Understanding PDE5 Inhibitors for Erectile Dysfunction: A Fresh Look at Penis Pills, Nasal Sprays & More
When it comes to treating erectile dysfunction (ED), PDE5 inhibitors—often colloquially called “penis pills”—remain one of the most popular options. In this brief guide, we review the basics of these medications and share some exciting updates from recent research that may help inform your treatment choices.
The Four Key PDE5 Inhibitors
The main medications in this group are:
Sildenafil (Viagra)
Tadalafil (Cialis)
Vardenafil (Levitra / Spontan)
Avanafil (Spedra)
While these drugs are typically available as oral tablets, recent developments have introduced a nasal spray formulation. For men seeking a faster onset of action or an alternative to swallowing a tablet, the nasal spray option may be worth discussing with your healthcare provider.
How Do PDE5 Inhibitors Work?
These medications require a degree of nerve function to trigger the natural release of nitric oxide—an essential chemical that helps relax the blood vessels in the penis. If nerve damage is significant, PDE5 inhibitors may not work, and alternative treatments like injections or penile implants might be necessary. Link to injection blog here
What’s New? Insights from the Latest Research
Safety and Cardiovascular Considerations
Recent consensus guidelines from the Princeton IV meeting highlight that, when used appropriately, PDE5 inhibitors are safe even for men with underlying cardiovascular disease. In fact, updated research suggests these drugs may even offer a mild cardioprotective effect by improving endothelial function and supporting overall vascular health. This is particularly important because ED can serve as an early marker for cardiovascular issues—meaning that your ED diagnosis might offer a valuable opportunity for early risk assessment and prevention.
Princeton IVconcsensus …insert reference
Managing Nonorganic ED
A study featured in the ISSM document has shed light on the management of nonorganic ED (often related to performance anxiety rather than underlying physical issues). The findings show that:
A majority of men respond well to an initial trial of maximum-dose PDE5 inhibitors—whether taken as oral tablets or via the new nasal spray option.
With consistent treatment—and sometimes a brief period using intracavernosal injections—many men regain enough erectile confidence to eventually wean off medication altogether.
Despite initial concerns, emerging evidence also confirms that PDE5 inhibitors are not linked to serious ocular events when used appropriately.
ISSM pde5i 23022025
Choosing the Right Treatment for You
No single option is ideal for everyone. Some men may find that oral PDE5 inhibitors (or the convenient nasal spray alternative) provide the spontaneity they desire, while others might benefit from injections or even implants, depending on their overall health and the underlying cause of their ED. Many couples start with injections and, as conditions improve (especially if illness or treatment was the cause), transition back to oral medications. Some continue with injections for many years without any issues.
Tips for Your Personal Journey:
Try Different Options: Your experience may differ from others—what works best for you might not be the “popular” choice.
Monitor Your Health: Since ED can be a marker for cardiovascular issues, it’s wise to have regular check-ups and discuss your ED with your doctor.
Consider Professional Advice: A tailored approach, including possible psychological support for nonorganic ED, may be key to long-term success.
In Summary
PDE5 inhibitors are a versatile and well‐studied treatment for ED. While each medication has its own pros and cons, recent guidelines affirm their safety—even in men with cardiovascular concerns—and highlight emerging evidence that they might even protect heart health. Whether you’re exploring your first treatment or revisiting your options after a while, an open, guided approach with your healthcare provider is essential.
Remember, the best treatment for ED is the one that suits your unique situation. Don’t be afraid to try different approaches—whether that means oral tablets, the innovative nasal spray, or even injections—to find your perfect match.
For more detailed information on ED treatments and the latest research, check out related blogs here.
Click here to purchase the Erectile Dysfunction Program.
Relevant The Penis Project Podcast Episodes
Episode 44 - Debunking the Mysteries of Erectile Dysfunction with “Melissa”
Podbean: Click here
Apple Podcasts: Click here
Spotify: Click here
Episode 46 - Nerve grafting to help with Erectile Dysfunction after Radical Prostatectomy with Urologist “Dr David Dangerfield”
Podbean: Click here
Apple Podcasts: Click here
Spotify: Click here
Episode 133 - Melissa’s Talk on Sexual Dysfunction
Podbean: Click here
Apple Podcasts: Click here
Spotify: Click here
Episode 156 - Help, my penis is stuck up! Priapism’s - the what, why and how.
Podbean: Click here
Apple Podcasts: Click here
Spotify: Click here
Episode 190 - Overcoming Hemochromatosis and Erectile Dysfunction
Podbean: Click here
Apple Podcasts: Click here
Spotify: Click here
Episode 192 - Up Your Nose and Up It Goes: Spontan Nasal Spray for Erectile Dysfunction
Podbean: Click here
Apple Podcasts: Click here
Spotify: Click here
References
Kloner, R. A., Burnett, A. L., Miner, M., Blaha, M. J., Ganz, P., Goldstein, I., Kim, N. N., Kohler, T., Lue, T., McVary, K. T., Mulhall, J. P., Parish, S. J., Sadeghi‐Nejad, H., Sadovsky, R., Sharlip, I. D., & Rosen, R. C. (2024). Princeton IV consensus guidelines: PDE5 inhibitors and cardiac health. The Journal of Sexual Medicine, 21(2), 90–116. https://doi.org/10.1093/jsxmed/qdad163
Jenkins, L. C., Hall, M., Deveci, S., Guhring, P., Parker, M., Nelson, C. J., & Mulhall, J. P. (2019). An evaluation of a clinical care pathway for the management of men with nonorganic erectile dysfunction. The Journal of Sexual Medicine. Advance online publication. https://doi.org/10.1016/j.jsxm.2019.07.013
European Association of Urology. (2025). EAU guidelines on sexual health: PDE5 inhibitors (Section 23). European Association of Urology.
Park, J., Agyemang, A., & Chow, M. S. S. (2019). Can currently available drugs for erectile dysfunction be reformulated to achieve rapid effect? Journal of Asian Association of Schools of Pharmacy, 8, 58–63.
ISSM ED Articles. (2025, 28 January). Exploring regenerative therapies for erectile dysfunction. ISSM ED Articles.
Hellstrom, W. J., Montague, D. K., Moncada, I., Carson, C., Minhas, S., Faria, G., & Krishnamurti, S. (2010). Implants, mechanical devices, and vascular surgery for erectile dysfunction. The Journal of Sexual Medicine, 7(1), 501–523. https://doi.org/10.1111/j.1743-6109.2009.01626.x
Rezaee, M. E., Ward, C. E., Brandes, E. R., Munarriz, R. M., & Gross, M. S. (2020). A review of economic evaluations of erectile dysfunction therapies. Sexual Medicine Reviews, 8(3), 497–503. https://doi.org/10.1016/j.sxmr.2019.06.001
