Few medications in modern medicine have shifted the therapeutic landscape as dramatically as sildenafil citrate. Once a compound developed for angina, it rapidly emerged as a first-line therapy for erectile dysfunction (ED) and profoundly altered how clinicians evaluate, counsel, and manage men with compromised sexual function. The sudden transition from invasive, often cumbersome treatments to a well-tolerated oral agent transformed expectations among patients and physicians alike. Yet, the excitement surrounding sildenafil also carried a practical question that academic trials rarely answered: How well does it actually work in the real world?

The study underlying this review sought to address that question with an elegant simplicity: assess all men who received sildenafil in the first six weeks after its FDA approval, measure their baseline sexual function, classify ED etiology, document their prior treatments, and determine satisfaction. The result is a rare snapshot of sildenafil in unfiltered clinical practice, free from the tight constraints of randomized controlled trials. By examining more than 300 consecutive patients—diverse in age, health status, etiology, and treatment history—the study offers insights highly relevant to contemporary urology.

This article reconstructs and expands upon those findings in a comprehensive, clinically oriented narrative intended to highlight the nuances clinicians must consider when prescribing sildenafil. While the drug remains impressively effective, its success is far from uniform—and understanding why can meaningfully improve patient counseling and treatment planning.

Understanding the Clinical Context: The Need for Real-World Data

Sildenafil’s approval in 1998 marked a watershed moment. Prior ED treatments—intracavernosal injections, vacuum devices, urethral suppositories—were often effective but came with pain, inconvenience, or discomfort that limited adherence. Patients had long voiced a preference for oral medications, even before an effective one existed. Once sildenafil became accessible, millions of men sought prescriptions, often with expectations shaped more by media enthusiasm than scientific nuance.

This created a unique challenge. Clinical trials had demonstrated sildenafil’s significant efficacy compared with placebo, but they enrolled select patient populations—those healthy enough for sexual activity, motivated to adhere to protocol, and screened for comorbidities. Clinical practice, however, includes men with complex medical histories, severe baseline dysfunction, psychological contributors, or limited response to previous treatments.

Therefore, the present study filled a critical gap by capturing the first wave of prescribing behavior, examining outcomes in an unfiltered clinical population far more heterogeneous than trial cohorts. This approach provided a realistic measure of sildenafil’s strengths and limitations and, importantly, clarified which patient characteristics influence therapeutic outcomes.

Design, Methodology, and Patient Selection: Strength Through Simplicity

The investigators reviewed 308 consecutive patients who received sildenafil in the first six weeks following FDA approval. By evaluating all eligible men—rather than selecting based on narrow inclusion criteria—they ensured that the cohort represented genuine clinical diversity. Follow-up was obtained for 267 patients, a strong 86.7% response rate.

Each participant completed pre-treatment and post-treatment questionnaires assessing:

sexual function (using a five-item abbreviated International Index of Erectile Function),
etiology of ED,
libido,
response to prior therapies,
quality of life,
and satisfaction with sildenafil.

Patients received standardized instruction on dosing, initiating therapy with 50 mg, taken 1.5 hours before sexual activity, escalating to 100 mg if needed. Exclusion criteria were minimal—primarily individuals with unstable cardiac disease or those taking nitrates. Follow-up occurred only after several attempts with sildenafil at full titration, ensuring that transient or inconsistent exposure did not bias results.

The methodology allowed the investigators to correlate treatment efficacy with ED severity, etiology, and history of prior therapy. In doing so, they constructed one of the earliest and most informative analyses of sildenafil’s performance in clinical practice.

Overall Efficacy: A Solid, Real-World Success Rate

The headline finding is clear: 65% of patients were satisfied, rating their outcome as 4 or 5 on a 5-point scale. Notably, the mean erectile function score increased from 8.1 to 16.3, a highly significant improvement. Quality-of-life scores likewise increased, and 85% of men indicated they would use sildenafil again.

These numbers confirm sildenafil’s transformation of ED management. Despite diverse etiologies and varying degrees of dysfunction, the majority experienced clinically meaningful benefits. But the study also uncovered subtler points essential for clinical decision-making.

For example, only 51% of patients reported that sildenafil met their expectations. This discrepancy suggests that hope, hype, and misinformation likely influenced perceived success. Expectations were, in many cases, unrealistic—particularly among men with severe dysfunction or significant nerve injury. Nevertheless, most were satisfied, even if the medication did not deliver a “miraculous” recovery.

Adverse events were reported in 35% of patients, primarily headache (15%), facial flushing (14%), nasal congestion (4%), and visual disturbances (2%)—all consistent with known vasodilatory effects. Importantly, none were severe enough to discontinue treatment.

In short, sildenafil works for most men, is well tolerated, and improves sexual function and quality of life in a clinically meaningful manner. But real-world outcomes vary dramatically based on specific patient characteristics, most notably the etiology and severity of ED.

The Role of Etiology: Why the Cause of ED Matters

One of the study’s most important findings is that ED etiology significantly influences sildenafil responsiveness.

Patients were grouped broadly into:

psychogenic ED,
vasculogenic ED,
post-prostatectomy ED,
diabetes-related ED,
neurological disorders,
Peyronie’s disease,
and idiopathic cases.

Psychogenic and vasculogenic ED showed the highest satisfaction rates.

This is consistent with sildenafil’s mechanism: the drug enhances nitric-oxide–mediated vasodilation, but proper neural signaling is required to initiate the erectile cascade. Psychogenic ED preserves neural integrity, while vasculogenic ED often involves modifiable hemodynamic impairment.

Diabetic, post-prostatectomy, and neurogenic ED showed lower satisfaction rates.

These etiologies involve impaired nerve function or structural penile changes. In post-prostatectomy patients, for example, cavernous nerve disruption compromises the initial neural signal required for sildenafil to exert its effect. Similarly, long-standing diabetes may affect neurovascular function, reduce responsiveness, or increase fibrosis.

Yet even among these challenging groups, sildenafil offered benefit. Importantly, no etiology predicted universal failure, reinforcing the clinical recommendation that all eligible men should at least attempt sildenafil therapy.

Baseline Severity of ED: A Strong but Not Exclusive Predictor

Baseline erectile function, unsurprisingly, correlated positively with treatment success. Patients were categorized as:

Mild ED: IIEF-5 score >20
Moderate ED: 5–20
Severe ED: <5

Mild ED:

Every patient responded positively—100% satisfaction.

Moderate ED:

A strong 78% satisfaction rate was recorded.

Severe ED:

Despite significant dysfunction, 41% reported satisfaction, demonstrating that even severe cases may respond robustly.

This reinforces a clinically helpful message: sildenafil is not reserved only for men with mild or moderate dysfunction. Even those with near-complete erectile failure can benefit meaningfully, and dismissing sildenafil prematurely may deprive patients of improvement.

Influence of Prior Treatments: Expectations vs Reality

One might expect that failure of previous therapies—such as urethral alprostadil, intracavernosal injection, oral vasodilators, hormonal therapy, or vacuum devices—would predict poor response to sildenafil. However, the study conclusively demonstrated no such correlation.

Patients dissatisfied with prior treatments responded to sildenafil at rates similar to those who were previously satisfied. This counterintuitive finding reflects several realities:

Some prior treatments failed due to discomfort or inconvenience, not lack of physiological response.
Injection techniques may have been poorly executed or anxiety-laden.
Sildenafil’s mechanism differs significantly from testosterone replacement, vacuum devices, or older oral agents such as yohimbine.

This finding is clinically liberating: previous treatment failure does not diminish sildenafil’s potential efficacy, and sildenafil should not be excluded based on historical outcomes.

Quality of Life: The Broader Impact of Improving Sexual Function

Beyond measurable improvements in erectile rigidity or penetration ability, sildenafil demonstrated broad benefits in overall quality of life. Scores improved from 1.7 to 3.1, showing that even partial restoration of erectile function positively impacts emotional well-being, relationship satisfaction, and self-perception.

Interestingly, quality-of-life improvements were sometimes smaller than improvements in satisfaction. This suggests that ED is often embedded within broader psychological and relational contexts. A medication can improve erections but cannot fully address communication difficulties, performance anxiety, or mismatched expectations.

Nevertheless, sildenafil remains a powerful tool for restoring confidence and reducing distress—critical clinical outcomes often undervalued in purely physiologic assessments.

Safety and Tolerability: Consistent with Long-Term Data

The adverse events observed mirror those widely documented in large-scale clinical trials. Importantly:

no patient discontinued therapy due to side effects,
no severe cardiovascular events occurred,
and side effects were mild, transient, and predictable.

This real-world tolerability reinforces sildenafil’s strong safety profile and supports its role as a first-line therapy for ED.

Clinical Implications: What This Means for Practitioners

The study’s core implications can be distilled into several clinical principles:

Sildenafil is effective across a wide range of ED severities.
Etiology is the strongest predictor of response, with neurogenic causes posing the greatest challenges.
No patient group demonstrated universal failure—supporting a “try sildenafil unless contraindicated” approach.
Prior failure of other therapies does not predict sildenafil failure.
Proper counseling is essential to align expectations with achievable outcomes.

These insights remain relevant decades after the study was conducted, particularly as clinicians navigate patient expectations shaped by direct-to-consumer advertising and social media.

Conclusion

Sildenafil citrate remains one of the most influential therapeutic innovations in the management of erectile dysfunction. Its efficacy in real-world practice closely resembles that observed in controlled trials, with a 65% satisfaction rate, meaningful improvements in erectile function, and a strong quality-of-life benefit. Although etiology and baseline severity influence outcomes, even men with severe dysfunction or prior treatment failures may achieve significant improvements.

By understanding sildenafil’s strengths and limitations—and by counseling patients honestly and thoroughly—clinicians can support higher satisfaction, better adherence, and improved sexual health outcomes. Above all, sildenafil’s real-world performance underscores a timeless truth in urology: never underestimate a well-chosen oral therapy, even in the face of complex etiologies.

FAQ

1. Does the cause of erectile dysfunction affect how well sildenafil works?

Yes. Men with psychogenic or vasculogenic ED respond best. Those with diabetes, neurological disorders, or post-prostatectomy ED typically show lower—but still clinically meaningful—response rates.

2. If a patient failed previous ED treatments, is sildenafil likely to fail as well?

Not necessarily. This study showed that response to prior therapies does not predict sildenafil efficacy. Many patients who discontinued other treatments due to inconvenience or anxiety responded well to sildenafil.

3. Is sildenafil effective for men with severe erectile dysfunction?

Yes. While response is stronger among men with mild or moderate ED, more than 40% of men with severe ED reported satisfaction, and many showed major improvements in erectile function scores.