Biology Reference
In-Depth Information
6 Nonmalignant Diseases of the Prostate: The Benign
Prostatic Syndrome
Benign prostatic syndrome (BPS) represents a major health care problem in western
countries. BPS comprises obstructive and irritative symptoms: lower urinary tract
symptomatology (LUTS), as well as benign prostatic enlargement (BPE) with vari-
able degrees of bladder outlet obstruction (BOO) (Guess
1995
;ChiricosandSanford
1996
). Major symptoms include urinary frequency, nocturia, and slow stream. It is
estimated that approximately 50% of men older than 50 years have moderate to
severe symptoms arising from LUTS (Jacobsen et al.
1993
). The current pharmaco-
logical management of LUTS and BPE involves alpha
1
-adrenergic blockers, such as
alfusozin, doxazosin, and tamsulosin, to diminish urethral resistance by reducing the
tension of smooth muscle fibers located in the transitional zone and periurethral
region (Hieble and Ruffolo
1996
). Intervention into the hormonal control of prostate
growth by using inhibitors of 5-alpha-reductase activity is another approach to ease
symptoms (Andersen et al.
1995
; Roehrborn et al.
2004
).
The expression of several cAMP- and cGMP-PDE isoenzymes (PDEs 1, 2, 4, 5,
7, 8, 9, 10) in the human prostate was shown by means of molecular biology and
protein chemistry. Later, the distribution of PDE4 and PDE5 in stromal and
glandular areas of the transition zone was shown using an immunohistochemical
approach (Uckert et al.
2001b
; Uckert et al.
2006
). In organ bath studies, the tension
of prostate strip preparations mediated via the activation of alpha
1
-adrenergic
receptors was dose-dependently reversed by the PDE4 inhibitor rolipram and
PDE5 inhibitor sildenafil ( Uckert et al.
2001b
). The role of PDE5 inhibitors in the
treatment of symptoms of LUTS/BPH has been addressed by some open-label
studies and, more recently, placebo-controlled clinical trials. Sairam et al. (
2002
)
were the first who examined the effects of sildenafil citrate in patients presenting
with ED and LUTS. From the 112 patients enrolled in the open-label study, 20
subjects complained of LUTS, from these, 32% had moderate-to-severe symptoms
(IPSS
7). After 12 weeks of treatment with sildenafil, there was an overall
improvement in the IPSS and LUTS-specific quality of life (QoL) score. All
patients who had severe LUTS showed a moderate improvement of the disease,
60% of those who initially presented with moderate LUTS showed only a mild
symptomatology. The authors concluded that treatment with sildenafil appears to
improve urinary symptom scores (Sairam et al.
2002
). McVary et al. (
2007a
,
b
)
assessed in a randomized, double-blind, placebo-controlled trial the effects of
sildenafil given for 12 weeks in 366 men suffering from ED and LUTS secondary
to BPH (IPSS
>
12). Patients received 50 mg sildenafil at bed-time or up to 1 h
before sexual activity for at least 2 weeks, followed by 100 mg sildenafil once daily
for 10 weeks. Primary outcome measures were changes in the erectile function
domain of the IIEF, secondary outcome measures were changes in all other
domains of the IIEF and IPSS including QoL, BPH
Impact Index
(BPH II), and
Q
max
. Sildenafil significantly improved LUTS, mean IPSS decreased by 6.3
points vs. 1.93 in the placebo group. Interestingly, patients with severe LUTS
