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Sleep disturbances and mood changes are common during the climacteric, often linked to hormonal fluctuations caused by reduced ovarian function. Evidence suggests that long-term melatonin administration may improve the quality of life in climacteric women. This study aimed to evaluate the effects of exogenous melatonin on climacteric symptoms, sleep quality, and reproductive hormones in women working fixed shifts. A randomized clinical trial was conducted with 46 nurses working fixed shifts at a hospital in São Paulo: morning (7:00-13:00, n = 16; intervention = 7, placebo = 9), afternoon (13:00-19:00, n = 15; intervention = 8, placebo = 7), and night (19:00-7:00, n = 15; intervention = 7, placebo = 8). Participants were randomly assigned to receive either 0.3 mg of melatonin or placebo. For night shift workers, melatonin was administered only on nights off, when they were sleeping at home; the same procedure was applied to morning and afternoon workers. Data collection included sociodemographic information, self-reported sleep quality, and menopausal symptoms. Blood samples were collected at home to measure luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, and progesterone before and after the intervention. A significant main effect of melatonin was observed, with a 15.8% reduction in climacteric symptoms compared with placebo (p = 0.01), independent of age or sleep duration, while no significant interaction with work shift was detected. Sleep quality improved by 35.33% on days off in the intervention group (p < 0.001), with morning shift workers showing a 32.46% improvement (p < 0.05). No significant changes were observed in reproductive hormone levels or total sleep duration. Exogenous melatonin effectively alleviates climacteric symptoms and improves sleep quality on days off, particularly among day-shift workers, without affecting reproductive hormone concentrations or total sleep duration. Trial Registration: RBR-10whktxm (UTN: U1111-1305-6221). Registered on 13 August 2025, retrospectively registered.