@misc{10481/107737,
year = {2025},
month = {10},
url = {https://hdl.handle.net/10481/107737},
abstract = {Frozen shoulder (FS), traditionally regarded as an idiopathic musculoskeletal disorder characterized by pain, stiffness, and capsular fibrosis, is increasingly recognized as the clinical
manifestation of systemic endocrine, metabolic, vascular, and immunological dysfunctions.
This narrative review reframes FS within a broader neuro–endocrine–immunometabolic
model, emphasizing the central role of estrogen deficiency, resistance, and receptor-level
disruption, together with their interactions with thyroid dysfunction, endothelial health,
and lifestyle-related low-grade inflammation (LGI). Evidence from epidemiological, clinical,
and mechanistic studies shows that estrogen signaling failure weakens anti-inflammatory,
antifibrotic, and antioxidant defenses, predisposing peri- and postmenopausal women to
more severe FS phenotypes. Thyroid dysfunction, particularly hypothyroidism, further
contributes to fibrosis and pain sensitization. Endothelial dysfunction—driven by poor
diet, advanced glycation end-products (AGEs), and oxidative stress—impairs vascular
integrity and promotes local microvascular inflammation. In parallel, lifestyle factors such
as sedentarism, circadian misalignment, psychosocial stress, and environmental exposures
sustain systemic LGI and hormonal resistance. Together, these interconnected mechanisms
suggest that FS is not merely a localized joint pathology but a systemic disorder requiring
integrative clinical strategies that combine orthopedic management with endocrine evaluation, metabolic monitoring, dietary interventions, circadian health, and stress regulation. In
addition, this review outlines specific clinical implications, highlighting how an integrative,
personalized approach that targets hormonal, metabolic, vascular, and lifestyle dimensions
may improve pain, function, and long-term prognosis in FS. This paradigm shift underscores the need for future research to focus on stratified patient profiling and interventional
trials targeting hormonal, vascular, and lifestyle axes to improve outcomes, particularly in
women who remain disproportionately affected by FS.},
publisher = {MDPI},
keywords = {Frozen shoulder},
keywords = {Lifestyle},
keywords = {Inflammation},
title = {Frozen Shoulder as a Systemic Immunometabolic Disorder: The Roles of Estrogen, Thyroid Dysfunction, Endothelial Health, Lifestyle, and Clinical Implications},
doi = {10.3390/jcm14207315},
author = {Navarro-Ledesma, Santiago},
}