Screening and managing erectile dysfunction in diabetic patients (review)

Sexologies (2013) 22, e1—e8

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ORIGINAL ARTICLE

Screening and managing erectile dysfunction in diabetic patients (review)夽 M.-H. Colson (MD) ∗, G. Roussey (MD) CRIR-AVS, hôpital Ste-Marguerite, 270, boulevard Ste-Marguerite, 13009 Marseille, France Available online 13 April 2012

KEYWORDS Diabetes; Erectile dysfunction; Endothelial dysfunction; Patient-physician communication; Sexuality

Summary Sexuality is frequently affected in diabetic patients. While one man in five suffers from erectile dysfunction (ED) in the general population, ED is 4.5 times more frequently observed in diabetic patients and starts 10 to 15 years earlier than in non-diabetics. ED in diabetic patients has significant semeiological value: it shows a significant change in the diabetes and its impact on the organs. It appears today to be the most reliable indicator of microangiopathic complications of diabetes and an important marker of possible silent ischemia. From the outset, ED is usually associated with major relationship and emotional problems. In diabetic patients, the consequences are even more serious and responsible for a significant deterioration in all aspects of quality of life, responsible for lower tolerability to the constraints of diabetes that will sometimes have an impact on therapeutic compliance and metabolic balance. General practitioners still experience many barriers and difficulties in consistently screening ED in diabetic patients and treating it. Nevertheless, it is possible to achieve and we should improve our clinical practices to better integrate screening and treatment of sexual pathologies in our patients, especially diabetics, to go beyond their demands and propose efficacious therapeutic solutions adapted to their needs. © 2012 Published by Elsevier Masson SAS.

Introduction Today a sustained increase of cases of diabetes can be observed. General practitioners have become the first line DOI of original article: http://dx.doi.org/10.1016/j.sexol.2012.02.001. 夽 Également en version franc ¸aise dans ce numéro : Colson, M.-H, Roussey G. Dépistage et prise en charge de la dysfonction érectile des patients diabétiques : une nécessité pour tout praticien ; revue de littérature. ∗ Corresponding author. E-mail addresses: [email protected] (M.-H. Colson), [email protected] (G. Roussey).

players in the screening, treatment and regular follow-up of patients with diabetes. The impact of sexual problems arising especially in patients with diabetes is still greatly underestimated and the screening as well as the treatment of erectile dysfunction (ED) continues to be marginalized even more in patients with diabetes than in the general population. Erectile problems are nevertheless more frequent, more serious and therefore less tolerable in men with diabetes than in men without diabetes. Delay in addressing erectile pathology is all the more damaging to the patient in that the semeiological value of the onset of ED is well established. Erectile disorders mark a decisive stage of the installation of degenerative complications of diabetes and provide the most reliable

1158-1360/$ – see front matter © 2012 Published by Elsevier Masson SAS. doi:10.1016/j.sexol.2012.02.002

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M.-H. Colson, G. Roussey

sign of aggravation of the disease. Therefore, screening for erectile dysfunction in men with diabetes should become a priority in routine general practice consultation.

Men with diabetes are affected by erectile dysfunction more frequently, more seriously and earlier in life than other men The number of patients with diabetes has been increasing at an alarming pace for the last decade, reaching an annual increase of more than 6 million; general estimations indicate that by the year 2030, the world population will include 366 million persons with diabetes (Wild et al., 2004). Although the impact of diabetes is greater in certain populations, particularly in Asia, Africa and the Maghreb, its prevalence in Europe is 5.9% and the disease remains largely undiagnosed among people of 50 years old or more (DECODE Study Group, 2003).

Erectile dysfunction is more frequent in men with diabetes than in the general population Over the last ten years, diabetes has been analysed in welldocumented epidemiologic studies (Table 1). The Olmsted longitudinal study, which included 2115 Americans between 40 and 79 years old, showed 31.4% of ejaculation problems in men with diabetes vs 6.6% in the general population; also, 50% of men with diabetes presented with ED vs 12.5% in the general population of the same age group (Burke et al., 2007). Similar data were reported by the other important reference investigations (Bacon et al., 2002; De Berardis et al., 2002; Fedele et al., 2000). In France, the reference study continues to be the investigation conducted by Giuliano et al. (2004), who applied the internationally recognized ED definition criteria provided by the IIEF scale, with 67% of positive answers in 2377 men with type I and type II diabetes. In general, the risk for ED in men with diabetes is 4.5 times the risk of other men (Burke et al., 2007). It seems that diabetes type does not have an effect on the onset of ED and the different major international studies show a comparable incidence of ED among men with diabetes, insulin dependent or not (Kalter-Leibovici et al., 2005). On the other hand, the longer the duration of diabetes, the greater the risk of increase in erection pathology (Alberti et al., 2004). In a recent study conducted in 555 patients with diabetes and taking into account the duration of the diabetes, six out of ten men under diabetes treatment for an average of 5 years (4.9 ± 1.5) suffer from ED (Feldman et al., 1994).

Table 1

We know today that the prevalence of erectile dysfunction increases with age, as has been shown by the big cohort studies. These studies teach us that ED occurs earlier in men with diabetes (Feldman et al., 1994; Zheng et al., 2006), nearly twice as rapidly as in men without diabetes and 10 to 15 years earlier (Johannes et al., 2000). Complaints of ED may be the only warning symptom of undiagnosed diabetes in older men (Lewis, 2001).

More erectile dysfunction risk factors and more emotional disturbances in men with diabetes The onset of ED in men with diabetes is directly correlated to the age of the patient and the duration of diabetes. But the other ED risk factors are also more common in men with diabetes, thereby aggravating its incidence. Diabetes is often associated with hypertension (Giuliano et al., 2004), obesity (El-Sakka and Tayeb, 2003), metabolic syndrome (Ford, 2005; Wilson et al., 2005) or with dyslipidemia (Fedele et al., 1998), which is also the case with ED, considered today a clinical form of endothelial illness, especially after the age of 40 (Calver et al., 1992; Elliot et al., 1993). Treatments for the foregoing pathologies are often involved in the onset or the aggravation of erection problems, thereby reinforcing or upholding the incidence of erection problems. More than any other chronic illness, diabetes predisposes patients to a higher risk for depression (Golden et al., 2007) and anxiety disorders (Corona et al., 2004). Standard psychological evaluations have shown that this risk is even higher when an erection problem is added to the diabetes condition (De Groot et al., 2001). Diabetes has a strong impact on emotional resistance and adaptation capacities vis-a-vis an erection problem. The men with diabetes suffer more because of erection difficulties than other men, in particular with regard to self-confidence (Penson et al., 2003) and self-esteem scores. All of their quality of life domains are seriously affected by erection problems (De Berardis et al., 2005).

The consequences of failure to screen for erectile dysfunction in men with diabetes: the neglect of an important early warning sign of diabetes aggravation The occurrence of ED in men with diabetes, who are patients at an increased cardiovascular risk, is therefore strongly correlated to diabetes aggravation. This is evidenced by

Frequency of erectile dysfunction among population with diabetes.

Fedele et al., 2000 De Berardis et al., 2002 Bacon et al., 2002 Giuliano et al., 2004 Burke et al., 2007

Country

n=

Mean age

Type of diabetes

Duration of diabetes (years)

Erectile dysfunction (%)

Italy Italy USA France USA

9868 1460 2057 2377 2115

NK 62 ± 10 65.8 59 ± 9 40—79

I + II II I + II I + II I + II

1 to 30 10 ± 9 0 to > 20 ND ND

36 34 45.8 67 50

Screening and managing erectile dysfunction in diabetic patients (review) the frequent concordance between ED onset and the elevation of the glycosylated hemoglobin levels in patients with diabetes (Feldman et al., 1994). The most recent publications report that the risk for cardiovascular disease is 1.6 times higher in men with diabetes presenting with ED than in other men (Ma et al., 2008). Erectile dysfunction is considered today as the most reliable indicator of the occurrence of vascular complications. Onset of ED marks a decisive aggravation stage of diabetes and of its complications. To neglect ED in patients with diabetes and failure to screen for it systematically is to neglect the installation of degenerative complications of diabetes (Gazzaruso et al., 2008). Adherence to antidiabetic treatment is a serious and recurring problem (Ross et al., 2011). The importance of emotional disturbances provoked by ED is frequently at the center of increased difficulties concerning compliance with the constraints imposed by diabetes (De Berardis et al., 2003). This psychological intolerance is also accompanied by an alteration in metabolic control in diabetes (KacerovskyBielesz et al., 2009). In a 2004 study, Lowentritt and Sklar (2004) demonstrated that 43% of men who spontaneously stop their antidiabetic treatments (insulin included) do it on their own initiative, upon the onset of erection problems, thinking that withdrawal from diabetes treatment will put an end to ED.

Treatment of erectile dysfunction in patients with diabetes by general practitioners: underdiagnosis The silent wait of patients Failure to screen for ED is a public health issue (Kirby et al., 2009) concerning the entire medical establishment. In 2009, only one in ten physicians included questions regarding the quality of erections in systematic questioning of their chronic patients (Buvat et al., 2009), while the large investigation on sexuality that has since become a reference and included 27,500 individuals in five continents, found that five men in ten would like their physician to pose these questions (Nicolosi et al., 2004). In 80% of cases, it is the patient who first introduces the subject of his erection problems to his physician, but it is well known that only 21.5% do this in practice (Laumann et al., 2009). Among patients with diabetes, the proportion is even lower than among the rest of patients (Sandoica et al., 1997). Physicians should more frequently ask their patients about their sexual health. In 2009, Cleveringa, questioning 1611 patients with diabetes and ED, treated by 42 general practitioners, made evident the reasons for that silence: the patients do not dare to talk directly to their physicians because they are afraid of putting them in an awkward situation, or because, ill-informed with respect to erection treatments, they think that ED is an unavoidable calamity without a solution (Cleveringa et al., 2009). The obstacles in medical consultation to address sexual problems are, from the physicians’ perspective, difficulty to find the right words, embarrassment, fear of putting the patient in an awkward position and lack of time. From the patients’

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perspective, embarrassment and lack of words are cited (Aschka et al., 2001).

The cautious discretion of physicians Physicians find it difficult to put into action their professional reflexes to respond to the demand of the patient who overcomes his reticence to talk. Most of the time, the patient will trivialize the problem. The more likely type of answer may often be: ‘‘it’s all in the mind, it will pass’’ (Marwick, 1999). Prescription in ED is not yet a first intention for most physicians (Berardis et al., 2009), even though it is recommended (Qaseem et al., 2009; Tsertsvadze et al., 2009). Diabetic patients seem subject to additional prescription difficulties, maybe because physicians, just like patients, do not imagine that ED can be cured. They are prescribed, five times more frequently than other men, ‘‘herbal medicine’’, instead of medications specific for erection problems, such as a PDE-5 inhibitor (De Berardis et al., 2005) (phosphodiesterase type 5 inhibitor).

Dare to talk with our patients The role of the general practitioner in ED screening and treatment is essential, thanks to the relationship of support and trust he/she builds during the face-to-face dialogue. He is often the first-line health professional chosen by the patient to talk about the distress linked to his ED. To approach the subject of sexual health during consultation is not as difficult as it seems.

Systematic screening is possible It is always possible to include a question about the quality of the erection in the case of new patients with diabetes or in the monthly follow-up of a patient with diabetes he already knows. This must be part of the systematic balance of other degenerative complications of diabetes usually looked for in consultation. The patient will be more open to addressing his sexual health in the middle of the consultation than at the beginning. It is a privileged period of the conversation, where the physician establishes a trust relationship, full of active empathy, allowing the building of a ‘‘clinical alliance’’. We show the patient that we are listening to him, that we are engaged in an interaction with him, with respect for his arguments and for him. Our will to help him is clearly perceptible for him. This form of anticipation makes it possible to avoid the pitfall of a statement like ‘‘Doctor, I have forgotten to talk you about my erection problems. . .’’ at the end of the consultation. It was most certainly the real reason for consultation of that patient. When the clinician takes the initiative of talking about sexuality within a context where the alliance is positively felt, the questioning may be voluntarily closed and wait for a yes or no answer: ‘‘do you have erection problems?’’, or ‘‘would you describe your sex life as satisfying?’’, or half open with an off-balance question, for example: ‘‘are you satisfied with your sex life or do you have erection problems?’’

e4 Sometimes, in order to avoid a feeling of embarrassment for the patient, it can be useful to generalize the problem, for example: ‘‘some of my patients with diabetes tell me that they have problems to achieve or maintain an erection during sexual intercourse, have you experienced that problem?’’ It is with a feeling of relief that the patient sees that he is not alone in the suffering caused by ED and that his physician has counselled other patients like him. Another advantage of this approach is that it suggests to the patient a reflection on the link between the sexual problem and diabetes. Even if the relationship is not systematic, it will be recalled later during the consultation. It is possible that the physician may try to approach the sexuality question with his/her patient without the latter’s agreement. Even if he refuses categorically to approach the sexuality question, the patient knows that he is talking with a reference person, who is able to help him in case of need or if he decides to approach the subject. A professional attitude combining active empathy, clinical alliance and clinician’s proactivity must be the rule.

Pitfalls to be avoided It is difficult for the patient to be the first to approach the sexual question with his physician and the physician should always maintain a professional attitude when addressing the sexual concerns of his/her patients. Some attitudes are to be avoided. Failure to take into consideration the patient’s demands will result in a rejection, leading to the final cancellation of the therapeutic dialogue. Trivialization is another way to hinder all treatment possibilities. Physicians must keep in mind that phrases such as ‘‘it’s all in the mind’’, or ‘‘it is only normal, it is a matter of fatigue, of stress. . .’’ will lead to the failure of future treatment possibilities. The common sense advice must be avoided. Advising your patient to ‘‘try with another (partner) to see if. . .’’ is not professional advice; the patient does not expect inappropriate advice from his physician.

The therapeutic algorithm The essence of diagnostics is a well-conducted interview (Cour et al., 2005). A positive diagnosis is fairly easy and it is led by the patient’s complaint. Differential diagnostic is a more delicate issue, because it is not rare that patients mistake ED with problems to achieve a new erection after a too rapid ejaculation for example. The confusion between desire and libido problems and erection problems is often important and, frequently, these two issues are entangled, especially in men with diabetes. The reduction of desire is sometimes caused by the erection problems, but if the condition existed before the installation of ED, there is a possible androgenic deficit. The etiologic diagnosis is more complex because the erectile disease affects various domains of the patient’s life, including the organic, the psychological and the relational domains and different elements present tend towards the mutual reinforcement in a synergic way. However, it is possible, especially in men with diabetes, to eliminate two important problems that are susceptible to resolution

M.-H. Colson, G. Roussey by informative and therapeutic action: dyspareunia may disrupt the normal course of the erection. Balanites are common in men with diabetes and one out of four acquired phimoses concerns a man with diabetes (Bromaqe et al., 2008). Delayed ejaculation is common in diabetic neuropathies and may cause a failure of the mental excitation, thereby compromising the erection and may be mitigated by providing the necessary information to patients. Diagnostic of gravity allows a better orientation concerning the level of treatment and particularly, if the treatment will fall within the field of a general practitioner or the field of a specialist.

What patients may be successfully treated by the general practitioner? A simplified questionnaire may provide, in few minutes, the necessary data to determine whether the patient should be referred to specialist care (Fig. 1). Persistence of good quality spontaneous erections is frequent and leads to excitation problem with erection integrity. These erections reassure the patient that ED is reversible. The sexuality of a great number of patients with diabetes is disturbed by sensitive problems that cause the loss of their arousal in the absence of sexual stimulation. Erection medications, specially the PDEI5, are often very effective at this stage if we take the precaution of simply explaining the origin of the problem. A positive role of the partner is to be assessed by means of a simple question: ‘‘What does your partner think about this?’’ It is better to be cautious when treating patients whose partners seem to reproach or exhibit a hostile attitude towards resuming sexuality. Most of the time, women are rather reassuring and positive about their husbands ED and wish to play a supporting role.

Which patients should be referred to a specialist? For the great majority of patients with diabetes presenting erection problems, the GP may be the only practitioner needed, but long-standing EDs may be difficult to treat. A persistent mentality of failure that results in early discontinuation of sexual intercourse or an anxious focus on erection deepened with the passing of time, modifies sexual behavior so deeply that it is not easy to remedy it by means of medication accompanied by some simple recommendations. ED developed during marital conflicts, where ED is only one of the emergent symptoms, cannot be solved simply with an erection medication. Hostile and demanding partners cannot play a positive role in the recuperation of confidence of the men affected by ED. Generally, lack of communication in the relationship results in discontinuation of ED treatment and the deepening of the problem (McCabe et al., 2010). ED, namely going back to early sexual experiences, is often rooted in social phobias, timidities, self-assertion problems, body dysmorphic disorders and have to be treated in specific ways.

Screening and managing erectile dysfunction in diabetic patients (review) ED

Simple cases - Maintained spontaneous erections - Positive partner

PDEI5

Follow- up

Improvement Recovery

Failure

e5

Complex cases - Long-standing ED (>3 years) - Associated premature ejaculation - Couple problems - Hostile partner or partner with sexual problems - Primary ED - Anxious focalization on erection +++

PDE-5 inhibitor

Urologist, psychiatrist, sexologist

Follow up by a general practitioner + an ED specialist

Figure 1

When should GPs treat erection problems in men with diabetes?

Premature ejaculation bringing about an ED complication, as a cause or as a consequence, is to be treated by the specialist. It is rare that reference to a psychiatric context results in a specialized consultation with a psychiatrist.

hypogonadism and in the absence of contraindications resulting from prostatic problems. The cardiovascular risk marked by ED installation may require a cardiological assessment. This assessment allows the application - in a more detailed fashion - of the lifestyle measures, thus reinforced.

Clinical examination ED complaint requires a urogenital examination and assessment of the secondary sexual characteristics: testicles (size, consistency), the penis (search for Peyronies’s disease, balanites, or other morphologic anomalies), a breast examination, a rectal examination for men aged more than 50 years, if there is no family history of prostate cancer, and after 46 years of age in the presence of family history. Neurological examination is important since it is a well-known fact that onset of ED may be the first symptom of peripheral neuropathy. Association with other peripheral neurologic signs, that are often more sensitive than motor signs, the presence of a saddle block anesthesia (at the moment of the rectal examination) is of great help.

Complementary tests Other than a biological test to examine the diabetes balance, there is no need to prescribe (Sharlip et al., 2008) complementary tests to treat ED. The amount of circulating androgens may be of interest when the diabetic patient with ED presents a pre-existent libido loss (Dandona and Dhindsa, 2011). Association of a PDE 5 inhibitor with an androgenic treatment is recommended in case of associated

How to treat erectile dysfunction? The general practitioner may take the initiative to prescribe PDEI5 and treatment follow-up. Prescription of erection medications should be accompanied by simple recommendations: avoid all haste during sexual intercourse and do not get discouraged in case of failure of the erection, but to restart sexual excitement by means of the appropriate caressing. Erection medication may be effective only after several attempts and it is important not to abandon the treatment too early for lack of effects of initial doses.

What about the partner? Women in general are hostile to erection treatment and consider themselves to be in competition with it. One woman in three is opposed to her partner’s pharmacologic treatment of ED. Her presence during consultations will facilitate the information exchange and overturn preconceived ideas in order to improve adherence to treatment. As a general rule, detailed explanation of the objectives and safety of the treatment are enough to obtain her active consent and participation.

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Prescription rules PDEI5s are oral erection medications of first line prescription (Sharlip et al., 2008). As with antidiabetics, antidepressants and sleep medication, it is not possible to issue a prescription of PDEI5 without a corresponding therapeutic strategy.

Patient’s information An informed patient is essential and justifies the specific time devoted to information during consultation. Therapeutic education plays a major role in ED treatment (Colson, 2007), just as in diabetes treatment. ED onset totally disorganizes the sexual behaviour of a man, and medication should be accompanied by straightforward instructions for the management of anxious behaviour to prevent hastiness or disheartening. It is important to explain the recommendations for use corresponding to each medication to prevent discontinuation of treatment. Clear explanations are enough to transform rapidly the initial non-responders into responders to the same erection treatment (Hatzichristou et al., 2005). As for any pharmacological treatment, there should be no hesitation in aligning with a real therapeutic strategy, including a therapeutic target (recovery or palliative care?) and a therapeutic strategy (what medication, what treatment duration, weaning modalities, cost. . .) in order to improve the awareness of the patient regarding his treatment and adherence. It must be remembered that erection medications are not aphrodisiacs and that a sexual stimulation is essential for the action of the medication. However, oral erection medications do not allow for sexual stimulation unless under natural conditions, namely adequate desire and excitation.

What medication should be chosen? PDEI5s have demonstrated their efficacy and should be preferred in first intention according to all current recommendations (Hatzichristou et al., 2005; McCabe et al., 2010; Paige et al., 2001). In practice, there are medications of short duration of action, circa 4 to 5 hours (Sildenafil [Viagra® ], Vardenafil [Levitra® ], and tadalafil, with a long duration of action of 36 hours [Cialis® ]). These treatments are indicated for on-demand administration and, therefore, would be appreciated if the frequency of sexual intercourse is limited and intercourse may be programmed (Sharlip et al., 2008). Since 2007, there is a new therapeutic alternative represented by the daily administration of tadalafil (5 mg/day, susceptible of reduction to 2.5 mg according to tolerability), allowing for a disconnection between the medication administration and the sexual activity (Hatzimouratidis et al., 2010). Among men with diabetes and chronic patients in general, daily administration of PDE 5 inhibitors (Cialis 5 mg) seems easier since it is best integrated in the context of daily habits, allowing the erection problem to be forgotten (Hatzichristou et al., 2008). In general, it is also preferred by the partner, and for the same reasons (Althof et al., 2010). In all cases, the participation of the patient in the design of his treatment is essential and

M.-H. Colson, G. Roussey the best choice is the patient’s own choice, enlightened by physician’s explanations. Major contraindications of PDEI5 treatment are the concomitant administration of nitrate derivates, a recent infarct or sexual activity contraindication for any reason. There is no need for a previous cardiac assessment for the prescription of a PDEI5, unless we think that the physical exercise represented by sexual intercourse, namely the equivalent to walking up two flights of stairs or 20 min/day walking, is not possible for the patient (Kostis et al., 2005).

Follow-up Follow-up time is an essential element of the therapeutic strategy. Often the patient needs to be encouraged. ED entails an important feeling of failure that results in the underestimation of the current improvement. It will be necessary to take the time to reassure and help the patient with his management of anxious behaviour or the premature discontinuation of the treatment. In case of resistance to treatment not explained by particular conditions of severity (relationship problems, major anxious focalization, associated premature ejaculation. . .), it is appropriate to suggest intracavernous injections of alprostadil, and on failure, the use of vacuum constriction devices.

Results It is not necessary to cite the many studies showing the extreme efficacy of PDEI5s in the treatment of erection problems in general and their excellent tolerability. A recent study, based on data from the US Cochrane database, examined the results of eight randomized studies with control groups, including 976 men with diabetes and ED (vs 741 in the control group), has shown the significant efficacy (an average 60% of satisfied patients) of PDE-5 inhibitor versus placebo, as well as their good tolerability (Vardi and Nini, 2007). Treatment with PDEI5 significantly improves the quality of erections, general well-being (Paige et al., 2001), and the quality of the relationship of the couple (Althof et al., 2006).

Conclusion For the majority of patients with diabetes, ED represents an important aggravation stage in the course of diabetes. ED is indicative of the evolution of endothelial disease and other degenerative complications of diabetes. This condition makes a significant impact on the personal and relational quality of life, while endangering the metabolic balance of diabetes and, in general, the life balance of the patient. Consequently, ED should not be neglected by the general practitioner. On the contrary, ED should be subject to systematic screening and treated in simplified ways, associating erection medications and therapeutic education to give the patient with diabetes the opportunity to regain a gratifying sex life.

Screening and managing erectile dysfunction in diabetic patients (review)

Disclosure of interest The authors declare that they have no conflicts of interest concerning this article.

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