In a brief report of five normal men, a single 100 mg dose of sildenafil caused changes in the electroretinogram one hour later that were completely reversible at six hours. There were no changes in visual acuity, visual fields, or visual-evoked potentials. The long-term effects of sildenafil on visual function are unknown, but at this time monitoring of visual function does not appear to be necessary in the average man without retinal disease.

Other side effects
Among more than 3700 men with 1631 patientyears of exposure to sildenafil, most adverse events were mild to moderate and self-limited in duration. Among men taking 25 to 100 mg of sildenafil, 16 percent reported headache, 10 percent flushing, 7 percent dyspepsia, 4 percent nasal congestion, and 3 percent abnormal vision (described as a mild and transient color tinge or increased sensitivity to light). These rates were twice as high among men taking 100 mg of sildenafil as among men who were taking lower doses. The visual effect is probably related to inhibition of phosphodiesterase type 6 in the retina. No chronic visual impairment has been reported, and the incidence of visual side effects was similar in diabetic and nondiabetic men

Recommendations.

There are no clinical data on the safety and efficacy of sildenafil in the following groups:
• Men who have had a myocardial infarction, stroke, or life-threatening arrhythmia within the last six months
• Men with resting hypotension (<90/50 mmHg) or hypertension (>170/110 mmHg)
• Men with cardiac failure or coronary artery disease causing unstable angina
• Men with retinitis pigmentosa (a minority of whom have genetic disorders of retinal phosphodiesterase)

Men who are considering sildenafil therapy should be questioned regarding exercise tolerance; resumption of sexual activity after a prolonged period of inactivity is analogous to beginning a new exercise regimen. Sildenafil can be considered in men who are participating in aerobic activities that are roughly equivalent in energy expenditure to sex. If such activity cannot be documented, more formal testing of exercise tolerance (eg, exercise treadmill testing) should be considered.

Other Drugs

Tadalafil
The PDE5 inhibitor tadalafil exhibits high selectivity for PDE5.

For instance, as compared with its inhibitory capacity for PDE3, which influences cardiac contractility, tadalafil is about 20,000 to 44,000 times more selective for PDE5, while the selectivity of tadalafil for PDE5 over PDE6, which influences visual function, is nearly 800 times higher. This PDE5:PDE6 selectivity ratio is, in turn, more than 2 orders of magnitude higher than that reported for the PDE5 inhibitor sildenafil.

Further, the maximum serum tadalafil concentration is reached in 2 hours, but the geometric mean half-life of tadalafil is 17.5 hours. This pharmacologic profile is consistent with a broader clinical period of responsiveness.

In initial studies, a significant response to on-demand tadalafil (20 mg) occurred as early as 16 minutes after dosing, at which point nearly 1 of every 3 men achieved an erection judged by the patient to be adequate for vaginal penetration.

Within 30 minutes, more than 50% of men who received 20 mg tadalafil experienced a successful erection.

Furthermore, among responders, proportions of administrations that resulted in erections adequate for vaginal penetration within 30 minutes was 80%

As compared with placebo, on-demand therapy with tadalafil (10 mg to 20 mg) also enabled multiple successful intercourse attempts within 24 hours after dosing, and a dose-response effect was evident. Of men who received placebo or tadalafil at a dose of 10 mg or 20 mg, 12%, 38%, and 53% had erections that resulted in multiple successful sexual intercourse attempts (P </= .025 for each comparison vs placebo).

Although rates of dyspepsia (7.7%), back pain (4.6% to 7.7%), and myalgia (4.6% to 6.2%) and headache (5.4% to 0%) were higher on tadalafil treatment as compared with placebo (0%), there was no significant dose effect with regard to frequency, severity, or duration of AEs over the dose range of 10 mg to 20 mg. Dizziness was reported by 4.6% and 6.2% of patients receiving on-demand tadalafil doses of 10 mg and 20 mg, respectively, as compared with 3.0% of placebo controls.

Vardenafil
A selective, orally active PDE5 inhibitor with a mean tmax of 34 minutes, vardenafil has already undergone phase 2 clinical trials. Phase 2 data have also shown that vardenafil improved EF regardless of age, etiology, or severity of ED. Vardenafil may also benefit patients with ED and concurrent diabetes, as reported in a phase 3 trial.

No treatment-related SAEs were reported in the vardenafil phase 2b trials. Adverse events with frequencies in excess of 2% included flushing in 10% to 11% of vardenafil patients (vs < 1% on placebo). Dose-related trends in AE frequency were in evidence for headache, which was reported by as many as 15% of men on the 20-mg dose (vs 4% on placebo); and dyspepsia, with a maximum frequency of 7% in patients on the 20-mg dose (vs 0%). Vision disturbances, consisting of transient brightness or haziness, were noted in 4% of patients who received the 20-mg dose (vs 0% on placebo).

Compound 14.
Investigators have reported on a N-3-substituted imidazoquinazolinone, which they claim to be as potent and selective a PDE5 inhibitor as sildenafil in vitro; investigators reported that a functional assay of erectile function of compound 14 using rabbit corpus cavernosum tissue demonstrated enhanced potency and improvement in PDE5 selectivity compared with sildenafil.

T-1032.
Based on pelvic nerve stimulation studies using anesthetized dogs, researchers reported that T-1032, a PDE5 inhibitor, induced penile tumescence together with an increase in total NO metabolite levels. In vitro T-1032 augmented canine corpus cavernosum levels of cGMP and cAMP and produced dose-dependent smooth muscle relaxation.

Hormonal Therapy

Testosterone
Historically, androgens were touted as enhancing male sexual function. Testosterone is usually ineffective in treating erectile dysfunction in patients with normal serum testosterone concentrations and may exacerbate the problem by increasing a patient's sexual drive without improving his ability to perform. It may be given orally but is usually given as an intramuscular depot injection at intervals of 3-4 weeks, by daily patches, or by implants every six months. Great care should be exercised in patients with possible carcinoma of the prostate, and levels of prostate specific antigen (PSA) should be checked initially and every six months.

Testosterone Therapy for Older Men.
Testosterone therapy is not usually recommended for men with natural testosterone levels normal for their age group. Some experts believe it may be helpful for older men whose testosterone levels are deficient. It may improve bone density, increase muscle mass and weight and sexual interest. High, prolonged levels of testosterone may trigger prostate enlargement. Taking the drug finasteride appears to prevent such prostate enlargement. It should be strongly noted, however, that a recent study reported that finasteride does not protect against prostate cancer. In younger men, however, it worsens cholesterol levels. Although some studies indicate that taking testosterone does not increase the risk for prostate cancer, some experts remain concerned. Testosterone also lowers sperm count and can cause sleep apnea and polycythemia. Testosterone can also be prescribed in oral form and as a skin patch. Depending on the brand, patches may be applied to the skin of the scrotum every 24 hours or to the abdomen, back, thighs, or upper arm. In the latter case, two patches are required every 24 hours.

DHEAS.
Dehydroepiandrosterone sulfate (DHEAS) is a male hormone used in the production of testosterone; levels of this hormone fall as a man ages. In one small study, those who took DHEA for 16 weeks experienced some improvement in erectile dysfunction. It should be noted, however, that the long-term effects of this potent hormone are unknown, particularly on the risks for prostate cancer.

Bromocryptine
If excessive levels of the hormone prolactin are the cause of erectile dysfunction, the drug bromocriptine is helpful in lowering these levels. All attempts have to be made to find the cause for the raised prolactin levels before blindly starting bromocryptine therapy.

For a brief list of the causes of raised prolactin, click here