When the Pills Do Not Work: Injections, Vacuum Devices and Implants

The phrase “the pills do not work for me” covers two completely different situations. In one, a man has taken the highest dose on an empty stomach, with proper stimulation, on at least six occasions, and got nothing. In the other, which is far more common, he took 50 mg after a large dinner, twice, and gave up. The treatments below are for the first man. The evidence says most men who believe they are the first man are actually the second.

Most failure is not failure

The commonly cited figure is that 30 to 35 percent of men fail to respond to PDE5 inhibitors, and one review puts the upper bound at 40 percent. Those numbers are real. What they conceal is how many of those men never had a fair trial.

A study of 100 self-reported non-responders found that 56 of them had used the medication inappropriately. Forty-five had never tried the highest dose. Thirty-two had taken it with food. Twenty-two had taken it immediately before sex rather than allowing time for absorption. Twelve did not know that sexual stimulation was required for the drug to work at all. Only 34 had been given any follow-up appointment by the prescriber. After dose adjustment and instruction, 31 of those 56 men responded.

A larger series told the same story. Of 250 men referred to a specialist andrology unit as non-responders, 172, or 68.8 percent, had made at least one administration error. Of the 115 who accepted structured re-education, 88 went on to respond, a conversion rate of 76.5 percent.

The European Association of Urology treats this as a formal recommendation: fully inform patients of the mechanism and of how the drugs should be taken, because incorrect use and inadequate information are the main causes of a lack of response.

So before anything on the rest of this page, the checklist. Take it on a relatively empty stomach, because a heavy meal, particularly a fatty one, delays and blunts absorption of sildenafil. Allow adequate time, which for sildenafil means roughly an hour rather than ten minutes. Use the maximally tolerated licensed dose rather than the starting dose. Understand that the drug enables an erection in response to arousal; it does not produce one on its own. And try it properly on at least four to six separate occasions before drawing a conclusion, which is the entry criterion most salvage studies use.

One more number worth knowing. Even among men for whom the tablets work, adherence collapses: pooled across 22 studies and 162,936 patients, discontinuation ran at about 4 percent per month, approaching 50 percent by one year. Stopping is not the same as failing, and the two get reported as one.

Injections

Intracavernosal injection means a very fine needle into the side of the shaft, delivering a drug that relaxes the smooth muscle directly. It bypasses the nitric oxide pathway that PDE5 inhibitors depend on, which is precisely why it works in men for whom the tablets do not.

Alprostadil is the licensed agent, in doses from 5 to 40 micrograms. The EAU reports general efficacy above 70 percent, with patient satisfaction of 87 to 93.5 percent and partner satisfaction of 86 to 90.3 percent. The AUA’s systematic review found erections sufficient for intercourse in 53.7 to 100 percent of patients across the literature, without marked differences between agents.

Two combination formulations are widely used and neither is licensed for ED. Bimix and trimix add papaverine and phentolamine, reaching roughly 90 and 92 percent response respectively. Trimix tends to hurt less because it uses a lower alprostadil dose, alprostadil being the component responsible for most of the pain.

That last row is the honest problem with injections. They work, and most men stop. A study following 119 men on self-injection found 40 percent attrition, with the leading stated reason being lack of efficacy, followed by spontaneous return of function and by negative feelings about the procedure itself.

Priapism, an erection lasting more than four hours, is the complication that matters most and the one to have a plan for in advance. It is a urological emergency and delay causes permanent damage. Anyone starting injections should be told what number to call and where to go before the first dose, not after.

Both guidelines rate injections strongly. The EAU recommends them as an alternative first-line therapy in well-informed patients, or as second-line, which is a notably stronger position than treating them as a fallback.

The urethral pellet

Intraurethral alprostadil, sold as MUSE, is a small pellet inserted into the urethra. It avoids the needle, and it is meaningfully less effective.

The EAU reports 30 to 65.9 percent of patients achieving intercourse-sufficient erections at the 500 microgram dose. The direct comparison is more informative: in 103 patients given both, total response was 43 percent with the urethral pellet at up to 1,000 micrograms against 70 percent with injected alprostadil at up to 20 micrograms. Fully rigid erections occurred in 10 percent against 48 percent. Penile pain or burning was more common with the pellet, at 31.4 percent against 10.6 percent. The authors concluded that self-injection remained the standard.

Long-term adherence sits at about 30 percent. The AUA gives intraurethral alprostadil a conditional recommendation, the weakest grade it assigns to any established option here.

Vacuum devices

A cylinder is placed over the penis and air is withdrawn, drawing blood in mechanically. A constriction ring is then rolled onto the base to hold it. The process can take up to ten minutes.

Efficacy is high: the EAU puts it as high as 90 percent regardless of the cause of the ED, which makes sense given that the mechanism is physical rather than pharmacological. Satisfaction is where it gets complicated, reported across a range of 27 to 94 percent, with the AUA reporting a mean of 77 percent for both patients and partners. Continued use falls to 50 to 64 percent after two years.

Two safety points are non-negotiable. The constriction ring must not be left on for more than 30 minutes. And the device is contraindicated in men with bleeding disorders or taking anticoagulants. Other reported effects are pain, bruising, petechiae, numbness, and a weakened or blocked ejaculation, which does not prevent orgasm but does surprise people who were not warned.

The device produces an erection that is hinged at the base and often cooler to the touch, because the blood in it is not being continuously replenished. Men who know that in advance tend to do better with it than men who do not.

Implants

A penile prosthesis is a surgical implant, and it is the only treatment on this page that removes the option of the others: the procedure destroys the erectile tissue it replaces. That is the trade, and it is why it sits last despite having the best satisfaction figures in the entire field.

Those figures are 92 to 100 percent patient satisfaction and 91 to 95 percent partner satisfaction. One review notes that implant recipients showed greater improvement in erectile function scores than men treated with tadalafil or with injections.

Infection is the complication that defines the risk profile, because an infected implant usually has to come out. Rates are higher in men with diabetes or spinal cord injury, and most infections appear within three months of surgery.

The AUA gives penile prosthesis a strong recommendation, the only second-line option in its guideline to receive one.

Where testosterone fits

If tablets are not working, a morning testosterone is worth checking, and the reason is more specific than general hormone optimisation.

A meta-analysis of 8 randomised trials and 913 patients found adding testosterone to a PDE5 inhibitor improved erectile function with a standardised mean difference of 0.663 (95% CI 0.299 to 1.027). But the subgroup analysis is the whole story. In men whose baseline testosterone was above 10 nmol/L, the effect was 0.42 and not statistically significant. In men at or below 10 nmol/L, it was 0.97 (0.39 to 1.55). The benefit lives entirely in men who are genuinely deficient.

The counterweight is the best-designed single trial. It randomised 140 men with low testosterone and poor erectile function to testosterone gel or placebo, but only after their sildenafil had been properly optimised first. Sildenafil alone produced a large improvement of 7.7 points. Adding testosterone produced a further difference of 2.2 points, which did not reach significance. The conclusion was that testosterone added nothing once the tablet had been used properly.

Both guideline bodies use permissive language rather than a recommendation to treat: men with erectile dysfunction and testosterone deficiency should be informed that a PDE5 inhibitor may be more effective combined with testosterone therapy. That is a conversation to have, not a protocol to follow, and it reinforces the theme of this article. Optimise the simple thing before adding the complicated one.

Sold ahead of the evidence

Three treatments are marketed aggressively to men who have run out of options, and none of them is established. This is where a clinic’s willingness to sell you something diverges most sharply from the evidence base.

Platelet-rich plasma. The AUA classifies PRP for ED as experimental, its weakest evidence tier, assigned by expert opinion rather than data. The EAU states that current evidence remains insufficient to recommend it and that it should be used only in a clinical trial setting, though it does report a pooled improvement of 3.21 points (1.82 to 4.60) against placebo at six months. The Sexual Medicine Society of North America notes there have been only two clinical trials of PRP for ED and that it simply does not have enough evidence to support any current application.

Stem cell therapy. The AUA classifies it as investigational. The EAU says data are insufficient for a clinical recommendation, and that while the safety of intracavernous stem cell injection has been demonstrated, efficacy has not. SMSNA counted fewer than 70 patients in total across the published literature, in small open-label cohorts with endpoints designed to show safety rather than benefit.

Low-intensity shockwave. Here the two major guidelines genuinely disagree, and anyone quoting one at you should be asked about the other. The AUA says shockwave therapy should be considered investigational. The EAU gives it a weak recommendation for mild vasculogenic ED and for poor responders to PDE5 inhibitors, reporting that 40 to 80 percent of such men report satisfactory improvement. SMSNA counts 13 published trials with mixed results, most lacking randomisation against a sham control, while noting that no adverse events were documented across any of them. A treatment can be simultaneously safe and unproven, and this one is.

The society’s overall position is worth quoting as a principle: it does not advocate for restorative therapies to be offered or used in routine clinical practice, and it calls for adequately powered, multicentre, randomised, sham-controlled trials before adoption.

One final point on sequence. It is tempting to read this article as a ladder to be climbed in order, and the AUA explicitly rejects that framing. Although many men will choose to begin with the least invasive option, the guideline panel states that it is valid for men to begin with any type of treatment, regardless of invasiveness or reversibility. A man who has watched his father go through fifteen years of escalating half-measures is entitled to start at the end.

This article is for information only and is not medical advice. Injections, devices and implants all require assessment by a clinician who knows your history. An erection lasting more than four hours is a medical emergency and needs urgent care.