Metabolic state shapes cortisol reactivity to acute stress: A systematic review and meta-analysis of metabolic and hormonal modulators

Kördel, M.; Meier, M.; Kühnel, A.; Kroemer, N. B.

doi:10.1101/2025.08.05.668684

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bioRxiv · 10.1101/2025.08.05.668684

Metabolic state shapes cortisol reactivity to acute stress: A systematic review and meta-analysis of metabolic and hormonal modulators

Kördel, M.·Meier, M.·Kühnel, A.·Kroemer, N. B.

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Abstract

Individual variability in cortisol stress responses is shaped by multiple physiological factors. Yet the interaction with metabolic and hormonal states remains poorly understood. Therefore, we conducted a systematic review and meta-analysis to examine how metabolic factors (particularly glucose) and sex hormone levels (progesterone and estradiol) influence cortisol reactivity to acute stress. We identified 21 studies (N = 1216 participants) and conducted random-effects meta-analyses for metabolic and hormonal states. Across studies, glucose administration was associated with a significant increase in cortisol responses to acute stress compared to fasting or non-glucose control conditions (d = 0.30, 95% CI = [0.05, 0.60], BF10 = 2.42, NNT = 10.63). In contrast, the effects of sex hormones on cortisol responses were smaller and more variable, with both progesterone and estradiol showing weak and inconsistent associations. Our results highlight a robust modulatory role of metabolic state, specifically glucose availability, on HPA axis reactivity, while evidence for sex hormone effects remains inconclusive. Future research should focus on better harmonization of designs concerning sex hormones and systematically examine interactions between metabolic and hormonal states to better explain sex differences in the prevalences of metabolic and stress-related disorders.

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Kördel, M., Meier, M., Kühnel, A., Kroemer, N. B.. 2025-08-06. Metabolic state shapes cortisol reactivity to acute stress: A systematic review and meta-analysis of metabolic and hormonal modulators. https://doi.org/10.1101/2025.08.05.668684

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