benign prostatic hyperplasia ( bph ) is a progressive and androgen - dependent disease that causes lower urinary tract symptoms ( luts ) .
although bph is not a life - threatening disease , it can have a negative effect on the quality of life .
alpha - adrenergic receptor antagonists ( -blockers ) and 5-alpha reductase inhibitor ( 5ari ) are the first - line treatment option in patients with bph .
5ari blocks the conversion of the sex steroid hormone testosterone to dihydrotestosterone ( dht ) , which is an essential component of bph pathogenesis .
previous studies reported that the serum prostate - specific antigen ( psa ) level and prostate volume were decreased by approximately 50% and 20% , respectively , after treatment with 5ari .
however , some clinical questions remain as to how to interpret the psa level in men treated with 5ari .
furthermore , the effects on luts and prostate volume after discontinuation of 5ari are not well understood .
therefore , in the present study , we analyzed the changes in luts , prostate volume , and psa level after discontinuation of 5ari .
from december 2003 to december 2012 , 81 men more than 40 years of age with moderate to severe bph symptoms as determined by the international prostate symptom score ( ipss8 ) and a prostate volume of greater than 25 cm measured by transrectal ultrasonography ( trus ) were collected retrospectively for the study .
two patients ( case 1 , 4.91 ng / ml ; case 2 , 5.43 ng / ml ) with a psa level of 4 or more and with a negative pathologic result on the initial prostate biopsy were included in the study .
patients were excluded from the study if they had chronic urinary tract infection ; a history of prostate or testicular surgery , prostate cancer , acute urinary retention , or chronically large postvoid residual urine volume ; or 5ari treatment history .
the patients were classified into group 1 ( n=42 ) and group 2 ( n=39 ) according to 5ari use .
a combination of dutasteride 0.5 mg with tamsulosin 0.2 mg was given daily to all patients for 1 year .
, group 1 ( n=42 ) received a combination of dutasteride 0.5 mg with tamsulosin 0.2 mg daily , and group 2 ( n=39 ) received -blocker monotherapy only .
the ipss , prostate volume , and psa level were measured at baseline and at 12 and 24 months . with trus ( aloka , tokyo , japan ) , prostate volume was measured by use of the prostate ellipsoid formula and was calculated by multiplying the longest anteroposterior ( height , h ) , transverse ( width , w ) , and cephalocaudal ( length , l ) diameters and 0.524 ( hwl/6 ) .
pasw ver . 18.0 ( ibm co. , armonk , ny , usa ) was used for all statistical analyses .
student t - test was used to compare the baseline values of ipss , prostate volume , and serum psa level in each group .
the repeated - measures analysis of variance was performed to compare the change in ipss , prostate volume , and psa level from 0 to 12 months and also from 12 months to 24 months .
the mean age of the patients ( n=81 ) was 71.70 years ( standard deviation [ sd ] , 7.80 ) .
the mean prostate volume was 43.96 cm ( sd , 17.38 ) and the mean baseline serum psa level was 3.00 ng / ml ( sd , 1.98 ) .
the patients were classified into group 1 ( n=42 ) and group 2 ( n=39 ) .
there were no statistically significant differences between the two groups in mean age , total ipss , baseline prostate volume , or psa level ( table 1 ) .
the differences in total ipss , prostate volume , and serum psa level according to the absence of dutasteride are shown in table 2 . at 1 year after combination therapy , total ipss
had decreased by 17.6% ( from 17.88 [ sd , 7.77 ] to 14.95 [ sd , 7.27 ] ; p<0.001 ) in group 1 and by 13.3% ( from 15.50 [ sd , 7.60 ] to 13.45 [ sd , 2.50 ] ; p<0.001 ) in group 2 . however , at 1 year after dutasteride had been withdrawn , total ipss had increased by up to 7.6% ( from 13.45 [ sd , 2.50 ] to 14.93 [ sd , 5.48 ] ; p<0.001 ) in group 2 ( table 2 ) . at 1 year after combination therapy , the prostate volume was reduced by 21.9% ( from 41.59 cm [ sd , 13.97 ] to 32.95 cm [ sd , 10.10 ] ; p<0.001 ) in group 1 and by 15.5% ( from 45.96 cm [ sd , 23.02 ] to 38.96 cm [ sd , 23.91 ] ; p<0.001 ] in group 2 . at 1 year after dutasteride had been withdrawn , the prostate volume had increased by up to 13.1% [ from 38.96 ( 23.91 ) cm to 43.82 ( 23.45 ) cm ; p<0.001 ] . at 1 year after combination therapy ,
the transition zone volume had been reduced by 20.0% ( from 15.62 cm [ sd , 5.76 ] to 12.23 cm [ sd , 4.50 ] ; p<0.001 ] in group 1 and by 17.6% ( from 17.84 cm [ sd , 10.35 ] to 14.61 cm [ sd , 9.81 ] ; p<0.001 ] in group 2 . at 1 year
after dutasteride had been withdrawn , the prostate volume had increased by up to 14.2% ( from 14.61 cm [ sd , 9.81 ] to 16.46 cm [ sd , 10.06 ] ; p<0.001 ] in group 2 .
the psa level had decreased by 48.4% ( from 3.30 ng / ml [ sd , 2.09 ] to 1.75 ng / ml [ sd , 1.33 ] ; p<0.001 ) in group 1 and by 49.4% ( from 2.67 ng / ml [ sd , 1.82 ] to 1.35 ng / ml [ sd , 0.92 ] ; p<0.001 ) in group 2 .
however , 1 year after discontinuation of dutasteride , the psa level had increased up to 108.2% of the baseline level ( from 1.35 ng / ml [ sd , 0.92 ] to 2.89 ng / ml [ sd , 2.10 ] ; p<0.001 ) in group 2 ( fig .
the changes in ipss , prostate volume , and psa over time also did not differ significantly between groups 1 and 2 ( table 2 ) .
patients discontinued dutasteride in group 2 owing to adverse events , including loss of libido ( n=9 ) or erectile dysfunction ( n=17 ) , lack of therapy efficacy ( n=7 ) , abnormal ejaculation ( n=5 ) , and gynecomastia ( n=1 ) .
these symptoms may be associated with bph , which causes extrinsic compression of the prostatic urethra leading to impaired voiding .
bph is a common disease in aging men that leads to deterioration in symptoms , acute urinary retention , bph - related prostatic surgery , gross hematuria , urinary tract infection , bladder stones , and renal insufficiency .
men who have a prostate volume of more than 30 ml are more likely to have moderate - to - severe symptoms ( 3.5 times ) , decreased flow rates ( 2.5 times ) , and acute urinary retention ( 3 - 4 times ) than are men with a prostate volume of less than 30 ml .
bph can significantly affect quality of life in a negative direction , thus requiring treatment .
bph can be managed medically with alpha - blockers , 5-ari , or a combination of both .
alpha - blockers relax the smooth - muscle tone in the prostate and bladder neck .
however , alpha - blockers do not provide long - term reduction in the risk of acute urinary retention or bph - related surgery .
the main role of 5ari is to induce glandular epithelial atrophy , which causes volume reduction in the prostate .
5ari is responsible for impeding the conversion of testosterone to dht by inhibiting the nuclear - bound steroid 5-reductase ( 5ar ) isoenzymes .
both normal prostate development and hyperplasia of the prostatic transitional zone are regulated by dht .
men taking 5ari have a 57% reduction in the risk of acute urinary retention compared with those taking placebo and a 34% reduction in the risk of surgery .
dutasteride results in a reduction of 20% or more in the size of the prostate and a reduction of 48% in the risk of bph - related surgery . in our study ,
total ipss improvement and prostate volume reduction were evident in all men after treatment with dutasteride 0.5 mg .
few reports have discussed the effect of discontinuation of 5ari on luts , prostate volume , and psa level .
stoner   demonstrated that the prostate volume returned to near the baseline values at 12 weeks after discontinuation of 5ari . in our study , the mean percentage of prostate regrowth had reached 95.5% of the baseline prostate volume 1 year after discontinuation of dutasteride . owing to the complex etiologies of prostate enlargement , the mechanism of prostate regrowth after 5ari withdrawal is not fully understood .
the hyperplastic changes in bph are an androgen - dependent process , and it is possible that the sensitivity to dht is increased or overly activated as a result of the prolonged pharmacologic inhibition of 5-reductase by the 5ari .
androgen receptors , which become more sensitive or up - regulated during treatment with 5ari , may be considered as an alternative mechanism .
our study showed that the total ipss had increased 1 year after cessation of dutasteride .
therefore , we propose that reuse of 5ari is helpful in cases that have aggravated bph symptoms or complications of bph .
the psa level is also commonly used as a screening tool for prostate cancer , and the level of 4.0 ng / ml or greater , or more recently , greater than 2.5 ng / ml , has predictive value for prostate cancer detection .
psa velocity also has some predictive potency for detection of the cancer , especially in men with a psa level of 4.0 ng / ml or less .
the epithelial cells of the prostate secrete psa , and it is synthesized by androgen regulation . at 1 year of 5ari treatment , the treatment results in an approximate 50% decrease in the psa level compared with the baseline serum level . the use of 5ari changes the psa level , and this may distract the clinician 's attention .
the psa level must be multiplied by 2 to maintain its usefulness as a marker .
the psa level increases after discontinuation of 5ari because psa is secreted by the epithelial cells of the prostate . in our study , the psa level had decreased 1 year after combination therapy and had increased 1 year after discontinuation of 5ari . in group 1 ,
two patients had continued psa level elevation , and they were finally diagnosed as having prostate cancer .
thus , regular monitoring of the psa level may be helpful for prostate cancer detection .
although it is not mandatory , we suggest measuring prostate volume by using trus in selected patients with aggravated bph symptoms or a high psa level .
trus can provide psa density , which helps clinicians make decisions about further evaluations such as prostate biopsy .
the limitations of this study include it being a retrospective review and having a small number of cases .
prospective randomized clinical trials with a larger number of cases are needed to fully determine the effect of discontinuing 5ari .
maximal urinary flow rate is needed to evaluate the changes in urinary symptoms with the use of 5ari .
last , our study investigated changes 1 year after the discontinuation of dutasteride , but longer follow - up is necessary to make therapeutic decisions about the effect of 5ari .
our study showed that withdrawal of 5ari during combination therapy resulted in prostate regrowth and deterioration of luts .
the psa level was reduced by the use of 5ari , but discontinuation of the drug resulted in an increase in the psa level . as a result , regular checkup of the ipss and psa level may be helpful for all patients who continue or discontinue use of 5ari .
we recommend measuring prostate volume by using trus in selected patients with aggravated bph symptoms or a high psa level .
 purposeto assess changes in lower urinary tract symptoms ( luts ) , prostate volume , and serum prostate - specific antigen ( psa ) after discontinuation of 5-alpha reductase inhibitor ( 5ari ) combination therapy in patients with benign prostatic hyperplasia ( bph).materials and methodsfrom december 2003 to december 2012 , data were collected retrospectively from 81 men more than 40 years of age with moderate to severe bph symptoms ( international prostate symptom score [ ipss]8 ) . 
 the men were classified into group 1 ( n=42 ) and group 2 ( n=39 ) according to the use of 5ari therapy . 
 a combination of dutasteride 0.5 mg with tamsulosin 0.2 mg was given daily to all patients for 1 year . 
 for the next 1 year , group 1 ( n=42 ) received the combination therapy and group 2 ( n=39 ) received tamsulosin 0.2 mg monotherapy only . 
 the ipss , prostate volume , and psa level were measured at baseline and at 12 and 24 months according to the use of dutasteride.resultsdiscontinuation of dutasteride led to significant deterioration of luts , increased prostate volume , and increased psa level . 
 the repeated - measures analysis of variance showed that the changes in ipss , prostate volume , and psa level over time also differed significantly between groups 1 and 2 ( p<0.001).conclusionswithdrawal of 5ari during combination therapy resulted in prostate regrowth and deterioration of luts . 
 the psa level is also affected by the use of 5ari . 
 therefore , regular check - up of the ipss and psa level may be helpful for all patients who either continue or discontinue the use of 5ari . 