PDE5 inhibitors, the primary second-line therapy, have been the mainstay of ED treatment since the release of sildenafil (Viagra) in 1998, with the subsequent development of many others, and still more in the development stage. These medications do improve erectile quality for the majority of men, and they work by enhancing blood flow in the corpora cavernosa. These medications are generally used on demand and need to be taken about an hour before sexual intimacy. Tadalafil (Cialis) is longer acting and does come in a daily preparation potentially eliminating the ‘on-demand’ need. The daily dosing of tadalafil, 2.5–5 mg\day, has also been approved by the FDA for treatment of symptoms of BPH.41 PDE5 inhibitors are contraindicated in men taking nitrates, but otherwise PDE5 inhibitors are very safe and effective. When PDE5 inhibitors are coadministered with nitrates, pronounced systemic vasodilation and severe hypotension are possible. Many patients with ED are elderly and have the same risk factors as patients with CAD, so these drug combinations are commonly considered or encountered in clinical practice.42
An erection might last indefinitely if it weren’t for chemicals in the body called phosphodiesterases. They work at reversing the process trying to return the penis to being soft (i.e., flaccid). Usually there is a balance between the chemicals that result in an erection lasting for as long as it is needed, which allows the phosphodiesterases to do their job when they should and no sooner. You wouldn’t want an erection forever so it is a good thing that phosphodiesterases exist.
As blood flows into the penis, the corpora cavernosa swell, and this swelling compresses the veins (blood vessels that drain the blood out of the penis) against the tunica albuginea. Compression of the veins prevents blood from leaving the penis. This creates a hard erection. When the amount of cGMP decreases by the action of a chemical called phosphodiesterase type 5 (PDE5), the muscles in the penis tighten, and the blood flow into the penis decreases. With less blood coming into the penis, the veins are not compressed, allowing blood to drain out of the penis, and the erection goes down.
A system for inserting a pellet of alprostadil into the urethra is marketed as MUSE. The system uses a pre-filled applicator to deliver the pellet about an inch deep into the urethra at the tip of the penis. An erection will begin within 8 to 10 minutes and may last 30 to 60 minutes. The most common side effects of the preparation are aching in the penis, testicles, and area between the penis and rectum; warmth or burning sensation in the urethra; redness of the penis due to increased blood flow; and minor urethral bleeding or spotting.
The Prostate Cancer Prevention Trial was a landmark study by Thompson et al that prospectively assessed the time to developing CVD after the diagnosis of ED. There were 4247 men with no ED at study entry; 2420 developed incident ED (defined as the first report of ED of any grade) over 5 years. Those men that developed ED had a 1.45-fold higher probability of experiencing a CV event compared with men who did not develop ED.27
The mechanisms by which testosterone plays a role in erectile function are not completely understood. A study evaluating the effect of testosterone on erections in surgically castrated rabbits and control animals, in which the rabbits’ intracavernosal pressures were compared after cavernosal nerve stimulation, determined that castrated rabbits had much lower pressures after stimulation than control rabbits did.  Notably, the pressures increased when castrated rabbits received exogenous testosterone replacement.
Experts often treat psychologically based impotence using techniques that decrease anxiety associated with intercourse. The patient's partner can help apply the techniques, which include gradual development of intimacy and stimulation. Such techniques also can help relieve anxiety during treatment of physical impotence. If these simple behavioral methods at home are ineffective, a doctor may refer an individual to a sex counselor.
Willful and capricious – erections are funny things. When you're a young man, they seem to pop up at the most inappropriate moments (and the only thing between you and embarrassment is a carefully placed notebook). As you get older, however, they go the other way, and fail to appear on demand no matter how much you try. The sad thing is, my patients often equate this with a loss of masculinity.
Another study compared the response of surgically and medically castrated rabbits to vardenafil with that of control rabbits.  Castrated rabbits did not respond to vardenafil, whereas noncastrated rabbits did respond appropriately. This result suggests that a minimum amount of testosterone is necessary for PDE5 inhibitors to produce an erection.