Savvidis C, Thomopoulos C, Ilias I. Melatonin supplementation, hyperprolactinemia, and incident heart failure: A proposed prolactin-mediated pathway for cardiovascular risk. World J Exp Med 2026; 16(2): 120754 [DOI: 10.5493/wjem.v16.i2.120754]
Corresponding Author of This Article
Ioannis Ilias, MD, PhD, Director, Department of Endocrinology, Hippocration General Hospital, No. 63 Evrou Street, Athens 11527, Greece. iiliasmd@yahoo.com
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Endocrinology & Metabolism
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review-article
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Savvidis C, Thomopoulos C, Ilias I. Melatonin supplementation, hyperprolactinemia, and incident heart failure: A proposed prolactin-mediated pathway for cardiovascular risk. World J Exp Med 2026; 16(2): 120754 [DOI: 10.5493/wjem.v16.i2.120754]
World J Exp Med. Jun 20, 2026; 16(2): 120754 Published online Jun 20, 2026. doi: 10.5493/wjem.v16.i2.120754
Melatonin supplementation, hyperprolactinemia, and incident heart failure: A proposed prolactin-mediated pathway for cardiovascular risk
Christos Savvidis, Costas Thomopoulos, Ioannis Ilias
Christos Savvidis, Ioannis Ilias, Department of Endocrinology, Hippocration General Hospital, Athens 11527, Greece
Costas Thomopoulos, Department of Cardiology, Laikon General Hospital, Athens 11527, Greece
Author contributions: Savvidis C, Thomopoulos C, and Ilias I searched the literature, wrote the original draft, and wrote the final draft. All authors have read and approved the final manuscript.
AI contribution statement: Chat GPT was used for language polishing of the original draft.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Ioannis Ilias, MD, PhD, Director, Department of Endocrinology, Hippocration General Hospital, No. 63 Evrou Street, Athens 11527, Greece. iiliasmd@yahoo.com
Received: March 9, 2026 Revised: April 27, 2026 Accepted: June 10, 2026 Published online: June 20, 2026 Processing time: 97 Days and 21.1 Hours
Core Tip
Core Tip: A single unpublished conference abstract reported an association between ≥ 1 year of melatonin therapy in adults with insomnia and increased new-onset heart failure, heart failure hospitalization, and all-cause mortality. Confounding by indication (insomnia as an independent cardiovascular risk factor) has not been excluded. We propose a speculative, hypothesis-generating mechanistic pathway involving prolactin (PRL): Melatonin may modulate hypothalamic dopaminergic tone, potentially increasing PRL release. Whether chronic melatonin use sustains hyperprolactinemia is an unconfirmed critical knowledge gap. In susceptible cardiovascular milieus with elevated oxidative stress and systemic inflammation, if sustained hyperprolactinemia occurs, it might theoretically favor PRL cleavage to the cardiotoxic 16-kDa fragment implicated in peripartum cardiomyopathy. This hypothesis requires validation in prospective studies before clinical implications can be drawn.
