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Laurance Johnston, Ph.D.

Sponsor: Institute of Spinal Cord Injury, Iceland




Sildenafil (Viagra®)

Vardenafil (Levitra)

Tadalafil (Cialis®)

Intracavernosal Injection

Intraurethral Suppository

Topical Agents

Vacuum Devices


Introduction: A common consequence of SCI is erectile dysfunction (ED), defined by the National Institutes of Health as the inability to achieve or maintain an erection sufficient for satisfactory sexual activity. Because SCI disproportionately affects young men, restoration of sexual function is a high priority, often listed ahead of walking. Many approaches of varying effectiveness have been used to asddress SCI-associated ED, including topical and intraurethral agents, penile injections, vacuum-tumescence devices, penile implants, sacral stimulators, and oral medications.

Reflex versus Psychogenic Erection: Because the biology behind erectile function is complex, an in-depth discussion is not possible. Basically, there are two types of erections: reflex (produced by touch) and psychogenic (mentally induced). Each type is controlled by different nerves and neurophysiology, and is affected differently and in a contrasting fashion by injury level. 

The ability to generate reflex erections depends on the preservation of neural circuitry in the lower, sacral (S2-4) spinal-cord segments. Hence, although there is less overall paralysis from a sacral than a high-level injury, reflex-erection potential will be more compromised. In contrast, the required sacral neural circuitry is undamaged in higher injuries, preserving reflex erections.

Psychogenic erections (e.g., visual stimulation, titillating talk, fantasies, sexual memories, seductive perfumes, provocative music, etc) are mediated, in part, through the thoracic T-10 to lumbar L-2 spinal regions. Hence, individuals with injuries above this level have lost the ability to generate psychogenic erections but have maintained reflex-erection capacity. In contrast, although unable to produce a reflex erection, those with a sacral injury have the neural pathways necessary to mediate a psychogenic erection. Men with injuries between the T10- L2 and S2-4 levels may retain both psychogenic and reflex erections.

This synergistic situation is confounded with incomplete injuries in which some function-controlling neurons still transverse the injury site, often the situation even in those injuries clinically classified as complete.

Erection Physiology: An erection develops when cylindrical, sponge-like regions surrounding the penis become filled with blood. Penile tumescence is initiated by nerve branches releasing a key neurotransmitter called nitric oxide, which, in turn, causes penile arteries to dilate, filling the sponge-like cavities with blood.  This process is mediated by the nitric-oxide-stimulated production of a secondary messenger molecule called cGMP (cyclic guanosine monophosphate). This molecule is especially important because Viagra-like drugs inhibit its enzymatic degradation, letting it accumulate and, in turn, promoting erection. So to speak, it is like disabling the brakes on a cGMP-fueled car.

Sildenafil (Viagra®): The development of popular oral drugs over the past decade such as Viagra has greatly influenced how SCI-related ED is treated. As mentioned above, Viagra inhibits cGMP degradation, therefore, shifting the physiological balance more toward erection maintenance.  Often funded from the drug sponsor, studies have documented Viagra’s SCI benefits:

1) Maytom (UK) et al carried out a two-part pilot study in men with SCI-related ED (Spinal Cord, 37, 1999). In part 1, 27 subjects (age 18-55, sustaining injuries at least 1/2 years earlier) received either Viagra or placebo. After a three-day washout period to get the drug out of the system, the treatments were reversed. Sixty-five percent had erections sufficient for penetration after taking the drug compared with only 8% for the placebo. In Part 2, subjects were randomized to receive either Viagra or placebo over a 28-day period. Based on questionnaires, 75% and 8% of the Viagra- and placebo-treated patients, respectively, indicated that treatment had improved their erections. The study concluded that Viagra “is an effective, well-tolerated oral treatment for ED in SCI subjects.”

2) In a somewhat similar but larger study, Giuliano (France) and colleagues examined Viagra’s effects on 178 men with SCI, who were injured at least six months before study recruitment (Ann Neurol, 46(1), 1999). The subjects received either Viagra or a placebo before sexual activity for six weeks. After a two-week washout period, treatments were reversed. Evaluated by patient questionnaires and feedback, 80% reported that Viagra improved sexual intercourse compared with only 10% for placebo. The most common side effects were headaches, flushing, and indigestion.

3) Schmid and colleagues (Switzerland) prospectively studied the effects of Viagra in 41 men with SCI (Eur Urol, 38(2), 2000). Ninety-three percent responded positively to Viagra, obtaining a sufficiently rigid erection for sexual intercourse. About 10% had side effects, such as headaches or dizziness

4) Green and Martin (Atlanta, GA, USA) studied Viagra’s effects in 40 men with spinal cord dysfunction (both SCI and MS) (NeuroRehabilitation, 15(2), 2000). Followed for up to two years, erectile response improved from 4.9 to 7.8 on a scale of 1-10, and 90% obtained erections sufficient for intercourse.

5)  Ramos et al (Spain) studied Viagra’s safety and efficacy in 170 men with SCI (Spinal Cord, 39, 2002). Assessed by questionnaires, 88% of the subjects and 85% of their partners reported improved erections as a result of the drug.  The investigators concluded that Viagra is an “effective, well-tolerated treatment for erectile dysfunction caused by spinal cord injury, regardless of the cause, neurological level, ASIA grade, and time since injury.”

6) One of Viagra’s side effects in neurologically intact men is hypotension or low blood pressure. Because individuals with higher level injuries are prone to hypotension, Ethans and colleagues, (Manitoba, Canada) studied Viagra’s effects on blood pressure in men with SCI (J Spinal Cord Med, 26(3), 2003). Although blood pressure changed little in subjects with thoracic injuries, it decreased significantly in those with cervical injuries. The investigators recommend the drug be prescribed with caution.

7) Dr. Sureyya Ergin et al studied the effects of Viagra on 50 men with SCI recruited at five centers in Turkey (ref). Subjects averaged 39 years in age and had been injured at least six months before recruitment. Approximately 58% had ASIA-A classified complete injuries, and the remainder had incomplete injuries. The subjects were randomized to receive either Viagra or placebo for six weeks. This was followed by a two-week washout period in which nothing was administered, i.e., ensuring the drug was out of the system. Following this washout period, the treatments were reversed (i.e., a crossover design). Based on subject feedback obtained by various questionnaires and other mechanisms, the investigators concluded that Viagra “produced higher levels of successful stimulation, intercourse success, satisfaction with sexual life and sexual relationship, erectile function, overall sexual satisfaction…”

Vardenafil (Levitra): Levitra is in the same class of drugs as Viagra and promotes erectile potential through similar physiological mechanisms.

In a large multi-center, double-blind study, Giuliano et al (France) evaluated the effectiveness and tolerability of Levitra in 418 men with SCI sustained at least six months before study enrollment (Neurology, 66(2), 2006).  Subjects were randomized to receive either Levitra or an inactive placebo. Erectile function was measured by questionnaires and diary questions concerning penetration, maintenance of erection to completion of intercourse, and ejaculation. All of these measures improved in the Levitra-treated group relative to placebo. Side effects reported most often included headache, flushing of the skin, nasal congestion, and dyspepsia (stomach Pain). The investigators concluded Levitra “significantly improved erectile and ejaculatory function and was generally well tolerated in men with erectile dysfunction due to spinal cord injury.”

In a non-blinded study, Kimoto and colleagues (Japan) treated 32 men with SCI with varying doses of Levitra (Int J Urol, 13(11), 2006). The investigators concluded that drug was “well tolerated and improved erectile function in patients with SCI.” Although no serious side effects occurred, 22% of patients reported mild and transient effects such as hot flushes and headaches.

In addition to improving erectile function, Levitra seems to enhance bladder function in men with SCI as measured by a variety of urodynamic assessments.

Tadalafil (Cialis®): Cialis is yet another oral medication that works in a fashion similar to Viagra or Levitra. However, unlike these other drugs, whose effectiveness is limited to about four hours, long-lasting Cialis will enhance erection potential for up to 36 hours.

Dr. Francois Giuliano (France) and associates reported the results of a double-blind study comparing erectile function, measured by a number of parameters, in 186 subjects with SCI treated with either varying doses of Cialis or a placebo control. Of these individuals, 69% had complete injuries; 84% had thoracic, lumbar, or sacral injuries; and 69% had moderate to severe ED. 

Eighty-five percent of the Cialis-treated subjects reported improved erections compared with only 19% for placebo-treated subjects. Seventy-five percent of the Cialis-treated men were able to penetrate their partner compared with only 44% before treatment; and 48% reported successful intercourse compared with only 11% before treatment. Headaches and urinary tract infections were the most common reported side effects.

Dr. Giuseppe Lombardi (Italy) and co-investigators followed 65 men with SCI who had been taking Cialis an average of nearly 34 months. They reported a significant statistical improvement in erectile function, sexual satisfaction, and overall satisfaction…” and concluded that Cialis “represents an effective and safe long-term option for SCI patients with ED.”

Intracavernosal Injection: Erectile tumescence occurs when cylindrical, sponge-like regions on each side of (corpus cavernosa) and below the penis shaft become engorged with blood. Injection of certain agents alone or in combination into one of the cavernous regions (i.e., the side of shaft) consistently produces rigid erections in men with SCI-related ED. Basically, these substances enhance erection-promoting blood flow into the penis. An occasional side effect is priapism, a prolonged, often painful erection, in which the penis does not return to its flaccid state within about four hours.





Alprostadil is identical to natural occurring prostaglandin E1 (PGE1). Although originally isolated from prostate secretions (hence, the name), prostaglandins are found in most tissues and hormonally exert many physiological effects. Alprostadil intracavernosal injections are marketed under various brand names, including Caverject® (www.caverjectimpulse.com) and Edex® (www.edex.com). Other substances used for SCI-related ED include papaverine, a non-narcotic opiate; phentolamine, a drug used to treat adrenal-gland tumors; and atropine. Combination products available through compounding pharmacies, which create custom medications on a doctor’s prescription, include Bimix (papaverine and phentolamine), Trimix (Bimex plus alprostadil), and Quadmix (Trimix plus atropine).

Several studies have been carried out evaluating the use of intracavernous injections to treat SCI-related ED, including the following:

Beretta et al (Italy) treated 22 men with SCI with intracavernous injections of papaverine, of whom, 20 obtained complete penile rigidity (Acta Eur Fertil, 17(4), 1986). Seven had erections lasting more than 300 minutes.

Sidi and colleagues (Minnesota, USA) treated 66 patients with SCI with intracavernous injections containing either papaverine or a combination of papaverine and phentolamine (J Urol, 138(3), 1987). All 52 patients who completed the protocol “achieved transient functional penile erections”; four suffered priapism requiring treatment.

Earle et al (Australia) treated 22 men with SCI with various intracavernosal agents, including papaverine, papaverine plus phentolamine, or PGE1 (i.e., alprostadil) (Paraplegia, 30(4), 1992)). Nineteen responded to therapy. Twelve of 14 who participated in a follow-up mail survey continued to periodically use the drugs and reported satisfaction with their use.

Kapoor and colleagues treated 65 men with paraplegia and 36 with quadriplegia with intracavernous papaverine. Of these, 98 had erections sufficient for coital penetration (Paraplegia, 31(10), 1993)), and three had prolonged erections lasting more than four hours.

Hirsch et al (Pennsylvania, USA) evaluated intracavernous PGE1 (alprostadil) treatment in 27 men with neuropathic erectile dysfunction (14 with SCI) (Paraplegia, 32(10), 1994). “Quarterly monitoring up to 28 months demonstrated satisfactory erectile rigidity and duration of erection.” No priapism was observed.

Zaslau and colleagues (New York, USA) treated 28 men with intracavernous injections containing a combination of papaverine and prostaglandin E1 (alprostadil) (J Spinal Cord Med, 33(12), 1999). Of those who completed the study, 85% indicated that their erections were good or excellent, and 77% were moderately or extremely satisfied with treatment. Average erection duration was 43 minutes.  

Intraurethral Suppository: Alprostadil can also be administered by inserting a small medicated pellet in the urethral opening (the passage from the bladder to the outside through which urine flows). Absorbed by the urethral tissue, the medicine passes through to the surrounding erectile tissue. This ED treatment is marketed under the name MUSE®, an acronym for “medicated urethral system for erections” (www.muserx.net).

The method is less invasive and considered easier for quadriplegics who may lack the hand function needed for intracavernosal injections. To enhance erectile rigidity, it has been used with a constrictor band at the base of the penis, which also limits the systemic absorption of the drug into the rest of the body.

Studies suggest that the treatment is less effective than the injections, and high doses of the drug were required to produce sufficient tumescence.  For example, Bodner and colleagues (Ohio, USA) evaluated the ability of MUSE to treat ED in 15 patients with SCI (Urology, 53(1), 1999). The investigators concluded: “MUSE appears somewhat effective in creating erections; however, these were less rigid erections than those obtained with intracavernosal therapy and provided less overall satisfaction.”  

Topical Agents: A number of less-invasive, but less-effective, topical agents enhance erectile potential. For example, Topiglan, which is rubbed on the penis tip, contains alprostadil together with a substance that increases skin absorption. Goldstein and colleagues randomized 60 men with moderate to severe ED to receive either Topiglan or a placebo gel (Urology, 57(2), 2001). About 40% of those who received the active gel developed erections sufficient for vaginal penetration compared with only seven percent of controls.

Several studies have been carried out evaluating the effects of various topical agents in treating SCI-related ED, including the following:

Sonksen and Biering-Sorensen (Denmark) studied the erection-producing effects of placing nitroglycerin-containing plasters on the penile shaft of 17 men with SCI (Paraplegia, 30(8), 1992). (nitroglycerine is a vasodilator, i.e., a blood-flow-increasing substance) All of these men had responded previously to intracavernous papaverine injections sufficient for vaginal penetration. A positive response was obtained in 12 of the men. Five were able to achieve erections sufficient for vaginal penetration at home and preferred the method over the previously used injections.

Beretta et al (Italy) examined the erectile properties of minoxidal (another vasodilatory agent) topically applied to the penile shaft in 15 men with SCI (Acta Eur Fertil, 24(1), 1993). Of the four who reported a positive erectile response, three preferred to continue with this noninvasive treatment over intracavernous injections. 

Kim and McVary (Illinois, USA) evaluated the effect of topically applied alprostadil on erection function in 10 men, nine of whom had SCI (J Urol, 153(6), 1995). Blood flow in the arteries serving the erection-producing cavernous tissue increased in 7 of the 10.

In a somewhat similar study, Kim and associates (Illinois, USA) examined the effects of topically administered papaverine gel in 20 men with ED, of whom 13 had SCI (J Urol, 153(2), 1995). The investigators concluded that “papaverine gel appears to be safe and well tolerated… and increases blood flow to the penis.” They also noted that the application of the gel to the genitalia resulted in little systemic absorption and, as a result, less potential to exert physiological effects in other parts of the body.

Renganathan and colleagues (India) compared the effectiveness of intracavernous injections of papaverine with nitroglycerin transdermal patches in treating ED in 28 men with SCI (Spinal Cord, 35(2), 1997). Ninety-three percent of the subjects who received an intracavernous injection of papaverine demonstrated a complete erectile response compared with only 61% who used the transdermal nitroglycerin. 

Vacuum Devices: Vacuum devices have been shown to enhance erections in men with SCI-related ED. With these devices, a cylinder attached to a vacuum pump is placed over the penis, and the resulting vacuum draws blood into the penis, creating an erection. A constriction ring is then temporarily placed around the penis base to maintain the erection. For men with poor hand function, battery-operated devices are available. As a non-pharmaceutical option for ED, vacuum devices can be used as a backup for other approaches and more than once in a 24-hour period. The devices have been evaluated in a number of SCI-focused studies:

Zazler and Katz (Virginia, USA) prospectively examined vacuum-device effectiveness in 20 men with injuries ranging from the cervical C-4 to lumbar L-2 level (Arch Phys Med Rehabil, 70(9), 1989). Subjects ranged in age from 21 to 65 (average: 40), had been injured for at least a year, and had a steady sexual partner. Evaluated by subject and partner questionnaires, all reported successful vaginal intercourse after having used the device at least 20 times. The majority indicated that intercourse quality was very good or excellent compared to the previous best since injury. The investigators concluded the device “was an effective, safe, non-invasive alternative for the management of impotence secondary to cord injury.”

Heller et al (Israel) studied the use of such devices in 30 subjects with chronic neurological impotence (Paraplegia, 30(8), 1992). After training at the clinic, 17 chose to use the device at home, and 21 months later, 50% were still using it. Intercourse frequency increased from 0.3 to 1.5 times a week.

Denil and associates (Michigan, USA) evaluated the erection-promoting potential of vacuum devices in 20 men with SCI-related ED (Arch Phys Med Rehabil, 77(8), 1996). At three months, 93% and 83% of their female partners reported erection sufficiently rigid for vaginal penetration (average duration 18 minutes). At six months, 41 and 45% of the men and women, respectively, were satisfied with the device, with early rigidity loss the most common complaint. Although minor side effects occurred often, including petechiae (red spots under the skin caused by blood that has leaked from the capillaries) and skin edema, none required treatment.

Penile Implants: Both malleable and inflatable penile implants have a relatively long history of use for SCI-related ED. With the former, semi-rigid cylinders are implanted into erectile tissue; the device is bent outward for sex and back toward the body for concealment. With a two-piece inflatable device, inflatable cylinders are connected to a ball-shaped pump locate in the scrotum, which, when squeezed, sends fluid from the back of the cylinder to its mid-area, producing erectile rigidity. When the middle of the penile shaft is bent, the fluid returns to the cylinder base. In addition to the cylinders and scrotal pump, the three-piece device includes a fluid reservoir located behind stomach muscles.

In Spinal Cord Medicine: Principles and Practices (2003), Elliot (British Columbia, Canada) notes: “Men with SCI experience a much higher infection rate and erosion rate with these devices when compared to nonneurological patients…Because these devices are placed in the spongy tissue of the corpora cavernosal bodies, much of the tissue is permanently destroyed. This precludes the use of other erection enhancement techniques….”

In a review article focused on SCI-related ED, Deforge and colleagues (Ontario, Canada) stated “Penile implants are very satisfactory for those who do not have complications, but the serious complication rate was consistently close to 10%. Furthermore, patients who have an implant removed are likely to have damage to the penile tissues that would make them nonresponsive to intracavernous injections or vacuum devices.” (Spinal Cord, 44, 2006)

In a recently published study, Zerman et al (Germany) reported the results of following 245 men (197 SCI) with neurological impairment with ED, who had received implants between 1980 and 1996 (J Urol, 175, 2006). Fifty percent had a semi-rigid device implanted, and the rest inflatable devices.  The investigators concluded “The implantation of a penile prosthesis is a safe procedure for erectile dysfunction… in neurologically impaired. Based on technical advances the complication rates significantly decreased during the years.”