You’ve tried sildenafil or tadalafil. It helped some, but not enough. Or it worked great at first and the effect has diminished. Or you’ve tried all four PDE5 inhibitors and none produced satisfactory results. You’re not alone — PDE5 inhibitors don’t work adequately for approximately 30-35% of men, and the non-response rate is even higher in men with diabetes or severe vascular disease. Here’s what comes next.
Step 1: Rule Out Contributing Factors
Before escalating treatment, it’s worth ensuring the PDE5 inhibitor was given a fair trial. Common reasons for apparent treatment failure include: not waiting long enough for onset (sildenafil needs 30-60 minutes), taking the pill with a heavy meal (reduces absorption for sildenafil and vardenafil), not having adequate sexual stimulation (these drugs enhance erections, they don’t create them automatically), insufficient dosing (many men start at a low dose that could be safely increased), and underlying hormonal issues like low testosterone reducing libido and arousal.
A thorough telehealth evaluation can identify these factors before moving to more complex treatments.
Medication + Therapy Combination
For men whose ED has a psychological component — performance anxiety, relationship stress, depression — combining PDE5 inhibitors with psychotherapy or sex therapy produces significantly better outcomes than either approach alone. The medication provides the physical capability, while therapy addresses the mental and emotional factors. Online therapy makes this combination accessible without multiple in-person appointments.
Tadalafil + Testosterone (for Hypogonadal Men)
If blood work reveals low testosterone alongside ED, combining a PDE5 inhibitor with testosterone replacement therapy can be synergistic. Testosterone restores libido and arousal, while tadalafil ensures the vascular response is adequate. This combination has strong evidence in men with confirmed hypogonadism and is available through telehealth platforms that offer both TRT and ED treatment.
Key finding: PDE5 inhibitors don’t work adequately for approximately 30-35% of men. But treatment failure with one approach doesn’t mean treatment failure overall — multiple effective options exist.
Injection Therapy (Alprostadil)
Intracavernosal injection therapy — injecting medication directly into the base of the penis — sounds intimidating, but it’s the most effective pharmacological treatment for ED, with success rates exceeding 85%. The most common medication is alprostadil (brand name Caverject), which works through a completely different mechanism than PDE5 inhibitors.
The needle is very small (similar to an insulin needle), and most men report minimal discomfort after the first few uses. Injection therapy is particularly effective for men with severe vascular disease, post-prostatectomy ED, or neurological causes of ED. It can be prescribed through telehealth with proper education on self-injection technique.
Vacuum Erection Devices
Vacuum devices (penis pumps prescribed by a physician, not the novelty products) use negative pressure to draw blood into the penis, followed by a constriction ring to maintain the erection. They’re non-pharmacological, have no drug interactions, and work regardless of the underlying cause of ED. Many couples find that incorporating a VED into their routine becomes natural after a short adjustment period.
Emerging Options
Low-intensity shockwave therapy (LiSWT): Uses acoustic waves to stimulate angiogenesis (new blood vessel growth) in penile tissue. Some studies show promising results, though long-term data is still emerging. It’s not yet widely available through telehealth but is offered at specialty clinics.
Platelet-rich plasma (PRP): Similar to PRP for hair loss, this involves injecting concentrated growth factors into penile tissue. Evidence is still early-stage and insufficient for a strong recommendation, but clinical trials are underway.
Compare telehealth providers offering comprehensive ED treatment options — from first-line medication to advanced therapies.
Compare Providers →The Bottom Line
A PDE5 inhibitor not working well enough is not the end of the road — it’s the beginning of a more personalized treatment approach. The vast majority of men can achieve satisfactory erectile function through combination therapy, alternative medications, or devices. The key is working with a provider who doesn’t stop at “try this pill” but explores the full spectrum of options with you.