Thyroid Hormones in Prostate Cancer: A Systematic Review and Bibliometric Study

© 2025 by the Authors. Licensee Whioce Publishing, Singapore. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )

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Abstract

Prostate cancer (PCa) is a prevalent malignancy in men, traditionally linked to androgen receptor signaling. Emerging evidence suggests thyroid hormones (THs, particularly T3/T4) play a complex role in PCa biology. THs regulate gene transcription via nuclear receptors TRα/β, modulating proliferation, apoptosis, and AR signaling, while non-genomic pathways through integrin αvβ3 activate MAPK/PI3K–Akt signaling, driving metabolic reprogramming, migration, and angiogenesis. Local DIO enzymes fine-tune T3/T4 levels, with DIO2 enhancing proliferation and DIO3 creating a low-TH microenvironment to facilitate immune evasion. Epidemiological studies associate hyperthyroidism or low TSH with elevated PCa risk, whereas experimental models show inconsistent effects, reflecting regulation by hormone levels, receptor distribution, and tumor molecular features. Bibliometric analyses reveal a shift from epidemiological studies to molecular, immune, and metabolic mechanistic research, though clinical translation remains limited. This review synthesizes current knowledge on THs in PCa, highlighting mechanistic insights, evidence gaps, and future directions, aiming to inform early detection, stratification, and therapeutic strategies.

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