Sex Differences in Stress Response: Classical Mechanisms and Beyond

Abstract

Neuropsychiatric disorders, which are associated with stress hormone dysregulation, occur at different rates in men and women. Moreover, nowadays, preclinical and clinical evidence demon- strates that sex and gender can lead to differences in stress responses that predispose males and females to different expressions of similar pathologies. In this curated review, we focus on what is known about sex differences in classic mechanisms of stress response, such as glucocorticoid hor- mones and corticotrophin-releasing factor (CRF), which are components of the hypothalamic- pituitary-adrenal (HPA) axis. Then, we present sex differences in neurotransmitter levels, such as ser- otonin, dopamine, glutamate and GABA, as well as indices of neurodegeneration, such as amyloid β and Tau. Gonadal hormone effects, such as estrogens and testosterone, are also discussed throughout the review. We also review in detail preclinical data investigating sex differences caused by recently- recognized regulators of stress and disease, such as the immune system, genetic and epigenetic mech- anisms, as well neurosteroids. Finally, we discuss how understanding sex differences in stress re- sponses, as well as in pharmacology, can be leveraged into novel, more efficacious therapeutics for all. Based on the supporting evidence, it is obvious that incorporating sex as a biological variable into preclinical research is imperative for the understanding and treatment of stress-related neuropsychiat- ric disorders, such as depression, anxiety and Alzheimer’s disease.

Pre-exercise cryotherapy reduces myoglobin and creatine kinase levels after eccentric muscle stress in young women

“…After WBC, women experience a greater decrease in average skin temperature compared to men, showing a negative correlation with body fat content ( Cuttell et al, 2017 ). Sex differences in cellular stress responses across endocrine, inflammatory, and redox pathways were observed ( Hodes et al, 2024 ). During adaptations to cold stress, men predominantly used strategies involving greater metabolic and shivering responses, while women demonstrated more effective insulating responses ( Solianik et al, 2014 ).…”

Thematic Selection: Stress and Stress-related Disorders Developmental and Neuroendocrine Aspects of Stress and Stress-related Disorders (Part 1)

“…Another four review articles focus on neuroendocrine aspects of stress and stress-related disorders. Hodes et al [ 25 ] provide an expert review on the very important and often neglected topic of gender-related differences in stress response mechanisms. The next two articles by Kulakova et al [ 26 ] and Colizzi et al [ 27 ] investigate the interaction between the HPA axis and social cognition as well as the endocannabinoid system in the examples of borderline personality disorder and psychosis, respectively.…”