A lecture about the effect of diabetes mellitus on the erectile function. Dr. Mohand Yaghi was an invited speaker in Al-Jahra scientific day, Kuwait 2015.

1. Dr. Mohand Yaghi
PgDip urol (MU) ChM urol (RCSEdin.)

2.  Physiology of erection :

4.  KUW: of 323 patients with DM 2, 31%
had ED, IIEF-5 used. (The prevalence and
predictors of erectile dysfunction in men with newly diagnosed
with type 2 diabetes mellitus. BJU Int. 2007 Jan;99(1):130-4)
 KSA: 376 pts, DM 2, 81% reported ED.
(Erectile Dysfunction and Other Sexual Activity Dysfunctions
among Saudi Type 2 Diabetic Patients. AlMogbel . Int J Health Sci
(Qassim). 2014 Oct;8(4):347-59)
 Risk factors – age, smoking, glu
control, duration of DM & smoking,
occupation, income, education.

9.  beta blockers, diuretics, hydralazine, CCB
 Centrally acting: Methyldopa, Clonidine.
 Antidepressants: Benzodiazepines,
Phenothiazines, Haloperidol, Li, MAOIs,
Tricyclics.
 Hormones: anti-androgens, LHRH agonists
 Others: Cimetidine, Digoxin, Metoclopromide,
Statins.

10.  Controversial
 Any drugs which lowers BP can cause ED (J.
Jensen et al. “The prevalence and etiology of impotence in
101 male hypertensive outpatients,” American Journal of
Hypertension, vol. 12, no. 3, pp. 271–275, 1999)
 small studies suggested that some
antihypertensive drug classes could have less
harmful or even beneficial effect on sexual
function like CCB (C. A. Derby 2001), angiotensin
II receptor blockers (M. Böhm et al. 2007) , and
nebivolol (S. Bansal 1998)

11.  96 patients (all males, age 52+/-7 years) with
newly diagnosed CVD and not suffering from ED.
 Divided to 3 groups: group A didn’t know the drug,
Group B knew the drug but not the side effect,
Group C knew the drug and the side effects.
 Results: ED in Group A 3.1%, group B 15.6%, group
C 31.2%/

12.  Endothelial dysfunction, neuropathy, vascular changes.
 Penile tissue from diabetic men with ED demonstrates
impaired neurogenic and endothelium-mediated relaxation of
smooth muscle. (aenz de Tejada I et al. 1989, N Engl J Med
320:1025 –1030, 1989)
 Increased accumulation of advanced glycation end products
(AGEs),23 and upregulation arginase, a competitor with nitric
oxide synthase for its substrate L-arginine. (Seftel AD et al.,
Urology 50:1016 –1026, 1999)
 decreased synthesis, release, or activity of nitric oxide
through increased polyol pathway flux, intracellular
accumulation of AGEs, activation of protein kinase C, and
increased flux through the hexosamine pathway. (Brownlee
M: Biochemistry and molecular cell biology of diabetic
complications. Nature 414:813 –820, 2001)

13.  Experimental hyperglycemia may also affect
cavernosal smooth muscle cell contractile
responses.
 penile smooth muscle has augmented force
responses to vaconstrictors, possibly mediated
by changes in expression of protein kinase C
(Chitaley K et al., Nat Med7 : 119–122,2001)
 Arterial morphology, flow, and diameter differ
between diabetic and nondiabetic populations
with ED. (Ruzbarsky V et al. Invest Urol 15::194
–199, 1997. Lehman TP et al., J Urol129 : 291–
294,1983)

14. EAU guidelines 2015
• History ( sexual relations, emotional status,
duration, rigidity, morning erection), IIEF-5,
depression? Hypogonadism? IPSS.
• Physical exam.(GU, Vascular, neurology,
endocrine).
• Lab. (HBA1c, FBG, lipids profile, morning
Testosterone, PSA, TFTs). Prolactin & LH if
Testosterone is low.

15.  Nocturnal penile tumescence and rigidity test
(NPTR)- erection with 60% of rigidity for >
10min. (Rigiscan)
 Intra-cavernous injection test- functional test.
 Duplex US- PSF > 30cm/s, end-diastolic
velocity < 3cm/s.
 Internal pudendal Arteriography- rarely
performed only perform reconstruction
surgery.
 Psychiatric assessment- specially in young pts.

20.  Life style changes particularly important in
individuals with ED and comorbidities like
DM/HT. Increase PDE5Is response.
Derby CA, Mohr BA, Goldstein I, et al. Modifiable risk factors
and erectile dysfunction: can lifestyle changes modify risk?
Urology 2000 Aug;56(2):302-6.
 Prospective study, 1097 pts, age (40-70),
examined life changes in smoking, physical
activity, alcohol consumption, obesity.
 Results: Only obesity (p 0.006), and physical
activity (p 0.01) were associated with ED.

21.  RCT, single blinded, 110 obese pts, age 35-
55.
 After 2 yrs, BMI decreased from 36.9 to 31.2
in the interventional arm.
 IIEF-5 increased from 13 to 17
 17 men reported IIEF score of 22 or higher.
 Conclusion: 1/3 of the pts reported
improvement in sexual activity after weight
loss .

22.  Sildenafil (Viagra) : first PDEIs 1998, doses 25,
50, 100 mg.
 Initiation dose 50mg, effect starts from 30-
60min., may last for 12 hrs.
 In patients with diabetes, 66.6% reported
improved erections (GAQ) and 63% successful
intercourse attempts compared to 28.6% and
33% of men taking placebo.
Stuckey BG, Jadzinsky MN, Murphy LJ, et al. Sildenafil citrate for
treatment of erectile dysfunction in men with type 1 diabetes:
results of a randomized controlled trial. Diabetes Care 2003
Feb;26(2):279-84.

23.  Effect after 30min, peak after 2 hours, maintained eff.
Up to 36 hrs. absorption not affected by fatty food
like Viagra/Levitra.
 10, 20mg approved. Initial dose 10mg.
 Diabetics- 64% reported improved erections versus
25% of patients in the control group.
 But diabetic pts remain poor responders to ON
DEMAND Tadalafil (45% for 10mg and 50% for 20mg)
Fonseca V, Seftel A, Denne J, et al. Impact of diabetes
mellitus on the severity of erectile dysfunction and
response to treatment: analysis of data from tadalafil
clinical trials. Diabetologia 2004 Nov;47(11):1914-23.

24.  Starts 30min., 5mg, 10mg, 20mg approved
from “on-demand”.
 diabetic patients remain poor responders
to on-demand with a successful intercourse
rates increasing from 23% with placebo to
49% and 54% with 10 and 20 mg of
Vardenafil on-demand.

25.  Highly selective PDE5Is, fast ( 15-30min), lasts
for > 6hrs, half-life 6-17hrs.
 Side effects is lower than other PDE5.
 Recommended dose 100mg (15-30min before
intercourse).
 Success rates: 41.3%, 57.1%, and 57.0% for
avanafil 50 mg, 100 mg, and 200 mg
respectively in the general population with ED.
(Goldstein et al. 2012b).
 34.4% and 40.0% for 100 mg and 200 mg in
men with diabetes (89.5% type 2). Goldestein et
al. 2012b

26.  Daily tadalafil led to a significantly higher IIEF score
and higher completion of successful intercourse
attempts compared to on-demand tadalafil. McMahon C.
Comparison of efficacy, safety and tolerability of on-demand tadalafil and daily dosed
tadalafil for the treatment of erectile dysfunction. J Sex Med 2005 May;2(3):415-25.
 Alternative to on-demand dosing of tadalafil for
couples who prefer spontaneous rather than
scheduled sexual activities
 Double-blind, placebo-controlled study of 298 men
with diabetes and ED, 2.5 and 5 mg tadalafil once
daily for 12 weeks was efficacious and well tolerated.
Hatzichristou D, Gambla M, Rubio-Aurioles E, et al. Efficacy of tadalafil
once daily in men with diabetes mellitus and erectile dysfunction. Diabet
Med 2008 Feb;25(2):138-46.

27.  Between 70-90% of patients choose Tadalafil (Cialis).
1. von Keitz A, Rajfer J, Segal S et al. A multicenter,
randomized, double-blind, crossover study to evaluate patient
preference for tadalafil and sildenafil. Eur Urol 2004; 45: 499-
507.
2. Stroberg P, Murphy A, Costigan T. Switching patients with
erectile dysfunction from sildenafil citrate to tadalafil: results
of a European multicenter, open-label study of patient
preference. Clin Ther 2003; 25: 2724-37.
3. Eardley I, Mirone V, Montorsi F et al. An open-label,
multicentre, randomized, crossover study comparing sildenafil
citrate and tadalafil for treating erectile dysfunction in men
nave to phosphodiesterase 5 inhibitor therapy. BJU Int2005;
96: 1323-32.

28.  Doesn’t increase MI, or time to ischemia in
pts with stable angina. In fact, there is
evidence that PDE5Is improve exercise test.
 Nitrates contraindicated
 If patient on PDE5Is develops angina,
Nitroglycerine should be given 24hrs
(Viagra)/48hrs (Cialis)
 α-Blockers + PDE5Is (Viagra) = orthostatic
hypotension (first 4 hrs)
 patients should be stable on α-blocker
therapy prior to initiating combined
treatment, and that the lowest dose should
be started initially of PDE5Is

30.  Empty stomach, no alcohol, no fatty food,
sexual stimulation, appropriate time for
absorption (AT LEAST 60min required for
men using Sildenafil and Vardenafil, and up
to 2 h being required for men using tadalafil),
adequate dose.

31.  Alprostadil (Caverject)- PGE1
 most efficacious as monotherapy at a dose of
5-40 μg, starts 5-15min.
 Efficacy rates for intracavernous alprostadil of
> 70% in general ED populations, as well as
CVD, DM.
 sexual activity after 94% of the injections and
satisfaction rates of 87-93.5% in patients and
86-90.3% in partners.

32.  Penile pain (50%), prolonged erections (5%),
priapism (1%), fibrosis (2%), hypotension.
 Pain can be alleviated with the addition of
sodium bicarbonate or local anaesthesia.
 Cavernosal fibrosis clears within a few
months after temporary discontinuation of
the injection.
 Contraindications: bleeding disorders, risk
of priapism.
 Drop-out rates of 41-68%, with most
dropouts occurring within the first 2-3
months.

33.  MUSE- Erections sufficient for intercourse
are achieved in 30-65.9%, constricting ring
increase the response
 local pain (29-41%) and dizziness with
possible hypotension (1.9-14%). Penile
fibrosis and priapism(< 1%), urethral
bleeding (5%) and urinary tract infections
(0.2%).
 alternative to intracavernous injections in
patients who prefer a less-invasive and less
effective treatment.

37.  Penile Prosthesis – inflatable, malleable
devices.
 For non-responders to oral therapy or who
prefer a permanent solution.
 Peno-scrotal approach or infrapubic
approach.
 Highest satisfaction rates (92-100% in
patients and 91-95% in partners).
 Complications: mechanical failure (>5%
after 5yrs), infection (2-3%), diabetics have
the same incidents.

39.  ED evaluation is crucial in patients over 40.
 ED is treatable condition.
 Life style changes make some difference.
 Doctor-patient relationship and
communication is essential.
 Variety of ED treatments exists.