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Erectile dysfunction: tricks of the trade

Geoffrey Hackett
MD MRCPI MRCPI
GP
Consultant in Urology
President of British Society of Sexual Medicine
West Midlands

The availability of three excellent PDE5 inhibitors enables healthcare physicians to effectively treat around 70% of men with erectile dysfunction (ED). We must remember that these responses were obtained in clinical trials with well-motivated doctors and patients, with unlimited quantities of free medication provided by the sponsor.(1) In the real-life situation, with regulatory restrictions and lower motivation, response rates will be lower.
The majority of patients will experience a response to all three drugs within one hour, but vardenafil and sildenafil with half-lives of around four hours may have a slightly faster onset of action. For couples who find that their lifestyle makes it difficult to negotiate planned sexual activity, then tadalafil, with a half-life of 17.t they prefer (see Tabl5 hours, might provide the greater flexibility thae 1).

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The challenge is to optimise responses in the 30% of potential nonresponders, as most (but not all) men would prefer not to use second-line therapies such as intracavernosal injections, intraurethral PGE1 or vacuum devices. Several well-defined strategies for these nonresponders are now recognised.

Classification of nonresponders
In the UK, men with ED have a mean age of 57 and have suffered for an average of three years before seeking help. They will often have a perimenopausal partner with medical and hormonal problems that will affect their levels of desire, arousal, lubrication and motivation. These should, ideally, be addressed in all cases, with vaginal dryness being the most easily treated partner association.
This combination of conditions has often caused relationship difficulties, not easily solved by the administration of a single tablet.
Men should not be considered treatment failures until they have taken at least eight maximal doses of (preferably) at least two drugs in the class.(2)
Patients with severe diabetes, advanced vascular disease, pelvic surgery and radical prostatectomy form the bulk of nonresponders. In the case of diabetic patients, the longer that they have suffered and the greater the number of complications, the less likely they are to respond. This is a strong argument for routine questioning of all diabetic patients attending for chronic disease management.
Strategies for managing nonresponders are summarised in Box 1. Remember that more than one problem can coexist.

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Late-onset hypogonadism
Around 10% of all ED patients and 20% of type 2 diabetics have low or borderline testosterone levels,(3) and there is strong evidence that normalisation with testosterone injections (now available in a three-monthly formulation) or transdermal testosterone as gel or patch can convert these patients to PDE responders. Testosterone levels of less than 8nmol/l are generally regarded as confirmation of hypogonadism, usually causing symptoms such as low sex drive, tiredness or sweats, but levels of up to 14 nmol/l may be required to facilitate a response to oral medication. Remember that vascular and neurological factors may exist in the same patient.
Current evidence is that such patients merit a three-month trial of testosterone and PDE5 inhibitor, once levels are normalised. Initially, the PSA should be checked, and annual morning testosterone, PSA and full blood count should also be checked. There is currently no evidence that such patients are at risk of prostate cancer, but there is evidence of benefit in terms of cardiovascular risk, diabetic control and osteoporosis prevention. There is much ongoing debate as to the optimum blood test to accurately diagnose hypogonadism, but the desire to respond to oral ED therapy frequently drives the need for treatment.

Daily dosing
PDE5 inhibitors are vascular drugs that are established to exert more potent effects with daily dosing. The licensing of the three drugs for "on-demand use" was based on the perception that this would be the preferred method for the patient and also for cost implications. Studies have shown not only high rates of salvage for nonresponders but additional vascular benefits and even potential for reversing the vascular ED when daily therapy is administered for 12 months or more.(2,4)
Studies of daily dosing in hypertension, peripheral vascular disease, diabetic neuropathy and lower urinary tract symptoms (LUTS) are potentially exciting. In 2005, the FDA licensed sildenafil for the treatment of pulmonary hypertension.
Clearly the financial implications of daily dosing are important, but a change in pricing structure would be likely as other therapy areas develop and the first of the drugs approaches the end of its patent. Tablet splitting, although not advised by the manufacturer, is widely practised.

Treating the partner and the couple
The importance of associated sexual problems in the partner has long been appreciated by therapists for many years, but new research has shown that around 25% of partners have a coexisting sexual problem and that regular use of a PDE5 inhibitor by the man can greatly improve the sex life of the partner and the overall quality of life of the couple.(5) The importance of addressing the relationship cannot be overemphasised in this therapy area. Specialist sexual training is not required to recognise these problems, just a well-motivated nurse.

Second line therapies
These should be discussed at the outset, particularly vacuum devices (VCD), as a minority of couples may prefer a nonpharmacological approach. Erection with VCD differs from normal vascular erection in a lower skin temperature, cyanosis, venous distension and an increase in girth. The only relative contraindications are bleeding disorders. A recent prospective study suggests success rates as high as 92% with vacuum devices in selected and trained patients.
The WHO recommends that 1-1.5 days of training, ideally from an experienced professional, can produce excellent results, and the lack of patient support is the commonest reason for the discontinuation rates: 40-65% in earlier trials.(6)
VCDs can be prescribed on FP10 in the same way as other therapies and are very cost-effective, especially as a single device will cost between £150 and £200 and may last for several years.

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Schedule 2 regulations
The current UK prescribing regulations on impotence have little or no evidence base and have not been changed since 1999 despite considerable medical advances in this field.
Ministers have decided that NICE guidance on current therapies is "not necessary", and we must draw our own conclusion as to this strange decision. Certainly conforming to these bizarre regulations is a constant challenge for the up-to-date clinician wishing to practise evidence-based medicine.

References

  1. Montorsi F, Salonia A, Deho F. Pharmacological management of erectile dysfunction. BJU Int 2003;91:446-54.
  2. McMahon C. Efficacy and safety of daily tadalafil in men with ED previously unresponsive to on demand tadalafil. J Sex Med 2004;1(3):292-300.
  3. Shabsigh R. Testosterone and ED.J Sex Med 2005;2(6):785-92.
  4. Sommer F. Curing erectile dysfunction: long-term effects of taking PDE5 inhibitors on a daily basis.J Sex Med 2005;2(S1):61-2.
  5. Goldstein I, et al. Women's sexual function improves when partners are administered vardenafil for erectile dysfunction. J Sex Med 2005;1(3):819-32.
  6. Sexual medicine. Proceedings of Second International Consultation on sexual dysfunction. Paris; 2004. p. 485-8.