Erection physiology and ED

• The corpora cavernosa of the penis contains a network of smooth muscle cells, endothelial cells, and sinusoid cavities
• An erection begins when endothelial cells are stimulated, causing them to release nitric oxide, which relaxes smooth muscle cells
• Smooth muscle cell relaxation allows the sinusoids to dilate and fill with blood
• Engorged sinusoids compress veins, inhibiting blood flow out of the penis

While the actions above may seem straightforward, the formation of an erection is actually quite complex, relying on the interplay of psychologic, neurologic, endocrinologic, and vascular processes. Issues with one or a combination of these systems can cause ED. Risk factors for ED include the following: (1) Psychological - stress, trauma, guilt, relationship problems (2) Neurologic - neuropathy, prostatectomy, stroke, MS (3) Endocrinologic - low testosterone, diabetes, hypothyroidism (4) Vascular - advancing age, hypertension, obesity, smoking, atherosclerosis.

ED Treatment

ED is frustrating on many levels, but thankfully, there are effective treatments. Phosphodiesterase type 5 (PDE-5) inhibitors, first introduced in 1998 with the approval of Viagra, are highly effective at treating many forms of ED. Five PDE-5 inhibitors are now approved, and three have cheap generics. Another ED drug, alprostadil, is available as an injection and urethral suppository, but its use has fallen out of favor. A review of each drug is provided below.

• Sildenafil (Viagra®) - Viagra has the distinction of being the first PDE-5 inhibitor approved. It may be taken anywhere from 30 minutes to 4 hours before intercourse; after 4 hours, it may not be as effective in some people. It has a cheap generic, with thirty 100 mg tablets costing less than $20 at many pharmacies.


• Tadalafil (Cialis®) - Cialis has a half-life of 17.5 hours, making it the only PDE-5 inhibitor that is effective for an entire day. It can be taken once daily or as needed for ED, and the daily dosing is also approved to treat benign prostatic hyperplasia. A cheap generic is available, with thirty 10 mg tablets costing less than $20.


• Vardenafil (Levitra®, Staxyn®) - Vardenafil is available in two tablet forms, one that is swallowed (Levitra) and one that dissolves in the mouth (Staxyn). It is taken 60 minutes before intercourse and has a half-life of 5 hours, about the same as sildenafil. Levitra and Staxyn have generics, but they are more expensive than tadalafil and sildenafil, with 10 tablets of generic Levitra and 4 tablets of generic Staxyn both costing about $50.


• Avanafil (Stendra®) - Stendra has a quick onset of action and can be taken up to 15 minutes before intercourse; it has a half-life of 5 hours. It does not have a generic, and 6 tablets cost over $300.


• Alprostadil (Muse®, Caverject®) - Alprostadil works differently than the PDE-5 inhibitors, and it must be either injected into the penis (Caverject) or inserted into the urethra (Muse). There are no generic versions, and both drugs are very expensive.

Side effects - In general, PDE-5 inhibitors are well tolerated. Potential side effects include headache (7 - 21%), flushing (3 - 19%), nasal congestion (3 - 9%), and stomach upset (4 - 9%). Alprostadil side effects depend on the form used and can be significant.