Scientifically Proven Ways to Make Sildenafil and Tadalafil Work Again, According to a Urologist
When erectile dysfunction (ED) medications like Sildenafil (Viagra) or Tadalafil (Cialis) don’t seem to work as expected, it can be frustrating and confusing. As a urologist and pelvic surgeon, I’ve seen many men struggle with this issue, and I want to share evidence-based strategies to help you regain stronger, firmer erections. Understanding why these medications sometimes fail and what you can do next is crucial for improving your sexual health and quality of life.
In this comprehensive guide, we’ll explore the causes of erectile dysfunction, the mechanisms behind common ED medications, and scientifically supported ways to enhance their effectiveness. Whether you’ve tried these medications multiple times without success or want to optimize their impact, this article will provide you with actionable insights backed by research.
Understanding Erectile Dysfunction and Its Causes
Erectile dysfunction is more common than many realize. It is expected to affect 300 million men worldwide by 2025. The clinical definition of ED is the persistent inability to attain and maintain an erection sufficient for sexual penetration. This condition can stem from various causes, but the most frequent culprit is vascular or blood flow issues.
Blood flow is essential for achieving an erection. When the blood vessels that supply the penis are not functioning properly, it can prevent the necessary blood accumulation needed to create and sustain an erection. This vascular problem is often linked to conditions like high blood pressure, high cholesterol, and diabetes. Therefore, addressing these underlying health issues is the cornerstone of treating ED effectively.
Other causes of ED include hormonal imbalances, nerve damage, psychological factors, and side effects of certain medications. It’s important to identify the root cause of your ED before moving forward with treatment options.
How Do Common ED Medications Work?
Most men with ED are prescribed medications known as PDE5 inhibitors. These include Sildenafil (Viagra), Tadalafil (Cialis), and Vardenafil (Levitra). These drugs work by inhibiting the enzyme phosphodiesterase type 5 (PDE5), which breaks down cyclic guanosine monophosphate (cGMP), a molecule critical in the erection process.
By blocking PDE5, these medications increase levels of cGMP, leading to relaxation of smooth muscle cells in the penis, allowing blood to flow in and create an erection. However, these medications don’t cure ED; they assist in achieving erections when sexual stimulation occurs.
It’s important to note that PDE5 inhibitors are effective in about 70 to 80% of men. This means that 20 to 30% of men may not experience the desired results, even after multiple attempts. Sometimes it takes six to eight tries before the medication shows full efficacy, but if you’re still struggling, it’s time to explore additional strategies.
What to Do When ED Medications Don’t Work
If you’ve optimized how you take your ED medication and still see no improvement, there are several scientifically supported approaches to enhance their effectiveness. Below are some of the best options supported by research and clinical experience.
1. Adding Daily Low-Dose Tadalafil to On-Demand Medication
One of the most effective combination strategies is to use a daily low dose of Tadalafil alongside your on-demand PDE5 inhibitor. This approach improves blood flow to the penis continuously, not just when you plan to have sex.
Here’s why this works: At baseline, the penis is in a low oxygen state. Normally, men have three to five nocturnal erections every night, which provide oxygen-rich blood to the penile tissue and help maintain its health and flexibility. In men with ED, these nighttime erections often disappear, which means the penile tissue is deprived of oxygen, leading to fibrosis (scar tissue) and reduced elasticity.
Taking a daily dose of Tadalafil increases blood flow throughout the day and night, helping to preserve tissue health and potentially restoring the ability to have stronger erections. This is especially useful for men with severe ED who are less likely to respond to on-demand medications alone.
Research supports this approach. One study involving 180 men with ED randomly assigned participants to either 5 mg of Tadalafil daily combined with 50 mg of Sildenafil on demand or 5 mg of Tadalafil daily alone for 12 weeks. Both groups showed improvements, but combination therapy was notably better for men with severe ED.
Another study focused on men who did not respond to on-demand medications. These men took 5 mg of Tadalafil daily along with either 10 mg or 20 mg of Tadalafil on demand for 12 weeks. The addition of the daily dose significantly improved erectile function compared to on-demand medication alone.
In a separate trial, men who failed on-demand therapy were given 20 mg of Tadalafil every other day or 20 mg of Vardenafil daily for two weeks. About 11% of men in the Tadalafil group and 18% in the Vardenafil group experienced improved erections, providing hope for those who previously had no success with these drugs.
2. Considering Testosterone Replacement Therapy (TRT)
Testosterone plays a key role in sexual function, and low testosterone levels (hypogonadism) can contribute to erectile dysfunction. For men with clinically low testosterone and symptoms such as reduced libido, fatigue, and erectile difficulties, testosterone replacement therapy can be considered alongside PDE5 inhibitors.
However, the evidence is mixed. Three randomized controlled trials showed no significant benefit of adding testosterone therapy to PDE5 inhibitors for erectile function in men with normal testosterone levels. These studies were limited by small sample sizes and did not focus exclusively on men with low testosterone.
Nonetheless, for men with true androgen deficiency, TRT may improve nocturnal erections, which helps maintain oxygenation of penile tissues and supports erectile health. It is estimated that only 3 to 6% of men have low testosterone as the sole cause of ED, so it’s crucial to get tested before starting therapy.
Bottom line: If you suspect low testosterone or have symptoms, get your levels checked. Adding testosterone therapy may provide a synergistic effect when combined with PDE5 inhibitors, especially if you have confirmed low testosterone.
3. Adding Antioxidants to Your Treatment
Oxidative stress plays a role in ED by generating reactive oxygen species (ROS) that degrade nitric oxide (NO), a critical molecule that initiates and maintains erections. Antioxidants help neutralize these ROS, preserving NO availability and improving erectile function.
Two antioxidants that have shown promise in clinical studies are L-Arginine and Propionyl-L-Carnitine.
- L-Arginine: This amino acid is a precursor to nitric oxide, essentially “fueling” the erection process. Supplementing with L-Arginine can increase NO production, improving blood flow to the penis.
- Propionyl-L-Carnitine: This antioxidant reduces oxidative stress and helps preserve nitric oxide, supporting healthy erections.
A systematic review of nine studies involving over 300 men found that combining L-Arginine (2.5 to 5 grams per day) or Propionyl-L-Carnitine (2 grams per day) with on-demand PDE5 inhibitors (like Sildenafil 50 mg) led to significant improvements in erectile function. However, many of these studies had short follow-up periods (8 to 12 weeks) and small sample sizes, so more research is needed.
If you’re struggling with ED, adding L-Arginine or its precursor L-Citrulline, or Propionyl-L-Carnitine to your regimen might be worth discussing with your healthcare provider.
4. Exploring Other Combination Therapies
Besides antioxidants, some studies have looked at combining PDE5 inhibitors with other medications such as:
- Metformin (commonly used for diabetes)
- Folic acid
- 5-alpha reductase inhibitors (like finasteride, used for prostate issues)
- Angiotensin type 1 receptor antagonists (used for high blood pressure)
While some small studies showed promising results, the evidence is limited and not strong enough to recommend these combinations widely.
One interesting finding relates to folic acid supplementation. Men with low baseline folic acid levels or a genetic condition called hyperhomocysteinemia (often linked to the MTHFR gene variant) may benefit more from folic acid. Symptoms of this condition include weakness, dizziness, and mouth sores. Testing folic acid levels or genetic markers might help identify men who could gain from this approach.
5. Adding Shockwave Therapy
Shockwave therapy is an innovative treatment that uses low-intensity sound waves targeted at the erectile tissue. These waves induce microscopic trauma, which triggers the body’s natural healing response, including the release of growth factors that promote new blood vessel formation (angiogenesis).
In my clinical practice, I have seen significant benefits from shockwave therapy for men who do not respond adequately to medications alone.
Supporting this, a randomized controlled trial in 2020 studied 922 men with ED following prostatectomy for prostate cancer. These men received daily Tadalafil and eight weekly sessions of shockwave therapy. The study demonstrated a significant improvement in erectile function compared to medication alone.
While shockwave therapy is not a cure-all and requires more research across diverse populations, it represents a promising option before considering more invasive treatments such as penile injections or vacuum erection devices.
Summary and Next Steps
Dealing with erectile dysfunction can be challenging, especially when first-line medications like Sildenafil and Tadalafil don’t provide the desired results. However, several scientifically supported strategies can help you regain function and confidence:
- Consider adding a daily low dose of Tadalafil to your on-demand medication to improve continuous blood flow and tissue health.
- Get your testosterone levels checked; if low, discuss testosterone replacement therapy as a potential adjunct to medications.
- Incorporate antioxidants such as L-Arginine or Propionyl-L-Carnitine to protect nitric oxide availability and improve erectile function.
- Explore other combination therapies cautiously, especially if you have underlying health conditions that could benefit from folic acid or other supplements.
- Look into shockwave therapy as a non-invasive option to promote penile tissue healing and vascular growth.
Most importantly, always work with a healthcare provider specializing in urology or sexual medicine to identify the underlying cause of your ED and tailor treatment to your specific needs. Addressing cardiovascular health, lifestyle factors, and psychological well-being is essential alongside medical therapies.
Taking Care of Your Sexual Health
Your sexual health is a vital part of your overall well-being. Don’t hesitate to seek expert advice and explore the full range of options available to you. With the right approach, many men who initially struggled with ED medications can achieve satisfying sexual function again.
Remember, you are worth it. Prioritize your health, stay informed, and keep the conversation open with your healthcare provider.
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