Metabolic Adaptation During Hormonal Transition

Published February 2026 | Educational Resource

Overview of Metabolic Adaptation

Metabolic adaptation refers to the body's physiological responses to changes in energy balance. These adaptive processes are evolutionarily conserved mechanisms that have preserved human survival across varied environmental conditions. During perimenopause, the body undergoes multiple metabolic adaptations in response to hormonal changes and the resulting shifts in energy expenditure and intake.

Adaptive Thermogenesis Reduction

One primary adaptation is reduction in adaptive thermogenesis—the energy expended in response to cold exposure, stress, and other environmental challenges. When energy intake declines or energy balance becomes negative, the body reduces non-essential energy expenditure as a conservation mechanism.

This adaptation involves:

• Reduced sympathetic nervous system activity
• Decreased uncoupling protein (UCP) expression in mitochondria
• Blunted metabolic response to cold exposure
• Reduced spontaneous activity and fidgeting

During perimenopause, when oestrogen (which supports sympathetic tone) is declining, these adaptive reductions are more pronounced.

Nutrient Sensing and mTOR Signalling

Nutrient-sensing pathways, particularly the mTOR (mechanistic target of rapamycin) pathway, regulate cellular energy metabolism. When nutrient availability decreases or energy status declines, mTOR signalling suppresses energy-expensive anabolic processes (protein synthesis, cell growth) and promotes catabolic processes (breakdown of stored energy).

During perimenopause, shifts in hormonal status and body composition create a milieu where the body may preferentially conserve energy, suppressing muscle protein synthesis more readily than in younger years.

Hormonal Adaptation Cascade

Hormonal changes during perimenopause trigger cascading metabolic adaptations:

Reduced Leptin Sensitivity

Leptin, produced by adipose tissue, signals energy sufficiency to the hypothalamus. During energy deficit, leptin levels drop, signalling the need to increase appetite and reduce expenditure. During perimenopause, leptin sensitivity may be altered by oestrogen decline, potentially reducing the suppressive effects of leptin on appetite.

Altered Growth Hormone and IGF-1

Growth hormone and IGF-1, which promote muscle maintenance and metabolic health, both decline with age and may be further affected by oestrogen reduction. These declines contribute to greater muscle loss and reduced anabolic capacity during midlife.

Thyroid Hormone Regulation

Oestrogen influences thyroid hormone metabolism and thyroid-stimulating hormone (TSH) regulation. During perimenopause, some women experience subtle changes in thyroid function, which can affect metabolic rate.

Metabolic Flexibility

Metabolic flexibility refers to the body's ability to switch between fuel sources (carbohydrates and fats). Research suggests that oestrogen promotes fat oxidation, particularly in muscle tissue. As oestrogen declines, metabolic flexibility may decrease, and the body becomes relatively more glucose-dependent.

This shift has implications for glucose control and energy regulation, as carbohydrate-dependent metabolism is less flexible in response to dietary and activity variations.

Inflammatory State and Adaptation

Oestrogen has anti-inflammatory effects. Declining oestrogen during perimenopause is associated with increased systemic inflammation, marked by elevated cytokines (IL-6, TNF-α) and C-reactive protein. Chronic low-grade inflammation itself affects metabolic regulation, promoting insulin resistance and altered energy balance set-point.

Energy Balance Set-Point Shifts

The body appears to regulate around an energy balance set-point—a defended level of body energy stores. During perimenopause, this set-point may shift upward, leading to preferential energy conservation and increased fat storage at lower energy intakes than in younger years. This shift reflects both the adaptive conservation mechanisms described above and possible oestrogen-mediated changes in hypothalamic energy regulation centres.

Individual Variation in Adaptation

Metabolic adaptation capacity varies substantially between individuals based on:

• Genetic factors influencing adaptive thermogenesis and hormone sensitivity
• Metabolic health status prior to perimenopause
• Physical fitness and muscle mass baseline
• Nutritional status and adequacy
• Stress and sleep quality

Clinical Significance

These metabolic adaptations are not pathological—they represent normal physiological responses to hormonal and age-related changes. However, when combined with stable or increased energy intake, these adaptations contribute to the energy imbalance that many midlife women experience.

Summary

Metabolic adaptation during perimenopause involves coordinated physiological responses to hormonal decline and energy balance changes. These include adaptive thermogenesis reduction, altered nutrient sensing, hormonal cascade effects, and changes in metabolic flexibility. Together, these adaptations reflect the body's evolved mechanisms for conserving energy during periods of physiological change.

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