Can excessive use of exogenous testosterone (testosterone from outside the body) cause erectile dysfunction?

Exogenous Testosterone Does NOT Cause Erectile Dysfunction—It Treats It in Hypogonadal Men

Excessive exogenous testosterone does not cause erectile dysfunction; rather, testosterone therapy improves erectile function in men with hypogonadism, though supraphysiologic doses suppress spermatogenesis without directly causing ED. 1

Testosterone's Role in Erectile Function

Therapeutic Benefits in Hypogonadal Men

• Testosterone therapy relieves symptoms of erectile dysfunction in men with documented hypogonadism, as confirmed by the NCCN guidelines. 1
• The AUA guideline states that patients should be informed testosterone therapy may result in improvements in erectile function and low sex drive. 1
• A 2017 meta-analysis of 2,298 men demonstrated that testosterone therapy significantly improved erectile function by 2.31 points on the IIEF-EFD score compared to placebo (p<0.0001). 2
• Men with more severe hypogonadism (total testosterone <8 nmol/L) experienced greater improvements in erectile function (2.95 points) compared to those with milder deficiency. 2

Mechanism of Action

• Testosterone increases expression of nitric oxide synthase and phosphodiesterase type 5 (PDE5), both principal enzymes involved in the erectile process. 3
• Animal studies show that testosterone deficiency (castration) causes vascular smooth muscle cell atrophy, venous leakage, and increased collagen deposition—all reversible with testosterone replacement. 3
• Testosterone regulates the timing of the erectile process as a function of sexual desire, coordinating penile erection with sexual activity. 4

The Fertility Concern vs. Erectile Function

Critical Distinction

The major concern with exogenous testosterone is suppression of spermatogenesis and fertility—NOT erectile dysfunction. 1, 5

• The 2024 AUA/ASRM guideline explicitly states that exogenous testosterone should not be prescribed to males interested in current or future fertility because it causes azoospermia. 1, 5
• Exogenous testosterone provides negative feedback to the hypothalamus and pituitary, inhibiting gonadotropin (LH and FSH) secretion, which suppresses spermatogenesis. 1, 6
• The FDA label confirms that at large doses of exogenous androgens, spermatogenesis may be suppressed through feedback inhibition of pituitary FSH. 6

Recovery Timeline

• Although most azoospermic men recover sperm production after cessation of testosterone therapy, the time course may be prolonged—taking months or rarely years. 1, 5
• This fertility suppression is reversible but unpredictable in duration, making it critical to counsel patients appropriately. 1, 5

Clinical Algorithm for Testosterone Use

When Testosterone HELPS Erectile Dysfunction

1. Measure baseline testosterone levels in all men presenting with erectile dysfunction. 3
2. If hypogonadal (total testosterone <12 nmol/L or <8 nmol/L), testosterone therapy alone can restore erectile function in many cases. 3, 2
3. For men with low testosterone who fail PDE5 inhibitor monotherapy, adding testosterone converts over half into PDE5 responders. 3, 7
4. Combination therapy (testosterone plus PDE5 inhibitors) improves outcomes in hypogonadal men with more severe erectile dysfunction. 1, 7

Mandatory Pre-Treatment Screening

• Measure PSA in men over 40 years to exclude prostate cancer before starting testosterone. 1, 8
• Measure baseline hemoglobin/hematocrit; if Hct exceeds 50%, withhold therapy until etiology is investigated. 1, 8
• Explicitly counsel about fertility suppression if the patient may desire future children. 1, 5

Contraindications

• Absolute contraindication: Men currently trying to conceive or planning fertility in the near future. 1, 5
• Prostate cancer on active surveillance or androgen deprivation therapy. 1
• Hematocrit >54% warrants dose reduction or temporary discontinuation. 1, 8

Common Pitfalls to Avoid

Misunderstanding the "Too Much" Concern

• The question of "too much" testosterone relates to polycythemia, cardiovascular risk, and fertility suppression—not erectile dysfunction. 1, 6
• Supraphysiologic doses suppress the hypothalamic-pituitary-gonadal axis more profoundly, worsening fertility outcomes, but do not directly impair erectile mechanics. 1, 6
• The goal should be achieving testosterone levels in the middle tertile of the normal reference range, not supraphysiologic levels. 1, 8

Recognizing Bidirectional Relationship

• Interestingly, lack of sexual activity from erectile dysfunction is associated with reversible reduction in serum testosterone—sexual activity may increase testosterone levels. 9
• This creates a potential positive feedback loop where treating ED (by any means) can normalize testosterone, and normalizing testosterone can improve ED. 9

Metabolic Factors Reduce Response

• The magnitude of testosterone's effect on erectile function is lower in men with diabetes and obesity. 2
• These patients may require combination therapy with PDE5 inhibitors rather than testosterone monotherapy. 2

Monitoring During Treatment

• Recheck hematocrit periodically; intervene if >54%. 1, 8
• Monitor PSA using shared decision-making in accordance with prostate cancer screening guidelines. 1, 8
• Reassess erectile function at regular intervals to determine if additional interventions (PDE5 inhibitors, lifestyle modifications) are needed. 1