Low Testosterone Significantly Contributes to Erectile Dysfunction
Yes, low testosterone is a well-established contributor to erectile dysfunction, and testosterone levels should be routinely measured in all men presenting with ED. 1
The Evidence Linking Low Testosterone to ED
The relationship between testosterone deficiency and erectile dysfunction is supported by multiple lines of evidence:
Testosterone functions as a key central and peripheral modulator of erectile function, with animal studies demonstrating that castration causes vascular smooth muscle cell atrophy, venous leakage, and structural changes in penile tissue. 1, 2
Approximately 36% of men seeking consultation for sexual dysfunction have hypogonadism, with prevalence ranging from 12.5% to 36% across studies of men with ED. 1
Testosterone directly regulates the expression and activity of phosphodiesterase type-5 (PDE5) in penile tissue, explaining why some men fail to respond to PDE5 inhibitors when testosterone is low. 3, 2
Clinical Implications for Treatment
Hypogonadism is a potential cause of lack of response to PDE5 inhibitor therapy, and testosterone replacement therapy (TRT) improves response. 1
When to Suspect Low Testosterone:
- Decreased libido and decreased spontaneous erections are the primary symptoms suggesting hormonal dysfunction. 1
- Physical findings such as testicular atrophy or muscle atrophy support the diagnosis. 1
- Failure to respond to PDE5 inhibitors should prompt testosterone measurement. 1, 2
Guideline Recommendations Differ:
There is notable divergence in guideline recommendations regarding testosterone testing:
The Princeton III Consensus (2012) recommends measuring testosterone levels in all men with ED, based on accumulating evidence linking low testosterone to both ED and cardiovascular disease. 1
The American College of Physicians (2009) does not recommend for or against routine hormonal testing, citing insufficient evidence to determine net benefits and harms, and suggests individualizing decisions based on clinical presentation. 1
Given the more recent evidence and the potential mortality implications (low testosterone is associated with increased all-cause and cardiovascular mortality), the Princeton III approach of routine testosterone measurement is more defensible from a morbidity and mortality standpoint. 1
Treatment Outcomes
When testosterone deficiency is identified and treated:
TRT improves erectile function and response to PDE5 inhibitors, with evidence suggesting that a minimal testosterone level is required for complete PDE5 inhibitor efficacy. 1, 2
Combination therapy with testosterone and PDE5 inhibitors can convert over half of PDE5 inhibitor non-responders into responders in hypogonadal men. 4, 2
Expected improvements include enhanced sexual function and libido, though effects on other domains like energy and vitality are minimal. 5
Critical Diagnostic Thresholds
Testosterone levels below 300 ng/dL (10.4 nmol/L) generally define hypogonadism, though some guidelines use 275-350 ng/dL as the threshold. 1, 5
Morning measurements (8-10 AM) on two separate occasions are required to confirm the diagnosis due to diurnal variation and assay variability. 5
Free testosterone or bioavailable testosterone should be measured in conditions that alter sex hormone-binding globulin levels, such as obesity and aging. 1, 6
Common Pitfalls to Avoid
Never assume ED is purely vascular without checking testosterone, as approximately one-third of men with sexual dysfunction have hypogonadism. 1
Do not start testosterone therapy in men actively seeking fertility, as it suppresses spermatogenesis and causes azoospermia; gonadotropin therapy is mandatory instead. 5
Recognize that testosterone deficiency may be a marker of poor general health and cardiovascular risk rather than just a local penile problem, with multiple studies showing increased mortality in men with low testosterone. 1