How Sildenafil Citrate Works

Sildenafil citrate facilitates erections in men with psychogenic diabetic, vasculogenic, traumatic, and surgical causes of erectile dysfunction. It is not an “orgasm pill/* does not increase desire, and does not facilitate erection in the absence of psychological or tactile stimulation. Nevertheless, all these factors are interrelated; indirect effects are probably observed. Simplistically, erection is the process of sequestering blood within the penis to increase its size and rigidity. Tactile or psychological stimuli, or both, can initiate or sustain the process.

The blood is predominantly sequestered in the corpora cavernosa, two connected spongelike bodies in the penile shaft. The corpora cavernosa comprise a network of arteries, veins, nerves, smooth muscles, and sinuoids (i.e., the spaces that actually fill with blood). The tunica albuginea is a thick, fibrous bilaycr sheath that surrounds the corpora cavernosa. As the corpora cavernosa fill with blood, the tunica albuginea stretches to its capacity. The veins that drain the corpora cavernosa are compressed against and between the layers of the tunica albuginea, preventing outflow. The bulbocavernous muscles at the base of the penis contract, which raises the pressure above systemic blood pressure and results in a rigid penis.

The lining of the corpora cavernosa and some penile nerves produce nitric oxide (NO). The NO induces the production of cyclic guanosine monophosphate (cGMP), which specifically causes penile smooth muscle relaxation. In a process that is still not completely understood, smooth muscle relaxation leads to the trapping of blood in the corpora cavernosa. The NO also causes the arterioles (small arteries) to dilate, increasing the blood flow into the corpora cavernosa. The cGMP is degraded by phosphodiesterase type 5 (PDE5), an enzyme predominantly found in the penis. When the cGMP is degraded, the smooth muscle returns to its resting (contracted) state, the outflow of blood increases, and the erection re¬solves.

Sildenafil inhibits the action of PDE5, allowing smaller amounts of cGMP to produce an erection and for that erection to last longer. Similarly, less NO is needed to produce an equivalent amount of cGMP.

Sildenafil has been approved only for use in men; research on its effects in women is ongoing. Preliminary results are conflicting. Initial investigations reported that Sildenafil increased lubrication, genital sensation, ability to achieve orgasm, and sexual satisfaction among women with complaints of sexual dysfunction. Application of topical Sildenafil was reported to improve arousal, genital sensation, and ability to reach orgasm in a small sample of women with sexual dysfunction. Others, however, have found little evidence thus far that sildenafil is useful in the treatment of sexual dysfunction in women. Kaplan, Reis, Kohn. Ikeguchi, Laor, Те, and Martins, for example, concluded, “Our data do not support the use of sildenafil in treat¬ing postmenopausal women with sexual dysfunction.” Its effects and uses for women remain to be fully elucidated. In addition, sildenafil for women carries the same risks of misuse as for males.

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