Lifestyle Changes to Complement Medical Treatment

Each man completed the International Index

of Erectile Function at 0, 12, and

Metrics & Citations

The cause of erectile dysfunction was determined from the medical history, physical examination, and other diagnostic procedures, including a test involving the intracavernosal injection of a vasoactive drug (done in 31 percent of the men), a RigiScan test of nocturnal penile tumescence (26 percent), penile duplex ultrasonography (21 percent), and endocrine testing (21 percent). On the basis of these evaluations, the men were classified as having organic, psychogenic, or mixed erectile dysfunction. Of the 861 men studied, 605 (70 buy blue pill percent) were judged to have organic erectile dysfunction, 99 (11 percent) to have psychogenic erectile dysfunction, and 157 (18 percent) to have mixed erectile dysfunction. Men were excluded if they had penile anatomical defects, a primary diagnosis of another sexual disorder (e.g., premature ejaculation), spinal cord injury, any major psychiatric disorder not well controlled with treatment, poorly controlled diabetes mellitus, active peptic ulcer disease, a history of alcohol or substance abuse, major hematologic, renal, or hepatic abnormalities, or a recent (within the previous six months) stroke or myocardial infarction or if they were receiving nitrate therapy. Other erectile-dysfunction therapies were discontinued at the time of screening (four weeks before the subjects received the study medication).

Anxiety and Depression

Sildenafil (Viagra) and an identical-looking placebo were supplied by Pfizer. The men were instructed to take a dose approximately one hour before planned sexual activity but not more than once daily. The protocols were approved by the institutional review board at each center, and all the men gave written informed consent. We assessed efficacy by using the responses to question 3 (frequency of penetration) and question 4 (maintenance of erections after penetration) of the 15-question International Index of Erectile Function, a validated, multidimensional, self-administered questionnaire used for the clinical assessment of erectile dysfunction and treatment outcomes in clinical studies.11 The responses to these two questions pertaining to the ability to achieve and maintain an erection sufficient for sexual intercourse, as described in the definition of erectile dysfunction,1 were rated on a scale of 1 (almost never or never) to 5 (almost always or always). A score of 0 indicated no attempt at sexual intercourse. 24 weeks and was asked about

global efficacy at 12 and 24 weeks.

ED Treatment Options

Headache, flushing, and dyspepsia were the most common adverse effects in the dose-escalation study, occurring in 6 percent to 18 percent of the men. Ninety-two percent of the men completed the 32-week extension study. Oral sildenafil is an effective, well-tolerated treatment for men with erectile dysfunction. Erectile dysfunction, the persistent inability to achieve or maintain an erection sufficient for satisfactory sexual performance, is estimated to affect up to 30 million men in the United States.1 The disorder is age-associated,1–3 with estimated prevalence rates of 39 percent among men 40 years old and 67 percent among those 70 years old.2 The available treatments include vacuum-constriction devices; intracavernosal injections of vasoactive agents, including alprostadil (prostaglandin E1)4; transurethral delivery of alprostadil5; implantation of penile prostheses; and venous or arterial surgery. No effective oral therapy for erectile dysfunction is currently available.6 Normal penile erection depends on the relaxation of smooth muscles in the corpora cavernosa.

Which Medication Will Work Best for My ED?

In response to sexual stimuli, cavernous nerves and endothelial cells release nitric oxide, which stimulates the formation of cyclic guanosine monophosphate (GMP) by guanylate cyclase.7–9 The mechanism by which cyclic GMP stimulates relaxation of the smooth muscles remains to be elucidated. Sildenafil is a selective inhibitor of cyclic-GMP–specific phosphodiesterase type 5, the predominant isozyme metabolizing cyclic GMP in the corpus cavernosum.10 By selectively inhibiting cyclic-GMP catabolism in cavernosal smooth-muscle cells,11 sildenafil would be expected to restore the natural erectile response to sexual stimulation but not cause erections in the absence of such stimulation. Sildenafil is rapidly absorbed, with maximal plasma concentrations occurring within one hour after oral administration and a mean terminal half-life of three to five hours.10 In a placebo-controlled pilot study of 12 men, sildenafil significantly improved the erectile response during visual sexual stimulation.10,12 We therefore undertook two studies to evaluate in a home setting the efficacy and safety of sildenafil in men with erectile dysfunction. In two sequential studies, we studied a total of 861 men 18 years of age or older with a clinical diagnosis of erectile dysfunction (as defined previously1) of six months' duration or longer at 37 centers in the United States. Each man had to be in a stable relationship with a female partner that had begun at least six months earlier. The event logs were reviewed at 0, 2,

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4, 8, 12, 16, 20, and 24 weeks.

• Counseling may help if emotional or psychological factors cause ED.
• Psychotherapy can address performance anxiety.
• Relationship counseling improves communication.
• Stress, depression, and anxiety can affect erections.
• Mental health support can enhance treatment outcomes.
• Combining therapy with medication often yields better results.

In the flexible dose-escalation study, 329 different

General Considerations

The mean score for each of the two questions was 4.3 for 109 normal men, 31 to 86 years old, with an age distribution similar to that of the men with erectile dysfunction (unpublished data). Efficacy was also assessed on the basis of the scores for the five separate response domains of male sexual function of the International Index13: erectile function (questions 1 through 5 and 15; possible total score, 1 to 30); orgasmic function (questions 9 and 10; possible total score, 0 to 10); sexual desire (questions 11 and 12; possible total score, 2 to 10); intercourse satisfaction (questions 6, 7, and 8; possible total score, 0 to 15); and overall satisfaction (questions 13 and 14; possible total score, 2 to 10). The domain scores were computed by adding the scores for the individual questions in each domain. Other means of assessing efficacy were an event log, in which we asked the men to record the date and dose of medication taken, the presence of sexual stimulation, the hardness of erections (graded on a four-point scale), and whether sexual intercourse was successful, and a global-efficacy question (“Did the treatment improve your erections?”), with a response of yes or no. The end points of the International Index quantified the magnitude of the response, and the global-efficacy question and the event log provided qualitative assessments of efficacy.

Figure 1. Diagnosis and Treatment of Erectile Dysfunction

Physical examinations and standard blood-chemistry and hematologic laboratory tests were performed throughout the studies. Adverse effects were recorded by the investigators. In this double-blind, placebo-controlled, fixed-dose study, 532 men were randomly assigned to take placebo or 25, 50, or 100 mg of sildenafil (approximately one hour before planned sexual activity but not more than once daily) for 24 weeks. Each dose consisted of three tablets from the same row of a blister pack (placebo–placebo–placebo; placebo–placebo–25 mg; placebo–placebo–50 mg; or placebo–50 mg–50 mg). The men were instructed not to consume more than two alcoholic drinks within one hour of sexual activity. men were randomly assigned to take placebo

or 50 mg of sildenafil approximately one

• Penile implants are a surgical option for severe ED cases.
• Types include inflatable and semi-rigid devices.
• Surgery has a high success rate but involves risks.
• Implants are usually considered after other treatments fail.
• They provide a permanent solution to ED.
• Requires consultation with a urologic surgeon.

hour before sexual activity for 12 weeks.

Journal Articles References and abstracts from MEDLINE/PubMed (National Library of Medicine)

We evaluated the efficacy and safety of sildenafil, administered as needed in two sequential double-blind studies of men with erectile dysfunction of organic, psychogenic, or mixed causes. In a 24-week dose–response study, 532 men were treated with oral sildenafil (25, 50, or 100 mg) or placebo. In a 12-week, flexible dose-escalation study, 329 different men were treated with sildenafil or placebo, with dose escalation to 100 mg based on efficacy and tolerance. After this dose-escalation study, 225 of the 329 men entered a 32-week, open-label extension study. We assessed efficacy according to the International Index of Erectile Function, a patient log, and a global-efficacy question.

Do ED medications work for everyone?

In the dose–response study, increasing doses of sildenafil were associated with improved erectile function (P values for increases in scores for questions about achieving and maintaining erections were <0.001). For the men receiving 100 mg of sildenafil, the mean score for the question about achieving erections was 100 percent higher after treatment than at base line (4.0 vs. 2.0 of a possible score of 5). In the last four weeks of treatment in the dose-escalation study, 69 percent of all attempts at sexual intercourse were successful for the men receiving sildenafil, as sex tablet for men price compared with 22 percent for those receiving placebo (P<0.001). The mean numbers of successful attempts per month were 5.9 for the men receiving sildenafil and 1.5 for those receiving placebo (P<0.001).