Sex and Gender Differences in Obesity: Biological, Sociocultural, and Clinical Perspectives.

Sex and gender differences significantly influence the prevalence of obesity, patterns of fat distribution, metabolic health outcomes, and responses to treatment. While women generally exhibit a higher overall prevalence of obesity, men are more susceptible to visceral fat accumulation, which increases the risk of cardiovascular disease (CVD), type 2 diabetes, and other obesity-related complications. This review examines the biological, genetic, and sociocultural foundations of sex-based differences in obesity. Estrogen plays a crucial role in regulating subcutaneous fat deposition and brown adipose tissue (BAT) activity in women, whereas men tend to accumulate more visceral fat and demonstrate reduced BAT thermogenic function. Genetic investigations, including genome-wide association studies, have identified sex-specific loci associated with central adiposity and fat metabolism. Additionally, emerging research indicates distinct gut microbiome profiles between obese men and women. Sociocultural and psychosocial factors, such as gender norms, body image perception, and healthcare-seeking behavior, also influence the risk and management of obesity. Women are more inclined to seek treatment and participate in structured weight-loss programs, while men often face under diagnosis due to stigma and limited healthcare access. These sex-based differences are evident in comorbidities, with women being more vulnerable to obesity-related cancers and mental health disorders, whereas men experience an earlier onset of CVD and diabetes. Despite these distinctions, most obesity interventions lack gender-specific considerations. This review underscores the necessity for sex- and gender-tailored strategies in the prevention, diagnosis, and treatment of obesity. A more nuanced understanding of these differences can improve clinical outcomes and inform policy development for equitable obesity care.