Weight gain in midlife women: Understanding drivers and underlying mechanisms

Overweight and obesity patterns demonstrate a sexual dimorphism, with women being more prone to weight gain and overweight/obesity compared to men. As a result, weight gain is an important concern in women, particularly during midlife, when reproductive and physiological aging coincide, altering body composition. During this time, multiple factors contribute to the accumulation of body weight and adipose tissue, inducing a decrease in lean mass. These factors include hormonal changes -mainly hypoestrogenism-, genetic and exogenous factors, poor nutritional intake and physical inactivity, all of which might act synergistically to promote weight gain. Basal metabolic rate is also reduced due to aging, muscle mass loss, and the reduction in brown tissue activity. Impairments of the circadian system are associated with reduced endogenous melatonin secretion, altered sleep–wake cycles and metabolic inflexibility. Inflammaging, gut dysbiosis and physical inactivity further promote weight gain and the loss of lean skeletal muscle, leading to sarcopenic obesity.