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Diabetes-associated Erectile Dysfunction
Nonetheless, the peripherally acting oral PDE5Is are usually the first- Dissassociating the temporal relationship between sexual
line oral medical treatment for ED in diabetes. Upon sexual intercourse and treatment may be of benefit for some patients,
stimulation, sildenafil, vardenafil and tadalafil promote prolonged because planning sexual activity around a pill intake is a burden to
intracellular levels of cyclic guanosine monophosphate (cGMP) by some couples.
65,66
Preference studies will show whether some
inhibiting this enzyme, thereby improving SM cell relaxation.
55
All patients with diabetes and ED prefer to take daily tadalafil rather
PDE5Is are less efficacious in men with diabetes according to the than on demand. As ED severity with diabetes correlates with
complex pathophysiological mechanisms involved. Generally, endothelial dysfunction due to impairment in eNO-dependent
patients with diabetes require the maximum dose of each agent vasodilatation responses, tadalafil was shown to improve serum
taken on demand, i.e. sildenafil 100mg, vardenafil 20mg and tadalafil biomarkers of endothelial dysfunction, such as C-reactive protein
20mg. Sildenafil and vardenafil work better on an empty stomach, and vascular adhesion molecule-1.
67
The chronic use of tadalafil is
and tadalafil has a longer half-life, with a window of opportunity of therefore quite attractive, as it may ameliorate endothelial
36 hours, which may aid spontaneity.
56
Adverse effects are generally dysfunction, as well as improve erectile function. In addition,
mild and well tolerated. chronic therapy with tadalafil also improved endothelial function in
patients with increased cardiovascular risk, regardless of their ED
PDE5Is are contraindicated in individuals who are on nitrates, due to degree. The benefit of this therapy was sustained for at least two
the risk of profound and dangerous hypotension. However, it is weeks after the discontinuation of the treatment.
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A chronic
important to stress that no controlled or post-marketing studies of schedule also produces a dramatic increase in morning erections,
the three available PDE5Is have demonstrated an increase in the which determines better oxygenation of the penis, thus providing a
rates of myocardial infarction or death. This was observed in double- rationale for vascular rehabilitation.
67
In type 2 diabetes patients,
blind, placebo-controlled trials and in open-label studies (compared daily sildenafil administration improves endothelial function and
with expected rates in the study populations).
57
Although the reduces markers of vascular inflammation, suggesting that the
efficacy of PDE5Is is significantly lower in diabetes, there is an diabetes-induced impairment of endothelial function may be
important issue concerning treatment failure due not only to the improved by prolonged PDE5I therapy.
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severity of its pathophysiology but also to the inappropriate use of
the medication, unrealistic patient expectations, difficult ICIs and transurethral application of vasoactive substances are
relationship dynamics, severe performance anxiety and other generally used as a second-line treatment of ED in patients with
intrapsychic conflicts and problems of the individual.
58
Fewer than diabetes. As mentioned previously, ICIs should be considered as
four doses/attempts was the most common factor in treatment first-line treatment when the clinical evaluation shows severe
failures, followed by insufficient dose titration to the maximum endothelial dysfunction with less chance of PDE5I therapeutic
tolerated dose. Timing of intercourse and food instructions are also effectiveness. The most common injectable agents include
important. Many patients need to be reminded that these agents papaverine, phentolamine and PGE1. They may be delivered alone
should not be considered a ‘magic pill’ for outstanding sex and that (PGE1) or in association when additional efficacy is needed.
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PGE1
they do not work well without erotic stimulation. Up to 55% of initial is the most commonly used agent and can also be delivered
non-responders to sildenafil experienced improvement after transurethrally with lesser efficacy and increased adverse effects. In
education.
59
Monotherapy with testosterone appears to be of limited a heterogeneous group of men with ED, the intracavernous
effectiveness in ED but is most promising in younger hypogonadal administration of PGE1 was shown to be more effective than the
patients without vascular risk factors. transurethral approach (92.6 versus 61.8%).
71
Diabetes patients,
particularly those who are on insulin therapy, have a better and
The combination of testosterone and PDE5Is appears beneficial in easier acceptance of injections. Compliance is also better compared
men with ED and TDS.
60,61
Blute et al.
62
demonstrated that testosterone with non-diabetic men.
72
In a 10-year follow-up period, type 1 and
therapy can convert over half of men who failed to respond to PDE5Is type 2 diabetes patients used a similar number of injections for the
into PDE5 responders. However, it is still unclear whether men with treatment of their ED. Interestingly, patients with insulin-dependent
TDS should be treated initially with PDE5I, testosterone or a diabetes progressed more quickly to the final standardisation
combination of both. Different preparations are available, including treatment than those with non-insulin-dependent diabetes, possibly
gel, patches and injections. Gel and patches are the most commonly due to their familiarity with self-injecting and willingness to utilise
used preparations, but intramuscular injections can be considered injection therapy.
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Mild, short-lasting penile pain is a common
when testosterone levels are significantly low and long-term adverse effect of the treatment with PGE1, and prolonged erections
administration is indicated. were reported by 5% of men.
74
Contraindications to ICIs are scarce,
including priapism, multiple myeloma and sickle cell disease.
A continuous administration scheme of PDE5Is may also be
considered. McMahon
63
treated men with ED with continuous, Vacuum erection devices are an additional treatment for diabetes-
flexible doses (10 and 20mg) of tadalafil on a daily basis for 12 associated ED. In spite of being universally accepted and not requiring
weeks. Daily tadalafil significantly improved patients’ IIEF and sexual a prescription, they are cumbersome and give an unnatural erection.
encounter profile question 3, compared with on-demand tadalafil. In This approach is overall the most economical therapy for ED. Vacuum
a study of men with diabetes and ED, once-daily tadalafil 2.5 and erection devices promote satisfactory erections in approximately 70%
5mg was efficacious and well tolerated, suggesting that this may be of men with diabetes.
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However, up to 30% of patients discontinue
an alternative to on-demand treatment for some men, thereby their use due to inadequate rigidity, appearance of the penis while
eliminating the need to plan sex within a limited time-frame.
64
In fact, using the device (congestion or petechiae), penile pain, coldness,
once-a-day therapy with tadalafil in men with diabetes with ED delayed ejaculation and a sense of trapped ejaculate.
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No specific
significantly improved various aspects of patient satisfaction. conditions are contraindicated in the use of vacuum erection devices,
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