Revista de Geopolítica · Oct 12, 2026
THE THEORETICAL MODULATION OF THE NLRP3 INFLAMMASOME BY 17Β-ESTRADIOL BASED GAHT IN CELLULAR AGING: A SCOPING REVIEW
By Magella AS, de Lima AMS, Ortiz SRM
This study aims to map and synthesize the available scientific literature on the impact of affirmative hormone therapy on the molecular regulation of the NLRP3 inflammasome and the progression of neuroimmunological inflammaging in aging transfeminine individuals. In this scenario, 17β-estradiol emerges as a master regulator of immunometabolic homeostasis. However, a profound translational gap exists in geroscience regarding the transfeminine population, unlike cisgender women experiencing menopause, trans women maintain continuous, exogenous estradiol levels through Gender-Affirming Hormone Therapy (GAHT) during the aging process. To map this dynamic, a scoping review was conducted guided by the JBI Institute guidelines and the PRISMA-ScR checklist, analyzing the biomedical literature published from 2013 onwards. The literature establishes that estrogen deprivation acts as the primary trigger for the assembly of the NLRP3 complex and microglial hyperreactivity. In contrast, the prolonged maintenance of estrogenic signaling promoted by GAHT acts as a true immunometabolic and epigenetic shield. By keeping hormone receptors actively engaged in silencing cellular alarm pathways (such as the NF-κB cascade), GAHT chronically represses NLRP3 activation, preventing the degradation of neuroplasticity and peripheral oxidative stress. This continuous modulation also serves as a crucial buffer against allostatic load and minority stress, preserving immunological resilience via epigenetic axes (e.g., miR-138-5p/SIRT1/HMGB1). 17β-estradiol-based GAHT transcends phenotypic congruence, establishing itself as a highly complex systemic physiological intervention. The uninterrupted suppression of NLRP3 radically alters the biological course of immunosenescence, providing trans women with the neurobiological and vascular foundation necessary for resilient and cognitively preserved aging.