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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
         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-
                                                             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
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