Hormone Replacement Therapy

As individuals age, there is a natural decline in the levels of various hormones and a change in the sensitivity of the hormone axis to feedback, which is related to some of the physical changes associated with aging (Lamberts et al., 1997) (van den Beld et al., 2018). This hormonal decline is linked to loss of muscle mass and bone mass and to low mood (Chahal & Drake, 2007) (van den Beld et al., 2018). Longevity medicine explores the potential of hormone replacement therapy and other interventions to mitigate these changes and improve healthspan, but the risk-benefit profile of these therapies requires careful consideration.

In men, testosterone levels decline with age, a phenomenon sometimes called andropause (Chahal & Drake, 2007) (Lamberts et al., 1997). Lower testosterone levels are associated with reduced muscle mass, increased fat deposition, decreased libido, and mood changes (Chahal & Drake, 2007) (Volpi et al., 2004). In women, menopause brings a decline in estrogen production (Chahal & Drake, 2007) (Davis et al., 2015). This hormonal shift is associated with symptoms such as hot flashes, night sweats, mood changes, and urogenital atrophy, as well as long-term effects like bone loss and a higher risk of cardiovascular disease (Chahal & Drake, 2007) (Davis et al., 2015). Growth hormone and insulin-like growth factor 1 levels also decline with age, contributing to reduced protein synthesis (Xing et al., 2023) (Chahal & Drake, 2007) (Lamberts et al., 1997).

Levels of dehydroepiandrosterone, a precursor to sex hormones, also decline with age, which may contribute to decreased immune function (Chahal & Drake, 2007) (Dharia & Parker, 2004). Evidence suggests that diurnal cortisol, a stress hormone, may increase with age, although cross-sectional studies limit the conclusions that can be drawn (Gaffey et al., 2016). Chronic elevation of cortisol, as in Cushing's syndrome, is linked to impaired cognitive function, muscle disease (myopathy), and impaired glucose metabolism (Pivonello et al., 2016).

However, the use of hormone replacement therapy in the context of age-related endocrine decline has drawbacks. The risk-benefit profile of these therapies requires careful consideration, as they may be associated with potential adverse effects (van den Beld et al., 2018); for example, in women, combined continuous hormone therapy probably increases the risk of breast cancer and may increase the risk of stroke and venous thromboembolism (Bofill Rodriguez et al., 2025).

The evidence suggests that a comprehensive approach, including exercise, nutrition, and other lifestyle interventions, may be more effective in maintaining muscle mass, bone health, and overall physical and cognitive function as individuals age (Siparsky et al., 2014) (Volpi et al., 2004).

The decline in hormone production and sensitivity with aging is a complex process that impacts various physiological systems, including metabolism, body composition, and cognitive function. While hormone replacement therapy may have a role in addressing some of these changes, a holistic approach incorporating lifestyle interventions is essential for promoting healthy aging and improving longevity.

Hormone replacement therapy has shown some promise in addressing the age-related decline in certain hormones, such as testosterone in men and estrogen in women.