Hormonal Modulation in Chronic Coronary Syndrome: From Neurohormonal Activation to Endocrine Targets.

Background

Chronic coronary syndrome (CCS) has evolved from a stenosis-centered concept to a dynamic clinical entity in which obstructive and non-obstructive coronary disease, microvascular dysfunction, and vasomotor abnormalities coexist with complex neurohormonal and endocrine activation. However, CCS has rarely been examined through an integrated endocrine lens, and no unified hormonal-phenotype framework currently links neurohormonal, sex-hormone, thyroid, and cardiometabolic pathways across CCS presentations.

Objective

To synthesize contemporary evidence on how neurohormonal and endocrine pathways shape CCS phenotypes and to outline potential endocrine targets for phenotype-guided therapy. Methods for Synthesis of Data: We performed a structured literature appraisal in PubMed, Embase, the Cochrane Library, and ScienceDirect from inception to May 2026, using CCS/stable coronary artery disease and hormone-related search terms, and included comparative clinical studies in adults that evaluated neurohormonal or endocrine interventions with clinically relevant cardiovascular outcomes.

Results

From 851 records, 34 studies were retained for qualitative synthesis, encompassing randomized trials, observational cohort studies, systematic reviews, and consensus documents. These data support a central role for renin-angiotensin-aldosterone and sympathetic activation, counterregulatory natriuretic peptides, endothelin-1, sex and thyroid hormones, and adipose-derived mediators in modulating CCS phenotypes, symptoms, and residual risk. Hormone-targeting therapies-including RAAS blockade, beta-blockers, mineralocorticoid receptor antagonists, sex- and thyroid-hormone modulation, and cardiometabolic agents such as GLP-1 receptor agonists and SGLT2 inhibitors-show variable yet often significant impact on outcomes across specific CCS subsets.

Conclusions

CCS is best conceptualized as a state of coordinated neurohormonal and endocrine disturbance rather than a purely anatomical disease. A hormonal phenotype framework may support more biologically rational, individualized management and define a research agenda for phenotype-stratified trials in CCS. This review proposes a hormonal-phenotype framework that is conceptually novel compared with anatomy- or comorbidity-based CCS classifications and is intended to be hypothesis-generating rather than prescriptive, by highlighting specific knowledge gaps and potential endocrine targets for future phenotype-guided trials.