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Archivio Italiano di Urologia e Andrologia 2016; 88, 2
136
REVIEW
The role of Cucurbita pepo in the management of patients
affected by lower urinary tract symptoms due to benign
prostatic hyperplasia: A narrative review
Rocco Damiano 1, Tommaso Cai 2, Paolo Fornara 3, Corrado Antonio Franzese 4,
Rosario Leonardi5, Vincenzo Mirone 6
1 Department of Urology, University of Catanzaro, Catanzaro, Italy;
2 Department of Urology, Santa Chiara Regional Hospital, Trento, Italy;
3 Department of Urology, Martin-Luther-University, Halle Saale, Germany;
4 Urology, ASL NA3 SUD, Naples, Italy;
5 Urology, GECAS Institute, Catania, Italy;
6 Department of Urology, University of Naples, Federico II, Naples, Italy.
Objective: Phytotherapeutic compounds
are largely used in the treatment of lower
urinary tract symptoms (LUTS) related to benign prostatic
hyperplasia (BPH) due to low side-effect profiles and costs,
high level of acceptance by patients and a low rate of drop-
out. Here, we aimed to analyze all available evidence on the
role of Cucurbita pepo in the treatment of LUTS-BPH.
Material and methods: In May 2016 a systematic search
was carried out thorough National Library of Medicine
Pubmed, Scopus database and the ISI Web of Knowledge
official website in order to identify all published studies on
Cucurbita pepo and BPH. The following search strings were
used: “Cucurbita pepo” OR “pumpkin seed” AND
“prostate”; “Cucurbita pepo” AND “antiandrogen” OR
“antiproliferative” OR “anti-inflammatory” OR “antioxidant
activities”; “cucurbita pepo” OR “pumpkin seed” AND
“LUTS” AND “symptoms improvement” OR “quality of
life”. We consider for the present analysis only studies relat-
ed to LUTS-BPH.
Results: Among all 670 screened, 16 were related to LUTS-
BPH and finally analyzed. Among all, ten of them were per-
formed in “in vitro setting” showing anti-inflammatory and
antiandrogen effect, and a reduction in prostate growth and
detrusor activity, while six were clinical studies. In all stud-
ies an improvement in International Prostatic Symptoms
Score (IPSS) and uroflowmetry parameters has been report-
ed. In 4 studies, an improvement in quality of life has been
reported.
Conclusion: On the basis of our narrative review, the use of
Cucurbita pepo in the management of patients affected by
LUTS-BPH seems to be useful for improving symptoms and
quality of life. However, future clinical trials are requested
to confirm these promising results.
KEY WORDS:BPH; Cucurbita pepo; LUTS; Prostate disease;
Pumpkin seed.
Submitted 27 May 2016; Accepted 5 June 2016
Contributions: RD, TC, CAF, RL data collecting; RD,
TC analyzing and manuscript writing; VM, CAF, RL
and PF supervision.
Summary
Conflict of interests: the Authors declare no potential conflict of interests.
Funding: Chefaro pharma supported the publication of this narrative review.
INTRODUCTION
Benign prostatic hyperplasia (BPH) affects most men
after the age of 50 years and is considered the most com-
mon urologic disease among elderly men (1). BPH is a
chronic disease with early initiation and slow progres-
sion, due to an overgrowth of the epithelial and stromal
cells from the transition zone and the periurethral area
(2). It is essentially a histological diagnosis, which can be
clinically manifested as benign prostatic enlargement
(BPE) in almost half of the cases. BPH starts as a simple
micro nodular hyperplasia and evolves into a macro-
scopic nodular enlargement that gradually results in
benign prostatic obstruction (BPO). The increase in pro-
static size may eventually compress the urethral canal
leading to BPO characterized by progressive develop-
ment of lower urinary tract symptoms (LUTS) as urinary
hesitancy and frequency, dysuria, sexual dysfunction,
increased risk of urinary infection and at least urinary
retention. Aging, dietary factors, presence of androgens,
growth factors, oxidative stress and chronic prostatic
inflammation are necessary for the development and
progression of BPH, but the pathogenesis is still largely
unresolved and there is no consensus as to which is the
primary one (3). In the management of BPH, is necessary
to reduce cell growth by blockage of testosterone con-
version in DHT, and reduce the sustaining of the chron-
ic prostatic inflammation. Patient acceptability of treat-
ment is key to decreasing the human and economic bur-
den of this condition. Maintaining sexual function is a
crucial topic nowadays. Alpha blockers, 5-alphareduc-
tase inhibitors (i-5AR) and phosphodiesterase 5
inhibitors (i-PDE5), as monotherapy or in combination,
have been used in BPH treatment (4). Notwithstanding
these drugs have a positive effect on the patient with BPH,
side effects (including sexual ones) progressively favor
patient withdrawal from therapy and progressively
enhance interest in drugs of plant origin with less adverse
effects (5). Phytotherapy dates back thousands of years,
and currently represent almost 50% of all medicine pre-
DOI:10.4081/aiua.2016.2.136
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Cucurbita pepo in BPH
scribed for BPH in Italy. Nowaday, due to low side-effect
profiles and costs, high level of acceptance by patients and
low rate of drop-out, the use of phytotherapy is progres-
sively increasing. Here, we focused our attention on
Cucurbita pepo. Cucurbita is a well-known traditional
herbal medicinal product used from centuries worldwide
and its medicinal use was described in many manuscripts
and textbooks. The Cucurbita genus comprises many
species widespread in Europe, Asia and America.
Cucurbita pepo in the form of ethanolic pumpkin seed soft
extract has been used for more than thirty years in the
European Community, mainly as a remedy for various dif-
ficulties associated with an enlarged prostate gland and
micturition problems related to overactive bladder (6, 7).
The active compounds in Cucurbita pepo L. seeds are
Δ5-, Δ7- and Δ8-sterols: Δ7-sterols, which are largely
predominant in Cucurbita pepo, are considered to be the
key active constituents of pumpkin seed in the treat-
ment of benign prostatic hyperplasia. Much smaller
amounts of Δ5- and Δ8-sterols are also present in
Cucurbita pepo (7-11). High content of carotenoids,
polyunsaturated fatty acids and liposoluble vitamins
have also a role in its activity (12). Therefore, in the
present narrative review, we summarize all evidence
available on the role of Cucurbita pepo in the manage-
ment of patients affected by LUTS due to BPH.
MATERIALS AND METHODS
Search strategy and evidence acquisition
We searched electronic databases including PubMed, the
Scopus database and the ISI Web of Knowledge for pub-
lished studies that analyzed the role of Cucurbita pepo in
the management of patients affected by LUTS due to
BPH up to May 31, 2016. The following Medical Subject
Headings terms and free text were used: “Cucurbita pepo”
OR “pumpkin seed” AND “prostate”; “Cucurbita pepo” AND
“antiandrogen” OR “antiproliferative” OR “anti-inflammato-
ry” OR “antioxidant activities”; “cucurbita pepo” OR “pump-
kin seed” AND “LUTS” AND “symptoms improvement” OR
“quality of life”. There was no restriction on population or
publication year. Additionally, we conducted a manual
search using the bibliographies of all the identified stud-
ies, reviews, and editorials to identify references that we
may have missed during our primary search. Finally, the
search included original articles, review articles and edi-
torials and these were reviewed in order to select relevant
articles. When necessary, we contacted the authors to
obtain any relevant information we found to be missing
from published papers.
The Figure 1 shows the study selection process diagram.
Selection criteria
Inclusion criteria: (1) all studies related to LUTS-BPH; (2)
all pre-clinical and clinical trials.
Exclusion criteria: (1) the language of the studies was not
English or German; (2) if multiple publications for the
same data from the same study group occurred, only the
most informative and recent article was recruited into final
analysis; (3) letters to Editor, review articles, commen-
taries, clinical guidelines, or case reports and case series.
RESULTS
Six-hundred and seventy studies were selected up to May
31, 2016. After the first-step analysis, 16 studies were
included in this narrative review. Ten studies were consid-
ered in the pre-clinical setting and 6 in the clinical setting.
Pre-clinical setting
Antioxidant activity. Four commercially available pump-
kin seeds (Cucurbita pepo, Cucurbita moschata, Cucurbita
maxima and Cucurbita mixta) extracts were screened for
their antioxidant activity and their inhibitory activity
against lipid peroxidation (13). The results showed that
radical scavenging activity depends on their total pheno-
lic content. In particular, pumpkin seed water extracts
inhibited lipid peroxidation at 1.5 mg/ml, while the ace-
tone extracts inhibit 50% of lipoxygenase activity at the
range from 0.16 to 0.80 mg/ml.
Antiandrogen activity. In an in vitro study in human
prostate fibroblasts, the isolated pumpkin Δ7-sterols
showed antiandrogenic activity dose-dependently block-
ing the binding of dihydrotestosterone (DHT). The cul-
tures were incubated with 120 ng labeled DHT for 24
hours and the binding rate was calculated as a difference
from the concentration remaining in the supernatant.
The binding rate in the control was 63%. In the cultures
pre-treated with 120 ng or 240 ng pumpkin sterols (each
in a double set-up) the binding rate was 51.7% and
43.3% or 37.5% and 38.3% respectively (14).
Furthermore, Schmidlin and Kreuter (15) described influ-
ence of the Cucurbitae pepo extract on activity of aro-
matase and 5-α-reductase Type II in the homogenates of
human and rat placenta. By using 10 mg/ml-concentration
extract, about 50% reduction of aromatase activity and
90% of 5-α-reductase Type II inhibition were achieved.
Subsequently, in the “in vivo” prostate hypertrophy model
the pumpkin extract (100mg/kg) reduced prostate weight
of 31% vs 76% of the subcutaneous Finasteride injection
(1 mg/kg).
Figure 1.
Selection process of studies.
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Anti inflammatory activity. Three different extracts of
pumpkin seeds showed immunological activity suppress-
ing dose dependently mitogen-induced neopterin produc-
tion and tryptophan degradation induced by cytokine
interferon-γ(IFN-γ) (16). In particular, pumpkin seeds of
Cucurbita pepo (citrullinina GREB. var. styriaca GREB) from
biological culture were finely grounded (10 g of the pow-
der was added to 100 ml of medium Roswell Park
Memorial Institute (RPMI 1640). Then the peripheral blood
mononuclear cells (PMBC) were isolated from the whole
blood from healthy human donors and stimulated with
phytohaemagglutinin and concanavalin-A. Tryptophan
and neopterin concentrations, two biochemical pathways
stimulated by cytokine interferon-γ, were measured in the
supernatants in order to assess the anti-inflammatory
activity of the pumpkin seeds extracts. Finally, a dose
dependant suppression of mitogen-induced neopterin
production and tryptophan degradation was recorded
compared to control PMBCs. Likewise, Fahim et al. (17)
used an experimental murine model of arthritis to test
anti-inflammatory activity of pumpkin seed oil adminis-
tered in intramuscular injection. For comparison, other
two groups of rats respectively received indomethacin –a
classic anti-inflammatory agent – and no further treat-
ment. Blood samples were collected to measure: blood
glutation (GSH), plasma total proteins, albumin serum
sulfhydryl group (SH-gps), ceruloplasmin (CP) and lyso-
somal marker – N-acetyl-β-D-glucosaminidase (NAG).
After completing the experiment, liver samples were used
for determination of glucose-6-phosphate dehydrogenase
(G6P DH) activity and protein content of liver
homogenates was established. Adjuvant inoculation
resulted in decrease of serum SH-gps, with an increase of
serum CP reduction of blood glutathione and total pro-
teins and albumins levels. Liver G6P DH activity was
markedly increased. The treatment with pumpkin seed oil
resulted in normalization of altered parameters, notably in
chronic phase, except serum NAG influence. Pumpkin oil
administration inhibited paw oedema during the chronic
phase in about 44% as compared to the control untreated
group. It reduced also liver G6P DH activity to almost
50% of the arthritic groups’ level. No increase in the anti-
inflammatory effects of indomethacin combined with
pumpkin seed oil was observed.
Bladder contractility. The effects of non-specified water sol-
uble extract of pumpkin seeds and soybean germ extract
on in-bladder pressure (cystometrogram) and urination
frequency of male rats were tested (18). Pumpkin seed
water-soluble extract (250 mg/kg) compared to control
solvent (1% dimethyl sulfoxide diluted in sterile physio-
logical saline) and soybean germ extract significantly
increased bladder volume, decreased urination frequency
and increased urination delay index. According to the
authors, the observed effects of the relaxation of the blad-
der and decrease of in-bladder pressure are related to the
increased productions of NO via the arginine/NO path-
way. Arginine is present in the pumpkin seed extract in
two fold the concentrations of other amino acids. It was
suggested that arginine/NO metabolism, independently of
adrenaline and acetylcholine, is involved in relaxation of
urination muscle at a stage of full bladder (19).
Prostate gland growth. Abdel-Rahman et al. (20) performed
a comparative study to examine the effect of pumpkin
seeds diet implementation on prostate growth. The
authors used an experimental model where benign pro-
static hyperplasia (BPH) in ventral prostate was induced
by orally administering citral (C10H16O) into stomach of
male rats. Citral was administered to all rats except nega-
tive control group. The rats were subsequently grouped
according to their diet – normal or different level of pump-
kin seeds – and sacrificed. Briefly, citral significantly
increased prostate weight (P < 0.05), while pumpkin seeds
given orally dose-dependently inhibited citral induced
hyperplasia of the prostate, especially at high concentra-
tion seed dose (10%, p < 0.02). In a testosterone-induced
BPH murine model Gossell-Williams et al. found that
administration of testosterone significantly increased
prostate size ratio (weight of prostate/b.w. of the rat) (p <
0.05) although this increase was significantly inhibited by
treatment with pumpkin seed oil at 4.0 mg/100 g b.w.
Gossell-Williams (21). Likewise, Tsai et al. (22) tested
pumpkin seed oil efficacy for 14 days, in experiments per-
formed in rats on the model of prostatic growth induced
by subcutaneous daily injection of testosterone (1.25
mg/kg/day) together with prazosin (30 μg/kg/day) (T-P).
Pumpkin seed oil (PSO) (2.5 ml/kg/day) extracted from
pumpkin seeds was administered concomitantly together
with T-P. As compared with T-P alone group, the T-P
group treated with PSO had significant lower weight ratio
for ventral prostate (p = 0.01) and lower protein levels
within ventral lobe and dorsolateral lobe (p = 0.03 and p
= 0.003, respectively).
Table 1 summarizes all evidence available in the pre-clin-
ical setting.
Clinical setting
Hamvas et al. (23) reported an overall improvement of
urinary symptoms after 10 months of medication with
Cucurbita pepo. The daily dosage was 3 x 2 capsules in
the first month and 3 x 1 capsule for the rest of the time.
Changes despite pre-treatment conditions in uroflow test
and patients symptoms perception were the used out-
comes. Control visits were scheduled after 4-7-10
months of medication. At the end of follow up, an
improvement in uroflowmetry parameters was recorded
(respectively: Qmax 15.4 vs 18 ml/sec, Qave 9.5 us 12.5
ml/sec, post voiding residual 90 vs 50 ml). Furthermore,
a reduction of nocturia, urinary frequency and relief of
urinary pain were reported. Finally, about 90% of
patients felt a “very good” or “good” improvement of their
urinary symptoms after therapy. In a multicentre setting,
Bach et al. (24) performed a randomized double-blind,
placebo-controlled study enrolling 476 men (mean age
63 yrs) suffering from mild or moderate BPH symptoms
and at early stages (I or II) of clinical BPH as defined by
Alken (25). The study was carried out in accordance with
recommendations of the International Consultation on
Benign Prostatic Hyperplasia (26). The duration of treat-
ment was 12 months and the main efficacy criterion was
the International Prostate Symptom Score (IPSS). After a
1 - month run-in-period under placebo, patients were
randomized to daily treatment for 12 months with either
2 x 500 mg of the soft extract (15-25:1, ethanol 92%,
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m/m) from pumpkin seeds (n = 233) or placebo (n =
243). Five post-randomization visits were scheduled
after 1, 3, 6, 9 and 12 months. An improvement of at
least 5 points in the IPSS at study end was defined as a
therapy response. Even though the 'placebo effect' was
considerable, this therapy response was reported by sig-
nificantly more patients in the Cucurbita group than in
the placebo group (65% vs. 54%, p = 0.021). Also, an
improvement of at least 3 points in the IPSS was report-
ed by more patients in the Cucurbita group (82.5%) than
in the placebo group (67.9%, ITT population). The mean
reduction in IPSS of 6.7 points (from 17.6 to 10.9) in the
pumpkin seed group was significantly greater than the
mean reduction of 5.5 points (from 17.7 to 12.2) after
placebo treatment (p = 0.014). No significant changes
were evident in either group in uroflowmetry parame-
ters, residual urine, quality of life, prostate volume or
serum prostate specific antigen levels. Likewise,
Friederich (27) performed an observational study includ-
ing 2245 patients with mild or moderate BPH symptoms
and administering 500 mg or 1.000 mg of pumpkin seed
soft extract daily for 12 weeks. During therapy IPSS
scores improved by 41% (7.7 points, from 18.6 to 10.9)
and quality of life index scores by 46% (from 3.4 to 1.8).
The average frequency of micturition decreased from 6.7
to 5.1 during the day and from 2.3 to 1 during the night.
Improvement of dysuric disorders, such as painful uri-
nation, micturition burning, feeling of pressure and ten-
sion was reported by 52 % of the patients. Diary record-
ed micturition frequency during the day and during the
night was reduced within just 4 weeks to mean values of
5.8 (day) and 2.1 (night), with further improvement
after 8 weeks to 5.2 and 1.5, reaching 4.8 during the day
and 1.1 during the night after 12 weeks of treatment. At
subgroup analyses, the most pronounced improvement
was observed for the micturition frequency during the
night, whereas patients with acute disorders benefited
most. In these patients nocturia was reduced by 60%
(from 2.35 to 0.94), and in patients with chronic com-
plaints by 48% (from 2.75 to 1.43). In a retrospective
survey involving urologists in private practice the treat-
ment progression of 185 patients (aged between 44 and
85 years) receiving pumpkin seed soft extract was
recorded and evaluated (28). Among those, 173 patients
received pumpkin seed soft extract as therapy to treat
LUTS due to BPH. Most patients (63%) took 1 capsule
per day, 27% took 2 capsules, and 9% of the patients
were treated with more than 2 capsules. The recorded
observation periods for individual patients ranged
between one week and several years. However, for the
majority (81%) data on the course of treatment were
recorded within the first 3 months. Urge symptoms and
micturition frequency were reduced in most patients.
The proportion of patients having reported more than
one micturition during the night at start of treatment was
reduced from 90% to 30%. Residual urine was found to
be reduced in 80% of the patients. Hong et al. (29) car-
ried out a randomized, double-blind, placebo-controlled
trial over 12 months, enrolling 47 patients with BPH
with mean age of 53.3 years and international prostate
symptom score over 8. The study design contemplated
four comparative study arms: sweet potato starch (group
Table 1.
Summary of experimental studies supporting a role of pumpkin seeds in the treatment of BPH-LUTS.
BPH-LUTS Author, year
etiology role Part of plant Model Main study finding
Xanthopoulou 2009
Winkler 2005
Fahim et al. 1995
Schilcher 1990
Schmidlin and Kreuter 2003
Hata 2005
Abdel-Rahman 2006
Gossell-Williams 2006
Tsai 2006
Seed extract
Seed extract
Seed oil
Pumpkin Δ7-sterols
Seed extract
Seed extract
Seed
Seed oil
Seed
Biochemical for Lipid peroxidation
Biochemical: blood stimulated
mononuclear cells from healthy men
Arthritis rats model
Biochemical: human prostate
fibroblasts culture
Biochemical: homogenates
of human and rat placenta
Urodynamic test in rats
BPH induced with citral in rats
BPH induced with testosterone in rats
Testosterone plus Prazosin
induced prostate growth in rats
Inhibited lipid peroxidation
Inflammatory induced pathways (IFN-γ
mediated) were reduced
Oxidative parameters commonly altered
during arthritis were modulate; furthermore a
reduction of rats’paw oedema was achieved
Dihydrotestosterone binding
Aromatase and 5-α-reductase Type II activity
reduction; reduction of prostate weight
Increase bladder volume
Decrease frequency
High concentration seed dose inhibites
prostate growth
Inhibition of testosterone induced prostatic
hyperplasia
Prostate weight was decreased
Prostate growth Androgen Inflammatory
Bladder
contractility
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A, placebo, 320 mg/day), pumpkin seed oil (group B,
320 mg/day), saw palmetto oil (group C, 320 mg/day) or
pumpkin seed oil plus saw palmetto oil (group D, each
320 mg/day). International prostate symptom score,
quality of life, serum prostate specific antigen, prostate
volume and maximal urinary flow rate were measured.
So far, in groups B, C and D, the international prostate
symptom score were reduced after 3 months (respective-
ly from 20.7 ± 2.3, 18.3 ± 2.0, 19.0 ± 2.6 to 8.7 ± 1.5,
9.1 ± 1.4, 4.7 ± 17). Quality of life score was improved
after 6 months in group D (pumpkin seed oil plus saw
palmetto oil) from 3.8 ± 0.4 to 2.5 ± 0.4 and was main-
tained stable afterwards while those of groups B (pump-
kin seed oil) and C were improved after 3 months, com-
pared to the baseline value respectively from 4.2 ± 0.4 to
3.0 ± 0.4 and from 3.6 ± 0.3 to 3.0 ± 0.4). Finally, no
difference was found in prostate volume in all treatment
groups. Maximal urinary flow rate were gradually
improved in groups B (pumpkin seed oil) and C, with
statistical significance after 6 months in group B and
after 12 months in group C. More recently, Vahlensieck
et al. (30) investigated the efficacy of pumpkin seed in
men with LUTS suggestive of BPH performing a placebo
controlled three-armed randomized trial. Overall 1431
patients (aged 50-80 years) were randomly assigned to
either pumpkin seed (5 g b.i.d.), capsules with pumpkin
seed extract (500 mg b.i.d.) or placebo. The primary
outcome was a decrease in IPSS of > 5 points from base-
line after 12 months. Secondary outcome measure
included IPSS – related quality of life, IPSS single items
and diary recorded nocturia. After 12 months, the
response rate differed significantly between pumpkin
seed and placebo (58% vs 47%). Overall, 12 months of
treatment with pumpkin seed led to a clinically relevant
reduction in IPSS from (15.9 ± 1.8 and 15.8 ± 1.9, to
11.4 ± 5.5 and 10.2 ± 5.1) compared with placebo (from
16.1 ± 1.9 to 11.7 ± 5.4).
Adverse effects
To note, no adverse effects were registered from above
open clinical studies of pumpkin seeds. Only mild gas-
trointestinal complaints (diarrhoea, nausea, vomiting) in
Table 2.
Clinical studies on pumpkin seeds in men affected of BPH-LUTS.
Figure 2.
International Prostatic Symptoms Score analyzed
in clinical studies.
Author, year Study design Patients Comparator Treatment Outcomes measured
number length
Hamvas 1991 60 Pre-treatment 10 mo - Uroflow features improvement: Qmax 15.4 vs 18 ml/s;
Qave 9.5 vs 12.5 ml/s;
- Decrease in nocturia time, relief of dysuria and painful discharge
- About 90% referred a mild or very good improvement
in symptoms gravity
Bach 2000 Randomized 476 Placebo 12 mo - Significative Increase in response rate (ITT population):
controlled trial 67.5% vs 56.2%
- Decrease in IPSS 17.6 ± 3.7 vs 10.9 ± 4.5
- Mean IPSS after treatment/change to baseline (ITT): 10.9 ± 4.5
change: -6.7 (-38%) vs 12.2 ± 5.1 change: -5.5 (-31%)
Friederich 2000 Multicentric 2245 Pre-treatment 12 weeks - IPSS decreased from 18.6 to 10.9 (by 1.4%) and QoL score
improved from 3.4 to 1.8 (by 46.1%)
- 96% reported no undesired side effects
Burbach 2002 Retrospective 185 Pre-treatment 3 mo - Decrease in storage symptoms, nocturia (and PVR)
Hong 2009 Randomized placebo- 47 Placebo (four arms) 12 mo Overall:
controlled trial - Decrease IPSS: 20.7 ± 2.3 vs 8.7 ± 1.5
- Improvement of QoL score: 3.4 ± 0.4 vs 2.5 ± 04
Vahlensieck 2015 Randomized 1431 Placebo 12 mo - Decrease in IPSS (ITT): -5.4 ± 5.1, -4.2 ± 5.4 vs -4.0 ± 5.6
controlled trial (three arms: - IPSS response rate increased by 6%
pumpkin seed, - Improve in QoL 36% and 33,4% vs 29,2%
pumpkin seed
extract and placebo)
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no more than 4% of the patients was reported in in
Friederich study whereby it seems that upon administra-
tion within the therapeutic dose range, there is no risk of
serious side effects on all three RCTs. No sexual side
effects were reported during the use of Cucurbita pepo
compounds.
Table 2 shows all clinical studies performed in the man-
agement of LUTS-BPH. Moreover, Figure 2, Figure 3 and
Figure 4 show impact of the Cucurbita pepo on IPSS,
uroflowemetry parameters and patients QoL, respectively.
DISCUSSION
Main findings
Several studies performed in the pre-clinical and clinical
setting showed that the use of Cucurbita pepo in the man-
agement of patients affected by LUTS-BPH seems to be
useful for improving symptoms and quality of life.
Several aspects should be taken into account; in particu-
lar, some limitations of the evidence available need to be
considered.
Analysis of the evidences in the context
of the current knowledge
More recent knowledge about the physiological regula-
tion of bladder function makes it plausible that ubiqui-
tous substances may also contribute to the overall effect
of pumpkin seeds, in particular for maintaining normal
bladder function and preventing functional disorders.
Fatty oil of pumpkin seeds is characterized by a high
content of linoleic acid, accounting for 35-68% of the
total fatty acids (31, 32) Administration of this essential
precursor of prostaglandin metabolism (formation of
PGE2 and PG2α) might cause an increase in
prostaglandin synthesis. Prostaglandins are formed by
the detrusor muscle and increase its tone (33) resulting
in an improved bladder function.
The average tocopherol content of soft-shelled pumpkin
seeds is 0.5 mg/g, whereas – in contrast to most other
plant oils – γ-tocopherol is present in five- to ten-fold
higher concentrations than the α-isomer (34, 35).
According to more recent studies, γ-tocopherol is thought
to be significantly involved in the preventive role of vita-
min E and also to have a beneficial effect in chronic
inflammation (36-40). Medicinal pumpkin seeds are rich
in amino acids such as the NO precursors arginine, gluta-
mine and aspartic acid as well as γ-aminobutyric acids.
These are involved in the regulation of bladder function as
direct or indirect central neurotransmitters (41-43).
Observational studies (27), retrospective surveys (28)
and randomized controlled trials (24, 29, 30) provide
further evidence on beneficial effects of Cucurbita pepo
for patients with LUTS related to benign prostatic hyper-
plasia, as reduction of urge and micturition frequency
was observed. The published literature shows that the
benefits of pumpkin seeds treatment depend on the tonic
influence on the bladder, sphincter relaxation and allevi-
ation of micturition symptoms. It was therefore suggest-
ed that pumpkin seeds could be used in patients without
significant obstruction of the prostate and low risk for
disease progression (44). Provided that the patient
undergoes regular urological control visits, medical treat-
ment with seeds of Cucurbita pepo can be recommended
for patients with micturition symptoms related to BPH in
early disease stages, including those with symptoms of
overactive bladder.
Limits
The few available studies were often outdated and enrolled
a small number of patients, and only three RCTs were of
good quality. Other limits are difficulties in data extraction
on changes in patients classification (Alken versus IPSS).
Nevertheless all studies analyzed showed improvement in
micturition parameters related to LUTS/BPH.
CONCLUSION
In the context of the present narrative review, Cucurbita
pepo seems to show significant efficacy in improving uri-
nary symptoms with mild adverse effects however few
clinical studies support the use of that drug. Moreover,
Figure 3.
Quality of Life assessment.
Figure 4.
Qmax assessment in clinical studies.
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Archivio Italiano di Urologia e Andrologia 2016; 88, 2
R. Damiano, T. Cai, P. Fornara, C.A. Franzese, R. Leonardi, V. Mirone
142
all clinical studies are based on the evidence raising from
experimental studies in pre-clinical setting that showed
an interesting action of pumpkin seed elements on some
BPH etiological mechanism. Large randomized study are
needed to confirm these interesting result and recom-
mend the use of pumpkin seed in the management of
patients affected by LUTS due to BPH.
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Correspondence
Rocco Damiano, MD
damiano@unicz.it
Department of Urology, Magna Graecia University of Catanzaro
Viale Europa - Germaneto 88100 Catanzaro, Italy
Tommaso Cai, MD
Department of Urology, Santa Chiara Regional Hospital
Trento, Italy
Paolo Fornara, MD
Department of Urology, Martin-Luther-University
Halle Saale, Germany
Corrado Antonio Franzese, MD
Urology, ASL NA3 SUD, Naples, Italy
Rosario Leonardi, MD
Urology, GECAS Institute, Catania, Italy
Vincenzo Mirone, MD
Department of Urology, University of Naples, Federico II
Naples, Italy
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