Do Low Testosterone and High Cortisol Frequently Coexist?
Chronic corticosteroid use is a recognized risk factor for low testosterone, but the two conditions do not frequently coexist in the general population—their co-occurrence is primarily seen in specific clinical contexts such as chronic steroid therapy, Cushing's syndrome, or certain stress-related states. 1
Evidence for the Association
Corticosteroid-Induced Hypogonadism
Chronic corticosteroid use is explicitly identified as a risk factor for testosterone deficiency, warranting testosterone measurement even in asymptomatic men. 1
Long-term systemic prednisolone therapy reduces testosterone levels by approximately 33% compared to controls (14.5 vs 21.7 nmol/L), confirming that exogenous corticosteroids suppress testosterone production. 2
Men with chronic conditions requiring corticosteroid therapy (COPD, inflammatory diseases, chronic infections) have high prevalence rates of hypogonadism, though this may be multifactorial. 3
Endogenous Cortisol-Testosterone Relationship
The relationship between endogenous cortisol and testosterone is context-dependent and generally weak. At rest, no significant correlation exists between circulating cortisol and testosterone levels (r < +0.01 for total testosterone). 4
Following exercise-induced stress, a modest negative correlation emerges between cortisol and total testosterone (r = -0.53), but this relationship is associative rather than causal and only moderate in strength. 4
In executive males studied for status attainment, testosterone's effects on hierarchical position were only evident in low-cortisol individuals, suggesting cortisol may modulate testosterone's biological effects rather than directly suppressing its production. 5
Clinical Contexts Where Co-occurrence is Relevant
Cushing's syndrome represents the primary endogenous condition where elevated cortisol and low testosterone coexist, requiring evaluation with morning cortisol, dexamethasone suppression testing, and 24-hour urinary free cortisol. 1, 6
Prevalence Considerations
The prevalence of low testosterone in men with erectile dysfunction ranges from 12.5% to 35%, but this is not specifically linked to elevated cortisol in most cases. 1
Hypogonadism prevalence in men aged ≥45 years presenting to primary care is estimated at 39%, but this is predominantly related to aging, obesity, metabolic syndrome, and chronic diseases rather than hypercortisolism. 7
Obesity-related hypogonadism occurs through increased aromatization of testosterone to estradiol in adipose tissue with subsequent negative feedback on LH secretion—a mechanism unrelated to cortisol elevation. 1
Clinical Implications
When evaluating a patient with suspected low testosterone, measure morning total testosterone (drawn 8-10 AM) on two separate occasions, with levels consistently <300 ng/dL confirming deficiency. 1
Screen for corticosteroid exposure (including high-dose inhaled steroids at 1500-2250 mcg/day, though these show less suppression than systemic therapy) as a reversible cause of hypogonadism. 1, 2
If clinical features suggest Cushing's syndrome (facial swelling, central obesity, striae, proximal muscle weakness), pursue cortisol evaluation with dexamethasone suppression testing and 24-hour urinary cortisol. 1, 6
Measure LH and FSH to distinguish primary testicular failure from secondary (hypothalamic-pituitary) hypogonadism, as chronic corticosteroid use typically causes secondary hypogonadism with low or inappropriately normal gonadotropins. 1