Why ED Medications Sometimes Fall Short

Viagra (sildenafil) and Cialis (tadalafil) are PDE5 inhibitors. They amplify the nitric oxide signalling pathway that relaxes smooth muscle in the penis so blood can flow in. That pathway depends on adequate testosterone to function.

Testosterone drives production of nitric oxide synthase, the enzyme that starts the erection cascade. In men with low testosterone (total T below 10 nmol/L or free T below 180 pmol/L), the nitric oxide system is blunted. PDE5 inhibitors can only boost a signal that already exists. They can't create one from scratch.

The Evidence for Combination Therapy

Several studies have investigated what happens when testosterone replacement therapy (TRT) is added to PDE5 inhibitors in men who did not respond to ED medications alone:

• A 2005 randomized controlled trial by Shabsigh et al. found that men with low testosterone who failed sildenafil alone showed significant improvement in erectile function scores when testosterone gel was added. International Index of Erectile Function (IIEF) scores improved by a mean of 4.4 points in the combination group, versus no improvement with sildenafil alone.
• A meta-analysis by Isidori et al. (2005) across 17 trials confirmed that testosterone therapy improves erectile function, with the strongest effects in men with the lowest baseline testosterone.
• A 2012 study by Spitzer et al. showed that testosterone supplementation in hypogonadal men improved response to PDE5 inhibitors across erection quality, orgasm, and overall satisfaction.

The benefit is strongest in men with confirmed hypogonadism (clinically low testosterone with symptoms). If your testosterone is already in the normal range, adding TRT is unlikely to help.

Who Should Consider Testing?

Consider checking your testosterone levels if you:

• Have tried Viagra or Cialis at the maximum recommended dose without adequate results
• Have other symptoms of low testosterone: fatigue, reduced muscle mass, low libido, mood changes, or increased body fat
• Are over 40. Testosterone drops roughly 1-2% per year after age 30.
• Use anabolic steroids or have in the past. Exogenous steroids suppress natural testosterone production.

A simple blood test measuring total testosterone and free testosterone can identify whether low T is contributing to your ED. Test in the morning, before 10 AM, when testosterone peaks.

Important Considerations

• TRT is not for everyone. Testosterone therapy can suppress sperm production. Men planning to conceive should ask their provider about alternatives like clomiphene citrate.
• Monitoring is required. TRT means regular blood work to track testosterone, hematocrit (red blood cell concentration), PSA (prostate-specific antigen), and liver function.
• Lifestyle factors matter. Sleep, exercise, stress management, and a healthy weight all influence testosterone and may improve ED on their own.

Next Steps

If you've tried ED medication without success, checking your testosterone is a logical next step. TeleTest offers convenient online testosterone testing. Complete a 5-minute intake, get your requisition, and visit a lab near you. Results are usually back within days.

Disclaimer: This blog post is intended for educational purposes only and should not be taken as medical advice. Always consult your healthcare provider for personal health concerns.