Biological Sex Differences in Metabolism

Oct 16, 2023

Metabolism is the intricate network of biochemical processes that occur within living organisms to sustain life, and it exhibits fascinating differences between males and females. Emerging evidence highlights the critical role of sex in influencing metabolic processes, including energy expenditure, fat distribution, and nutrient utilization.

Understanding these sex differences in metabolism is crucial for personalized healthcare and optimizing interventions for various metabolic disorders.

Research has uncovered underlying mechanisms and shed light on the intricacies of sex-specific variations in metabolism.

Energy Expenditure

One of the prominent sex differences in metabolism is energy expenditure. Numerous studies have consistently demonstrated that men tend to have higher resting metabolic rates (RMR) compared to women. For instance, a comprehensive study conducted by Weinsier et al. in 2001 found that, on average, men had a 5-10% higher RMR than women, even after adjusting for lean body mass.

This discrepancy can be attributed to several factors, including differences in body composition, hormonal profiles, and characteristics of existing muscle mass. Testosterone, a predominantly male hormone, has been implicated in promoting higher muscle mass and consequently increasing RMR, and potentially increasing the energic demands of muscle with higher skeletal muscle protein synthesis, etc.

Fat Distribution

Another striking sex difference lies in fat distribution patterns. Men generally tend to accumulate fat in the abdominal region, a phenomenon referred to as android or visceral fat distribution. In contrast, women predominantly store fat in the hips and thighs, known as gynoid or subcutaneous fat distribution.

This disparity in fat distribution is believed to be hormonally regulated. Estrogen, the primary female sex hormone, is thought to promote the accumulation of fat in the gluteofemoral region. This hormone-driven change is lipogenesis and lipolysis serves an important evolutionary advantage for creating an energy surplus during pregnancy and lactation.

Higher testosterone and overall androgen levels in woman are typically associated with high central fat accumulation, adipocyte hyperplasia, and reduced insulin sensitivity. Optimal testosterone levels in men can minimize abdominal fat, but age-associated lower testosterone in men (and aromatization) is associated with higher visceral fat accumulation. Higher visceral fat in both sexes is considered metabolically detrimental and has been linked to an increased risk of cardiometabolic disorders, and higher risk of certain cancers.

Nutrient Utilization

Sex differences in metabolism extend to nutrient utilization and metabolic fuel preferences. Research suggests that women exhibit a greater reliance on fat oxidation during exercise compared to men, but these reasons for this remain largely unknown.

A study conducted by Tarnopolsky et al. in 2007 revealed that women oxidized a higher percentage of fat as an energy source during moderate-intensity exercise, whereas men relied more on glycolytically driven energy systems. This difference may be attributed to variations in hormone levels, muscle fiber type distribution, and enzyme activity involved in fat metabolism. For example, men are more likely to have a greater percentage of fast twitch glycolytic fibers (type-2B)

Additionally, studies have shown that women have a higher rate of fatty acid mobilization from adipose tissue, indicating a greater propensity to utilize stored fat during energy-demanding activities. This metabolic trait would help to preserve glycogen and glucose homeostasis for the brain during times of limited food and carbohydrate availability.

Hormonal Influences

Hormones play a vital role in orchestrating the sex differences observed in metabolism. Estrogen, progesterone, and testosterone exhibit distinct effects on metabolic processes.

Estrogen has been associated with enhanced insulin sensitivity and regulation of lipid metabolism, potentially contributing to the lower prevalence of metabolic disorders in premenopausal women. Estrogen also play a profound role in male hormone health and low levels of estrogen (<10pg/ml) can have negative effects of cardiometabolic health and cognitive function.

Progesterone, primarily produced during the menstrual cycle, may influence appetite and energy expenditure. Testosterone, on the other hand, is associated with increased muscle mass, higher energy expenditure, and anabolic effects on protein metabolism. Skeletal muscle protein synthesis is an energy-dependent process and thus post-exercise recovery is associated with high RMR.

Implications for Metabolic Disorders

Understanding sex differences in metabolism has significant implications for the prevention, diagnosis, and management of metabolic disorders. For example, obesity and type 2 diabetes exhibit distinct sex-specific patterns.

Men tend to develop central obesity and are more prone to insulin resistance, whereas women are more likely to develop peripheral obesity and have a higher risk of developing gestational diabetes. This is why longitudinally tracking and optimizing hormone levels through lifestyle changes, and if needed HRT, can have a profound effect on cardiometabolic health and body composition. Recognizing these sex-specific patterns can aid in tailoring interventions and treatment strategies to address the unique metabolic profiles of males and females.


Sex differences in metabolism are evident in energy expenditure, fat distribution, nutrient utilization, and hormonal influences. These variations have substantial implications for understanding the impact and management of metabolic disorders.

By recognizing and considering sex-specific differences, healthcare providers can develop personalized interventions, improve disease prevention strategies, and optimize treatment outcomes.

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