Sex Hormones as Regulators of the Age‐ and Sex‐Dependent Benefits of Caloric Restriction: An Emerging Research Protocol of a Controlled Dietary Intervention (The GendAge Weight Loss Study)

With nearly two-thirds of the UK population living with overweight or obesity, there is an urgent necessity for evidence-based public health guidance to promote a healthy weight. Current weight management advice centres on lifestyle modification. However, existing dieting recommendations fail to consider sex or age. This is a surprising oversight, as it is well established that health outcomes vary significantly between men and women across the lifespan. Our preliminary work in mice and humans suggests young females are more resistant than males to calorie-restriction (CR)-induced fat loss and reductions in energy expenditure, and that this resistance diminishes in older, post-menopausal participants-implicating oestrogen as a possible modulator of CR response. Further, the menopause may have an impact on fat storage linked to changes in sex hormones. This article describes emerging research being done through a controlled feeding study in 75 younger and older men and women. This study will directly test whether CR's effects on fat mass, energy expenditure and glucose homeostasis are age- and sex-dependent, and whether HRT use in post-menopausal women restores a CR response more similar to that of younger women. Energy expenditure and body composition will be assessed using gold-standard techniques, including doubly labelled water, alongside blood and abdominal adipose tissue sampling to investigate underlying hormonal mechanisms. The findings of this new study will clarify whether dietary weight-management advice should be tailored by sex, age, or menopausal/HRT status, informing more precise, evidence-based obesity guidance and supporting women's health and healthy ageing.