benign prostatic hyperplasia ( bph ) is a pathological symptom frequently found in the elderly population .
treatment options for men with symptomatic bph include active monitoring , phytochemical treatment , medical therapy with -blockers or 5--reductase inhibitors , and surgery ( barry et al . , 1997 ; watson et al . , 2004 ) .
the use of complementary and alternative medicine ( cam ) for the treatment of bph patients has a long history , especially in european countries ( ortiz , 1998 ; pathak et al . , 2003 ) .
nevertheless , there is still a considerable degree of skepticism from the urologic community about the efficiency and safety of these cam products .
this is mainly due to the lack of an established mechanism of action for cam ( melo et al . , 2002 ;
the cam used in this trial was pumpkin seed oil , saw palmetto oil and a combination of pumpkin seed oil and saw palmetto oil ( ernst , 2002 ; hirsch , 2000 ) .
for these materials , the mechanisms of action may include alteration of cholesterol metabolism , anti - androgenic activity ( including 5--reductase inhibitor activity ) , anti - inflammatory effects , and a decrease in available sex hormone binding globulin ( cristoni et al . , 2000 ) .
although the mechanisms of action of these materials have been investigated in many in vitro and indirect in vivo studies , they have yet to be clearly defined ( shoskes , 2002 ; wilt et al . , 2000 ) .
nevertheless , many bph patients are currently taking these cam materials everyday without apparent adverse effects ( vickers , 2000 ) . yet
, long - term treatment of bph patients with cam is necessary in order to assess the occurrence of side effects .
therefore , the objective of this study was to carry out a long - term study to determine the effectiveness and the potential side effects of pumpkin seed oil and/or saw palmetto oil in the treatment of korean men with symptomatic bph .
bph patients with an international prostate symptom score ( ipss ) of 8 or more participated in a randomized , double - blind , placebo - controlled trial of pumpkin seed oil and saw palmetto oil for a 12-month period .
volunteers were requested to sign the documents of clinical examinations agreement after careful review of the instructions .
clinical examinations were conducted for 18 months at chung - ang university medical center , department of urology . by baseline checkup of general health ,
patients with any major diseases except bph or patients who had bph related treatment such as 5--reductase inhibitor , -receptor blocker , urogenital surgery or any other alternative therapy for bph were excluded . any other medication or surgery related to bph
sixty - two patients were distributed into 4 separate groups according to their time sequence of participation ; group a ( placebo , control , sweet potato starch , 320 mg / day ) , group b ( pumpkin seed oil , 320 mg / day ) , group c ( saw palmetto oil , 320 mg / day ) and group d ( the combination of pumpkin seed oil , 320 mg / day and saw palmetto oil , 320 mg / day ) . sweet potato starch ( bum - ah , seoul , korea ) , standardized pumpkin seed oil and saw palmetto oil ( ria international , new jersey , usa ) were prepared in hard capsules .
patients took 2 capsules per day in the morning and the evening after a meal , over a 12-month period .
after the baseline assessment of general health , each participant visited the hospital every 3 months to measure bph parameters such as ipss , quality of life score ( qol ) , serum prostate specific antigen ( psa ) , prostate volume ( pv ) and maximal urinary flow rate ( mfr ) .
fifteen patients ( 24% ) were dropped during the trial due to aggravation of symptoms ( n=13 ) , movement ( n=2 ) and initiation of bph medication ( n=1 ) .
they have been checked on overall functioning , difficulties with intervention adherence and adverse symptoms weekly by phone , and visited hospital every 3 months .
ipss and qol were assessed using standard questionnaire forms ( 2003 american urology association guideline on the management of bph : diagnosis and treatment recommendations ) ( zhang et al . , 2008 ) .
the questionnaire for ipss is composed with seven questions and each measured on a 5 point scale . for the assessment , the patients responded on a scale of 0 ( delighted ) to 6 ( terrible ) to the question , " if you were to spend the rest of your life with your urinary condition just the way it is now , how would you feel about this ? "
the serum psa was measured using an electrochemiluminescence method ( cho et al . , 2005 )
2005 ) ( voluson 730 prov ge healthcare , austria ) , and mfr was done using an uroflowmeter ( willetts et al . , 2003 )
pv and mfr measurements started after 6 months because the urologists advised that there would not be a significant change over a short period such as the first 3 months of treatment .
all patients were measured for body weight , height and body mass index ( bmi ) ( fanics co. ltd , hm-170 , korea ) at the beginning of the experiment .
the differences among groups and experimental periods of each group were analyzed by tukey 's studentized range test for bph parameters .
bph parameters for ipss , qol , serum psa , pv and mfr were expressed as the mean  standard error , and were age adjusted against group a ( control ) , in which acquired by analysis of covariance ( ancova ) with least square mean ( lsmean ) .
bph patients with an international prostate symptom score ( ipss ) of 8 or more participated in a randomized , double - blind , placebo - controlled trial of pumpkin seed oil and saw palmetto oil for a 12-month period .
volunteers were requested to sign the documents of clinical examinations agreement after careful review of the instructions .
clinical examinations were conducted for 18 months at chung - ang university medical center , department of urology . by baseline checkup of general health ,
patients with any major diseases except bph or patients who had bph related treatment such as 5--reductase inhibitor , -receptor blocker , urogenital surgery or any other alternative therapy for bph were excluded . any other medication or surgery related to bph
sixty - two patients were distributed into 4 separate groups according to their time sequence of participation ; group a ( placebo , control , sweet potato starch , 320 mg / day ) , group b ( pumpkin seed oil , 320 mg / day ) , group c ( saw palmetto oil , 320 mg / day ) and group d ( the combination of pumpkin seed oil , 320 mg / day and saw palmetto oil , 320 mg / day ) . sweet potato starch ( bum - ah , seoul , korea ) , standardized pumpkin seed oil and saw palmetto oil ( ria international , new jersey , usa ) were prepared in hard capsules .
patients took 2 capsules per day in the morning and the evening after a meal , over a 12-month period .
after the baseline assessment of general health , each participant visited the hospital every 3 months to measure bph parameters such as ipss , quality of life score ( qol ) , serum prostate specific antigen ( psa ) , prostate volume ( pv ) and maximal urinary flow rate ( mfr ) .
fifteen patients ( 24% ) were dropped during the trial due to aggravation of symptoms ( n=13 ) , movement ( n=2 ) and initiation of bph medication ( n=1 ) .
they have been checked on overall functioning , difficulties with intervention adherence and adverse symptoms weekly by phone , and visited hospital every 3 months .
ipss and qol were assessed using standard questionnaire forms ( 2003 american urology association guideline on the management of bph : diagnosis and treatment recommendations ) ( zhang et al . , 2008 ) .
the questionnaire for ipss is composed with seven questions and each measured on a 5 point scale . for the assessment , the patients responded on a scale of 0 ( delighted ) to 6 ( terrible ) to the question , " if you were to spend the rest of your life with your urinary condition just the way it is now , how would you feel about this ? "
the serum psa was measured using an electrochemiluminescence method ( cho et al . , 2005 )
( voluson 730 prov ge healthcare , austria ) , and mfr was done using an uroflowmeter ( willetts et al . , 2003 )
pv and mfr measurements started after 6 months because the urologists advised that there would not be a significant change over a short period such as the first 3 months of treatment .
all patients were measured for body weight , height and body mass index ( bmi ) ( fanics co. ltd , hm-170 , korea ) at the beginning of the experiment .
the differences among groups and experimental periods of each group were analyzed by tukey 's studentized range test for bph parameters .
bph parameters for ipss , qol , serum psa , pv and mfr were expressed as the mean  standard error , and were age adjusted against group a ( control ) , in which acquired by analysis of covariance ( ancova ) with least square mean ( lsmean ) .
the average age of patients who completed the 1 year trial was 53.3 years , and the average age of group d was significantly higher than those of groups b and c ( table 1 ) .
the average height , weight and bmi of patients were not significantly different among groups , and the average bmis of all groups were within an overweight range based on korean obesity evaluation criteria ( lee et al . , 2006 ) .
ipsss in groups b , c and d were significantly reduced ( p < 0.05 ) after 3 months of treatment ( table 2 ) .
ipss of group b was decreased by 12.0 points ( 58.0% change ) , from 20.7 to 8.7 after 12-month treatment .
ipss of group c was also decreased by 9.2 points ( 50.3% change ) , from 18.2 to 9.1 .
the average ipss of group d showed a constant decline from the beginning ( 19.0 ) to the end of the 12-month treatment ( 4.7 ) by 14.3 points , indicating 75.3% improvement in voiding symptoms .
in particular , bph status of group d was improved from moderate ( 8~19 ) to mild ( 7 ) according to ipss .
the reduction of ipss after 12 month treatment was highest in group d , however , there was no significant difference among the groups .
the qol were significantly improved in groups b and c after 3 months , and in group d after 6 months ( p < 0.05 ) ( table 3 ) .
the qol score of group a ( placebo ) was not changed , but those of group b and group c were reduced by 1.7 points ( 40.5% change ) and 1.4 points ( 38.9% change ) after 12-month treatment , respectively .
the qol score of group d was reduced by 2.2 points ( 57.9% change ) after 12-month treatment .
the serum psa levels of groups a , b and c remained unchanged during the 12 month trial .
the serum psa levels of group d showed a constant decline from the beginning ( 1.2 ng / ml ) to the end of the 12-month treatment ( 0.7 ng / ml ) , indicating 41.7% reduction .
the pv of groups b , c and d showed a gradual decline over the experimental period , but these changes were not statistically significant ( table 5 ) .
as shown in table 6 , the mfr of group a was gradually decreased over the experimental period with a worsening in urinary symptoms .
the mfr of group b was significantly increased after 6 months and that of group c was significantly increased at 12 months ( p < 0.05 ) .
the mfr of group b was increased from 14.8 ml / second at the initiation of the study to 17.0 ml / second at the end , for an improvement of 14.9% .
the mfr of group c was increased from 14.0 to 21.2 ml / second after 12-month treatment , which was an improvement of 51.4% .
the mfr score of group d , however , was not changed significantly during the treatment period .
correlation between parameters existed ; ipss vs qol ( correlation coefficient = 0.635 , p < 0.05 ) , ipss vs mfr ( correlation coefficient = -0.375 , p < 0.05 ) , qol vs mfr ( correlation coefficient = -0.255 , p < 0.05 ) , and prostate volume vs serum psa ( correlation coefficient = 0.323 , p < 0.05 ) . in the meanwhile , there were no statistically significant differences in all bph parameters among groups at every treatment time .
the use of phytochemicals ( phytosterols ) as an alternative therapy for the relief of lower urinary tract symptoms due to a prostatic disease seems to be growing quickly all over the world , including the republic of korea ( buck , 2004 ) .
a phytochemical based therapy is widely given to men with symptomatic bph in western europe , where physicians prescribe phytochemical products in the same manner as they prescribe drugs ( marks et al .
the results of this study show that the symptoms of bph for all patients receiving treatment with pumpkin seed oil , saw palmetto oil , or a combination of pumpkin seed oil plus saw palmetto oil were improved over 12 months , in comparison with placebo . but therapeutic efficiency was not improved by combination of these two compounds . during the experimental period ,
according to braeckman 's study ( 1994 ) , oral doses of saw palmetto oil 160 mg twice daily for 3 months improved ipss about 22% after 45 days and 35% at 90 days .
this was comparable with our result in which group b ( 33.8% ) and group c ( 33.2% ) showed similar improvement after 3 months . in the study by bach ( 2000 ) ,
12-month pumpkin seed treatment improved the ipss at least 5 points and overall improvement of 64.8% . in a double - blind randomized trial that compared the effects of saw palmetto ( 320 mg / day ) with 5--reductase inhibitor
( 5 mg / day ) , the ipss was declined by 37% and 39% , respectively ( carraro et al . , 1996 ) after 6 months of treatment .
hisashi et al . ( 2005 ) reported a significant linear relationship between ipss and qol score , a finding in agreement with our own , in which ipss was correlated exactly with qol score .
both ipss and qol score tended to decline significantly at the 3rd month of treatment in our study , a finding similar to that of other researchers ( nickel , 1998 ; willetts et al . , 2003 ) .
there have been recent reports suggesting that the serum psa value may not be the best marker for prostate cancer detection , but it still remains one of the simplest means of early diagnosis and follow - ups for this disease .
serum psa is also increased in other conditions such as bph , prostatitis and others ( lee et al . , 2005 ;
( 2002 ) showed saw palmetto does not affect serum psa level within 12 months of treatment . in our study , only a minimal change of psa was observed within the normal range ( 0.0~4.0 ng / ml ) , although a synergistic combination of pumpkin seed oil and saw palmetto oil may have contributed to the decrease of serum psa level observed in our study .
braeckman ( 1994 ) showed that prostate volume was significantly decreased by 9% after 45 days and 10% after 90 days of treatment with saw palmetto oil .
but several of reports demonstrated only a minimal change of prostate volume within 1 year ( marks et al .
. we also could not detect any significant decrease of the prostate volume even within 12 months . in a randomized trial of natural products by preuss et al .
( 2001 ) , the ipss was decreased significantly after 90 days , but serum psa , mfr and pv were not changed .
this is in contrast to the present study in which the serum psa of patients fed the combination of pumpkin seed oil and saw palmetto oil was decreased , and mfr in the pumpkin seed oil group was increased , significantly after 6 months . in a study by moon et al .
( 1990 ) , urinary flow rate of bph patients supplemented with sitosterol was increased from a baseline mfr of 9.3 ml / s to 12.2 ml / s after 4 weeks of treatment , and continued to increase consistently for 12 weeks .
( 1996 ) reported that the average mfr was increased from 10.36 ml / s to 14.44 ml / s without any adverse effects after 12 months of treatment with saw palmetto oil .
in addition , this treatment did not influence the effectiveness of drugs taken for other chronic diseases by these patients .
1990 ) studied the combination of saw palmetto with pumpkin seed oil and reported a significant increase in mfr value in bph patients after 3 months of treatment .
our study showed a similar effectiveness on mfr in the pumpkin seed oil group and the saw palmetto oil group , but the combination of pumpkin seed oil with saw palmetto oil group did not significantly affect mfr .
the action mechanism of pumpkin seed oil is well known by its inhibition on 5--reductase which converts testosterone into dht ( dihydrotestosterone ) ( gossell - williams et al .
. meanwhile various action mechanisms are suggested for saw palmetto oil , including nuclear estrogen receptor inhibitor ( di silverio et al . , 1992 ) , inhibition of cyclooxygenase and 5-lipoxygenase pathway ( breu et al . , 1992 ) as well as 5--reductase inhibition ( weisser et al . , 1996 ) .
recently , epithelial contraction in the prostate transition zone was demonstrated by marks et al .
according to the difference in action mechanisms , a synergistic effect on bph was expected from combination treatment of pumpkin seed oil and saw palmetto oil . in our study ,
combination treatment of pumpkin seed oil and saw palmetto oil induced a higher symptomatic improvement , though not statistically significant , in ipss , qol and psa than a single treatment .
a better result is expected by increasing subject numbers and longer observation period as well as in vitro mechanism studies .
based on the results of this study , it could be suggested that pumpkin seed oil and saw palmetto oil are clinically safe and may be effective complementary and alternative medicine for bph .
 this study was to investigate the role of complementary and alternative medicine in the prevention and treatment of benign prostatic hyperplasia . 
 for this purpose , a randomized , double - blind , placebo - controlled trial was performed over 12 months on 47 benign prostatic hyperplasia patients with average age of 53.3 years and international prostate symptom score over 8 . 
 subjects received either sweet potato starch ( group 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 . in groups 
 b , c and d , the international prostate symptom score were reduced by 3 months . 
 quality of life score was improved after 6 months in group d , while those of groups b and c were improved after 3 months , compared to the baseline value . 
 serum prostate specific antigen was reduced only in group d after 3 months , but no difference was observed in prostate volume in all treatment groups . 
 maximal urinary flow rate were gradually improved in groups b and c , with statistical significance after 6 months in group b and after 12 months in group c. none of the parameters were significantly improved by combined treatment with pumpkin seed oil and saw palmetto oil . from these results , it is suggested that administrations of pumpkin seed oil and saw palmetto oil are clinically safe and may be effective as complementary and alternative medicine treatments for benign prostatic hyperplasia . 
Introduction
Materials and Methods
Study design
Measurements
Statistical analysis
Results
Discussion