LUTS Not just 'a part of ageing'

This article was published in the Australian Doctor, www.australiandoctor.com.au 12 February 2015 by Dr Jeremy Grummet.

A better understanding of lower urinary tract symptoms and possible treatment options is the aim of a new men’s health campaign.

Lower urinary tract symptoms (LUTS) are highly prevalent in men over 50 in Australia, and the most common cause in this age group is benign prostatic hyperplasia (BPH).1,2 Despite having a higher mortality from cardiovascular disease, accidents, suicide and cancer, men see doctors less often than women.3

The new More than once a night campaign, endorsed by men’s health group Foundation 49, has been launched to address both of these issues in one hit.

The multimedia campaign focuses in a light-hearted way on the symptom of nocturia ­— one of the most common symptoms in the cluster of LUTS — and its effect not only on the man, but also his partner, and the disrupted sleep it can cause them both.

It’s a call to action for men with these symptoms to see their GP for an assessment, and — if necessary — gain access to the highly effective treatment options that are now available.

When to treat
Of course, many men with such symptoms may not need any treatment at all. If the presentation is clearly of mild uncomplicated LUTS (ie, not neurogenic, and no haematuria or infection) and symptoms are not too irritating, then reassurance is all that is required.4 In addition, many of these men have concerns about their risk of prostate cancer, which can also be appropriately addressed at the consultation.

About 20% of all men in this age group have moderate to severe LUTS.5 Many of these men may not seek medical attention for various reasons, including the belief that such symptoms are just part of ageing and that they simply need to “put up with them”.

BPH, the most common cause of such symptoms, is certainly age-related, but if it is interfering with quality of life, men need to know there is an array of simple and effective interventions that may make all the difference.

Lifestyle management
The first line of intervention for mildly irritating symptoms is lifestyle advice.4 This includes reducing intake of caffeine and alcohol, both of which may have a diuretic and irritant effect. Timing of general fluid intake can also be modified. In the absence of chronic retention, a bladder training nurse may be of help. Constipation should also be treated.

If lifestyle changes prove inadequate, or the symptoms are more severe, there is now a plethora of medications that GPs can prescribe which have been shown in randomised control trials to be beneficial (see Table 1).

Medical management
Alpha blockers remain a commonly used option. By relaxing smooth muscle at the bladder neck and within the prostate, they act quickly so that relief can be felt within just a few days of use.6 However, they do not arrest the growth of the prostate in BPH.

Prazosin is as effective as any other alpha blocker, but is not selective for the receptors at the bladder outlet alone, and so has a higher rate of postural hypotension than selective alpha blockers, such as tamsulosin. As a result, prazosin should be introduced in slowly increasing doses while monitoring blood pressure, especially in the elderly. Retrograde ejaculation is another side effect.

The 5-alpha reductase inhibitors dutasteride and finasteride are another treatment option. They shrink the prostate by altering the levels of androgen within the gland. They are therefore only useful if the prostate is enlarged enough to cause a mass effect. Their effect is slow to manifest, and it can take 3-6 months before any improvement is noticeable.

In shrinking the prostate gland, 5-alpha reductase inhibitors do change the natural history of BPH — unlike alpha blockers — and so have been found to reduce the risk of acute retention and the need for surgery.7,8

Due to the different mechanisms as well as onset of action, alpha blockers and 5-alpha reductase inhibitors complement each other well, with combination therapy providing greater benefit than treatment with either agent alone.9 In recent years, tamsulosin and dutasteride have been made available together in a single preparation, taken once daily.

However, 5-alpha reductase inhibitors carry risks that need to be borne in mind before prescribing. Erectile dysfunction and reduced libido are well-documented side effects, but their true incidence is yet to be quantified. Gynaecomastia is rare. In addition, a higher incidence of high-grade prostate cancer has been found in men on 5-alpha reductase inhibitors compared with placebo.10

Men taking 5-alpha reductase inhibitors need PSA levels followed up periodically, with discussion about the risks. As 5-alpha reductase inhibitors shrink prostate glandular tissue, the PSA is expected to drop by 50% within 12 months. Therefore, any rise in PSA while taking the drug prompts immediate referral to a urologist.

LUTS in older men also comprise the overactive bladder symptoms of urinary frequency and urgency, which can be the most irritating. These storage symptoms may be a result of the bladder’s response to outlet obstruction from BPH, but they can also occur de novo as a part of ageing, as evidenced by older women having a similar rate of this kind of LUTS.11

Anticholinergic medications are effective in treating overactive bladder symptoms by reducing contractions of the detrusor muscle, and can be used in conjunction with other agents, particularly if storage symptoms predominate.

Table 1: Medication options for GPs treating LUTS

Drug type Examples Comments
Alpha blockers Prazosin, tamsulosin Relax bladder outlet, rapid onset, risk of postural hypotension
5-alpha reductase inhibitors Dutasteride, finasteride Shrink prostate gland, slow onset, risk of sexual dysfunction, lowers PSA
Anticholinergics Oxybutinin, solifenacin, darifenacin Reduce OAB symptoms, risk of dry mouth
Beta-3 agonists Mirabegron Reduce OAB symptoms, early experience only
PDE-5 inhibitors Tadalafil Relax lower urinary tract smooth muscle, also treats erectile dysfunction
Alpha blocker/5-alpha reductase inhibitors Tamsulosin/dutasteride More effective than either agent alone, single daily tablet combination
Vasopressin analogue Desmopressin For nocturia only, monitor sodium level-risk of hyponatraemia

Like alpha blockers, anticholinergic drugs can be bladder receptor selective (eg, solifenacin and darifenacin) or non-selective (eg, oxybutynin), with the latter more likely to cause dry mouth. Contrary to traditional thinking, the risk of precipitating acute retention with these drugs is very low.12

Mirabegron is the first beta-3 agonist to be recently approved for use for overactive bladder LUTS. It has a similar action to the anticholinergics on the bladder. Its potential advantage lies in its lack of anticholinergic side effects. Preliminary evidence of its effectiveness in men is encouraging, but it is yet to enter official guidelines.13

Further adding to the ever-expanding armamentarium in this field are the phosphodiesterase-5 (PDE-5) inhibitors, better known for their efficacy in treating erectile dysfunction. They appear to act by relaxing smooth muscle in the bladder, prostate and urethra.14

To date, only the daily 5mg dose of tadalafil has been approved for use in LUTS. These drugs have the obvious potential advantage of simultaneously treating erectile dysfunction, also common in this age group.

The final medical therapeutic option with proven efficacy is the vasopressin analogue, desmopressin. This agent is sometimes used for men who have nocturia as the predominant symptom. However, it is less often prescribed than the other available agents due to its risk of hyponatraemia, and the consequent need for monitoring of sodium levels, and its gastrointestinal side effects.15

Phytotherapy
Phytotherapy (use of plant extracts) has long been thought to be of potential benefit for older men with LUTS. However, in 2013, the European Association of Urology Guidelines Committee could not make any recommendations due to the heterogeneous nature of phytotherapy products and the poor methodology of trials.14

Surgical management
For the most severe LUTS, lifestyle advice and medical therapy may need to be bypassed for surgical intervention. Absolute indications for surgery include acute retention, bladder stones, recurrent UTI and obstructive uropathy.

Surgery involves removal of obstructing tissue and is most commonly performed as a standard transurethral resection of the prostate (TURP), or by using laser technology to either vaporise or enucleate affected tissue.

These surgical options are highly effective and, apart from the expected side effect of retrograde ejaculation, carry a low risk of other side effects, such as erectile dysfunction, urethral stricture and urinary incontinence.16

So with all the available highly effective interventions to treat LUTS in middle-aged and older men, from lifestyle advice through medications to surgery, men need not suffer in silence.

It is hoped that the “More than once a night” campaign will encourage men to see their GPs, not only to have their LUTS assessed and treated if necessary, but also to provide an opportunity for them to get a general check-up. In doing so, we might just be able to reduce the higher rate of preventable illness and death seen in men.

Dr Grummet is a urological surgeon. He is chair, genito-urinary cancer multidisciplinary team, Alfred Health; adjunct senior lecturer, department of surgery, Monash University; and member and spokesman Foundation 49: Men’s Health, Cabrini, Victoria.

Online resources

References:

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  2. Lancet 2005; 366:218-24.
  3. Medical Journal of Australia 2006; 16:81-83.
  4. European Urology 2013; 64:118-40.
  5. World Journal of Urology 2013; 31:673-82.
  6. Urology 2004; 64:1081-88.
  7. New England Journal of Medicine 1998; 26:557-63.
  8. NEJM 2003; 349:2387-98.
  9. European Urology 2010; 57:123-31.
  10. NEJM 2003; 349:215-24.
  11. European Urology 2006; 50:1606-14.
  12. Journal of Urology 2006; 3:999-1004.
  13. Journal of Urology 2014. PubMEd; 25254938; online.
  14. Journal of Sexual Medicine 2014; 11:1539-45.
  15. Neurourology and Urodynamics 2004; 23:302-05.
  16. European Urology 2010; 58:384-97.