Symptoms of ED¹

The DSM-5 has identified 3 symptoms for ED:¹

• Marked difficulty in obtaining an erection during sexual activity
• Marked difficulty in maintaining an erection until completion of sexual activity
• Marked decrease in erectile rigidity or hardness
What might be causing ED?²
To establish what might be causing ED, a simple question to ask is: Is the ED
circumstantial or is it always a problem?²

• If ED occurs all the time, the causes are likely to be physical²
• If ED happens only now and again, psychological reasons may be the cause²

There are 4 main types of physical conditions that can result in ED:²

• Vasculogenic conditions, for example, atherosclerosis, high BP, diabetes and high cholesterol
• Neurogenic conditions, for example, multiple sclerosis, Parkinson’s disease or stroke
• Hormonal conditions, for example, hypogonadism and hypo- or hyperthyroidism
• Anatomical conditions, for example, Peyronie’s disease (a condition affecting the tissue of the penis), and hypospadias (abnormal development of the urethra)

The pathophysiology of ED may be drug-induced³

Some medications that can cause erection problems:³

• Antihypertensives
  • Diuretics are the most common medication causing ED
• Antidepressants
• Hormone therapy for prostate

Recreational/illicit drugs can also cause erection problems.³

BP: blood pressure; DSM: Diagnostic and Statistical Manual of Mental Disorders; ED: erectile dysfunction; NCD: non-communicable disease.

Common risk factors of ED and CVD^3,4

CV safety and medications for ED⁵

• No evidence of increase in MI rates in men taking PDE-5 inhibitors to treat ED³
• Nitrate preparations used to treat angina are contraindicated with PDE-5 inhibitors³
• Can cause unpredictable falls in BP and symptoms of hypotension

• Antihypertensive drugs may be co-administered with PDE-5 inhibitors³
• May result in small additive decreases in BP

• PDE-5 inhibitors can be given to men who are stable on alpha-blocker therapy³
• Sildenafil should be used with caution in patients taking an alpha blocker (especially doxazosin)
• Interaction under some conditions may cause orthostatic hypotension
• Initiation of PDE-5 inhibitors at the lowest dose should be considered

The recognition of ED as a warning sign of silent vascular disease has led to the concept that a man with ED and no cardiac symptoms is a cardiac (or vascular) patient until proven otherwise ^5,6

Screening in men with ED and known CVD⁶

Management of ED in all men with ED, especially those with known CVD, according to the Princeton III Consensus Recommendations.⁶

Adapted from Nehra A, et al, Mayo clin Proc. 2012.

When to treat or refer patients with ED⁶

Adapted from Nehra A, et al, Mayo clin Proc. 2012.

By 2025, the worldwide prevalence of ED is estimated to be approximately 320 million men*¹

• The combined prevalence of mild, moderate, moderate or severe and severe ED in men aged >30 years is 56.9%¹
• A majority were mild cases (32.7%), while the remainder were classified as moderate (18.0%), moderate or severe (4.3%) or severe (2.3%)¹

ED is a globally prevalent sexual problem²

• The prevalence of ED increases with age³
• ED affects 20%-40% of men who are 60 and above, and 50%-75% of men older than 70 years³

Overall ED prevalence according to National Health and Wellness Surveys in 2016⁴

• Overall prevalence of ED was found to be 40.5% according to a large cross-sectional, internet-based National Health and Wellness Survey that represented adult populations in Brazil, China, France, Germany, Italy, Spain, UK and US⁴

Increasing prevalence of ED with age⁵

In the European Male Ageing Study, it was reported that ED increases with age. Importantly, the prevalence of severe ED (defined as an IIEF score of 1-7) increases at a steeper rate than that of moderate ED (score of 8-11) in men over 60 years of age.⁴

Increasing prevalence of ED with age⁵

      Adapted from Yafi F. A, et al, Nat Rev Dis Primers. 2016.

ED: erectile dysfunction; IIEF: International index of erectile function; NCD: non-communicable disease; UK: United Kingdom; US: United States.

In the “Multinational Men’s Attitudes to Life Events and Sexuality (MALES)” study:
Men with comorbid medical conditions and risk factors all reported higher prevalence of ED.¹

ED, appearing in otherwise healthy men, may be an indicator of serious systemic conditions that have not yet manifested in other ways.⁵

Erection as the most efficient marker of the phenotypic condition of biological systems

Management of NCD-generated ED

CVD

• ED may be an early indicator for identifying men at higher risk of CVD,⁸ which has been demonstrated to occur on average 3 to 5 years prior to the CV event.⁹
• Incidence of cardiac disease tends to be higher in those with ED.⁸ Studies have reported an increased prevalence of ED in patients with CAD compared with men without CAD as well as an increased risk of CVD in men with ED compared with men without ED.⁹
• In a retrospective study of 62 men admitted to the hospital for first MI, 51.6% of patients were reported to have pre-existing ED.⁹
• ED and CVD share many common risk factors, including age, hypertension, diabetes, insulin resistance, smoking, increased BMI, cholesterol and lower HDL.⁹
• The artery size hypothesis stipulates that ED is an earlier symptom of systemic atherosclerosis.¹⁰

The artery size hypothesis. (A) Early stage of the atherosclerotic process. Significant vascular obstruction (>50% lumen artery narrowing) of penile circulation leading to ED symptoms is shown. (B) Late stage of the atherosclerotic process. Significant vascular obstruction of coronary circulation leading to angina pectoris is shown.¹⁰

The relationship between ED and CVD in various multivariate models.¹¹

*Hazard ratio compared with men with no ED.
†Wald Chi-square test.
‡The multivariate model includes BMI (continuous) and the variables that are part of the Framingham risk score: Age, HDL cholesterol and TC (all as continuous variables), as well as current smoking (yes/no), and hypertension categorised according to BP readings by JNC-V definition (optimal, normal, high normal, Stages I-IV).¹¹

Why screening for ED matters for CVD⁸?

A systematic literature review was conducted to analyse the relationship between ED and CVD, including pathological links between these conditions. A systematic literature review searching Medline, Embase and Web of Science databases was performed. The search strategy included the terms erectile dysfunction, cardiovascular disease, coronary artery disease, risk factors, pathophysiology, atherosclerosis, low androgen levels, inflammation, screening and phosphodiesterase type 5 inhibitors alone or in combination. ED and CVD should be regarded as 2 different manifestations of the same systemic disorder. ED usually precedes CVD onset, and it might be considered an early marker of symptomatic CVD.⁸
A systematic review discusses the role of cardiologists and urologists in the characterisation of risk and management of CVD in the setting of ED, as well as contrasting the current evaluation of CVD and ED from the standpoint of published consensus statements.⁹
A pathophysiologic mechanism was proposed to explain the link between ED and CAD called the artery size hypothesis. Given the systemic nature of atherosclerosis, all major vascular beds should be affected to the same extent. However, symptoms rarely become evident at the same time. This difference in rate of occurrence of different symptoms is proposed to be caused by the different size of the arteries supplying different vascular beds that allow a larger vessel to better tolerate the same amount of plaque compared with a smaller one.¹⁰
A prospective, population-based study of 1709 men (of 3258 eligible) aged 40-70 years was conducted. ED was measured by self-report. Subjects were followed for CVD for an average follow-up of 11.7 years. The association between ED and CVD was examined using the Cox proportional hazards regression model. The discriminatory capability of ED was examined using c-statistics. The reclassification of CVD risk associated with ED was assessed using a method that quantifies net reclassification improvement.¹¹

BMI: body mass index; BP: blood pressure; CAD: coronary artery disease, CI: confidence interval; CV: cardiovascular; CVD: cardiovascular disease, ED: erectile dysfunction, HDL: high-density lipoprotein, JNC: Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure; MI: myocardial infarction, NCD: non-communicable disease; TC: total cholesterol; TIA: transient ischaemic attack.

According to a Global Sexual Habits survey,* a majority of men with ED plan for sexual intercourse.^†2

In 9/10 men, the 2 most important attributes of ED medications were:

• Providing a rigid erection (93%)²
• Low level of side effects (90%)²

83% of men taking medication for sexual intercourse always or sometimes plan a specific time for intercourse.²

Median frequency of sexual intercourse:¹

6 times a month

Median frequency of ED medication use:¹

5 times a month

Importance of product attributes³

The highest rated attribute in terms of importance when purchasing an ED medication is efficacy – provides rigid erection (93%) and low levels of side effects (90%).³

Base: all respondents (see brackets)

Q6b. To what extent do you consider the following attributes to be important when thinking about purchasing an erectile dysfunction medication?

*Brazil, China, Italy, Japan, Russia, Taiwan and Turkey.

^†In total, 1458 men were screened in this survey.

ED: erectile dysfunction; NCD: non-communicable disease.

Evaluating hardness with EHS¹

Penile rigidity is the most important determinant of the quality of an erection.¹

The EHS is a validated instrument.¹

Adapted from Mulhall J. P, et al, J Sex Med. 2007.

• Completely hard erections should be considered a treatment goal in most men²
• Erection hardness affects self-esteem, overall relationship satisfaction, confidence and sexual satisfaction³

In men with ED, VIAGRA^® delivered an increase in Grade 4 erections versus placebo⁴

Men with ED were able to attain Grade 4 erection hardness with increasing dose of VIAGRA^®.⁴

Adapted from Goldstein I, et al, N Engl J Med. 1998.

*P<0.001 for the comparison with placebo of Grade 4 and of Grade 3 plus Grade 4.⁴

In a 24-week, dose-response study, 532 men were treated with oral sildenafil (25 mg, 50 mg or 100 mg) or placebo. In a 12-week, flexible dose-escalation study, 329 different men were treated with sildenafil or placebo, with dose escalation to 100 mg based on efficacy and tolerance. After this dose-escalation study, 225 of the 329 men entered a 32-week, open-label extension study. We assessed efficacy according to the IIEF, a patient log and a global-efficacy question.⁴

ED: erectile dysfunction; EHS: erectile hardness score; IIEF: International Index of Erectile Function; NCD: non-communicable disease.