Lower Urinary Tract Symptoms in Men

Lower urinary tract symptoms (LUTS) are common in men and increase with age. These symptoms can be classified as either voiding symptoms or storage symptoms. Voiding symptoms are often related to prostate enlargement. This may present with urinary hesitancy, weak stream, and incomplete bladder emptying. Storage symptoms are typically due to overactivity of the detrusor muscle and may present as nocturia and urinary urgency or frequency. Therapies for LUTS in men include alpha blockers, 5α reductase inhibitors, and antimuscarinics.

Alpha blockers

The selective alpha blockers available for the management of LUTS are alfuzosin, prazosin, silodosin, and tamsulosin. These agents reduce the resistance to urinary flow through the blockade of presynaptic alpha₁ receptors, which causes smooth muscle relaxation in the bladder neck and prostate. Prazosin also blocks postsynaptic alpha₁ receptors, which can result in vasodilation.

There are three subtypes of alpha₁ receptors: alpha_1A, alpha_1B, and alpha_1D. Alfuzosin and prazosin are non-subtype selective. Tamsulosin is considered subtype selective as it has a ten-fold greater affinity for alpha_1A and alpha_1D subtypes than alpha_1B. Silodosin is also subtype selective as it has a 162-fold higher affinity for alpha_1A compared to alpha_1B. Greater affinity at alpha_1A receptors may be advantageous as these receptors are primarily located in the prostate and bladder. In comparison, alpha_1B receptors are primarily located in the cardiovascular system.

Common adverse effects include first-dose hypotension, orthostatic hypotension, dizziness, nasal congestion, urinary urgency, and fatigue. Cardiovascular effects are more likely to occur with prazosin.

A meta-analysis suggests that the efficacy of selective alpha blockers for the management of LUTS is similar. Interestingly, this analysis found little to no difference in the incidence of cardiovascular adverse events for silodosin compared to alfuzosin or tamsulosin. However, silodosin was associated with a higher rate of sexual adverse events (e.g. retrograde ejaculation and anejaculation).

5α reductase inhibitors:

Dutasteride and finasteride inhibit 5α reductase. This enzyme is responsible for converting testosterone to dihydrotestosterone, a potent stimulant of prostate growth. Therapy with a 5α reductase inhibitor reduces prostate size and improves urinary flow rate.

Dutasteride inhibits both type 1 and type 2 isoenzymes, while finasteride only inhibits the type 2 isoenzyme of 5α reductase. Following two weeks of continuous dosing, dutasteride can reduce dihydrotestosterone levels by around 90%. In comparison, long-term finasteride dosing is associated with a 70% reduction in circulating dihydrotestosterone levels. However, evidence suggests that there are not any major differences between the two agents for reduction of prostate size, symptom improvement, urinary flow rate, or adverse effects.

Women who are pregnant or may become pregnant should avoid exposure to 5α reductase inhibitors as they are pregnancy category X drugs. They are associated with a potential risk of feminisation of the male foetus. As dutasteride and finasteride can be absorbed through the skin, women should not handle capsules that are leaking or tablets that have been broken or crushed. Finasteride tablets are coated, which prevents contact with the active ingredient during normal handling of whole tablets. Patients must refrain from donating blood while taking a 5α reductase to prevent administration to a pregnant female. As dutasteride has a long half-life (3 to 5 weeks), there is a recommended waiting time of at least six months after the last dose before blood donations can resume.

A fixed-dose combination of dutasteride plus tamsulosin is available. The combination of alpha blocker and 5α reductase inhibitor is more effective in reducing disease and symptom progression in benign prostatic hyperplasia and also decreases the risk of acute urinary retention.

Antimuscarinics

Antimuscarinic medications can be used to manage storage symptoms. Detrusor contraction is mediated via the action of acetylcholine on the M₃ receptor subtype. Therefore, medications that are M₃ selective (e.g. darifenacin and solifenacin) may be associated with less anticholinergic adverse effects than non-selective antimuscarinics.

Potential adverse effects include urinary retention, dry mouth, constipation, dyspepsia, blurred vision, dry eyes, tachycardia, arrhythmia, dizziness, memory impairment, confusion, and insomnia. Adverse effects tend to be dose-related. Older individuals are typically more sensitive to anticholinergic adverse effects, and the lowest effective dose should be used.

An antimuscarinic may be combined with an alpha blocker if storage and obstructive symptoms exist.

An overview of medications used in the management of LUTS is shown in Table 1.

Table 1. Medications for LUTS in men