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The American Urological Association’s 2003 Annual
Meeting included research presentations on chronic prostatitis/chronic
pelvic pain syndrome (CP/CPPS) in a poster session on infections
and inflammation of the prostate, urethra, and genitalia,
as well as in other poster sessions.
During a typical poster session, researchers’ work
is mounted on poster boards throughout a conference room.
Attendees can view these exhibits and talk with the researchers
about their studies. Then, one researcher (designated by
the asterisk) from each team gives a brief presentation of
they study and answers questions from the audience.
This year, research addressed possible causes, diagnosis,
classification and characterization of the disease, symptoms
and quality of life, and potential treatments.
CAUSES
Infection?
LEVELS OF 16S BACTERIAL DNA IN SEMEN BY REAL TIME PCR DO NOT
CORRELATE WITH CLINICAL DIAGNOSIS OR TREATMENT RESPONSE IN
CATEGORY III CHRONIC PROSTATITIS
Daniel A. Shoskes*, Chantale Lapierre, Weston, FL; Scott Zeitlin,
Los Angeles, CA
Could CP/CPPS be caused by some bacteria that just can’t
be grown in a culture? These researchers used a different way
of looking for evidence of bacteria in semen; instead of trying
to grow bacteria, the researchers measured the amount of one
kind of genetic material from bacteria. In 28 men who had CP/CPSS,
22 had detectable genetic material from bacteria, but the amount
of material didn’t correspond with anything about their
condition before treatment, including white cell counts and
conventional cultures. Fifteen of the 28 men were given antibiotics,
and of those, 7 improved; 8 of the 28 got quercetin, and of
those, 7 improved, but again, there was no correlation with
improvement and levels of bacterial genetic material in the
semen. These investigators think that antibiotics could have
helped the men either because they killed bacteria or because
they had anti-inflammatory effects.
THE 2001 GIESSEN COHORT STUDY ON PATIENTS WITH CPPS/CP - AN
EVALUATION OF INFLAMMATORY STATUS AND EVIDENCE OF BACTERIA
10 YEARS AFTER A FIRST ANALYSIS
Henning Schneider*, Martin Ludwig, Hamid M. Hossain, Thorsten
Diemer, Wolfgang Weidner, Giessen, Germany
These German researchers looked for infectious bacteria of
various kinds in men with symptoms of prostatitis. Of the 168
men they saw, 81% met the criteria for CP/CPPS. Only seven
men (4%) had evidence of chronic bacterial prostatitis. Although
the researchers found many different kinds of bacteria in low
numbers in the men with symptoms, true chronic bacterial prostatitis
was rare. In addition, there was little evidence of sexually
transmitted microorganisms.
DOES ABACTERIAL PROSTATITIS REALLY EXIST?
Federico Guercini*, Rome, Italy; Sandra Mazzoli, Florence,
Italy; Elisabetta Costantini, Cinzia Pajoncini, Massimo Porena,
Perugia, Italy
These researchers think that hard-to-find-and-eliminate infections
could cause what looks like chronic abacterial prostatitis.
When they tested 56 men diagnosed with abacterial prostatitis
with urethral swabs, they found no infection. But then the
clinicians took samples directly from the men’s prostates
and found infectious organisms in 79% of them. Twenty one men
(38%) had more than two species of microorganisms identified,
and 9 (15%) had more than three.
Estrogen exposure/autoimmune disease?
PROSTATITIS INDUCED BY EARLY ESTROGENIC EXPOSURE IN THE RAT
IS PARTIALLY BLOCKED BY PROLACTIN SUPPRESSION
Jason Gilleran*, Gail Prins, Oliver Putz, Chicago, IL
Abnormal exposure of the prostate to estrogen and prolactin
are thought to play a role in chronic prostatitis, possibly
by bringing about a kind of autoimmune response. This kind
of hormone exposure has been associated with autoimmune diseases
in other contexts. These researchers exposed rats at birth
to an inert oil or an estrogen, then right before puberty,
some were given a drug that suppresses the hormone prolactin
and others to a placebo. The researchers looked at the size
of the prostate lobes, testes, spleen, adrenal glands, and
thymus glands in adulthood and also the structure of the prostate
glands, the animals’ immune responses, and white blood
cell populations. The rats exposed to estrogen who got the
prolactin-suppressing drug didn’t have different organ
sizes but did show that the inflammatory response of their
white blood cells was partially suppressed. All the rats exposed
to estrogen early, regardless of whether prolactin was suppressed,
had abnormal-appearing epithelial cells in the prostate as
adults. There may be an effect of estrogen on the prostate.
The researchers think that early, abnormal estrogen exposure
may affect inflammation and immune cell infiltration of the
prostate gland in men.
Genetic?
POSSIBLE FUNCTION OF SHORT TANDEM REPEATS FOR GENETIC TESTING
IN CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME PATIENTS
Donald Riley*, John Krieger, Seattle, WA
These researchers found some evidence that men who get CP/CPPS
may have a genetic predisposition to it. The DNA sequences
called short tandem repeats (STRs) near the androgen receptor
gene may be involved. The study showed that these STRs may
actually perform a function in cells, pointing to their potential
role.
DIAGNOSING, CLASSIFYING, AND CHARACTERIZING PROSTATITIS
MALE INTERSTITIAL CYSTITIS—TIME FOR A CHANGE?
Jordan D Dimitrakov*, Plovdiv, Bulgaria; Dorian Y. Dikov, Lagny-sur-Marne
Cedex, France
Do men with nonbacterial prostatitis and prostatodynia really
have interstitial cystitis instead? Previous studies using
cystoscopy with hydrodistention have shown that up to 70% of
men with these diagnoses have bladder abnormalities that meet
the NIH-NIDDK criteria for IC. These researchers tested 300
men with confirmed chronic pelvic pain for interstitial cystitis.
Testing included cystoscopy with hydrodistention, the potassium
sensitivity test, and measurements of potential markers of
interstitial cystitis in prostatic secretions and urine. Those
markers included nerve growth factor (NGF), tryptase, heparin-binding
epidermal growth factor-like growth factor (HB-EGF), and epidermal
growth factor (EGF). Of the 300 men, 240 (80%) had interstitial
cystitis, confirmed by the characteristic glomerulations seen
on the bladder wall during cystoscopy with hydrodistention.
All patients with interstitial cystitis had some degree of
erectile dysfunction and burning or pain during and/or after
ejaculation. The levels of NGF and tryptase were significantly
higher and the HB-EGF levels were significantly lower in the
interstitial cystitis patients than in with healthy controls.
NGF, HB-EGF, and tryptase may be promising new markers for
evaluating men with pelvic pain. Any young man who has burning
and/or pain after ejaculation should be evaluated for interstitial
cystitis, say these researchers.
EVALUATION OF THE CYTOKINES MACROPHAGE INFLAMMATORY PROTEIN-1
? AND MONOCYTE CHEMOATTRACTANT PROTEIN-1 AS INDICATORS OF INFLAMMATION
IN PROSTATIC SECRETIONS
Jeffrey A. Stern*, Alisa E Koch, Phillip L. Campbell, Anthony
J. Schaeffer, Chicago, IL
Certain proteins secreted by immune system cells, called cytokines,
may play a role in inflammation. Measuring the levels of some
cytokines, say these researchers, could help provide an objective
way to measure inflammation. Specifically, they looked at levels
of macrophage inflammatory protein-1? (MIP-1?) and monocyte
chemoattractant protein-1 (MCP-1) in expressed prostatic fluid
of healthy men and men with inflammatory and noninflammatory
chronic pelvic pain syndrome (CPPS). These cytokines are known
to increase the activity of or attract different types of white
blood cells. Although they found both cytokines in all the
groups, levels were highest in men with inflammatory CPPS.
There was no difference in levels between men with noninflammatory
CPPS and the control group for either cytokine. These cytokines,
say the researchers, may play a role in recruiting the white
blood cells that flock to the inflamed prostate.
THE USE OF INTRAPROSTATIC NITRIC OXIDE MEASUREMENTS TO DIFFERENTIATE
BETWEEN INFLAMMATORY AND NON-INFLAMMATORY ABACTERIAL CHRONIC
PROSTATITIS.
Abolfazl Hosseini*, Ingrid Ehrèn, Peter Wiklund, Stockholm,
Sweden
The NIH classification of chronic prostatitis distinguishes
between inflammatory and noninflammatory types. Often, the
only way to determine whether inflammation is present is to
look for white blood cells in prostatic secretions in urine
obtained through prostatic massage and the “four-glass” test.
These researchers tried another way to measure inflammation—looking
for levels of nitric oxide (NO) gas in the portion of the urethra
in the prostate by collecting samples of air there in a catheter.
Levels of the gas have been used to judge the degree of inflammation
in other problems, such as asthma, colitis, rheumatoid arthritis,
and lower urinary tract inflammation. The levels of NO did,
indeed, correlate with amount of white cells.
SEMINAL MARKERS OF INFLAMMATION IN CHRONIC PELVIC PAIN SYNDROME
(CPPS): SUGGESTION FOR APPROPRIATE CUTPOINTS
Martin Ludwig*, Andreas Vidal, Thorsten Diemer, Wolfgang Pabst,
Klaus Failing, Wolfgang Weidner, Giessen, Germany
Is there an easier way to distinguish inflammatory from noninflammatory
prostatitis than looking for white blood cells in prostate
secretions in urine obtained with prostatic massage and the “four-glass” test?
These researchers looked for white blood cells and levels of
elastase, an inflammation marker, in ejaculate and compared
the results with those of the four-glass test. The two types
of tests correlated well, helping distinguish inflammatory
from noninflammatory prostatitis. On the other hand, they concluded
that the World Health Organization (WHO) cutoff for having
significant amounts of white blood cells in the ejaculate is
too low. These researchers think it should be 0.113 million/mL
peroxidase-positive leukocytes (PPL) rather than the WHO’s
1 million/mL. The elastase level also correlated well with
the PPL count.
TOTAL PROSTATE-SPECIFIC ANTIGEN IS ELEVATED AND STATISTICALLY,
BUT NOT CLINICALLY SIGNIFICANT IN PATIENTS WITH CHRONIC PELVIC
PAIN SYNDROME/PROSTATITIS
Robert B. Nadler*, Anthony J. Schaeffer, Chicago, IL; Jill
S. Knauss, Kathleen J. Propert, Richard Landis, Philadelphia,
CA; Stephen D. Mikolajczyk, San Diego, CA; Richard B. Alexander,
Baltimore, MD
Prostate-specific antigen (PSA) levels don’t indicate
whether a man has CP/CPSS, and if a man does have a high PSA,
he should be evaluated for prostate cancer, say these researchers.
They looked at three different PSA measurements (total, free,
and percent free) in 424 CP/CPSS patients and 114 men the same
age with no symptoms. Total PSA was slightly higher in men
with CP/CPSS, but there were no real differences in any other
measurement.
SYMPTOMS AND QUALITY OF LIFE
PAIN AND AFFECTIVE DISTRESS AS PREDICTORS OF QUALITY OF LIFE
IN CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME (CP/CPPS)
Dean A. Tripp*, J. Curtis Nickel, Kingston, ON, Canada; Richard
J. Landis, Jill S. Knauss, Philadelphia, PA; and the CPCRN,
Bethesda, MD
Researchers at seven different centers in the United States
and Canada looked at how psychological factors and physical
symptoms affect the quality of life in men CP/CPSS. The 488
men studied were enrolled in the NIH Chronic Prostatitis Cohort
(CPC) study. The most important factors in qualify of life
were the degree of urinary symptoms, psychological distress,
and pain, with pain topping the list. Psychological distress
came in second. The man’s age and whether he was living
with a partner weren’t significant factors in quality
of life. These researchers say it is important to learn how
psychological distress and pain are related for men with CP/CPSS.
SEXUAL DYSFUNCTION IN YOUNG PATIENTS WITH CHRONIC PROSTATITIS/CHRONIC
PELVIC PAIN SYNDROME
Juza Chen*, Alexander Greenstein, Mario Sofer, Haim Matzkin,
Tel-Aviv, Israel
Many symptoms of CP/CPPS are well described, but it isn’t
known how much younger men with CP/CPPS may suffer with sexual
dysfunction. In 147 patients with CP/CPPS aged 18 to 50 years
(average 30 years) in Israel, 95 said they had some degree
of erectile dysfunction. Fifty-two had ejaculatory dysfunction,
30 had pain during ejaculation, 25 had premature ejaculation,
and 5 had unejaculation. Forty seven patients said their sexual
satisfaction was impaired and 40 said they had decreased sexual
arousal. This degree of sexual dysfunction is above what is
expected for this age group.
TREATMENT
LEVOFLOXACIN TREATMENT FOR CHRONIC PROSTATITIS/CHRONIC PELVIC
PAIN SYNDROME (CP/CPPS) IN MEN: A RANDOMIZED PLACEBO CONTROLLED
MULTICENTER TRIAL
J. Curtis Nickel*, Joe Downey, Janet Clark, and The Canadian
Prostatitis Research Group, Kingston, ON, Canada
Do antibiotics work for CP/CPSS? A multicenter Canadian study
aimed to find out. Sixty five men who had CP/CPSS (that is,
no infection identified in the prostate), were included in
the study. Their ages ranged from 36 to 78 years (average 56),
and they had had symptoms for as little as 7 months and as
long as 32 years (average about 7 years). For six weeks, 36
men were given 500 mg/day of the antibiotic levofloxacin (Levaquin),
and the other 29 were given a placebo. The researchers looked
at how they rated their symptoms at 3, 6, and 12 weeks. The
differences looked significant at the three-week mark, with
levofloxacin recipients doing better, but after that, the difference
between the groups wasn’t significant.
ALFUZOSIN TREATMENT FOR CHRONIC PROSTATITIS/CHRONIC PELVIC
PAIN SYNDROME (CP/CPPS): A PROSPECTIVE RANDOMIZED PLACEBO CONTROLLED
STUDY
Aare Mehik*, Oulu, Finland; Peeter Alas, Oulainen, Finland;
J. Curtis Nickel, Kingston, ON, Canada; Ari Sarpola, Pekka
Hellstrom, Oulu, Finland
Alpha blockers, often used to treat benign prostate enlargement,
help ease symptoms for men with CP/CPSS. These Finnish researchers
had information from 61 patients to evaluate: 19 took the alpha
blocker alfuzosin (Xatral, available in Europe and not the
United States), 16 took a placebo, and 26 underwent standard
therapy for six months, and then were followed up six months
later. The patients rated their symptoms using the Chronic
Prostatitis Symptom Index (CPSI). After six months of therapy,
the men taking alfuzosin had a significantly better reduction
in pain than the men in the other two groups, but there wasn’t
a significant difference between the groups in terms of voiding
or quality of life scores. Six months later the condition of
the men in the alfuzosin and placebo groups deteriorated compared
with that of the men undergoing standard therapy. Side effects
of the alfuzosin therapy were mild, with mild gastrointestinal
symptoms and a decrease in the volume of ejaculate for a few
of the men. The researchers concluded this alpha blocker offers
modest but real benefits and that it takes several months for
the benefits to appear.
LONG-TERM EFFECTIVENESS OF TERAZOSIN THERAPY FOR CHRONIC PROSTATITIS/CHRONIC
PELVIC PAIN SYNDROME (CP/CPPS)
Phaik Yeong Cheah, Men Long Liong, Kah Hay Yuen, Wing Seng
Leong*, Chu Leong Teh, Timothy Khor, Penang, Malaysia; Jin
Rong Yang, Kuala Lumpur, Malaysia; Hin Wai Yap, Penang, Malaysia;
John N Krieger, Seattle, WA
The alpha blocker terazosin (Hytrin) seems to help men with
CP/CPSS avoid relapse. In this study, men had already been
participated in a 14-week blinded study of the alpha blocker
versus placebo. Then, the men who didn’t respond to therapy
or who had a relapse got further therapy with either terazosin
or standard treatment (not in a blinded fashion) and were followed
up for another six months. Five of 23 men who took terazosin
(22%) had a relapse, whereas 6 of 12 men (50%) who took placebo
had a relapse. In addition, in those who didn’t respond
to treatment before or who had had a relapse, the men who got
additional terazosin had about a threefold better chance of
improving than men who chose no further treatment.
MYCOPHENOLATE MOFETIL IN THE TREATMENT OF CPPS: A DOUBLE-BLIND
PLACEBO-CONTROLLED STUDY
Jordan D. Dimitrakov*, Plovdiv, Bulgaria; Dorian Y. Dikov,
Lagny-sur-Marne Cedex, France
Because they had read about clinicians having some success
treating chronic prostatitis with an immunosuppressive drug,
these researchers decided to study the drug, mycophenolate
mofetil (CellCept), more formally in 200 men with CPPS. This
drug is usually used to combat rejection in kidney transplant
patients. One group of men received the drug 500 mg twice daily
for 4 weeks, and the other group got placebo. The ones who
got the drug did significantly better: After one month, 85%
of the men who received mycophenolate mofetil said their pain
was improved, compared with 25% of the men who got the placebo.
Six months later, 65% of the men who got the drug said they
were still better, compared with only 15% of those who got
the placebo. In addition, the levels of proinflammatory cytokines,
which are proteins involved in inflammation, were decreased
significantly in the men who received mycophenolate compared
with the men who got placebo. Side effects were mild and well-tolerated,
including headache, transitory skin rash, and nausea.
MULTICENTER AUSTRIAN TRIAL ON SAFETY AND EFFICACY OF PHYTOTHERAPY
IN THE TREATMENT OF CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN
SYNDROME
Andreas Reissigl*, Josef Pointner, Bregenz, Austria; Michael
Marberger, Mesut Remzi, Vienna, Austria; Juergen Brunner, Stefan
Obwexer, Bregenz, Austria; Bob Djavan, Vienna, Austria
European researchers tested a saw palmetto (Serenoa repens)
extract, called Permixon, on men with CP/CPPS symptoms. (Permixon
is used in Europe for benign prostatic hyperplasia or BPH.)
Although the men who got Permixon were better for a while after
the therapy ended, the effects didn’t last long-term.
Thirty-two men received the extract for 6 weeks, and 24 did
not. Researchers looked at how the men were doing 6 and 12
weeks after that based on the patients’ overall assessment,
scores on the NIH Chronic Prostatitis Symptom Index (CPSI),
safety data, PSA levels, and prostate volume. Overall, 75%
of the men who got Permixon had at least mild improvement,
compared with 20% of the control group, and 55% of Permixon
patients said they had moderate or marked improvement compared
with 16% of the control patients. At 6 weeks, Permixon patients
showed a 30% reduction in their total NIH-CPSI scores, but
at 12 weeks, there was no difference between the groups. Prostate
volume did not change significantly in either group. In the
control group, PSA did not differ from baseline, but Permixon
patients had a median decrease in PSA of 22% at 6 weeks. It
seems that this treatment may be helpful, and if men do get
benefit from it, they may need to keep taking it.
COOLED THERMOTHERAPY (TUMT) FOR CHRONIC ABACTERIAL PROSTATITIS
6 MONTHS AFTER TREATMENT
Christof Kastner*, Redhill, Surrey, UK; Werner Hochreiter,
Berne, Switzerland; Juan Cabezas, Christian Huidobro, Santiago,
Chile; Paul D. Miller, Redhill, UK
Transurethral microwave thermotherapy of the prostate as a
treatment for CP/CPPS has been only variable successful. A
newer kind of thermotherapy with a system that cools the urethra
to control was tried in 40 patients who had had intractable
symptoms for the last three to six months. For one patient,
therapy was stopped because of pain, but better pain killers
then allowed him to undergo therapy later. Thirty five of the
40 patients had had a 6-month evaluation at the time of the
study, and for them, the mean pain score on the NIH Chronic
Prostatitis Symptom Index (CPSI) went from 11.3 before treatment
to 3.5, the urinary score went from 4.7 to 2.2, and the quality
of life score from 7.2 to 3.1—all statistically significant
improvements. Only two patients had any score that got worse
by more than one point. Complications were called minimal and
transient, including urinary tract infection, acute urinary
retention, and lower urinary tract symptoms early after treatment.
One case of dry orgasm was reported. The other patients either
stayed the same or improved in terms of fertility, sexual activity,
libido, and erectile function. A larger trial is being planned
to see if the effects last.
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