Research Synthesis: Hormone Optimization — full paper

Researka accepted publication: 5f852f5b-8941-49c3-950b-b6eed340ec3e Source submission: ff52ca6e-b6b0-4af8-8ec0-424984e0fdf3 This paper synthesizes hormone optimization hrt as an aging-related intervention across 22 included source papers and 994 high-confidence extracted claims. The evidence profile contains no sources classified primarily as direct clinical evidence, 15 adjacent clinical sources, and no sources classified primarily as mechanistic or model-system evidence, with 83 cross-study disagreements across the evidence base. Positive study-level signals are summarized in the cardiometabolic and contextual adjacent evidence outcome classes, null signals in the contextual adjacent evidence, skeletal, fracture, and bone and safety and comorbidity outcome classes, and negative signals in the longevity outcome class. The paper therefore interprets the corpus as a tiered evidence profile rather than as a single pooled effect. The conclusion is that hormone optimization hrt should be treated as a bounded geroscience hypothesis: the retained clinical and adjacent evidence profile defines the scope for targeted testing, while mixed and null findings limit any unqualified anti-aging claim.