, radiotherapy, endocrine therapy, adjuvant follow-up and survivorship rehabilitation, at 1–20 mg/day for 10 days to three years. Sleep quality was the most reproducible benefit: both trials assessing it reported improvement at low risk of bias. Benefit was also reported for endocrine therapy-related symptoms, sexual function, quality of life and fatigue (3 of 5 trials), although a phase III radiotherapy trial was negative. No effect was seen on estradiol or insulin-like growth factor-axis biomarkers, body composition, or fitness. Six Iranian trials formed two clusters with overlapping authors; their removal left the fatigue and quality-of-life signals unsupported, but the sleep signal persisted. Oral melatonin is well tolerated (no grade 3/4 toxicity) and reproducibly improves sleep quality (moderate certainty), with less certain signals for endocrine therapy-related symptoms, quality of life, and fatigue (low certainty), justifying adequately powered, symptom-stratified trials. It is not supported as an antitumor therapy or a routine adjunct to exercise-based rehabilitation.