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Daily Phosphodiesterase Type 5
Inhibitor for Erectile Dysfunction:
Is It Ready for Prime Time?
The phosphodiesterase type 5 (PDE-5) inhibitors are an
unusual class of drugs because they upregulate the effect of
cGMP, which itself is activated by NO. Upregulation of
cGMP has been shown to inhibit both collagen synthesis
and apoptosis of certain parenchymal cells, such as those
found in the kidney and the corporal tissues. We in urolo-
gy are most familiar with the fact that these drugs are clas-
sically used for the treatment of ED and are taken on
demand when an erection is desired. However, many of the
disorders that afflict the genitourinary tract have to do with
loss of smooth muscle cells and/or increase in tissue colla-
gen or fibrosis. Examples of these are overactive bladder
(OAB), benign prostatic hyperplasia (BPH), and even aging-
related ED, in which there is a loss of corporal smooth mus-
cle cells and an increase in tissue fibrosis.
Therefore, it seems reasonable that if PDE-5 inhibitors
are antifibrotic and antiapoptotic, they may be considered
for the prevention of certain urologic disorders rather than
for the on-demand treatment of ED.2 However, this would
require that they be taken on a daily basis and possibly
early on in life, as one would take a statin or aspirin to
prevent certain cardiovascular diseases.
Evaluation of the Efficacy and Safety of
Once-a-Day Dosing of Tadalafil 5 mg and
10 mg in the Treatment of Erectile Dysfunction:
Results of a Multicenter, Randomized,
Double-Blind, Placebo-Controlled Trial
Porst H, Giuliano F, Glina S, et al.
Eur Urol. 2006;50:351-359.
To determine whether the daily ingestion of a PDE-5
inhibitor would be safe, Porst and colleagues performed a
study in which men with ED were randomized to either
placebo (n  54), tadalafil 5 mg (n  109), or tadalafil
10 mg (n  105) daily for 12 weeks. The investigators
found that besides the expected efficacy of the drug in men
with ED, the side effect profile was no different than that
seen with men taking those dosages of the drug on an on-
demand basis. Only 8 of the 214 patients (3.7%) who took
tadalafil reported an adverse event that precipitated their
withdrawal from taking the drug daily. There was a dose-
dependent increase in headaches (6.4% to 10.5%), dyspep-
sia (5.5% to 11.4%), back pain (3.7% to 9.5%), upper
abdominal pain (2.8% to 8.6%), and myalgias (2.8% to
6.7%) in the patients taking tadalafil.
Male Fertility
This study opens the way for testing these drugs over
the long term in the treatment of some of the aforemen-
tioned urologic disorders. Sildenafil, another PDE-5
inhibitor, is currently approved as a daily treatment for
pulmonary hypertension, and it does not seem far-fetched
that in the future a PDE-5 inhibitor could be one of the
drugs, like aspirin for cardiovascular disease, that is taken
daily to prevent or delay the onset of certain aging-related
urologic disorders, such as OAB, BPH, and even ED. In
addition, because the penis is the window to what is occur-
ring within the cardiovascular system, it is also plausible
that these drugs may play a role in the treatment of cer-
tain cardiovascular disorders, such as heart failure and
arteriosclerosis.
References
1. Ignarro LJ, Byrns RE, Sumi D, et al. Pomegranate juice protects nitric oxide
against oxidative destruction and enhances the biological actions of nitric
oxide. Nitric Oxide. 2006;15:93-102.
2. Sandner P, Hutter J, Tinel H, et al. PDE5 inhibitors beyond erectile dysfunc-
tion. Int J Imp Res. 2007;19:533-543.
Male Fertility
When Is Azoospermia Not
Azoospermia?
Reviewed by Jacob Rajfer, MD
Department of Urology, University of California at Los Angeles,
Los Angeles, CA
[Rev Urol. 2008;10(2):169-170]
© 2008 MedReviews, LLC
M
en with azoospermia, defined as no sperm in the
ejaculate as documented by semen analysis,
either have an obstruction to the excretory duc-
tal system or defective spermatogenesis. The observation
that more than 60% of men with defective spermatogen-
esis may have pockets of spermatogenesis within the
testis1,2 provides hope that many of these “azoospermic”
patients can potentially be fathers with testicular sperm
extraction (TESE) or testicular sperm aspiration (TESA)
together with intracytoplasmic sperm injection and in
vitro fertilization, provided these “pockets” of sperm,
which theoretically never make it out of the ductal sys-
tem, can be successfully harvested. TESE in these nonob-
structive azoospermic patients requires either the use of a
microscope to find the sperm (micro-TESE) or multiple
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Male Fertility continued
incision sites in 1 or both testes in the search for these
pockets of sperm.3 TESA also requires multiple aspirations
in these azoospermic patients, although the success rate
with TESA may not be as high as with TESE.4,5 In addition,
there is never any guarantee that any of these pockets of
sperm will be found when either of these 2 procedures is
performed.
Azoospermia: Is Simple Centrifugation
Indicated? A National Survey of Practice and
the Oxford Experience
Swanton A, Itani A, McVeigh E, Child T.
Fertil Steril. 2007;88:374-378.
Because of the time, cost, and invasiveness associated with
either a micro-TESE or multiple TESE procedures, it is
incumbent upon the urologist and reproductive endocrinol-
ogist to be 100% sure that there are definitely no sperm in
the ejaculate. Because a semen analysis is usually
performed using only a small sample of the specimen, it is
possible that if only a few sperm are present in an entire
ejaculate, they may be missed using the standard laborato-
ry-performed semen analysis. One option that has been
suggested is to centrifuge the ejaculated specimen to deter-
mine whether any sperm can be identified in this way. By
performing this simple step in the laboratory, Swanton and
colleagues found that 22% of 87 men who were azoosper-
mic according to conventional semen analysis had sperm
in their centrifuged specimen and therefore did not require
TESE for sperm harvesting. This study adds to the evidence
that all azoospermic men should have their samples cen-
trifuged,6 because the observation of even 1 or 2 sperm in
the ejaculate suggests that spermatogenesis is occurring
somewhere within the gonads. This simple observation has
significant prognostic and therapeutic implications in men
with azoospermia who are considering intracytoplasmic
sperm injection with in vitro fertilization.
References
1. Kim ED, Gilbaugh JH III, Patel VR, et al. Testis biopsies frequently demonstrate
sperm in men with azoospermia and significantly elevated follicle-stimulating
hormone levels. J Urol. 1997;157:144-146.
2. Schlegel PN, Palermo GD, Goldstein M, et al. Testicular sperm extraction with
intracytoplasmic sperm injection for nonobstructive azoospermia. Urology.
1997;49:435-440.
3. Okada H, Dobashi M, Yamazaki T, et al. Conventional versus microdissection
testicular sperm extraction for nonobstructive azoospermia. J Urol. 2002;
168:1063-1067.
4. Hauser R, Yogev L, Paz G, et al. Comparison of efficacy of two techniques for
testicular sperm retrieval in nonobstructive azoospermia: multifocal testicular
sperm extraction versus multifocal testicular sperm aspiration. J Androl.
2006;27:28-33.
5. El-Haggar S, Mostafa T, Abdel Nasser T, et al. Fine needle aspiration vs.
mTESE in non-obstructive azoospermia. Int J Androl. In press.
170 VOL. 10 NO. 2 2008 REVIEWS IN UROLOGY
6. Timm O Jr, Cedenho AP, Spaine DM, et al. Search and identification of sper-
matozoa and spermatids in the ejaculate of non-obstructive azoospermic
patients. Int Braz J Urol. 2005;31:42-48.
Timing of Sperm Harvesting: Is
There Room for Improvement?
Reviewed by Jacob Rajfer, MD
Department of Urology, University of California at Los Angeles,
Los Angeles, CA
[Rev Urol. 2008;10(2):170-171]
© 2008 MedReviews, LLC
F
or urologists who treat infertility as part of their
practice, it is not unusual to be “on call” to harvest
sperm from the male partner of a couple undergoing
in vitro fertilization (IVF). The timing of sperm harvesting
is directly related to the day that egg retrieval of the
female partner is going to occur. Some embryologists (who
manipulate the sperm in the IVF laboratory and perform
intracytoplasmic sperm injection [ICSI]) strongly believe
that the sperm should be retrieved from the male partner
on the same day that egg retrieval occurs. Conversely,
other embryologists have no objection to performing
sperm harvesting the day before egg retrieval, particularly
if the sperm harvesting procedure is to be testicular sperm
extraction (TESE). With TESE the sperm that are extracted
from the tubules of the testicular tissue may take a while
to obtain motility, which is the main in vitro criterion for
choosing which sperm are to be used for the IVF plus ICSI
process. By performing TESE the day before egg retrieval,
the laboratory personnel allow themselves enough time to
dissect the testicular tissue and retrieve the sperm, partic-
ularly in the case of nonobstructive azoospermic patients,
for whom spermatogenesis may be severely impacted and
in whom it may take a long time, relatively speaking, to
find sperm in the tissue. However, some embryologists
insist that sperm retrieved the day before egg retrieval do not
“survive” as well as sperm retrieved the day of egg retrieval.
This inconsistency and variability between IVF laborato-
ries and their embryologists is most likely due to the indi-
vidual experience of each laboratory rather than any solid,
evidence-based data. If it could be demonstrated that har-
vesting sperm earlier than the day of egg retrieval does not
severely impact the ability of the sperm to undergo fertiliza-
tion, this could make life easier for all concerned because on
many occasions the actual day of egg retrieval does not fall
on the date originally targeted. In fact, in some cases, the day
of egg retrieval may be a week or so later than anticipated
at the beginning of the stimulation cycle of the female