However, men still have a higher risk of sepsis-related mortality due to their combined overall immune response and comorbidity burden, which includes obesity and type 2 diabetes (30, 31).Progesterone has been shown in animal and cell studies to downregulate oxidative stress, myeloperoxidase activity, and TNF-α/IL-6 in sepsis, indicating that it may have immunosuppressive inflammation and organ protection properties. Here, TNF is linked to obesity due to melanocortin 4 receptor deficiency.