Hormonal Contributions to Metabolic Changes in Midlife
Thyroid Hormone and Metabolic Rate
Thyroid hormones (T3 and T4) exert direct regulatory effects on resting metabolic rate. These hormones increase mitochondrial oxidative capacity and influence protein synthesis rates. Cross-sectional population studies document age-related shifts in thyroid hormone concentrations and thyroid responsiveness in some cohorts, though substantial variation exists among individuals.
In euthyroid (hormonally normal) individuals without thyroid disease, age-related changes in thyroid function are generally modest. Clinically significant hypothyroidism—with dramatically reduced thyroid hormone activity—is not a normative component of healthy aging, though prevalence increases with age.
Sex Hormones and Body Composition in Women
In women, the transition from perimenopause to postmenopause involves dramatic reductions in oestrogen concentration. This hormonal shift correlates with accelerated fat accumulation, particularly central (abdominal) fat deposition, and accelerated muscle loss. Longitudinal studies of women across the menopause transition document increased resting metabolic rate decline during this period compared to premenopausal years.
The magnitude of metabolic change associated with menopause is modest—approximately 50 to 100 kcal per day—but measurable in population averages. Individual variation is substantial; some women experience marked metabolic decline during menopause, while others show minimal change.
Androgen Decline in Men
Men experience gradual reductions in testosterone across adulthood, declining approximately 1 percent per year on average after age 30. Testosterone influences muscle protein synthesis, fat distribution, and metabolic rate. Population studies show associations between lower testosterone levels and greater fat accumulation and muscle loss in midlife men.
However, the relationship is not deterministic; many men with modestly reduced testosterone maintain stable body composition and metabolic rate, while others show more pronounced changes. Longitudinal analysis suggests that testosterone decline contributes approximately 10 to 20 percent of the observed metabolic and body composition changes in aging men.
Growth Hormone and IGF-1 Signalling
Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) decline progressively with age and influence protein synthesis and muscle maintenance. Somatotroph cells in the pituitary gland show reduced responsiveness to stimulation with age, leading to lower GH secretion. Similarly, IGF-1 production decreases across midlife.
These hormonal changes correlate with accelerated sarcopenia and reduced anabolic signalling in muscle tissue, contributing to age-related metabolic decline. However, supplemental GH in healthy older adults shows modest effects on body composition and metabolic rate, suggesting that other factors beyond hormonal decline drive much of the metabolic aging process.
Cortisol and Metabolic Stress Response
Cortisol, the primary glucocorticoid hormone, influences metabolic rate and substrate utilization. Cross-sectional studies document age-related changes in cortisol secretion patterns and diurnal variation in cortisol concentrations. Chronic psychological stress and elevated cortisol exposure correlate with central fat accumulation and metabolic dysfunction in some populations.
However, absolute cortisol levels and metabolic effects appear relatively stable across healthy adult ageing in cross-sectional studies, suggesting that cortisol changes alone account for limited metabolic decline variance.
Insulin Sensitivity and Metabolic Health
Age-related changes in insulin sensitivity occur in many midlife populations, particularly those with increasing central adiposity. Reduced insulin sensitivity correlates with altered glucose metabolism and changes in energy substrate utilization. However, metabolic rate itself (energy expenditure at rest) appears relatively independent of insulin sensitivity in cross-sectional analyses, suggesting that insulin resistance does not directly reduce BMR.
Integrated Hormonal Context
Rather than single hormones driving metabolic decline, research suggests integrated hormonal changes across the lifespan interact with body composition and activity patterns. Multivariate statistical models indicate that hormonal changes account for approximately 10 to 20 percent of observed age-related metabolic decline, with fat-free mass changes explaining the majority of variance.