AUTHOR=Campos Luciana Aparecida , Bueno Clarissa , Barcelos Isabella P. , Halpern Bruno , Brito Leandro C. , Amaral Fernanda G. , Baltatu Ovidiu Constantin , Cipolla-Neto José TITLE=Melatonin Therapy Improves Cardiac Autonomic Modulation in Pinealectomized Patients JOURNAL=Frontiers in Endocrinology VOLUME=Volume 11 - 2020 YEAR=2020 URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2020.00239 DOI=10.3389/fendo.2020.00239 ISSN=1664-2392 ABSTRACT=The purpose of this investigational study was to assess the effects of melatonin replacement therapy on cardiac autonomic activity in pinealectomized patients. This was an open-label, single-arm, single-center, proof-of-concept study consisting of a screening period, a 3-month treatment period with melatonin (3 mg/day), and a 6-month washout period. The cardiac autonomic function was determined through heart rate variability (HRV) measures during polysomnography. Pinealectomized patients (n=5) with confirmed absence of melatonin were included in this study. Melatonin treatment increased vagal-dominated HRV indices including RMSSD (root mean square of the R-R successive differences: 39.7 ms [95%CI 2.0 to 77.4], p=0.04), pNN50 (% of successive R-R intervals that differ by more than 50 ms: 17.1% [95%CI 9.1 to 25.1], p=0.003), HF-band power (absolute power of the high-frequency band: 1390 ms2 [95%CI 511.9 to 2267], p=0.01) and also sympathetic HRV indices like SDNN (standard deviation of R-R intervals: 57.6 ms [95%CI 15.2 to 100.0], p=0.02) and LF-band power (absolute power of the low-frequency band: 4592 ms2 [95%CI 895.6 to 8288], p=0.03). These HRV indices returned to pretreatment values when melatonin treatment was discontinued. The HRV entropy-based regularity parameters were not altered in this study, suggesting that there were no significant alterations of the REM-NREM ratios between the time stages of the study. These data show that 3 months of melatonin treatment may induce an improvement in cardiac autonomic modulation in melatonin non-proficient patients.