DISCUSSION
Benign prostatic hyperplasia is a disease condition common in aging men. This disease can cause a reduction in the quality of life of these men and may rarely be fatal. Medical treatments have been utilised for this condition and where indicated various surgical procedures are available. This prospective study compared the efficacy of monotherapies with combination therapy of tamsulosin and finasteride in the medical treatment of BPH in Nigerian men seen in Lagos University Teaching Hospital over a period of 18 months.
The age range for the study was 44 to 81 years with a mean of 61.7 years. This compares favourably with recent local study43 with mean age of 66 years as well as the CombAT study17 and McConnell et al47.
IPSS
There was a progressive reduction in the IPSS in all groups studied. The percentage reductions in IPSS at 3months were 42.59%, 41.85%, 40.61% in the tamsulosin, finasteride and combination groups respectively. This differences between the groups at 3 months was however not statistically significant (p=0.72).
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At 6 months the percentage reductions in IPSS were 47.88%, 56.88%, 62.25% in the tamsulosin, finasteride and combination groups respectively. This reduction in IPSS was statically significant in each group compared to baseline values (p<0.01); thereby indicating that each form of therapy was effective in the reduction of IPSS score. However when this reduction in all 3 groups were compared together, there was no statistically significant difference thereby indicating that the 3 forms of treatment had comparable efficacy on the reduction of IPSS.
Tamsulosin produced the greatest reduction in IPSS at 3 months while at 6 months the greatest reduction in IPSS score occurred in the combination group, followed by the finasteride group. This is similar to the 6 months data of The Veteran Affair Cooperative Study61 which showed the greatest reduction in IPSS in the combination group(terazosin and finasteride) which was better than the monotherapies (terazosin or finasteride). Similarly the result at 6 months in the 4 year CombAT17 study showed the greatest reduction in IPSS in the combination group and the least reduction in the monotherapy groups. This study however did not show a statistically significant difference at 6 months between combination and monotherapies because of the duration of the study.
There was also progressive improvement in the quality of life score at 3 and 6 months. The percentage change in quality of life score were 38.10%, 36.93%,
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18.6% at 3 months and 36.26%, 36.72%, 24.10%. at 6 months in the tamsulosin, finasteride and combination groups respectively. These changes compared between the three groups at 6 months however did not achieve statistical significance (p= 0.20). It is however possible that a true statistical significance may be seen if the study has been of longer duration.
The improvement within each group was however statistically significant (p≤0.01) implying that individual therapy effectively improves quality of life.
The greatest improvement in quality of life score was in the tamsulosin group while the least improvement was in the combination group. This may not be unconnected to the higher occurrence of side effects in the combination group.
The finding in this study corroborates the improvement in quality of life score in another study17.
FLOW RATE
There was progressive improvement in the flow rate in all groups at 3 and 6 months. Compared to their baseline flow rate in each group caused a statistically significant improvement except for finasteride. The change in flow rate was most noticeable in the combination group at 3 months and this improvement was maintained at 6 months. This early improvement may be due to the synergistic effect of the tamsulosin and finasteride. The monotherapies had a gradual increase in flow rate at 3 and 6 months. Tamsulosin monotherapy had the greatest
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increase in flow rate while finasteride monotherapy had the least increase at 6 months.
This finding may be related to the mechanism of action of alpha-blocker which causes relaxation of smooth muscle in the prostate and bladder neck while 5 alpha reductase inhibitor (finasteride) causes a gradual reduction in prostate volume by inhibiting the production of dihydrotestosterone.1 The findings in this study is similar to the 6month data in The Veteran Affair Cooperative Study61 and the CombAT17 study. The greatest improvement was in the combination arm in these studies. 17,61
The multi-centered study17 however utilised dutasteride while in this study finasteride was used for the combination arm. It can be concluded from this study that tamsulosin monotherapy and combination therapy gives similar improvement in flow rate in the short term. It is clear that combination therapy is better than finasteride monotherapy in the short term.
PROSTATE VOLUME
The mean prostate volume at baseline in this study was similar to the mean baseline prostate volume in the CombAT17 study but higher (approximately 30-45% higher) than the mean baseline prostate volume in the Veterians Affairs Cooperative Study61.
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There was a gradual increase in prostate volume in the tamsulosin monotherapy group at 3 and 6 months. There was no significant change in prostate volume in the finasteride monotherapy and combination groups at 3 months but there was a decrease at 6 months. There was no statistically significant difference between combination therapy group and finasteride monotherapy group at 6 months.
However combination therapy achieved a statistically significant reduction in prostate volume compared to tamsulosin monotherapy group which recorded an increase. Compared to the baseline values, none of the changes within each group reached statistical significance.
The percentage change in prostate volume at 3 months were 3.94%, -0.89%
0.54% for the tamsulosin, finasteride and combination groups respectively were not significant. There was percentage increase in tamsulosin monotherapy at 6 months of 9.54% and decrease of 10.21%, 11.83% in the finasteride monotherapy and combination groups respectively. Combination therapy achieved similar reduction in prostate volumes as finasteride monotherapy. Combination therapy was superior to tamsulosin monotherapy in achieving volume reduction.
A study by Nacey et al63 recorded prostate volume reduction of 25%,27% and 43% at 6 months, 1 year and 3 years respectively in men on 5 milligrams of finasteride. This was corroborated by another study64 which noted a reduction in prostate volume of 21% in men on finasteride for 6 months. This correlated with reduction in the glandular epithelium and this was regarded as the
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mechanism for prostate volume reduction. Another study12 however recorded a lower 8% reduction in prostate volume in 6 months and 18% decrease at 4 years in men on finasteride. It is noted that most of the prostate volume reduction in this study12 occurred in the first year.
The Veterans Affair Cooperative Study61 recorded a similar trend of increase in prostate volume in the terazosin group and decrease in the finasteride and combination groups although over a longer period of 52weeks.
This pattern of increase in the prostate volume in alpha-blocker group and reduction in the 5 alpha reductase inhibitor group and combination group has been noted in other studies17, 47.
Prostate volume was assessed via the transrectal route in MTOPS47 Veterans Affair Cooperative Study61 and CombAT17 study while the transabdominal route was done in this study. There was no significant difference between these two ultrasound routes for prostate volume measurement. These studies are over a longer period of time giving the 5 alpha reductase inhibitors a longer time to have a greater effect on prostate volume. It is clear that alpha-blockers do not affect prostate volume or its progression. It is concluded that finasteride monotherapy and combination therapy both achieve reduction in prostate volume but may require a longer period for this effect to be significant.
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POST VOID RESIDUAL URINE
There was a decrease in the post void residual urine in all groups. Combination therapy had the greatest reduction in post void residual urine while finasteride had the least reduction. This difference between the groups was statistically significant and is obviously due to the additive effect of the alpha blocker in the combination therapy.
This agrees with another study43 that noted an increase of 24% in voided volume of urine in patients on alpha-blockers. It can be concluded that monotherapies and combination therapy lead to a reduction in post void residual urine.
SIDE EFFECTS
The drugs were well tolerated with only 2 (2.22%) patients withdrawing due to side effects. This is lower than withdrawal of 6% due to drug adverse event in the CombAT study17. The CombAT study was for 4 years.
Dizziness occurred more in patients on tamsulosin than combination though this difference was not statistically significant. Recent local studies42, 43 also recorded postural hypotension of 5% and11% on patient on alpha-blocker.
Patients in all the groups experienced reduction in ejaculate volume, weak erection and reduced libido. These were more in the combination group. The difference between the group was however not statistically significant. Erectile
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dysfunction is the only side effect on account of which 2 patients withdrew from the combination therapy arm of the study.
An international study17 noted drug related adverse events in 28%, 21% and 19%
in the combination, dutasteride and tamsulosin arms respectively.
Overall in this study most of the drug side effects were more in the combination arm than the monotherapy. This may be the additive effect of alpha-blocker and 5 alpha reductase inhibitor. This is consistent with other studies.17, 19
Two patients (2.22%) in the tamsulosin monotherapy and two patients (2.22%) in the finasteride monotherapy experienced acute urinary retention (AUR). These patients had spontaneous AUR with no obvious precipitants. No patient in the combination therapy group experienced acute urinary retention. Patient on finasteride experienced AUR earlier in the study; this may be before the volume reducing effect of the drug became effective.
Four patients (4.44%) in the finasteride monotherapy group withdrew due to perceived lack of effectiveness; this represents treatment failure in these patients.
Patients with a need for immediate improvement in symptoms may not benefit from finasteride due to the known mechanism of action via reduction in prostate volume which occur over a period of months. No patient in the tamsulosin monotherapy group or combination therapy group withdrew due to perceived lack of effectiveness. This is consistent with the relaxation of the smooth muscle
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which occurs within hours with alpha blockade and thus may provide an earlier improvement in symptoms.
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