Critical Review of T60 for Symptomatic Relief Of Lower Urinary
Tract Symptoms (LUTS) in Men
Harry G. Preuss1
Walter G. Chambliss3
1 Department of Physiology and Biophysics,
Georgetown University Medical Center, Washington, D.C. USA
of Pharmacy Sciences, School of Pharmacy and Health Professions, Creighton
University Medical Center, Omaha, NE. USA
3 National Center for Natural Products
Research, and Department of Pharmaceutics, University of Mississippi,
Research Institute of Pharmaceutical Sciences, School of Pharmacy, University,
We reviewed published data concerning the ability of a defined flower
pollen ex-tract derived from rye, corn, and timothy, commonly referred
to as T60 to provide symptomatic relief in men suffering from lower
urinary tract symptoms (LUTS). This same defined pollen extract has
also been called T60 in other reports and is commercially available
as Flower Pollen Extract. To maintain clarity, however, we
will only use the term T60 to describe the defined pollen extract.
In writing this review, our major goal is to present evidence concerning
the therapeutic role of T60 in the management of mild to moderate
LUTS. Nevertheless, we briefly describe prostatic perturbations in general
and other natural therapeutic approaches to alleviate symptoms caused
It is estimated that 9-10 million men have lower urinary tract symptoms
(LUTS) secondary to an enlarged prostate; and 400,000 surgeries are
conducted each year in the U.S to alleviate such symptoms [1,2]. Although
cancer might be a root cause, LUTS are more commonly found in men with
non-cancerous conditions such as benign prostate hyperplasia (BPH),
prostadynia, acute and chronic prostatitis caused by a bacterial infection,
as well as chronic non-bacterial prostatitis. BPH, the most common cause
of LUTS, does not distinguish between race and ethnic background, although
African-American men are at a slightly greater risk . It does not
relate to sexual activity, since it can occur in celibate priests as
well as the most sexually active of men . Regardless of the etiology
of the specific prostate-related disorders, health worries associated
with prostatic enlargement are significant. Over $1 billion dollars
are spent each year on treatment for prostatic enlargement, because
LUTS can lead to more serious health problems if not treated properly
The term LUTS describes men experiencing one or more symptoms listed
on the International Prostate Symptom Score (IPSS) questionnaire. Among
the mentioned urinary symptoms are daytime and night time (nocturia)
frequency, urgency, hesitancy, intermittency, sensation of incomplete
voiding, and decreased force of urinary stream . An individual often
becomes aware of the problem when urination occurs more frequently than
usual. He may eventually become the person who rarely can sit through
a movie or concert -- the one that requests the aisle seat on an airplane
so as not to disturb his fellow passengers on his frequent sojourns
to the restroom. At night, the trips to the bathroom caused by nocturia
steadily increase, and there is a definite impingement on sleep. Suffice
it to say, any experiencing of such frequency should lead to suspicion
of the disorder.
What do we know about this troublesome gland? The prostate gland is
associated with the male reproductive system. Its major function is
to produce and discharge a viscous, alkaline liquid that provides a
major portion of the seminal fluid. The prostate makes and stores fluid
almost continuously. Because of the environment afforded by the presence
of prostatic fluid, sperms are protected, at least to some extent, and
can survive longer after ejaculation. In addition, the prostatic fluid
contains prostaglandins, which are fatty acids that, similar to hormones,
affect smooth muscle fibers and blood vessel walls. Although the prostate
plays no direct role in the functioning of the male urinary system,
its location near the bladder and urethra cause many urinary perturbations
when it expands via growth or response to chronic inflammation [6-8].
At birth, the gland is the size of a pea and grows slowly until puberty.
Under the influence of sex hormones, the prostate grows at a faster
pace. During the 20's and 30's, the gland is characteristically the
size of a walnut and weighs roughly one ounce. The gland, made up of
muscular and glandular tissue, is located in front of the rectum and
below the urinary bladder. Importantly, the gland surrounds the urethra,
a tube that carries urine from the bladder to the tip of the penis for
expulsion. Obviously, this setting has the potential to cause problems
and unfortunately does. Around the age of 45, cells in the majority
of prostates began to multiply again and the gland can reach up to 10
times the normal adult size .
The prostate can be divided into various lobes, with the major problems
of BPH lying in the small transitional zone. The transitional zone that
lies within the so-called middle lobe is the sole site of BPH . Interestingly,
the small transition zone comprises only two per cent of the entire
prostatic mass before enlargement. Obviously, enlargement of this area
does not in itself increase the size of the prostate greatly. Because
of this, the degree of urethral obstruction may not directly relate
to the overall size of the prostate gland but instead to the direction
of growth enlargement. Some men with greatly enlarged prostates may
have no signs of obstruction, while those with relatively small prostates
may have severe obstruction.
While the exact mechanism behind age-related enlargement of the prostate
is uncertain, a highly active form of the male hormone, testosterone,
called dihydrotestosterone (DHT), is considered a major factor behind
prostatic enlargement . Excessive levels of DHT have been found in
men with enlarged glands, and high concentrations of DHT are also associated
with an increased risk of prostate cancer. To make matters worse, the
concentration of DHT within the prostate increases with age. A major
factor in the rise is that the enzyme responsible for the conversion
of testosterone to DHT, 5-alpha reductase, becomes more active over
the lifespan. Therefore, it is not too surprising that 5-alpha reductase
is an important focal point in the medical treatment of prostate enlargement.
Nevertheless, it is equally important to be aware that other prostatic
enzymes, such a 3 oxidoreductase, deficiency of minerals such as zinc,
and inflammation may also play a role in the enlargement process.
Background of Treatment
Bruskewitz points out that since serious complications from BPH and
related non-cancerous conditions are rare, the primary aim of pharmacological
treatment is to improve quality of life by relieving the vexing symptoms
. Studies conducted in the U.S. showed that urologists provided
no specific treatment 77% of the time to men with mild symptoms. With
moderate symptoms, however, prescription drugs were given 89% of the
time; and surgery was conducted 1% of the time. The primary therapeutic
treatment was use of alpha (1)-adrenoceptor antagonists such as terazosin
hydrochloride (Hytrin®) that provide symptomatic relief but have not
been shown to influence the incidence of surgery, acute urinary obstruction,
or other complications of BPH . In the past, treatment options for
significant prostate enlargement focused on surgery. In a given year,
approximately 400,000 men are driven to undergo a procedure called a
transurethral resection of the prostate (TURP). Even now, transurethral
resection is the standard treatment for BPH, i.e., the gold standard
by which all other procedures are measured . Unfortunately, while
many symptoms of obstruction are ameliorated, post urination dripping
may continue and may even result in severe incontinence. Even worse,
the operation may be followed by a decline in sexual function. This
may also occur with the use of the common pharmaceuticals as well .
Accordingly, a need exists for safe, effective products that can be
used to treat mild to moderate LUTS in lieu of or in addition to prescription
drugs and major surgery. Natural products have been considered among
the alternative therapies.
Natural Products to Treat LUTS
Saw Palmetto (Serenoa Repens)
Research carried out in Europe over the past 20 years shows that natural,
fat-soluble extracts from specific plants effectively inhibit the function
of 5-alpha-reductase, and block, at least in part, the formation of
DHT [13-16]. The best-known and most extensively researched plant is
saw palmetto. Saw palmetto is an extract of the pulp and seeds of a
dwarf, scrubby palm tree native to the West Indies and the Atlantic
coast of the United States. Saw palmetto works, for the most part, by
the same mechanism as the pharmaceutical Proscar®, i.e., preventing
the conversion of testosterone to DHT . Additional benefits from
plant extracts have also been found and may add to the good results
found with their use. Some plant extracts not only lower the rate of
DHT formation, but also block the ability of DHT to bind to cells, preventing
the action of hormone [17,18]. In addition, they may prevent severe
inflammatory responses. Saw palmetto, known to be popular in Europe,
has recently become recognized in America. In one study using saw palmetto
in 110 men, it decreased nighttime urination by 45 percent, increased
urinary flow rate more than fifty percent, and reduced the amount of
urine left in the bladder after urination by 42 per cent . In other
large trials, improvement in prostatic symptomatology was readily noted
and saw palmetto even compared favorable with Hytrin and Proscar when
they were compared head to head [20-24].
The powdered bark of the pygeum tree, a large tropical African evergreen,
has been used for centuries to treat urinary disorders . Pygeum
contains phytoesterols, which have been purported to have anti-inflammatory
properties. In addition, much benefit has been attributed to their ability
to decrease prostatic swelling, to reduce harmful prostaglandins that
induce inflammation, and to diminish circulating prolactin that decreases
the prostate uptake of testosterone. When 263 German men were tested
with Pygeum africanum, urinary symptoms improved in 66% compared to
31% in the placebo group . Occasional gastrointestinal upset seems
to be the major adverse side effect.
Stinging Nettle (Urtical dioica)
Less research has been performed using the stinging nettle to ameliorate
BPH. Laboratory studies have shown its ability to inhibit laboratory
induced prostate growth in mice . The results from one study suggest
that the steroidal components of stinging nettle roots suppressed prostate
cell growth .
Much attention has recently been focused on beta-sitosterol. In a randomized
double blind study reported in the Lancet, 200 patients from eight private
urological practices were treated for six months with either 20 mg of
beta-sitosterol or placebo . At the end of six months, modified
Boyarsky scores decreased statistically in the beta-sitosterol treated
group compared to placebo. The quality of life score improved, the peak
urine flow increased, the mean voiding time and the urinary volume retention
also improved from the initial scores in the verum group, whereas no
changes were noted in the placebo group. Results were also positive
in another randomized, double-blind and placebo-controlled study carried
out in Germany .
T60 is a natural product recently introduced in the USA to be used
to treat LUTS. However, it has actually been around a long time. In
1950, in a tiny Swedish village, a beekeeper found a way to collect
pollen artificially . Since it was good for bees, his hypothesis
was that it would be good for humans. Initially, the flower pollen was
used as a prophylactic agent against infections. Later the extraction
process was modified so that the active pollen was released and was
non allergenic. Found in the pollen are peptides, carbohydrates, fatty
acids, vitamins, minerals, nucleic acids, and enzymes. Whatever the
original hypothesis concerning overall health, the defined pollen extract
called "T60" proved specifically useful in treating BPH and other
prostate conditions [2,32].
T60 is a standardized extract of rye pollen (Secale cereale),
corn pollen (Zea mays), and timothy pollen (Phleum pratense).
From these combined pollens, two important, therapeutic extracts are
derived -- a water-soluble fraction and a lipid-soluble fraction with
different physiological functions. In vitro and in vivo
animal studies [33,34] have shown that both fractions have anti-inflammatory
properties emanating from inhibition of prostaglandin and leukotriene
synthesis. The water-soluble fraction has been shown to reduce the size
of the ventral and dorsal prostate in the rat  and to inhibit testosterone-induced
BPH in castrated animals . The combined extracts were shown to inhibit
growth of transplanted human BPH tissue in an athymic nude mouse model
(36). Both fractions have been shown to relax the smooth muscle of the
mouse and pig urethra, increase bladder muscle contractions , and
reduce prostate size in mature Wistar rats .
T60 extracts are also sold as Flower Pollen Extract and
are available in the marketplace in tablet and capsule forms, usually
contain 63 mg of a 20:1 ratio of water-soluble to lipid-soluble fractions.
T60 is contained in products regulated as drugs in Switzerland,
Germany, Austria, Japan, South Korea and South Africa. In the U.S.,
the use of botanicals for LUTS is relatively less. No botanicals are
approved as prescription or over-the-counter drugs for LUTS or BPH in
the U.S. Accordingly, they are sold as dietary supplements and are labeled
with non-specific information, e.g., "maintains prostate health." In
a study conducted in Chicago in 1997-1998 with 738 men having LUTS and/or
prostate disease, Bales et al  found that 13% of the group had used
botanicals for their condition (59% in combination with prescription
drugs), 37% were aware of botanicals as an option but had never used
them, and 50% were unaware of this treatment option. Such information
prompted our review of T60.
Literature searches were conducted on Medline and the Cochrane Library.
Sources such as review articles and monographs in botanical reference
books and other books referring to T60 were included in the analysis.
Open label and comparative trials were included in the assessment, although
more weight was given to placebo-controlled, double-blind studies. Emphasis
was placed on subject ratings of symptoms in light of the potential
for self-medication of this extract.
Reviews, Books, and Monographs
Four reviews [39-43] and a number of books/monographs [2,44-46] dealing
largely with the clinical efficacy and safety of T60 have been
published in recent years. Each used its own criteria to select studies
considered to be valid. Because all reviews concluded that T60
is very safe with few or no side effects, the summaries described below
are essentially limited to efficacy.
In the first, Commission E, an expert committee established by the
German government to evaluate the safety and efficacy of over 300 botanical
and botanical combinations sold in Germany, concluded in 1994 that combining
extracts of rye, corn, and timothy pollen was useful in the treatment
of "micturition difficulties associated with Alken stage I-II benign
prostatic enlargement (BPH)" . In the second, the Natural Medicines
Comprehensive Database concluded that rye grass pollen extract (T60)
was "possibly effective" for the management of BPH symptoms, for shrinking
prostate size, and for prostatitis and prostadynia based on the information
it gathered . In the third source, the same group published reviews
in 1999 and 2000 based upon results from 4 double-blind studies (444
men in total, 2 studies with placebo; 2 with active controls) [41,42].
Results consistently showed a "modest" improvement in subjective symptoms
and nocturia in the T60 groups compared to placebo, Paraprost (a
mixture of the amino acids L-glutamic acid, L-alanine, glycine) and
Tadenan (Pygeum africanum extract). The authors called for additional
studies to evaluate long-term effects. In the final review, Shoskes
concluded that there was credible clinical and scientific evidence that
treatment with T60 pollen extract was efficacious for the majority
of patients with non-bacterial prostatitis and prostadynia . The
books/monographs largely corroborate the conclusions of the reviews
Again, T60 was well tolerated in all of the published studies from
primary literature with minimal reported side effects. Therefore, the
discussion will continue to focus on efficacy.
In the 1960's, Leander  published results of a carefully controlled
trial. He compared placebo with T60 pollen extract in 179 cases.
Using pollen extract, Leander found a 60-80 per cent improvement over
placebo in symptoms of obstruction, probably through elimination of
inflammatory edema. Around the same time, much work was progressing
in Japan. Inada et al  reported favorable effects in 12 patients
suffering from prostatic hypertrophy. They reported that five cases
had "effective" results; five showed "slightly effective" results and
two reported "ineffective" results. In 1967, Ohkoshi, Kawamura and Nagakubo
of Keio University, reported impressive results in 30 patients with
prostatitis and/or urethritis . Examining 14 patients receiving
T60, it was found that treatment was "successful" in 10, "slightly
effective" in three, and "ineffective" in only one case. In 16 patients
given placebo, seven found the treatment to be "effective" and nine
reported "no change."
In 1981, Takeuchi  investigated both subjective and objective effects
of T60 on 25 men with BPH. The efficiency rate for T60 was
reported as 64%. There was a 50% improvement for nocturnal micturation.
Horii et al  reported the results of 30 subjects with BPH who were
given T60 2 tablets, 3 times daily for at least 12 weeks. The overall
clinical efficacy for subjective symptoms was rated at 80% and objective
symptoms at 43%. Ueda et al  treated 22 patients with stage I and
II BPH with T60 for over 4 weeks. Eighty-two percent of the patients
were rated as moderately improved or better. Hayashi et al  treated
20 BPH patients with T60, 6 tablets a day for an average of 13.2
weeks. They reported improvements in sense of residual urine (92%),
retardation (86%), night frequency (85%), strain on urination (56%),
protraction (53%), and forceless urinary stream (53%). Overall subjective
effectiveness was 80% and overall objective effectiveness was 54%.
In 1986, a field study of 2,289 patients being treated by 170 urologists
was undertaken . They examined the effectiveness of T60 pollen
extracts on chronic prostatitis and/or BPH. Improvement of symptoms
was reported in 64 to 82%, in contrast to a low rate of adverse reaction
found only in 2.9% of cases. In the same year , Brauer compared
the effects of T60 and beta-sitosterol in 39 patients. A significant
reduction in circulating levels of PSA with T60 therapy indicated
a reduction of cell lesions in BPH. In contrast, no such change occurred
with beta-sitosterol treatment. Although flower pollen extract proved
superior to beta-sitosterol in many respects, the mean values for residual
volume fell under 15 ml for both at the end of treatment. Jodai et al
 reported the results of a study on 32 patients with chronic prostatitis
given 6 tablets of T60 daily for an average of 12 weeks. Subjective
symptoms improved in 74.2% of the subjects as compared to 65.6% for
objective symptoms. The overall efficacy rate was 75.0%.
In a double-blind, placebo-controlled study, Becker et al  reported
data for 96 subjects with BPH in stages II or III according to the Vahlensieck.
Subjects received two T60 capsules or placebo three times daily
for 12 weeks. The results showed significant improvement in nocturia
(68.8% on T60 versus 37.2% on placebo, p = 0.005), daytime frequency
(65.8% on T60 versus 43.9% on placebo, p = 0.076), freedom from
daytime frequency (48.8% on T60 versus 19.5% on placebo, p = 0.010)
and freedom from sensation of residual urine (37.1% on T60 versus
7.7% on placebo, p = 0.016). In addition there was significant improvement
in global assessment scores of both the physicians (p = 0.001) and patients
(p = 0.01). Physicians rated the overall response as very good or good
for 68.1% of patients taking T60 versus 13.7% taking placebo group.
72.1% of patients taking T60 rated their overall response as very
good or good versus 27.3% in the placebo group. However, there was no
significant change in the size of the prostate as determined by palpation.
In an open study, Buck et al  studied the effect T60, 2 tablets
twice daily for up to 18 months on 15 patients with chronic, relapsing
non-bacterial prostatitis and prostadynia. Seven patients became symptom-free,
6 patients were significantly improved, and 2 patients failed to show
improvement in symptoms. Improvement in symptomatology occurred for
most patients after 3 months of treatment.
In a double-blind, placebo-controlled study, Buck et al  reported
data for 53 subjects awaiting operative treatment for outflow obstruction
due to prostate enlargement. Patients were instructed to take 2 capsules
of T60 or placebo twice a day over a 6-month period. The results
showed 60% of the subjects receiving T60 had less nocturia compared
to 30% receiving placebo (p < 0.063), and 57% showed improvement
in bladder emptying with T60 compared to only 10% taking placebo
(p < 0.004). There was a significant difference (p < 0.009) in
overall improvement in subjective symptoms in the T60 group (69%)
versus placebo (29%). Despite no significant change in peak urinary
flow rate or voided volume, residual urinary volume decreased significantly
in the T60 group compared to placebo (p < 0.025).
In a double-blinded, active-control study, Maekawa et al  conducted
a double-blind study comparing T60, 2 capsules twice daily for
12 weeks, to Paraprost (a mixture of the amino acids L-glutamic acid,
L-alanine, glycine) in 159 patients with BPH. The two botanical preparations
were comparable in improving symptoms (IPSS) from baseline (55% for
T60 and 62% for Paraprost). There was a significant improvement
in residual urinary volume, average flow rate, maximum flow rate and
prostatic weight in the T60 group versus Paraprost. Greater than
moderate effectiveness rating was 49.1% for T60 and 41.2% for Paraprost.
Becker et al  continued the placebo-controlled study described
above  with an open label study in which 92 subjects previously
treated in the first phase of the study with T60 (n=45) or placebo
(n=47) were continued or now treated with T60 for 12 weeks. Physicians
were blinded in this second phase as to whether the subjects received
T60 or placebo in the first phase. The results showed that the
differences observed between the two groups in the first phase were
eliminated in the 2nd phase. Subjects previously treated with placebo
improved significantly when treated with T60. Significant improvements
were observed in nocturia (p = 0.051), frequency (p = 0.039), feeling
of incomplete emptying (p =0.013), palpable enlargement of the prostate
(p = 0.046) and prostatic congestion (p=0.03).
Bach and Ebeling  reported the results from a large open-label
trial in Germany involving 208 physicians and 1798 patients with BPH
capable of being evaluated. The patients were treated for 24 weeks with
T60; 2 tablets 3 times daily. The patients were divided into 3
groups (stage 1, 2 and 3) for data analysis based on the severity of
the BPH symptoms. Patients in stage 1 had the most improvement of the
three groups in irritative symptoms whereas patients in stage 2 had
significant improvement in both irritative and obstructive symptoms.
Peak urinary flow rates increased significantly in all 3 groups. A continuing
improvement in symptoms was noted when comparing the results after 12
and 24 weeks of treatment. Efficacy in stage 1 and 2 patients was judged
to be satisfactory or better in 90% of the patients. Efficacy in stage
3 patients was judged to be satisfactory or better in 65% of the patients.
The authors concluded that treatment with T60 is justified even
for stage 3 patients until surgery is performed.
Rugendorff et al  reported the results of a study on 90 patients
with non-bacterial prostadynia and chronic prostatitis. Subjects were
given T60, 1 tablet 3 times daily for 6 months. Seven-two patients
were found to have complicating factors (such as bladder neck sclerosis,
prostatic calculi or urethral stricture), while the remaining 18 possessed
no complicating factors. Seventy-eight percent of the patients without
complications responded to the treatment with 36% of these becoming
asymptomatic. In contrast, only 6% of patients with complicating factors
improved. Peak urine flow rate in the uncomplicated group increased
significantly (p < 0.001) from 15.9 to 23.5 ml/s.
Braun and Peyer  in a 1993 double blind, placebo-controlled investigation
on 44 patients with Grade I and II BPH assessed the validity of treatment
with flower pollen extract on subjective and objective parameters. They
found by using questionnaires, echography, and laboratory analysis of
PSA that flower pollen extract had a clear benefit over placebo. In
25 patient receiving verum compared to 19 receiving placebo, there was
a significant reduction in the mean number of both diurnal and nocturnal
micturations with flower pollen extract (p<0.05). Using ultrasonic
measures, the mean volume of the prostate decreased significantly more
in the verum group (-29% vs. -8.8%, p<0.05). More reduction in residual
urine volume and PSA levels were noted in the verum group.
Yasumoto and colleagues  conducted an open-label trial with 79
BPH patients. Patients were given 2 T60 tablets 3 times a day for
at least 12 weeks. The results showed that symptom scores improved significantly
from baseline. Overall clinical efficacy was rated 85%. Clinical efficacy
at 12 weeks was rated satisfactory or better in 85% of the patients.
Dutkiewicz  gave T60 to 51 patients with BPH -- 2 capsules
three times daily for 2 weeks then 1 capsule 3 times daily for an additional
14 weeks. Thirty-eight subjects were given Tadenan (Pygeum africanum
extract) for 4 months. Significant improvement in subjective symptoms
was reported for both -- T60 group (78%) and the Tadenan group
(55%). In a recently published study, 24 patients with chronic prostatitis
(NIH-category III) were treated with T60 for at least 6 weeks.
The results showed a significant decrease in the symptom scores at 4
and 6 weeks .
Potential Role of Combination Therapy
Although published clinical trials support the efficacy of T60
in the relief of mild to moderate LUTS, a precedent exists to examine
beneficial effects of combining T60 with other botanical products.
A recently completed clinical study sponsored by the National Institutes
of Health concluded that the combination of finasteride and doxazosin
was more effective that either treatment alone in preventing progression
of BPH . This study demonstrates the therapeutic advantages of combining
drugs with different mechanisms of action.
The precise mechanisms behind the therapeutic benefits of T60
are not fully understood, but it is generally accepted that anti-inflammatory
and/or alpha adrenergic blocking effects are important. Therefore, combining
T60 with a botanical and/or prescription drug with different mechanisms
of action may provide additional symptomatic relief. Two recently published
trials using combinations of agents with T60 support this theory.
Preuss et al  reported on a double-blind, placebo-controlled trial
comparing a combination of T60 (378 mg); saw palmetto fruit standardized
to 43% B-sitosterol (286mg) and vitamin E (100IU). Seventy subjects
completed the combination therapy and 57 subjects completed the placebo
over a 90-day period. There was a significant reduction in nocturia
(p < 0.001), daytime frequency (p < 0.04) and overall symptomatology
as measured by the American Urological Association Symptom Score. This
combination therapy is logical, since saw palmetto may have different
mechanisms of action than T60. As an example, it is believed that
saw palmetto compared to T60 prevents to a greater extent the conversion
of testosterone to dihydroxytestoterone, a potent androgen that stimulates
enlargement of the prostate [17,21,22].
Aoki et al  conducted an open label trial to study tamsulosin hydrochloride
(Flomax®), an alpha1A adrenoceptor antagonist, T60, and the combination
in 243 patients with symptomatic BPH over a 12-week period. The results
showed that whereas symptoms improved in each group, supporting the
efficacy of T60, the best results were obtained in the group that
used the combination.
A review of placebo-controlled trials, active-controlled and open-label
studies indicate that T60 is a safe and effective therapy for the
management of mild to moderate LUTS. By reducing bothersome symptoms,
T60 improves quality of life. The placebo-controlled, double-blind
studies with T60 alone [47,57,59,60] and combined with other natural
products  especially provide evidence that T60 is effective
in reducing nocturia, daytime frequency, and sensation of residual urine.
The number of subjects in these studies was small relative to the studies
conducted for prescription therapeutics such as Terazosin  (Hytrin,
minimum of 430 subjects) and Doxazosin  (Cardura, minimum of 900
subjects), however the duration of the studies were comparable. T60
studies were generally conducted for 12 to 24 weeks, terazosin trials
were conducted for 12 to 24 weeks, and doxazosin studies were also conducted
over a 14 to 16 week period.
Since the number of subjects studied in placebo-controlled trials is
small, it was necessary to review open-label and active control studies
as supporting data. Concerning the use of T60 alone, we report
on 15 open label studies and 4 double-blind, placebo-controlled studies
that showed consistent reduction in subjective symptoms and overall
effectiveness ratings of 75% and greater. In addition, 1 double-blind,
active-controlled study, 1 open-label study on a combination, and 1
double-blind, placebo-controlled study on a combination strengthen the
conclusions on the therapeutic merits of T60.
Sufficient evidence exists in the primary and secondary literature
to indicate that a standardized flower pollen extract commonly referred
to as T60 is safe and effective for the treatment of mild to moderate
LUTS. This dietary supplement composed of pollen extracts from rye,
corn, and timothy has the potential to be used in combination with other
dietary supplements or pharmaceuticals to provide relief of bothersome
symptoms and improve quality of life for millions of men.
- Jacobsen SJ, Girman CJ, Guess HA, Oesterling JE, Lieber MM: New
diagnostic and treatment guidelines for benign prostatic hyperplasia.
Potential impact in the United States. Arch Int Med 155:477-481, 1995.
- Preuss HG, Adderly B: Benign prostatic hyperplasia: men's secret
disease. In: The Prostate Cure. (eds) HG Preuss, B Adderly. Crown
Publishing, Inc., New York, NY, pp 1-29, 1998.
- Oesterling JE: Benign prostatic hyperplasia: a review of its histogenesis
and natural history. The Prostate Supplement, 6:67-73, 1996.
- Buttyan R, Chen M-W, Levin RM: Animal model of bladder outlet obstruction
and molecular insights into the basis for the development of bladder
dysfunction. European Urology 32(Suppl 1):32-39, 1997.
- Knott MA, Bootman JL: The economics of benign prostatic hyperplasia
treatment: a literature review. Clinical Therapeutics 18:1227-1241,
- Salcedo H: The Prostate. Facts and Misconceptions. Birch Lane Press
Book, New York, NY, 1993.
- Berry SJ, Coffey DS, Walsh PC, Ewing LL: The development of human
benign prostatic hyperplasia with age. J Urol 132:474-479, 1994.
- Lytton B, Emery JM, Howard BM: The incidence of benign prostatic
hy-pertrophy. J Urol 99:639-645, 1968.
- Walsh PC, Worthington JF: The Prostate. A Guide for Men and the
Women Who Love Them. Baltimore and London: The Johns Hopkins University
Press, p 15, 1995.
- Bruskewitz, R: Management of symptomatic BPH in the US: who is treated
and how?, Eur Urol 36(Suppl 3):7-13, 1999.
- Hytrin® (terazosin hydrochloride) Capsules, 01G-501-0118-1 Master,
February 2001, http://www.rxabbott.com/hy/hypi.htm; accessed on 11/22/02.
- Fowler FJ, Wenneberg JE, Timothy RP, et al: Symptom status and
quality of life following prostatectomy. JAMA 259:3018-3022, 1988.
- Breu W, Stadler F, Hagenlocher M, Wagner H: Der sabalfrucht-extrakt
SG 291. Ein phytotherapeutikin zur behandlung der benignen prostatahyperplasie.
Zeitschrift Fur Phytotherapie 13:107-115, 1992.
- Breu W, Hagenlocher M, Redl K, et al: Antiphlogistische wirkung
eines mit hyperkritischem kohiendixid gewonnenen sabalfrucht-extraktes.
Arzneim Forsch Drug Research 42:547-551, 1992.
- Stenger A, Tarayre JP, Carilla F: Etude pharmacologique et biochimique
de l'extrait hexanique de serenoa repens. B: Gaz Med de France 89:2041-2048,
- Rhodes L, Primka RL, Berman C et al: Comparison of finasteride
(Proscar), a 5_ reductase inhibitor, and various commercial plant
extracts in in vitro and in vivo 5_ reductase inhibition. The Prostate
- Sultan C, Terraza A, Divillier C: Inhibition of androgen metabolism
and binding by a liposterolic extract of Serenoa repens B in human
foreskin fibroblasts. J Steroid Biochem 20:515-521, 1984.
- Carilla E, Briley M, Fauran F, Sultan C, Duvilliers C: Binding
of Permixon, a new treatment for prostatic benign hyperplasia, to
the cytosolic androgen receptor in the rat prostate. J Steroid Biochem
- Champault G, Patel JC, Bonnard AM: A double-blind trial of an extract
of the plant Serenoa repens in benign prostatic hyperplasia. Br J
Clin Pharmacol 18:461-462, 1984.
- Carraro JC, Raynaud JP, Koch G, et al: Comparison of phytotherapy
(Permixon) with finasteride in the treatment of benign prostate hyperplasia:
a randomized international study of 1,098 patients. The Prostate.
- Posker GL, Brogden RN: Serenoa repens (Permixon). A review of it
pharmacology and therapeutic efficacy in benign prostatic hyperplasia.
Drug and Aging 9:379-395, 1996.
- Denis LJ: Editorial review of Comparison of phytotherapy (Permixon)
with finasteride in the treatment of benign prostate hyperplasia:
a randomized international study of 1,098 patients. The Prostate 29:241-242,
- Braeckman J: The extract of Serenoa repens in the treatment of
benign prostatic hyperplasia: a multicenter open study. Curr Therap
Res 56:776-785, 1994.
- Champault G, Bonnard AM, Cauquil J, Patel JC: Medical treatment
of prostatic adenoma. Controlled trial PA 109 vs placebo in 110 patients.
Ann Urol 18:407-410, 1984.
- Steinman D: Enlarged prostate? Try tree bark. Natural Health 24:46-47,
- Barlet A, Albrecht J, Aubert A, Fisher M, Grof F, Grothhuesmann
HG, Masson JC, Mazeman E, Mermon R, Reichert H: Efficacy of Pygeum
Africanum extract in the medical therapy of urination disorders due
to benign prostatic hyperplasia: evaluation of objective and subjective
parameters. A placebo-controlled double-blind multicenter study. Wiener
Klinische Wochenschrift. 102:667-673, 1990.
- Lichius JJ, Muth C: The inhibiting effects of Urtica dioica root
extracts on experimentally induced prostatic hyperplasia in the mouse.
Planta Medica 63:307-310, 1997.
- Hirano T, Homma M, Oka K: Effects of stinging nettle roots and
their steroidal components on the Na+, K+ ATPase of the benign prostatic
hyperplasia. Planta Medica 60:30-33, 1994.
- Berges RR, Windeler J, Trampisch HJ, et al: Randomized, placebo-controlled
clinical trial of _-sitosterol in patients with benign prostatic hyperplasia.
The Lancet 345:1529-1532, 1995.
- Klippel KF, Hiltl DM, Schipp B: A multicenter, placebo-controlled,
double-blind clinical trial of _-sitosterol (Phytosterol) for the
treatment of benign prostatic hyperplasia. Br J Urol 80:427-432, 1997.
- Asplund A: Searching for the source of life and vitality. Sanomin
(SA) SDN, Singapore, p 36, 1991.
- Meares Jr EM: Prostatitis and related disorders. In: Campbell's
Urology, 6th edition. (ed) PC Walsh, Philadelphia, PA, pp 807-822,
- Loschen, G, Ebeling L: Hemmung der Arachidons~ureKaskade durch emen
Extrakt aus Roggenpollen. Arzneim-Forsch./Drug Rse 41:162-167, 1991.
- Ito R, Ishi M, Yamashita S, et al: T60 pollen-extract (T60®):
Anti-prostatic hypertrophic action of T60 pollen extract Pharmacometrics
- Hanamoto M, Liao M, Suzuki H, et al: Effect of T60 pollen-extract
on the sex-hormone-induced nonbacterial prostatitis in rats. Jpn Pharmacol
Ther 11:65, 1998.
- Wagner B, Otto H, Becker S, Schroder S, Klosterhalfen H: Experimental
treatement studies with T60 N in human benign prostatic hyperplasia.
In: Benign Prostatic Diseases. (eds) W Vahlensieck, G Rutishauser
, Georg Thieme Verlag, Stuttgart, Germany and Thieme Medical Publishers,
Inc. New York, NY, pp 123-127, 1992.
- Kamijo T, Sato S, Kitamura T: Effect of T60 Pollen-Extract
on Experimental Nonbacterial Prostatitis in Rats. Prostate 49:122-131,
- Bales GT, Christiano AP, Kirsh EJ, Gerber GS: Phytotherapeutic
agents in the treatment of lower urinary tract symptoms: a demographic
analysis of awareness and use at the University of Illinois. Urology
54: 86-89, 1999.
- Schulz, V, Hansel R, Tyler VE: Rational Phytotherapy, A Physicians'
Guide to Herbal Medicine, 3rd Edition, Springer, Berlin, 230-231,
- Rye Grass Monograph, Natural Medicines Comprehensive Database,
Therapeutic Research Faculty, Stockton, Ca, p 919, 2000.
- MacDonald R, Ishani A, Rutks I,Wilt TJ: A systematic review of
T60 for the treatment of benign prostatic hyperplasia. BJU Int
- Wilt T, MacDonald R, Ishani A, Rutks I, Stark G: T60 for
benign prostatic hyperplasia. Cochrane Database Syst Rev (2), CD001042,
- Shoskes DA: Phytotherapy and other alternative forms of care for
the patient with prostatitis. Curr Urol Rep 3:330-334, 2002.
- Vahlensieck W, Rutishauser G (eds): Benign Prostatic Diseases.
Georg Thieme Verlag, Stuttgart, Germany and Thieme Medical Publishers,
Inc. New York, NY, pp 1-207, 1992.
- Clouatre D: Pollen Extract for Prostate Health. Pax Publishing,
San Francisco, CA, pp 1-30, 1997.
- Stoffe JA, Clouatre D: The Prostate Miracle. Kensington Books,
New York, NY, pp 1-261, 2000.
- Leander G: A preliminary investigation on the therapeutic effect
of T60 N in chronic prostatovesiculitis. Svenska Lakartidningen
- Inada T, Kitagawa T, Miyakawa M: Use of T60 in patients with
prostatic hypertrophy. Tobishi Pharmaceutical Co, Ltd. Tokyo, Japan,
- Ohkoshi M, Kawamura N, Nagakubo I: Clinical evaluation of T60
in chronic prostatitis. Japanese Journal of Urology, 21:73-85, 1967.
- Takeuchi H, Yamauchi A, Ueda T et al: Quantitative evaluation on
the effectiveness of T60 on benign prostatic hypertrophy. Hinyoki
- Horii A, Iwai S, Maekawa M, Tsujita, M: Clinical evaluation of
T60 in the treatment of the benign prostatic hypertrophy. Hinyo
Kiyo 31:739-746, 1985.
- Ueda K, Kinno H, Tsujimura S: Clinical evaluation of T60
on benign prostatic hyperplasia. Hinyo Kiyo, 31:187-191, 1985.
- Hayashi J, Mitsui,H, Yamakawa G, et al: Clinical evaluation of
T60 in benign prostatic hypertrophy. Hinyo Kiyo, 32:135-141,
- Ebeling L: The therapeutic results of defined pollen extract in
patients with chronic prostatitis. In: Schmiedt E, Alken JE, Bauer
HW (eds). Therapy of Prostatitis. Zuckschwerdt Verlag, Munchen, pp
- Brauer H: The treatment of benign prostatic hyperplasia with phytopharmacia:
a comparative study of T60 and beta sitosterol. Therapeiwoche
36: 1686-1696, 1986.
- Jodai A, Maruta N, Shimomae E, et al: A long-term therapeutic experience
with T60 in chronic prostatitis. Hinyo Kiyo 34:561-568, 1988.
- Becker H, Ebeling, L: Conservative treatment of benign prostatic
hyperplasia (BPH) with T60. Results of a placebo-controlled
double-blind study. Urologe(b) 28:301-306, 1988.
- Buck AC, Rees RWM, Ebeling L: Treatment of chronic prostatitis
and prostatodynia with pollen extract. Br J Urol 64:496-499, 1989.
- Buck AC, Cox R, Rees, W, Ebeling L, and John A: Treatment of outflow
tract obstruction due to benign prostatic hyperplasia with the pollen
extract, T60. A double-blind, placebo-controlled study. Br.
J. Urol. 66:398-404, 1990.
- Maekawa M, Kishimoto T, Yasumoto R, et al: Clinical evaluation
of T60 on benign prostatic hypertrophy - a multiple center double-blind
study with Paraprost. Hinyo Kiyo, 36:495-516, 1990.
- Becker H, Ebeling L: Phytotherapy of BPH with T60. Results
of a controlled prospective study. Urologe (B) 31:113-116, 1991.
- Bach D, Ebeling L: Possibilities and limitations of phytotherapy
for benign prostatic hyperplasia (BPH): results of treatment with
T60 N for stages I-III according to Alken (or II-IV according
to Vahlensieck). In: Benign Prostatic Diseases. W Vahlensieck, G Rutishauser
(eds). Georg Thieme Verlag, Stuttgart, Germany pp 180-187, 1992.
- Rugendorff EW, Weidner W, Ebeling L, Buck AC: Results of treatment
with pollen extract (T60_) in prostatodynia and chronic prostatitis,
Br J Urol 71:433-438, 1993.
- Braun L, Peyer P, Ackermann, et al: A multicentre, placebo-controlled
study on the efficacy and tolerability of adenoprostal in patients
with benign prostatic hyperplasia (BPH). Tribuna Medica Ticinese,
- Yasumoto R, Kawanishi H, Tsujino T, et al: Clinical evaluation
of long-term treatment using T60 pollen extract in patients
with benign prostatic hyperplasia. Clin Ther 17:82-87, 1995.
- Dutkiewicz S: Usefulness of T60 in the treatment of benign
prostatic hyperplasia. Int Urol Nephrol 28:49-53, 1996.
- Monden K, Tsugawa M, Ninomiya Y, Ando E, Kumon H: A Japanese version
of the National Institutes of Health Chronic Prostatis Symptom Index
(NIH-CPSI: Okayama version) and the clinical evaluation of T60
pollen extract for chronic non-bacterial prostatitis. Nippon Hinyo
Gakkai Zasshi 93:539-547, 2002.
- National Institutes of Health, "Two-Drug Therapy is Best for Symptomatic
Prostate Enlargement, Combination Should Change Clinical Practice",
NIH News Release, May 28, 2002 (www.nih.gov/news/pr/may2002/niddk-28.htm).
- Preuss HG, Marcusen C. Regan J, et al: Randomized trial of a combination
of natural products (T60, saw palmetto, B-sitosteriol, vitamin
E) on symptoms of benign prostatic hyperplasia (BPH). Int Urol and
Neph 33:217-225, 2001.
- Aoki A, Naito K, Hashimoto O, et al: Clinical evaluation of the
effect of tamsulosin hydrochloride and T60 pollen extract on
urinary disturbance associated with benign prostatic hyperplasia in
a multicentered study. Hinyo Kiyo, 48:259-267, 2002.
- Cardura® (doxazosin mesylate) Tablets, 70-4538-00-8 www.pfizer.com/hml/pi's/cardurapi.pdf;
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