World Journal of Urology (2022) 40:1769–1775

https://doi.org/10.1007/s00345-022-04036-w

ORIGINAL ARTICLE

Extract from Cucurbita pepo improves BPH symptoms

without affecting sexual function: a 24‑month noninterventional
study
Gerit Theil1 · Michael Richter2 · Matthias Schulze3 · Tilo Köttig4 · Brigitte Patz5 · Stefan Heim6 · Yvonne Krauß6 ·
Miroslav Markov7 · Paolo Fornara1

Received: 25 November 2021 / Accepted: 4 May 2022 / Published online: 27 May 2022
© The Author(s) 2022, corrected publication 2022

Abstract
Purpose To assess the symptoms, quality of life and sexual well-being in patients with lower urinary tract symptoms due to
benign prostatic hyperplasia LUTS/BPH treated with pumpkin seed soft extract (PSE) in routine practice.
Methods This noninterventional study included 130 men treated for up to 24 months. The International Prostate Symptom
Score (IPSS) and related quality of life, Aging Males’ Symptoms Scale (AMS), and International Index of Erectile Func-
tion (IIEF-5) were recorded. Descriptive statistical methods were applied. The mean with 95% confidence interval (CI) was
calculated for the primary end point (change in IPSS after 12-month treatment).
Results Analysis at 12 months included 83 patients [mean (SD) age 65.2 (8.7) years and IPSS (15.6 (3.4), IPSS-QoL 3.4
(0.9)]. AMS and IIEF-5 indicated mild or mild to moderate disorder regarding sexual well-being and erectile dysfunction,
respectively. After 12 months, the mean IPSS change from baseline was − 4.7 (95% CI − 5.4 to − 3.9), with 83% (95% CI
65.3 to 84.1) and 53% (95% CI 42.3 to 63.7) of the patients achieving reductions by at least 3 and 5 points, respectively. The
proportion of patients with IPSS-QoL below 3 points (mostly satisfied) was 11% (9/83) at baseline and rose to 62% (51/83)
and 73% (40/55) at 12 and 24 months, respectively. AMS and IIEF-5 scores did not indicate a negative impact on sexual
function during treatment.
Conclusion In men with a moderate LUTS suggestive of BPH, a low progression risk and an active sex life, treatment with
pumpkin seed soft extract provided symptomatic relief, improved IPSS-QoL, and maintained sexual well-being.
Trial registration DRKS00010729, June 22, 2016.

Keywords Lower urinary tract symptoms · Prostatic hyperplasia · Phytotherapy · IPSS · Quality of life · Sexual health

Introduction

Lower urinary tract symptoms due to benign prostatic

* Gerit Theil hyperplasia (LUTS/BPH) are a widespread condition affect-
[email protected] ing quality of life [1]. Furthermore, epidemiological stud-
1 ies report a correlation between LUTS severity and sexual
University Clinic and Outpatient Clinic for Urology, Medical
Faculty of Martin Luther University Halle-Wittenberg, function problems such as erectile dysfunction and reduced
Halle (Saale), Germany ejaculation, irrespective of age [2, 3]. Therefore, the poten-
2
Coordination Center for Clinical Studies/Trial, University tial impact of medication on sex life has become a focus
Medicine Halle (Saale), Halle (Saale), Germany for patient-shared decision-making for symptomatic relief
3
Markkleeberg, Germany in patients with low risk of progression [4].
4 The most frequently prescribed substances for LUTS/
Hettstedt, Germany
5
BPH, such as alpha-blockers and 5-alpha-reductase inhibi-
Gaeufelden, Germany tors (5ARIs), can lead to various sexual function disorders
6
Omega Pharma Deutschland GmbH, Herrenberg, Germany depending on the drug class and individual substances [5, 6].
7
Halle (Saale), Germany Adverse effects on sex life may even persist or worsen after

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1770 World Journal of Urology (2022) 40:1769–1775

treatment has been terminated [7]. Consequently, attending practices. All patients provided written informed consent
physicians should inform their patients about these risks, before participation.
because sexually active men might not be willing to accept Men aged between 18 and 80 years with moderate LUTS
a possible impact on their sexual health [5, 6]. In fact, adher- suggestive of BPH (LUTS/BPH) were included if they had
ence to treatment is generally low in men with LUTS/BPH, symptoms for at least the previous 3 months, were previ-
and (sexual) side effects may be a reason [5]. ously untreated and had an IPSS ≥ 13. Patients were treated
Herbal extracts are considered to provide modest symp- twice daily with capsules containing 500 mg pumpkin seed
tomatic relief and to be well-tolerated medications that pre- soft extract (PSE).1
serve sexual well-being; however, due to the heterogeneity Exclusion criteria were neurogenic or malignant disease,
of the herbal extracts available, most guidelines do not offer recurrent urinary retention or infection, urolithiasis, any
a recommendation [8, 9]. Herbal medicines used to treat treatment for LUTS or procedure at the prostate or blad-
LUTS/BPH include extracts from saw palmetto fruit, sting- der during the past three months, catheterization, or renal
ing nettle root, African prune tree bark and pumpkin seed. In impairment. The maximum follow-up period was 2 years.
fact, pumpkin seed has long been used for the relief of over- At baseline, demographic data, concomitant diseases and
active bladder symptoms, as acknowledged by the European concurrent medications were recorded.
herbal monograph. Possible relevant compounds of herbal The following validated questionnaires were used to
drugs include phytosterols, fatty acids, and lectins [9]. measure the outcome. The self-administered International
Interestingly, the typical and putatively active phytos- Prostate Symptom Score (IPSS) questionnaire was employed
terols found in pumpkin seeds are Δ7-sterols (avenasterol, to evaluate symptomatic relief [20]. In addition, the patients
spinasterol), which exhibit structural differences from ubiq- completed the IPSS-related quality-of-life (QoL), Aging
uitous Δ5-sterols (ß-sitosterol, stigmasterol). Uniquely high Males’ Symptoms Scale (AMS) [21] and erectile function
concentrations of Δ7-sterols are present in pumpkin seed (IIEF-5) [22] questionnaires. The AMS measures health-
soft extract capsules [10]. In animal models, pumpkin seed related quality of life and symptoms in aging men and
oil inhibits testosterone-induced prostate growth [11, 12] reflects psychological, somatic and sexual domains.
and has beneficial urodynamic effects [13] and anti-inflam- The IIEF-5 was developed to diagnose the presence and
matory activity [14]. Oil, soft extract and Δ7-sterols from severity of erectile dysfunction (ED).
­Uromedic® pumpkin, a registered cultivar of the medicinal All questionnaires were completed at each visit, i.e., at
pumpkin, has shown anti-androgenic effects in experimental baseline and at 3, 6, 12, and 24 months after treatment initia-
studies [15]. In addition to specific Δ7-sterols, other com- tion. Safety evaluation included records of adverse events at
ponents in pumpkin seeds may contribute to the pharma- all follow-up visits.
cological effects, such as oleic acid with binding affinity
toward muscarinic receptors [16] and y-tocopherol with anti- Outcomes
inflammatory properties [17].
Pumpkin seed and its soft extract provide symptomatic The primary criterion for effectiveness was the absolute
relief in men with moderate LUTS/BPH and have good tol- change in the IPSS after 12 months of treatment compared
erability [18, 19]. One objective of treating such patients to baseline.
should be to improve or stabilize their quality of life, physi- Secondary outcomes included improvement in the IPSS
cally, psychologically, and sexually. of at least 3 and 5 score points after 12 months as well as
Here, we assess the quality of life, with a special empha- changes in the IPSS, IPSS-related QoL, AMS and its sexual
sis on sexual well-being, in a real-life practice setting of subscore (AMS-SEX), and IIEF-5 at all visits during the
LUTS/BPH patients under treatment with pumpkin seed soft 24-month observation.
extract up to 24 months.
Statistical methods

Methods All data were collected exploratively by using descrip-

tive statistical methods. The demographic and baseline
Study design characteristics of the study subjects are summarized as
the mean with standard deviation (SD) and median with
This prospective noninterventional study was planned by the
University Clinic for Urology, Medical Faculty of Martin
Luther University Halle-Wittenberg, approved by the respon- 1
Brands: GRANU FINK Prosta forte 500 mg (DE), GRANU FINK
sible ethics committee and conducted in six private urologist Prosta kemény (HU), GRANUFINK Prosta forte (AT, CH, NL, UA),
and Urostemol Prosta (UK).

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World Journal of Urology (2022) 40:1769–1775 1771

Table 1  IPSS, AMS, AMS-SEX, and IIEF-5 during the course of treatment
Baseline (n = 83) 3 months (n = 83) 6 months (n = 83) 12 months (n = 83) 24 months (n = 55)

IPSS total, range 0–35

Mean (SD) 15.6 (3.4) 12.0 (4.0) 10.7 (3.6) 10.9 (3.7) 10.1 (2.7)
Median (min; max) 15.0 [10; 32] 12.0 [3; 25] 11.0 [2; 21] 11.0 [3; 24] 10.0 [3; 17]
Mean change [95% CI] − 3.6 [− 4.3 to − 2.9] − 4.9 [− 5.7 to − 4.1] − 4.7 [− 5.4 to − 3.9] − 5.1 [− 5.9 to − 4.3]
IPSS-QoL, range 0–6
Mean (SD) 3.4 (0.9) 2.7 (1.0) 2.4 (0.8) 2.3 (0.7) 2.1 (0.7)
Median (min; max) 3 [1; 6] 3 [0; 5] 2 [1; 4] 2 [1; 4] 2 [0; 4]
AMS total score, range 17–85
Mean (SD) 24.0 (9.7) 23.4 (8.9) 23.6 (9.1) 23.6 (9.0) 23.5 (8.8)
Median (min; max) 20.0 [17; 59] 19.0 [17; 59] 18.0 [17; 62] 20.6 [17; 59] 17.0 [17; 54]
Mean change [95% CI] − 0.2 [− 0.9 to 0.4] − 0.4 [− 1.2 to 0.4] − 0.5 [− 1.2 to 0.1] 0.0 [− 1.0 to 1.0]
AMS-SEX subscale, range 5–25
Mean (SD) 7.7 (3.7) 7.7 (3.4) 7.8 (3.7) 7.9 (3.7) 7.9 (3.8)
Median (min; max) 5.0 [5; 19] 5.0 [5; 17] 5.0 [5; 18] 5.0 [5; 17] 5.0 [5; 19]
Mean change [95% CI] − 0.0 [− 0.5 to 0.5] 0.1 [− 0.2 to 0.4] 0.1 [− 0.2 to 0.5] 0.3 [− 0.2 to 0.7]
IIEF-5 score, range 1–25
Mean (SD) 16.4 (5.7) 16.6 (6.0) 16.9 (6.0) 16.7 (6.3) 15.7 (7.0)
Median (min; max) 19.0 [1; 25] 20.0 [1; 25] 20.0 [1; 25] 20.0 [1; 24] 20.0 [1; 24]
Mean change [95% CI] 0.2 [− 0.4 to 0.8] 0.5 [− 0.3 to 1.3] 0.3 [− 0.5 to 1.1] − 0.7 [− 2.0 to 0.6]

AMS Aging Male's Symptoms: 17 questions with a 5-point rating scale and scores range from 17 to 85; higher scores indicate a greater negative
impact on quality of life as follows: none/little 17–26, mild 27–36, moderate 37–49, severe 50–85 [21]
AMS-SEX AMS sexual subscore, 5-item sexual domain of the AMS; scores range from 5 to 25
IIEF-5 abridged International Index Of Erectile Function (5 questions) with a 5-point scale; scores range from 1 to 25 to specify the degree of
erectile dysfunction (ED) as follows: severe 1–7, mild 8–11, mild to moderate: 12–16, mild: 17–21, no ED (> 21) [22]

range. For the primary end point (absolute change in IPSS Baseline characteristics
after 12 months of treatment), the mean change with 95%
confidence interval (CI) was calculated. The mean (SD) age of patients in the primary analysis
Secondary outcomes were analyzed descriptively. No cohort (n = 83) was 65.2 years (8.7). Their mean PSA
imputation was used for missing total scores at individual value, as based on measurement in 52 patients, was 1.9
visits. For examination of safety, the evaluation included (1.3) ng/ml. The mean IPSS at the start of PSE treatment
all patients who had taken at least one capsule. Analyses was 15.6 (3.4) (Table 1), indicating moderate symptoms.
were carried out using SAS version 9.4, and GraphPad Regarding quality of life related to urological symptoms,
Prism software version 9.0. patients recorded “mostly satisfied/mixed: equally satis-
fied/dissatisfied”, corresponding to a mean (SD) of 3.4
(0.9) (Table 1). Only 10.8% (9/83) of the patients had
an IPSS-QoL index of “mostly satisfied”, “pleased”, or
Results “delighted” (2 points and below) (Supplementary Table 1).
For AMS and AMS sexual subscores, the mean (SD) val-
Recruitment and patient follow‑up ues at baseline were 24.0 (9.7) and 7.7 (3.7), respectively,
indicating the presence of mild symptoms (Table 1, Sup-
Between May 2016 and July 2020, 130 patients were plementary Tables 2 and 3). The AMS psychological and
enrolled. The cohort analyzed for the primary criterion somatic subscores are provided in Supplementary Tables 4
consisted of 83 patients, i.e., all patients with IPSS values and 5. The mean (SD) of the IIEF-5 was 16.4 (5.7), which
at baseline and at the 12-month follow-up. Supplemen- signified a mild to moderate degree of erectile dysfunction
tary Fig. 1 displays the number of patients per visit and (Table 1, Supplementary Table 6).
reasons for drop-out.

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Adverse events

Overall, a total of 16 adverse events were reported in 13 of

the 130 patients. However, a causal relationship to the treat-
ment was not found for any of them.

Discussion

In this study, the symptoms, quality of life, and sexual well-

being of 130 patients with LUTS/BPH treated with pumpkin
seed soft extract (PSE) were followed up for a maximum
period of 2 years in a real-life setting.
The cohort analyzed for the primary criterion consisted
of 83 patients treated for at least 12 months. At 12 and
24 months, the IPSS was reduced by 4.7 and 5.1 points
compared to baseline in 83 and 55 of the patients available
for analysis, respectively. Our results show a stronger effect
than that demonstrated by Roehrborn et al. at the 1-year
Fig. 1  Change in the IPSS over 12 months of treatment, with PSE follow-up in their randomized, double-blind study compar-
(n = 83) displayed as the mean with minimum and maximum IPSS
ing finasteride plus tadalafil with finasteride plus placebo;
in that study, three-quarters of the patients achieved an IPSS
Improvement in LUTS decrease of at least 3 points and thus perceptible symptom
relief [23].
The IPSS continuously decreased to a mean (SD) of 10.9 In general, comparisons with previously published studies
(3.7) at 12 months (Table 1, Fig. 1). The mean change from must be approached with skepticism because IPSS improve-
baseline was − 4.7 (95% CI − 5.4 to − 3.9). ment varies greatly between studies; even with placebo,
After 12 months, the proportions of patients who had LUTS/BPH patients can achieve a clinically significant IPSS
achieved an IPSS reduction by at least 3 and 5 points vs. reduction [24]. Another aspect contributing to diverse out-
baseline were 83% (95% CI 65.3 to 84.1) and 53% (95% CI comes is that the magnitude of the IPSS decrease depends
42.3–63.7), respectively, corresponding to 62 and 44 patients on the initial score [25].
of the 83 analyzed. Nonetheless, our results suggest a good effectiveness
of PSE compared to other phytotherapeutics used to treat
Quality of life and sexual function LUTS/BPH. The mean reduction in the IPSS of 4.7 points
in our investigation is well over the 3.2-point mean reduc-
IPSS improvement resulted in a relative IPSS-related QoL tion found in the real-life practice TRIUMPH study after
improvement compared to the baseline of 0.7 (3 months), 1.0 12 months of phytotherapy (Serenoa repens or Pygeum afri-
(6 months), 1.1 (12 months), and 1.3 (24 months) (Table 1). canum) [26] or the 3.0-point mean reduction in the more
At the individual patient level after 3, 6, 12 and 24 months, recent EVOLUTION European registry study [8].
43/4 (of 83 patients), 54/0 (of 81), 59/2 (of 83), and 44/1 (of Moreover, it is noteworthy that the change in the IPSS
55), respectively, rated their IPSS-related QoL as being bet- achieved after 12 months of treatment with PSE was greater
ter/worse than that at baseline. For the remaining patients, than the average effects of placebo in studies investigating
the score value was unchanged at the respective visit com- plant extracts (− 3.6) and 5ARIs (− 3.4) and, though less
pared to baseline. pronounced, also greater than the placebo response observed
The proportion of patients with an IPSS-QoL index of in studies with alpha-blockers and 5ARI/AB combinations
at least "mostly satisfied “ (2 points and below) increased (both − 4.3) [27].
from 10.8% (9 of 83 patients) at baseline to 61.4% (51 of 83 Consistent with previous findings [19], relief of LUTS/
patients) after 12 months and to 72.7% (40 of 55 patients) BPH under treatment with PSE resulted in better IPSS-QoL
after 24 months (Fig. 2, Supplementary Table 1). scores. The proportion of patients who felt at least "mostly
Relevant differences from baseline over the course of satisfied” (IPSS-QoL < 3) increased to 61% and 73% after
treatment was not observed for the mean scores for the sex- 12 and 24 months, respectively, from only 11% initially. Fur-
ual health questionnaires AMS, AMS-SEX, and IIEF-5 did thermore, our results show a mean IPSS-QoL difference of
not show (Table 1, Supplementary Tables 2–6). 1.2 (24 months), which is similar to the mean response of

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World Journal of Urology (2022) 40:1769–1775 1773

Fig. 2  Change in IPSS-related

quality of life (QoL) for all
study visits (n = 83). IPSS-
related QoL for all study visits
according to the question “If
you were to spend the rest of
your life with your urinary
condition the way it is now,
how would you feel about
that?” ( primary analysis set,
n = 83; *missing values for
two patients after 6 months.
**Treatment was continued for
up to 24 months in 55 patients
(Fig. 1). Data are presented in
Supplementary Table 1

1.1 points observed with tamsulosin or dutasteride [28], and to any medical therapy decreases over time in LUTS/BPH
higher than the mean change of 0.9 points observed in men patients. Indeed, recent reported rates for alpha-blockers and
treated with various other phytotherapeutics [8]. This also combination therapy at 1 year were just 39.2% and 45.6%,
confirms the benefit of PSE regarding QoL related to LUTS. respectively [30, 31]. Compared to this, the adherence rate
Moreover, during treatment over two years, the extract was in our study indicates a good acceptance of PSE by patients
well tolerated, with no impact on the patients' sexual health who had started it.
monitored using the AMS, especially the AMS sexual sub- During the entire study period, 28 patients switched to
score [21] and IIEF-5 [22]. In contrast, treatment of LUTS/ synthetic medication (mainly tamsulosin). However, in most
BPH patients with dutasteride 0.5 mg and tamsulosin 0.4 mg of them, the IPSS improved compared to baseline, implying
compared to placebo resulted in a significant worsening that nonmedical factors may have also been responsible, as
of Male Sexual Health Questionnaire and sexual activity opposed to symptomatic progression or an unsatisfactory
domain scores [29]. effect.
A limitation is that the planned sample size was not
obtained in this study. After 4 years and inclusion of 130
patients, the study was prematurely terminated due to little Conclusion
prospect of involving additional patients in an acceptable
time. One explanation for this is that phytotherapeutics are Patients with LUTS/BPH, who typically present in daily
prescribed less frequently than synthetic agents. Further- medical practice, were monitored under routine practice
more, herbal medicine is associated with higher costs for conditions. The patients had moderate LUTS impairing their
most patients, as herbal products are usually not reimbursed health-related QoL, but no relevant impairment of sexual
in Germany. health and were treated with pumpkin seed soft extract
Finally, of the original 130 patients, only 83 (64%) and for up to 24 months. The IPSS was reduced by at least 3
48 (37%) remained adherent to PSE treatment at 12 and points in three-quarters of the patients and by 5 points or
24 months, suggesting that financial aspects caused with- more in half of the patients after 12 months. Using valid
drawal from PSE treatment. On the other hand, adherence questionnaires, this study shows that long-term treatment

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1774 World Journal of Urology (2022) 40:1769–1775

with pumpkin seed soft extract has no negative impact on a 4. Fornara P, Madersbacher S, Vahlensieck W, Bracher F, Romics I
patient's sexual well-being. PSE may be offered as a long- et al (2020) Phytotherapy adds to the therapeutic armamentarium
for the treatment of mild-to-moderate lower urinary tract symp-
term treatment for those with a low risk of progression and toms in men. Urol Int 104(5–6):333–342
preference for treatment without impacting sexual health. 5. Fourcade RO, Théret N, Taïeb C (2008) Profile and management
For future studies, it would be interesting to compare the of patients treated for the first time for lower urinary tract symp-
effect of PSE on symptom reduction and sexual health to toms/benign prostatic hyperplasia in four European countries.
BJU Int 101(9):1111–1118
alpha-blockers in a randomized trial. 6. Gandhi J, Weissbart SJ, Smith NL, Kaplan SA, Dagur G et al
(2017) The impact and management of sexual dysfunction second-
Supplementary Information The online version contains supplemen- ary to pharmacological therapy of benign prostatic hyperplasia.
tary material available at https://d​ oi.o​ rg/1​ 0.1​ 007/s​ 00345-0​ 22-0​ 4036-w. Transl Androl Urol 6(2):295–304
7. La Torre A, Giupponi G, Duffy D et al (2014) Sexual dysfunction
Author contributions GT: project development, data collection, data related to psychotropic drugs: a critical review. Part III: mood
analysis, manuscript writing. PF: project development, data collection, stabilizers and anxiolytic drugs. Pharmacopsychiatry 47:1–6
data analysis. SH: project development. MR: data collection. MS: data 8. Bhatt NR, Davis NF, Witjes WP, Bjartell A, Caris C et al (2020)
collection. TK: data collection. YK: data analysis, manuscript writing. Contemporary use of phytotherapy in patients with lower urinary
BP: manuscript writing. tract symptoms due to benign prostatic hyperplasia: results from
the evolution European registry. World J Urol 39(7):2261–2667
Funding Open Access funding enabled and organized by Projekt 9. Gravas S, Cornu JN, Gacci M et al (2021) Management of non-
DEAL. This prospective noninterventional study was sponsored by neurogenic male LUTs. EAU guidelines edition presented at the
Omega Pharma Deutschland GmbH. EAU annual congress, Milan. European Association of Urology,
Europe
10. Muller C, Bracher F (2015) Determination by GC-IT/MS of phy-
Declarations tosterols in herbal medicinal products for the treatment of lower
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Conflict of interest SH and YK are employees of Omega Pharma. BP Planta Med 81(7):613–620
is a consultant for Omega Pharma. 11. Gossell-Williams M, Davis A, O’Connor N (2006) Inhibition
of testosterone-induced hyperplasia of the prostate of sprague-
Ethical approval The study was approved by the ethics committee dawley rats by pumpkin seed oil. J Med Food 9(2):284–286
of the medical faculty ethics committee of Martin Luther University 12. Tsai YS, Tong YC, Cheng JT, Lee CH, Yang FS et al (2006)
Halle-Wittenberg (number of ethical approval: 2016-06). Pumpkin seed oil and phytosterol-F can block testosterone/pra-
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Consent to participate Consent to participate was given by the patients 13. Zhang X, Ouyang JZ, Zhang YS, Tayalla B, Zhou XC et al (1994)
or their legal representatives. Effect of the extracts of pumpkin seeds on the urodynamics of
rabbits: an experimental study. J Tongji Med Univ 14(4):235–238
Consent to publish All authors consented to this publication. 14. Fahim AT, Abd-el Fattah AA, Agha AM, Gad MZ (1995) Effect of
pumpkin-seed oil on the level of free radical scavengers induced
during adjuvant-arthritis in rats. Pharmacol Res 31:73–79
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bution 4.0 International License, which permits use, sharing, adapta- derived Δ7-sterols, extract and oil inhibit 5α-reductases and bind
tion, distribution and reproduction in any medium or format, as long to androgen receptor in vitro. Pharmacol Pharm 9:193
as you give appropriate credit to the original author(s) and the source, 16. Ito Y, Kojma N, Suzuki A, Kurokawa M, Yamada S (2012) 140
provide a link to the Creative Commons licence, and indicate if changes Effects of SPE-contained fatty acids on bladder muscarinic recep-
were made. The images or other third party material in this article are tors and voiding function in rats, in International continence soci-
included in the article's Creative Commons licence, unless indicated ety meeting (ICS). Beijing, China
otherwise in a credit line to the material. If material is not included in 17. Damiano R, Cai T, Fornara P, Franzese CA, Leonardi R et al
the article's Creative Commons licence and your intended use is not (2016) The role of Cucurbita pepo in the management of patients
permitted by statutory regulation or exceeds the permitted use, you will affected by lower urinary tract symptoms due to benign pro-
need to obtain permission directly from the copyright holder. To view a static hyperplasia: a narrative review. Arch Ital Urol Androl
copy of this licence, visit http://​creat​iveco​mmons.​org/​licen​ses/​by/4.​0/. 88(2):136–143
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