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Elterman et al

We recommend alpha-blockers as an excellent first-line urgency, and urgency incontinence episodes. 34,35 Studies
therapeutic option for men with symptomatic bother due of contemporary antimuscarinics, such as tolterodine and
to BPH who desire treatment (strong recommendation, evi- fesoterodine, and the beta-3 agonist, mirabegron, have shown
dence level A). low rates of urinary retention, although caution should be
exercised in elderly men and those with significant bladder
2.3.2. 5-ARIs outlet obstruction (BOO) (with PVR >250–300 cc since there
Several studies have demonstrated that 5-ARI therapy, in is little evidence of safety in men with high PVRs).
addition to improving symptoms and causing a modest
(25–30%) shrinkage of the prostate, can alter the natural We suggest that antimuscarinics or beta-3 agonists may be
history of BPH through a reduction in the risk of AUR and useful in predominately storage symptoms and BPH, and
the need for surgical intervention. 25,26 Efficacy is noted in used with caution in those with significant BOO and/or
patients with a prostate volume >30 cc (and/or PSA levels an elevated PVR (conditional recommendation, evidence
>1.5 ng/ml). 5-ARI treatment is associated with erectile dys- level C).
function, decreased libido, ejaculation disorders, and rarely,
gynecomastia and post-finasteride syndrome. 27 2.3.5. Antimuscarinic or beta-3 agonists in combination with alpha-blockers
Mixed LUTS (storage and voiding symptoms) can be man-
We recommend 5-ARIs (dutasteride and finasteride) as aged safely with alpha-blockers in combination with anti-
appropriate and effective treatment for patients with LUTS muscarinics or beta-3-agonists. Clinical trials studied the
associated with demonstrable prostatic enlargement (strong following drug combinations: tamsulosin 0.4 mg plus solif-
recommendation, evidence level A). enacin 5 mg, tamsulosin plus tolterodine ER 4 mg, and tam-
sulosin 0.4 mg plus mirabegron 50 mg. 36-41 Evidence showed
2.3.3. Combination therapy (alpha-blocker and 5-ARI) that combination therapies provide significant improvement
Prognostic factors suggesting the potential for BPH progres- in storage symptoms without clinical or statistical evidence
sion risk 28,29 include: serum PSA >1.4 ng/mL, age >50 years, of decreased maximum flow rate on uroflowmetry (Qmax)
and gland volume >30 cc. Clinical trial results have shown or increased risk of retention. Patients with high PVR >200
that combination therapy significantly improves symptom ml or previous history of AUR were excluded.
score and peak urinary flow compared with either of the
monotherapy options. Combination medical therapy is asso- We suggest that an alpha-blocker combined with an anti-
ciated with decreased risk of urinary retention and/or pros- muscarinic or beta-3 agonist may be useful to treat LUTS/
tate surgery, but also the additive side effects of dual therapy BPH in men with both voiding and storage symptoms and
(in particular, ejaculatory disturbances). 30,31 failure of alpha-blocker monotherapy (conditional recom-
mendation, evidence level B).
We recommend the combination of an alpha-adrenergic
receptor blocker and a 5-ARI as an appropriate and effect- 2.3.6. Phosphodiesterase inhibitors
ive treatment strategy for patients with symptomatic LUTS PDE5Is have been shown to not only improve erectile
associated with prostatic enlargement (>30 cc) (strong rec- function, but also are an effective treatment for male LUTS.
ommendation, evidence level B). Tadalafil 5 mg daily, due to its longer half-life, is approved for
MLUTS. Studies have shown improvements in IPSS, storage
42
It may be appropriate to consider discontinuing the alpha- and voiding symptoms, and quality of life. Evidence shows
blockers in patients successfully managed with combination that combination therapy with PDE5I and alpha-blockers is
therapy after 6–9 months of combination therapy. 32,33 superior to alpha-blockers alone in men with voiding symp-
43
toms and erectile dysfunction.
We suggest that patients successfully treated with combina-
tion therapy may be given the option of discontinuing the We recommend long-acting PDE5Is as monotherapy for
alpha-blocker. If symptoms recur, the alpha-blocker should men with LUTS/BPH, particularly in men with both LUTS
be restarted (conditional recommendation, evidence level B). and erectile dysfunction (strong recommendation, evidence
level B).
2.3.4. Antimuscarinic and beta-3 agonist medications
Storage symptoms (urgency, frequency, nocturia) are a 2.3.7. Desmopressin
bothersome component of MLUTS associated with BPH. Nocturnal polyuria (NP) often coexists with MLUTS and BPH
Antimuscarinics (anticholinergics) and the beta-3 agonists but may not respond to typical BPH pharmacotherapies. NP
have demonstrated improvements in male storage LUTS is a major contributing factor of nocturia and is defined by
(with and without BPH), including reductions in frequency, the International Continence Society (ICS) as an abnormally

248 CUAJ • August 2022 • Volume 16, Issue 8