Are phosphodiesterase type 5 inhibitors effective for the management of lower urinary symptoms suggestive of benign prostatic hyperplasia?

Table 1 Characteristics and qualities of the studies included in the analysis of tadalafil, sildenafil and vardenafil

Ref.	Sample	Drug (mg)		Duration	Run-in	Inclusion criteria	Publications
	size	Trial	Control	(wk)	period (wk)
Tadalafil
Brock et al[39]	1089	5	Placebo	12	4	Mean age ≥ 45, LUTS/BPH ≥ 6 mo, IPSS ≥ 13 Qmax 4-15 mL/s	BJU Int
Dmochowski et al[13]	200	20	Placebo	12	4	Mean age ≥ 40, LUTS/BPH ≥ 6 mo, IPSS ≥ 13	J Urol
Donatucci et al[14]	427	2.5, 5, 10, 20	Placebo	12	4	Mean age ≥ 45, LUTS/BPH ≥ 6 mo, IPSS ≥ 13	BJU Int
Egerdie et al[15]	606	2.5, 5	Placebo	12	4	Mean age ≥ 45, LUTS/BPH ≥ 6 mo, IPSS ≥ 13 Qmax 4-15 mL/s	J Sex Med
Kim et al[16]	102	5	Placebo	12	6	Mean age ≥ 45, LUTS/BPH ≥ 6 mo, IPSS ≥ 13 Qmax 4-15 mL/s	LUTS
McVary et al[18]	281	5 + 20	Placebo	6 + 6	4	Mean age ≥ 45, LUTS/BPH ≥ 6 mo, IPSS ≥ 13 Qmax 4-15 mL/s	J Urol
Oelke et al[19]	343	5	Placebo	12	4	Mean age ≥ 45, LUTS/BPH ≥ 6 mo, IPSS ≥ 13 Qmax 4-15 mL/s	Eur Urol
Porst et al[21]	581	2.5, 5, 10, 20	Placebo	12	4	Mean age ≥ 45, LUTS/BPH ≥ 6 mo, IPSS ≥ 13 Qmax 4-15 mL/s	Eur Urol
Porst et al[36]	325	5	Placebo	12	4	Mean age ≥ 45, LUTS/BPH ≥ 6 mo, IPSS ≥ 13 Qmax 4-15 mL/s	Eur Urol
Porst et al[20]	1500	5	Placebo	12	4	Mean age ≥ 45, LUTS/BPH ≥ 6 mo, IPSS ≥ 13 Qmax 4-15 mL/s	Urology
Roehrborn et al[22]	1058	2.5, 5, 10, 20	Placebo	12	4	Mean age ≥ 45-60, LUTS/BPH ≥ 6 mo, IPSS ≥ 13 Qmax 4-15 mL/s, PVR 150-550 mL	J Urol
Roehrborn et al[12]	1500	5	Placebo	12	4	Mean age ≥ 45, LUTS/BPH ≥ 6 mo, IPSS ≥ 13 Qmax 4-15 mL/s	J Urol
Takeda et al[24]	610	5	Placebo	12	4	Mean age ≥ 40, LUTS/BPH ≥ 6 mo, IPSS ≥ 13	J Urol
Yokoyama et al[25]	460	2.5, 5	Placebo	12	2	Mean age ≥ 45, LUTS/BPH ≥ 6 mo, IPSS ≥ 13 Qmax 4-15 mL/s, prostate volume ≥ 20 mL	Int J Urol
Sildenafil
McVary et al[10]	369	50, 100	Placebo	12	4	Mean age ≥ 45, IIEF ≤ 25, IPSS ≥ 12	J Urol
Vardenafil
Stief et al[40]	222	10	Placebo	8	4	Mean age ≥ 45-64, LUTS/BPH ≥ 6 mo, IPSS ≥ 12	Eur Urol

IIEF: International index of erectile function; IPSS: International prostate symptom; LUTS/BPH: Lower urinary tract symptoms/benign prostatic hyperplasia; Qmax: Maximum urinary flow rate; PVR: Post-void residual volume.

Table 2 Least squares mean changes from baseline to end-point in lower urinary tract symptoms/benign prostatic hyperplasia in clinical studies for treatment in subjects with erectile dysfunction and without erectile dysfunction

Ref.	Drug	Remarks	Total IPSS		IPSS voiding subscore		IPSS storage subscore		IPSS QoL subscore		BII		Qmax		IIEF
	mg		T	P	T	P	T	P	T	P	T	P	T	P	T	P
	Tadalafil
Brock et al[39]	5	ED	-5.7	-3.3	-3.5	-1.9	-2.2	-1.3	-1.1	-0.7	-1.6	-0.9
	5	No ED	-5.4	-3.3	-3.5	-2	-1.9	-1.3	-1		-1.4	-1
Dmochowski et al[13]	20		-9.2	-5.1	-5.6	-2.8	-3.6	-2.3					0.4	0.5
Donatucci et al[14]	2.5		-5.7	-4.1	-3.8	-2.5	-1.9	-1.6	-1.2	-0.9	-1.3	-1.2			5.5	7.2
	5		-5.0		-2.8		-2.1		-1.1		-1.4				5.3
	10		-5.7		-3.6		-1.8		-1.3		-1.4				3.7
	20		-4.6		-3		-2.1		-1		1.2				7.6
Egerdie et al[15]	2.5		-6.1	-3.8	-2.7	-2.2	-1.9	-1.6	-0.9	-0.8	-2.1	-1.2			6.5	1.8
	5		-4.6		-3.6		-2.5		-1		-1.6				5.2
Kim et al[16]	5		-5.6	-3.6									2.5	2.3
McVary et al[18]	5		-6.2	-3.9	-4	-2.5	-2.2	-1.4	-0.7	-0.3	-0.7	-0.4	0.5	0.9	6.7	0.7
	5/20		-7.1	-4.5	-4.4	-2.8	-2.7	-1.8	-0.5	-0.2	-1.3	-0.6	0.5		8.4	1.6
Oelke et al[19]	5		-6.3	-4.2	-4.1	-2.6	-2.2	-1.6	-1.3	-1			2.4	1.2
Porst et al[21]	2.5		-4.2	-2.1											8.2	2
	5		-4.7												7.9
	10		-4.7												6.8
	20		-3.6												5.4
Porst et al[36]	5		-5.6	-3.6	-3.3	-2.3	-2.3	-1.3			-1.8	-1.3			6.7	2
Porst et al[20]	5		-7.9	-5.1
Roehrborn et al[22]	2.5		-5.17	-2.27	-2.94	-1.26	-1.96	-0.99	-0.92	-0.49	-1.38	-0.83	1.96	1.24	8.34	2.2
	5		-3.88		-2.23		-2.07		-0.88		-1.4		1.41		7.98
	10		-5.21		-3.12		-1.58		-0.74		-0.96		1.64		6.97
	20		-4.87		-3.13		-1.89		-0.86		-1.45		1.58		5.59
Roehrborn et al[12]	5	Qmax < 10	-5.2	-3.6	-3.2	-2.1							2.8	2.4
	5	Qmax of 10-15	-6.3	-3.8	-3.9	-2.5							1.4	0.9
	5	Qmax > 15	-6.8	-2.7	-3.9	-1.2							-1.1	-2.7
Takeda et al[24]	5		-6	-4.5	-2	-1.4	-2	-1.4	-2	-1.4
Yokoyama et al[25]	2.5		-5	-3	-3.3	-1.9	-1.7	-1.1	-0.8	-0.5	-1	-0.8	1.3	2.1
	5		-5.1		-3.72		-1.5		-0.8		-1.1		1.6
	Sildenafil
McVary et al[10]	50		-6.3	-1.9					-0.9	-0.3	-2	-0.9	0.31	0.16	9.17	1.86
	100
	Vardenafil
Stief et al[40]	10		-5.8	-3.6									1.6	1

IIEF: International index of erectile function; IPSS: International prostate symptom; Qmax: Maximum urinary flow rate; QoL: Quality of life; BII: Benign prostatic hyperplasia impact index; ED: Erectile dysfunction; T: Treatment; P: Placebo.

Table 3 Outcomes of the meta-analysis of total international prostate symptom score, international prostate symptom score storage subscore, international prostate symptom score voiding subscore, international prostate symptom score quality of life subscore, benign prostatic hyperplasia impact index, maximum urinary flow rate, and international index of erectile function score in lower urinary tract symptoms/benign prostatic hyperplasia or lower urinary tract symptoms/benign prostatic hyperplasia and erectile dysfunction patients

Outcome or	Studies	Participants	Weight	Statistical	Effect Estimate	Heterogeneity		Overall	P value
subgroup				method	(Mean difference, 95%CI)	χ2	I2(%)	Z value
Total IPSS in LUTS/BPH	13	9131	100%	Fixed	-2.17 (-2.42, -1.91)	16.44	0	16.75	< 0.00001
Tadalafil	11	8576	95.5%	Fixed	-2.14 (-2.40, -1.88)	13.27	0	16.18	< 0.00001
Sildenafil	1	341	1.0%	Fixed	-4.40 (-6.87, -1.93)			3.48	0.001
Vardenafil	1	214	3.4%	Fixed	-2.20 (-3.57, -0.83)			3.14	0.002
Total IPSS in LUTS/BPH and ED	6	3626	100%	Fixed	-1.97 (-2.43, -1.51)	12.33	3	8.41	< 0.00001
Tadalafil	5	3285	96.6%	Fixed	-1.88 (-2.35, -1.41)	8.49	0	7.90	< 0.00001
Sildenafil	1	341	3.4%	Fixed	-4.40 (-6.87, -1.93)			3.48	0.001
IPSS storage subscore in LUTS/BPH
Tadalafil	10	6848	100%	Fixed	-0.71 (-0.85, -0.57)	12.64	0	9.96	< 0.00001
IPSS voiding subscore in LUTS/BPH
Tadalafil	11	7916	100%	Fixed	-1.23 (-1.41, -1.04)	24.7	15	13.28	< 0.00001
IPSS QoL subscore in LUTS/BPH	8	5999	100%	Fixed	-0.33 (-0.40, -0.26)	8.26	0	8.70	< 0.00001
Tadalafil	7	5648	97.7%	Fixed	-0.32 (-0.40, -0.25)	6.26	0	8.38	< 0.00001
Sildenafil	1	351	2.3%	Fixed	-0.68 (-1.17, -0.19)			2.71	0.007
BII in LUTS/BPH
Tadalafil	5	3504	100%	Fixed	-0.43 (-0.61, -0.25)	3.89	0	4.64	< 0.00001
BII in LUTS/BPH and ED	4	2561	100%	Fixed	-0.52 (-0.74, -0.29)	8.02	13	4.51	< 0.00001
Tadalafil	3	2210	94.8%	Fixed	-0.48 (-0.71, -0.25)	6.59	9	4.11	< 0.0001
Sildenafil	1	351	5.2%	Fixed	-1.10 (-2.08, -0.12)			2.19	0.03
Qmax in LUTS/BPH
Tadalafil (2.5, 5, 10 and 20 mg)	9	5034	64.9%	Fixed	0.22 (-0.04, 0.49)	13.43	3	1.65	0.10
Tadalafil (only 5 mg)	7	2876	35.1%	Fixed	0.33 (-0.13, 0.80)	8.24	24	2.14	0.03
IIEF in LUTS/BPH
Tadalafil	2	2009	100%	Fixed	4.88 (3.31, 8.97)	2.28	0	8.96	< 0.00001
IIEF in LUTS/BPH and ED
Tadalafil	3	1746	100%	Fixed	4.54 (3.75, 5.33)	7.33	18	11.27	< 0.00001

IIEF: International index of erectile function; IPSS: International prostate symptom score; LUTS/BPH: Lower urinary tract symptoms/benign prostatic hyperplasia; Qmax: Maximum urinary flow rate; QoL: Quality of life; BII: Benign prostatic hyperplasia impact index; ED: Erectile dysfunction.