The information – erectile dysfunction

The patient’s unmet needs (PUNs)

A 67-year-old man attends, looking rather sheepish, accompanied by his wife. ‘Those magic blue pills are no good, doctor,’ he says. A quick review of the notes reveals that he is a heavy-drinking hypertensive with type 2 diabetes, who is on metformin, amlodipine, enalapril and atenolol, and was was prescribed Viagra for erectile dysfunction (ED) a few months ago. ‘I’m sure it’s my blood pressure pills,’ he continues. ‘Can’t I stop them? If not, are there any other erection pills I can try?’ It’s at this point that his wife chimes in. ‘I’ve told him that if they don’t work, nothing will,’ she says. ‘Besides, I’m worried it might bring on a heart attack at his age. He gets chest pain as it is.’

The doctor’s educational needs (DENs)

In a situation like this, there are many possible causes for the ED. Is individual or combined management of the relevant risk factors likely to help the ED without other treatment?

This particular patient has multiple risk factors that are likely to cause a combination of vasculogenic and neurogenic erectile dysfunction as a result of small vessel vascular disease, endothelial dysfunction and neuropathy affecting the pelvic plexus and cavernosal nerves.

A number of lifestyle modifications can help with mild ED, including regular exercise, cessation of smoking and a reduction in alcohol intake. However, significant risk factors such as diabetes and cardiovascular disease result in ED due to impairment of relaxation of the corpus cavernosum smooth muscle within the penis.

Although some cardiovascular drugs impair smooth muscle relaxation – resulting in ED – it is likely that damage to the smooth muscle in the penis has preceded the onset of the cardiovascular disease, which in this case has required treatment with antihypertensive medication. Recently, the third Princeton consensus defines cardiovascular risk as the risk of morbid events over a 3-5-year interval from the onset of ED in asymptomatic men.¹In younger men, the onset of ED is likely to precede a cardiovascular event by 5-10 years and therefore a cardiovascular assessment of these patients should be performed.

Although PDE-5 inhibitors offer a convenient first-line therapeutic option, provided that patients are not taking concomitant nitrate therapy, they also need to be fit enough to have sexual intercourse e.g. walking two flights of stairs or walking a mile in 20 minutes.

In a patient on multiple medications who blames his treatment regime, what is a logical approach the situation?

It is difficult to either stop or adjust multiple antihypertensive medications without patients developing poorly controlled hypertension. Occasionally switching one monotherapy to another may improve erections, but in practice the blood pressure needs to be controlled to prevent further small vessel disease in the penis and endothelial dysfunction.

This should be explained to the patient, with an emphasis on preventing long-term cardiovascular risk. If the exercise tolerance is good enough and there are no contraindications then lifestyle modifications should be combined with a PDE-5 inhibitor. Failing oral PDE-5 treatment, the next option would be intracavernosal or intraurethral prostaglandin.

Alternatives before surgery also include a vacuum device that can be used in all patient groups. Surgery in the form of a penile prosthesis can be offered as an end-stage surgical solution. The penile prosthesis may be either a malleable or an inflatable prosthesis. The inflatable prosthesis comprises two cylinders which are placed within the corpus cavernosum, a pump within the scrotum and a reservoir which is filled with saline and placed in the retropubic space. By using the pump, fluid can flow from the reservoir to the cylinders providing rigidity and girth to the penis for sexual intercourse (see fig. 1).

Fig 1: The new Coloplast Titan Touch Inflatable Penile Prosthesis showing the inflatable cylinders which are inserted into the corpora and the pump which is inserted into the scrotum. The reservoir is placed in the retropubic space. 

What are the main reasons for apparent treatment failure?

Pharmacological failures are commonly due to patients stopping the treatment too early or not taking the medication as instructed. Generally, it is recommended that at least eight attempts at the maximum dose of a PDE-5 inhibitor be tried before this is deemed a pharmacological failure. Patients should be advised to take the tablets at least one hour before sexual intercourse and require sexual stimulation in addition to taking the medication. Where the PDE-5 inhibitors may have been efficacious initially but then fail to work, it is likely that disease progression in the microvasculature, together with endothelial dysfunction, have resulted in impairment of smooth muscle relaxation.

What is the likelihood of other PDE type-5 inhibitors helping if sildenafil has been unsuccessful?

Although the three main PDE-5 inhibitors – sildenafil, vardenafil and tadalafil – have the same mechanism of action, they differ in some aspects of pharmacokinetics. Some patients feel that the timing of taking the tablet before intercourse adds extra pressure. If more spontaneity is required, then a longer-acting PDE-5 inhibitor, such as tadalafil, which has a half-life of 17.5 hours, is more suitable. Once a tablet is taken, sexual intercourse can be attempted within a 24-hour period. So it is worthwhile switching from a short-acting to a longer-acting PDE-5 inhibitor before deciding that oral pharmacotherapies have failed.

How likely is it that sexual activity might trigger an acute cardiac event? Which cardiac medications interact with PDE5 inhibitors, and how can GPs circumvent the issue of patients on GTN?

The clinical trials relating to PDE-5 inhibitors have demonstrated that there is no increase in the myocardial infarction rate, total exercise time or time to ischaemia in men with stable angina taking these drugs. If there are more than three coronary risk factors (excluding age and sex) and a history of moderate angina or congestive heart failure, or recent MI or CVA,  then referral for further cardiac investigations is required before advising on whether treatment for ED can commence.²

A number of cardiac medications are associated with erectile dysfunction:

• β blockers
• Verapamil
• Methyldopa
• Clonidine
• Reserpine
• Guanethidine
• Digoxin
• Amiodarone
• Spironolactone
• Thiazide

Due to unpredictable hypotension, nitrates are the most important cardiac drugs that are totally contraindicated with all PDE-5 inhibitors, and therefore alternative treatment options should be used such as intracavernosal/intraurethral prostaglandin or vacuum devices. Men prescribed doxazocin must also be advised to avoid PDE-5 inhibitors due to unpredictable hypotension.

More recently, non-invasive treatment options have focused on the effects of low intensity shock wave treatment, which is thought to promote neoangiogenesis in the penis. This is suitable for those patients who have a contraindication to PDE-5 inhibitors or those who do not tolerate the oral medication.

Mr Asif Muneer is a consultant urological surgeon and andrologist at Spire Bushey Hospital and University College London Hospital.

References

1. Nehra A, Jackson G, Miner M et al. The Princeton III Consensus recommendations for the management of erectile dysfunction and cardiovascular disease. Mayo Clinic Proceedings 2012;87(8):766-78
2. Kostis JB, Jackson G, Rosen R et al. Sexual dysfunction and cardiac risk (the Second Princeton Consensus Conference). Am J Cardiol 2005;96(12B) 313-21

Further reading and useful resources