How do cortisol and testosterone levels affect each other?

Cortisol and Testosterone Relationship

Cortisol and testosterone have an inverse relationship, with high cortisol levels suppressing testosterone production, particularly affecting the nocturnal rise in testosterone levels. 1

Physiological Relationship

• Cortisol administration leads to suppression of plasma testosterone levels, particularly affecting the nocturnal rise in testosterone 1
• This suppression occurs without corresponding decreases in luteinizing hormone (LH) or follicle-stimulating hormone (FSH), suggesting a direct effect rather than through the hypothalamic-pituitary-gonadal axis 1
• During acute stress, both cortisol and testosterone may initially increase, but the relationship becomes negative during prolonged stress 2

Stress Response and Hormonal Interactions

• During acute stressors like social evaluation or physical challenges, both cortisol and testosterone can increase simultaneously 2
• Baseline testosterone levels are negatively associated with acute cortisol response during certain types of stress (e.g., field exercises) 2
• During prolonged stress, such as military training, morning testosterone levels decrease over time (first 12 weeks) before returning to baseline 2

Clinical Implications

• In patients with adrenal insufficiency requiring cortisol replacement, testosterone levels may be affected 3
• DHEA replacement may be considered in women with low libido and/or energy who are otherwise well-replaced with cortisol, as DHEA is a precursor to testosterone 3
• Patients with congenital adrenal hyperplasia show significant fluctuations in both cortisol and testosterone levels, with testosterone staying in normal range even in untreated patients 4

Behavioral and Psychological Effects

• According to the context-dependent dual-hormone hypothesis, testosterone and cortisol interact to influence stress perception 5
• Higher testosterone is associated with lower stress perception in individuals with low cortisol levels 5
• Higher cortisol is associated with lower stress perception in individuals with lower testosterone levels 5

Exercise and Physical Stress

• Physical exercise creates a significant negative relationship between cortisol and total testosterone 6
• Interestingly, a positive relationship develops between cortisol and free testosterone following exercise, possibly due to adrenal cortex contribution or disassociation from sex hormone binding globulin 6
• The relationships between cortisol and testosterone during and after exercise are associative rather than causal and moderate in strength 6

Clinical Management Considerations

• When treating patients with cortisol replacement therapy (e.g., hydrocortisone), clinicians should be aware of potential impacts on testosterone levels 3
• In patients with hypophysitis affecting both adrenal and gonadal axes, corticosteroid replacement should be initiated before testosterone replacement to avoid precipitating adrenal crisis 3
• Testosterone or estrogen therapy may be needed in patients with central adrenal insufficiency who don't have contraindications (e.g., prostate cancer, breast cancer, history of DVT) 3