The purpose of this investigational study was to assess the cardiovascular effects of melatonin replacement therapy in pinealectomized patients. This was a prospective open-label, single-arm proof-of-concept study The study comprised 11 patients aged 16.7 ± 1.7 years, who had undergone pinealectomy, experienced no tumor recurrence, and exhibited undetectable salivary melatonin levels. A 6-month melatonin regimen (0.3 mg daily) was administered. Ambulatory blood pressure monitoring was conducted at baseline, 3-month, and 6-month intervals. First of all, no hypertension was observed in pinealectomized patients. Over the course of the study, diastolic blood pressure progressively decreased, reaching statistical significance at 6 months. Pulse pressure exhibited a gradual increase, reaching statistical significance after 6 months. Short-term blood pressure variability increased significantly for both systolic and diastolic pressures. Morning systolic and diastolic blood pressure levels were significantly decreased by melatonin replacement therapy. Melatonin had no effect on the average heart rate or its variability. Melatonin-deficient pinealectomized patients were normotensive. Melatonin replacement in these patients led to reduced diastolic pressure, increased pulse pressure, and enhanced short-term blood pressure variability. These results are consistent with improved cardiovascular health. Furthermore, melatonin's temporal specificity suggests that it might enhance nighttime recovery, heightening reactivity during wakefulness. While melatonin is used as a dietary supplement for similar effects, caution is advised, and further research is needed to optimize its use in various health and disease contexts. Further, considering the study's limitations, more extensive research would strengthen these findings.

Keywords: cardiovascular; melatonin; pineal tumor; pinealectomy; therapeutics.

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