Diogo Pinto da Costa Viana, Thiago Bracks Oliveira
Eurasian Journal of Medicine and Oncology - 2026;10(1):60-71
Obesity remains widely treated as a sex-neutral condition, despite decades of evidence revealing distinct sex-specific metabolic and behavioral trajectories between men and women. This neutrality perpetuates unequal outcomes: Men often achieve faster initial weight loss, whereas women face greater early resistance but display superior long-term resilience. The question persists: Why do men and women respond differently to the same intervention? The answer lies not in a single mechanism, but in the complex interplay among body composition, hormonal and neuroendocrine regulation, adaptive thermogenesis, and sociocultural determinants. To address this gap, this review proposes an integrative four-axis model encompassing: (i) Body composition and fat distribution, (ii) hormonal and neuroendocrine control, (iii) energy efficiency and adaptive thermogenesis, and (iv) sociocultural determinants. Drawing on literature from the past 25 years, it synthesizes physiological and behavioral evidence to explain how biological sex and menopausal status influence weight-loss responses. The narrative approach bridges clinical and experimental findings to offer a conceptual framework capable of guiding personalized strategies in obesity care. By integrating metabolic, hormonal, and psychosocial domains, the proposed model underscores that obesity cannot be reduced to a mere caloric equation. Recognizing sex-based dimorphism is essential for improving equity, sustainability, and precision in treatment outcomes. This framework invites a paradigm shift, from calorie-centered to complexity-informed medicine, where management is tailored to the distinct physiological and social realities of men and women.
