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Sexual and Reproductive Health

Male Erectile Response and Enhancement

In general, the majority of men can attain an erection after SCI either through the psychogenic (T11-L2) or reflexogenic (S2-S4) pathways, depending on the level and completeness of injury. However, these erections are often unreliable or inadequate for sexual intercourse with difficulties experienced in maintaining an erection (Alexander et al. 1993Courtois et al. 1993). Treatments for erectile dysfunction (ED) in men with SCI have advanced considerably in recent years with the availability of phosphodiesterase type 5 inhibitors (PDE5i) taken as a tablet orally. However, other methods are still being utilized when oral medication is ineffective or unaffordable. There is stronger evidence for treatment of erectile dysfunction than other areas of sexuality in SCI, primarily due to the advent of the PDE5i and their effectiveness in this population.

Therapies for erectile dysfunction (ED) include:

  1. Oral medications, which indirectly relax the penile smooth muscle and enhance an erection attained by sexual stimulation, such as the oral phosphodiesterase 5 inhibitors [PDE5i] Viagra®, Levitra® and Cialis®
  2. Intracavernosal injectable medications, which directly relax the penile smooth muscle creating an erection (prostaglandin E1 penile injections [Caverject® or compounded] and other injectable combinations of papaverine and phentolamine)
  3. Topical agents for penile smooth muscle relaxation (prostaglandin, minoxidil, papaverine and nitroglycerine)
  4. Intraurethral preparation of prostaglandin E1 (MUSE®)
  5. Mechanical methods, such as vacuum devices and penile rings
  6. Surgical penile implants
  7. Behavioural methods (perineal muscle training)
  8. Psychological and sex therapy (non-medicinal) adjunct to medical therapies after SCI

All methods except penile implants are clinically reversible. The use of implantable sacral stimulators to assist an erection via stimulation of S2 and S3 anterior roots has not been well explored due to its limited use in those with complete SCI lesions (Brindley et al. 1989). The detrimental effects on erectile function of baclofen and baclofen pumps are noted, but they appear to be clinically reversible with baclofen discontinuation.

Author Year; Country
Dates included in the
review
Total sample size
Level of evidence
Type of study
Score
Methods
Databases
Outcomes
DeForge et al. 2006; Canada
Review of published and
unpublished articles
between 1966 and 2003
N=49
Jadad Scale – RCTs
Newcastle-Ottawa Scale –
Non RCTs
Type of studies
Not reported
AMSTAR=7
Methods: Studies reporting on the
effectiveness of erectile interventions in
adolescents and adults with SCI.
Interventions included devices (e.g. penile
ring), prescription medications (oral, cream,
injections) surgery, hormones, and
behavioural (e.g. masturbation).
Databases: MEDLINE, PreMEDLINE,
CINAHL, Cochrane Central Register of
Controlled Trials, SocioFile, PsycINFO.
1. Penile injection and sildenafil were
successful in 90% and 79% of men
respectively. Differences of efficacy not
statistically significant.
2. No clear differences of efficacy between
injections of papaverine, phentolamine,
and prostaglandin E1.
3. High satisfaction rate of penile implants
with 10% complications.
Rizio et al. 2012; USA
Reviewed published
articles from 2000 to
August 2010
N=10
Level of evidence: not
reported
Type of studies
n/a
AMSTAR=6
Method: Studies reporting on the efficacy
and satisfaction of oral phosphodiesterase
type 5 inhibitors (PDE5i) to treat ED
secondary to SCI. Studies (any research
design and language) using the International
Index of Erectile Function (IIEF) as an
outcome measure and done on more than 20
men with SCI were included.
Databases: PubMed, CINAHL.
1. Statistically significant improvement of
erectile function with the use of PDE5i’s.
Sildenafil, tadalafil, and vardenafil were
equally effective.
2. Improved sexual function satisfaction
with all three.
3. Tadalafil has a longer time duration
effectiveness, which allows for more
spontaneity in the sexual experience.
4. Minimal adverse effects noted:
headache, flushing, and mild
hypotension were most common.
Lombardi et al. 2012; Italy
Reviewed published
articles from Medline and
PubMed up until June
2011
N=28 (21 for SCI)
Level of evidence
Reliability of studies
assessed but method not
specifiedType of studies
All clinical trials
AMSTAR=4
Method: Searched for all clinical studies
reporting efficacy/safety on treatments of at
least 4 weeks with PDE5i in human patients
with central neurological disorders suffering
from ED. Only full-text articles were included;
single case-reports and articles examining
the effect of a single dose of PDE5 were
excluded. No language restrictions were
imposed.
Databases: MEDLINE and PubMed
1. PDE5i represent first line ED therapy for
SCI patients.
2. Sildenafil, tadalafil, and vardenafil all
significantly improved erectile function in
SCI patients.
3. PDE5i efficacy was documented for SCI
patients for up to 10 years; treatment
resistance did not occur.
4. The most frequent predicable factor for
PDE5i success and efficacy at low
dosage was the presence of upper
motoneuron lesion
Martin et al. 2013; USA
Reviewed published
articles from July 2001-
July 2011
N=12 (1 SCI)
Level of evidence
Methodological quality not
assessed
Type of studies
Not described
AMSTAR=3
Method: Searched using keywords “cost,
budget, expenditure, resource use,
economic, pharmacoeconomic, productivity,
work loss, willingness to pay” to identify
relevant economic publications in English on
sildenafil in ED. Only studies with at least 20
patients were included. Relevant narrative
reviews were included if published between
2007-2011. Conference abstracts were also
examined for content.
Databases: Medline and Embase
1. Only one study, Mittman et al. 2001,
included patients with SCI. This study was
a cost-utility analysis conducted in
Canada, comparing sildenafil to
transurethral suppository, intracavernous
injections (ICI), vacuum erection device
(VED), penile prosthesis surgery (PPS).
2. The annual cost of sildenafil was
CAN$1,534, which was cheapter than
costs associated with alprostadil
intracavernous injections ($1908),
alprostadil transurethral suppositories
($2613) and surgery ($7875) but more
expensive than triple mix:
alprostadil/papaverine/phentolamine
($858) and VED ($730).
3. Sildenafil is the dominant economic
strategy for SCI patients as sildenafil is
less expensive and has a higher utility
than the other treatments.
Lombardi et al. 2009; Italy
Reviewed published
articles from 1998 to 2008
N=18
Level of evidence
methodological quality not
assessed
Type of studies
RCT (n=7), case series
(n=4), non-randomized CT
(n=3), prospective CT
(n=2), pre-post (n=1),
review (n=1)
AMSTAR=3
Method: 18 internationally published clinical
studies that enrolled SCI males treated with
at least one of the PDE5 inhibitors and
analyzed to evaluate how much the release
of PDE5 inhibitors changed the management of erectile dysfunction (ED) in men with SCI
and what remains to be seen of their
potential or limits.
Databases: Information not provided.
1. 705 participants used sildenafil, 305
vardenafil and 224 tadalafil. Median age
was <40 yrs. Only one study excluded
tetraplegic individuals
2. For measures of erectile dysfunction
(ED) evaluated, 11 out of 13 studies
reported significant statistical
improvement with PDE5 inhibitors vs.
placebo or erectile baseline.
3. The most frequent predicable factor for
the therapeutic success of PDE5
inhibitors was upper motoneuron lesion.
4. Statistical impact on ejaculation success
rates was shown in at least one paper
for all PDE5 inhibitors.
5. Overall 15 patients (7 using sildenafil)
discontinued the therapies due to
drawbacks. Only one sildenafil study
reported a follow-up max. of 24 mos.
Derry et al. 2002; UK
Non-systematically
reviewed articles from
1998 to 2001
N=6
Level of evidence
methodological quality not
assessed
Type of studies
RCT (n=2), Prospective
case series (n=4)
AMSTAR=2
Method: Search for articles examining
efficacy and safety of sildenafil treatment of
erectile dysfunction (ED) in men with SCI.
Databases: Information not provided.
1. For general efficacy the proportion of
patients who reported improved
erections and ability to have intercourse
was as high as 94%. Up to 72% of
intercourse attempts were successful.
2. For measures of erectile function, 5 of 6
studies showed statistically significant
improvements among sildenafil-treated
vs. placebo-treated patients.
3. Incidence of adverse events from all
causes in patients treated with sildenafil
ranged from 10% to 42%. The most
commonly reported adverse events were
headache, facial flushing, nasal
congestion, dyspepsia and visual
disturbances.
4. Existing evidence suggests oral
sildenafil is a highly effective and welltolerated treatment for ED associated
with SCI.
Brison et al. 2013;
USA
Reviewed publications
relevant to the field of
vacuum erection devices
N=5 (SCI)
Level of evidence
Methodological quality not
assessed
Type of studies
Not described
AMSTAR=1
Method: searched for all publications related
to vacuum erection devices (VEDs).
Databases: Not mentioned.
1. 5 studies investigating the effects of VEDs
in SCI patients showed that VEDs are a
viable alternative for treatment of ED in
the SCI population. VEDs are well
tolerated, and improve erectile function
and sexual satisfaction.
2. 70% of men using the VED reported
normal International Index of Erectile
Function-Erectile Function domain (IIEFEF) scores after treatment, compared
with 0^ before treatment. Men using
sildenafil or penile injections
comparatively reported 90% normal IIEF
scores.
3. In a 20 patient study, 93% of men
reported rigidity sufficient for vaginal
penetration after 3 months use with the
VED.
4. The most common complaint was
premature loss of penile rigidity during
intercourse.
Todd 2011; UK
Reviewed published
studies from 1950-2005
N=not stated
Level of evidence
Methodological quality not
assessed
Type of studies
1 case report, 1 case
series, other studies not
described
AMSTAR=1
Method: Searched using key terms priapism,
penile erection or clitorism plus spinal injury.
Only English articles were included.
Databases: Oldmedline (1950-1965),
Medline (1966-2005) and PubMed.
1. There is a very restricted literature that
has reported priapism in patients with
SCI. One study reported 6 patients with
priapism following acute SCI; all patients
had AIS A lesions. Another study
described a patient undergoing posterior
spinal fixation for a fracture of L2 who
awoke with priapism and a complete
motor and sensory paraplegia that was a
consequence of a large epidural
haematoma.
2. Priapism has been reported following
spinal shock. Typically, priapism that
follows acute traumatic SCI is high-flow
(non-ischaemic) priapism (blood within
the corpus is arterial in nature).
3. Following traumatic SCI, priapism usually
settles rapidly without specific treatment
required.
4. Priapism occurs at the moment of
complete motor and sensory paraplegia,
it does not occur following a delay.
Lombardi et al. 2015; Italy
AMSTAR=9
Non-systematically
reviewed articles from
1998 to 2001
N=6
Level of evidence
methodological quality not
assessed
Type of studies
RCT (n=2), Prospective
case series (n=4)
AMSTAR=2
Review study.
OBJECTIVES:
Alternative treatments to oral
phosphodiesterase type 5 inhibitors
(PDE5Is) in individuals with spinal cord
lesions (SCLs) and erectile dysfunction
(ED).
SETTING:
Italy.
METHODS:
Research clinical trials (1999-2014).
RESULTS:
Twelve studies were selected, 6
documenting conservative treatments and
6 documenting surgical treatments.
One article documented that 76% of
subjects reached satisfactory sexual
intercourse (SI) using intracavernosal
injection of vasoactive medications
(papaverine and prostaglandin E1). One
study regarding perineal training showed
a significant increase (P<0.05) in penile
tumescence in 10 individuals with
preserved sacral segment. Two studies
reported contrasting results on erectile
func tion (EF) using various dosages of
oral fampridine (25-40 mg). Furthermore,
95.1% of patients on fampridine 25 mg
experienced drawbacks. Disappointing findings were found with intraurethral
alprostadil (125-1000 μg) and sublingual
apomorphine 3 mg. Two studies
concerning penile prosthesis reported
valid SI more than 75% of the time with a
mean follow-up of 11 years, although
around 15% of individuals showed side
effects. As for surgical treatments, 88% of
males submitted to Brindley sacral
anterior root stimulator after sacral dorsal
rhizotomy achieved valid erection up to 8
years following the procedure. Three
studies documented the impact of
definitive sacral neuromodulation implant
(Medtronic, Minneapolis, MN, USA) also
on EF. After surgery, 20-37.5% of
patients with ED recovered normal EF.
CONCLUSIONS:
Data are scant on the efficacy of ED
treatments for SCL subjects who did not
respond to PDE5Is. Further research
should investigate the effects of any SCL
treatments even when they are not strictly
used for neurogenic sexual dysfunction.
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