|Year : 2006 | Volume
| Issue : 2 | Page : 130-134
A comparative study of fixed dose of Tamsulosin with finasteride vs Tamsulosin with dutasteride in the management of benign prostatic hyperplasia
NK Mohanty, Uday Pratap Singh, Nitin K Sharma, RP Arora, Vindu Amitabh
Dept. of Urology, V. M. Medical College and Safdarjang Hospital, New Delhi, India
N K Mohanty
C-Ii/124, Moti Bagh-I, New Delhi - 110 021
| Abstract|| |
OBJECTIVE: The aim of this study was to compare the efficacy, safety and tolerability of Dutasteride vs Finasteride in a fixed dose combination, with a uro-selective a-blocker Tamsulosin, in the management of symptomatic BPH associated with LUTS. MATERIALS AND METHODS: 105 males between 40-80 years, clinically diagnosed as Benign prostatic hyperplasia (BPH) having a baseline evaluation of their IPSS, UFR, PSA, LFT, KFT, sex health, ultrasound of prostate and PVUV, were randomized to receive a fixed dose combination therapy of Tamsulosin (0.4 mg) with Finasteride (5 mg), vs Tamsulosin (0.4 mg) with Dutasteride (0.5 mg), daily for six consecutive months. Follow- up at the end of the 2nd, 4th, 8th, 12th and 24th week was done with IPSS, UFR, PSA, ultrasound of Prostate, PVUV and sex health. RESULTS: There were five dropouts, three from the Finasteride arm and two from Dutasteride arm, leaving a total of 100 patients for the final evaluation. Patients in both the groups showed improvement in their symptoms score and urine flow rate from the baseline, but those with the Dutasteride combination not only showed much better improvement in their symptoms score and urine flow, but were also relieved of their obstructive symptoms earlier (10-14 days) than seen in the Finasteride group (24-35 days). None of the patients had acute retention of urine (AUR) during the trial. The post void urine volume was decreased more in the Dutasteride group, than in patients with Finasteride. Sexual dysfunction incidence was same in both the groups. Approximately 50% reduction in the PSA level was seen in both the groups, while LFT did not show significant difference from the baseline, in either group. Both the drugs were well tolerated, with the patient's good compliance and with no drop-out due to adverse effects. CONCLUSION : A combination of a-adrenergic blocker and 5-ARI is the best therapeutic option for medical management of BPH as it is safe, effective and well tolerated. A combination of Tamsulosin with Dutasteride results in early symptomatic relief and low PVUV, than seen with the Tamsulosin with Finasteride combination.
Keywords: Dutasteride, finasteride, tamsulosin
|How to cite this article:|
Mohanty N K, Singh UP, Sharma NK, Arora R P, Amitabh V. A comparative study of fixed dose of Tamsulosin with finasteride vs Tamsulosin with dutasteride in the management of benign prostatic hyperplasia. Indian J Urol 2006;22:130-4
|How to cite this URL:|
Mohanty N K, Singh UP, Sharma NK, Arora R P, Amitabh V. A comparative study of fixed dose of Tamsulosin with finasteride vs Tamsulosin with dutasteride in the management of benign prostatic hyperplasia. Indian J Urol [serial online] 2006 [cited 2014 Mar 8];22:130-4. Available from: http://www.indianjurol.com/text.asp?2006/22/2/130/26567
Benign prostatic hyperplasia (BPH), one of the most common disease of ageing men, can be associated with bothersome lower urinary tract symptoms (LUTS) that affect the quality of life. As surgery for BPH is limited to only 25-30% of those patients with severe obstructive symptoms, medical management remains the first line of treatment for the remaining 70-75% of these patients.
Since 1970, alpha adrenergic blockers have emerged as an effective therapeutic option for BPH. Although use of a-blockers remained the predominant form of medical therapy, the first drug approved for BPH therapy in 1992 was 5 a-reductase inhibitor (5-ARI) - Finasteride. Uro-selective alpha-adrenergic blockers like Tamsulosin, introduced in 2000, proved to be more specific with fewer side effects. Veteran affairs (VA) cooperative study represented the first large scale comparison of an a-blocker, 5-ARI and combination of both.
PLESS showed the indication of use of 5-ARI (Finasteride) in the treatment of BPH, focussing that Finasteride does reduce disease progression, acute urinary retention (AUR) and need for surgery for symptomatic progression of prostate. This study further showed Finasteride reduced AUR by 50%, as compared to placebo.
MTOPS (Medical therapy of prostate symptoms) established the role of combination therapy in the management of BPH and defined the role of alpha-blockers for symptom- relief, while 5-ARI was suggested for prevention of disease progression, surgery and AUR. Therefore, a combination therapy is the most effective therapeutic option for BPH symptoms and progression reduction.
At present, two 5-ARI are available - Finasteride (Isoenzyme type 2 inhibitor) and Dutasteride (Isoenzyme type 1 and 2 inhibitor). The dual inhibition by Dutasteride leads to near complete suppression of serum dihydrotestosterone (DHT) > 90%, whereas Finasteride reduces 70% of serum DHT., This greater degree of suppression of serum DHT also reduces the intraprostatic DHT milieu by Dutasteride, more than Finasteride.
In a 12 month study (Glaxo-Smithkline protocol AR 140001), Dutasteride compared with Finasteride produced numerically significant and early improvement of urinary flow rate and symptom score. Since Dutasteride inhibits both the isoenzymes type 1 and 2, a placebo- controlled clinical trial showed that Dutasteride reduces prostate volume by 26%, improves symptoms score, urinary flow rate and reduced incidence of acute urinary retention and likelihood of surgery for BPH.,
We undertook an open label randomized controlled study, with the main aim of our study being to compare the efficacy, safety, tolerability and time to early improvement in clinical symptoms, with a combination of Tamsulosin with Finasteride vs Tamsulosin with Dutasteride, in a fixed dose schedule.
| Materials and Methods|| |
Between Jan. 2004 till Dec 2005, out of a total number of 287 patients of BPH attending the Urology Department of our hospital, 105 patients with symptomatic BPH but not having absolute indication for surgery, between the age group of 40-80 years of age, were included in our study. The rest of the 182 patients were subjected to trans urethral resection prostate (TURP). All these patients were clinically evaluated using the international prostate symptom score (IPSS), sex health, vital parameters, ultrasound weight of prostate, post void urine volume (PVUV), uroflow rate (UFR), direct rectal examination (DRE), serum prostate specific antigen (PSA), liver function tests (LFT), kidney function tests (KFT), fasting blood sugar (FBS) and urine for routine and culture sensitivity, as the baseline.
Any patient with clinically suspected or diagnosed prostate cancer was not included in this study.
All the 105 patients gave consent for the study. A controlled randomization of the patients was done alternately into two groups - A and B.
In Group-A- A total of 53 patients received Tamsulosin (0.4 mg) + Finasteride (5 mg) (Urimax-F), while in Group-B - A total of 52 patients received Tamsulosin (0.4 mg) + Dutasteride (0.5 mg) (Urimax-D), once a day orally at night, for six months consecutively
The baseline demographic features were similar in both the groups.
Both the groups were followed up at the end of the 2nd, 4th, 8th, 12th and 24th week for clinical assessment using IPSS, sex health. weight of prostate, PVUR, LFT, UFR, KFT, PSA and DRE. Adverse effects if any, were recorded.
Statistical analysis was done using the graphed statistical package for windows. Uroflowmetry parameters and vital signs were analyzed using one- way ANOVA, followed by Tukey-Kramer Multiple Comparisons tests. Prostate volume, post void residual urine and PSA were analyzed by the Student's 't' test. IPSS was analyzed non-parametrically by the Kruskal-Wallis test, followed by the Dunns test. All computations were done at a 5% level of statistical significance.
| Results|| |
Three patients from Group A and two patients from Group B were lost to follow- up, leaving a total of 100 patients, 50 in each group for evaluation.
There was no significant decrease in the systolic or diastolic blood pressure and pulse rate, at 12th or 24th week vs the baseline, in both the groups [Table - 1].
In Group-A, there was a significant decrease in the IPSS obstructive and irritative scores, at end of the 12th and 24th weeks, vs the baseline ( P <0.001). These changes observed were reflected in total IPSS, at the end of the 12th and 24th weeks ( P <0.01).
In Group B, significant decrease in the IPSS obstructive and irritative scores were observed at the end of the 12th and 24th weeks vs the baseline ( P <0.001). There changes observed, were reflected in total IPSS at the end of the 12th and 24th weeks ( P <0.01).
When IPSS was compared between the two Groups A and B, it was observed that IPSS obstructive score and IPSS total score showed a greater reduction in Group B compared to Group A [Figure - 1][Figure - 2]. This reduction was statistically significant at both, week -12 ( P <0.05) and week- 24 ( P <0.001) in Group B, compared to Group A, at the respective weeks. The decrease in IPSS irritative scores was similar in both the groups [Table - 2].
Significant increase ( P <0.05) in maximum flow rate (MFR) was observed in Group B as compared to Group A, at the end of the 12th and 24th weeks. Decrease in hesitancy times was significantly greater ( P <0.05) in Group B, than in Group A. A significant decrease in maximum voided volume was also observed in Group B, as compared to Group A. Again, an increase in average flow rate (AFR) was better in Group B, compared to that observed in Group A. The rest of the parameters were equivocal in both the groups [Table - 3].
Prostate volume/ PVUV/ PSA
PSA, prostate volume and PVUV showed significant decrease ( P <0.01) in Group-A vs. baseline.
In Group-B - PSA, PVUV showed a significant reduction ( P <0.001) vs. baseline, while prostate volume also showed a significant reduction ( P <0.01) vs. baseline.
When the above parameters were compared between the two groups, prostate volume and PSA decrease was similar in either groups, but decrease in post void urinary volume was significantly more in Group-B, than in Group-A [Table - 4].
l Patients in Group-B experienced improvement in their urinary problems much earlier i.e. within 10-14 days of taking therapy, as compared to 24-35 days among patients in Group-A.
l 88% of patients in Group-B experienced improvement in symptom score, urine flow and overall well- being, as compared to 74% in Group-A, at the end of this study.
Male sexual health questionnaire (MSHQ) was adopted. 6 patients in Group-A complained of sexual dysfunction in the form of transient impotency and decrease in sexual libido in 4 and dry ejaculation in 2. Similar was the incidence in Group-B, where five patients complained of sexual dysfunction in the form of decreased libido, impotency among 4 and one reported dry ejaculation.
No significant changes were observed in either group in their liver function tests, from the baseline.
| Discussion|| |
Though Dutasteride inhibits isoenzyme type 1 and 2, the former being present in liver and skin apart from prostate, no significant differences between the Dutasteride and Finasteride groups was observed in LFT levels, from the baseline. A similar observation was seen in our study. None of our patients in either group reported bone pain or backache during the course. Combination therapy appears to be more effective in relieving and preventing the progression symptoms and risk of AUR, than 5-ARI monotherapy. We observed similar results in our study. Studies show that the serum PSA level decreases by 57.5% vs the baseline with Dutasteride, which was also observed in our study. Sexual function (impotence, decreased libido, ejaculation disorders and gynaecomastia) is affected by 5-ARI, but are transient and reversible., The same was observed in our study.
A long term follow up of 5 years using 5-ARI, has shown it to be safe, well- tolerated, effective in reducing prostate volume and improving flow rate.,,
The most significant observation in our study was the early relief from urinary obstructive symptoms in the Dutasteride group, than seen among patients with Finasteride. This may be attributed to the fact that Dutasteride reduces serum and intraprostatic DHT much more and faster than Finasteride, resulting in a better urinary flow, lower PVUV, less hesitancy time and voided volume. The PSA reduction was similar with both 5-ARI. Drug compliance was good among patients from both the groups. The percentage of reduction in size of the prostate volume did not show much differences in either groups, but post residual urine volume reduction was found to be more in Group B patients having the Dutasteride combination, than seen in Group A patients taking Finasteride. The incidence of sex health dysfunction were transient in the nature of low magnitude and intensity in both the groups and none of the patients in either group had AUR during the therapy.
| Conclusion|| |
The exact place of the combination therapy in medical management of BPH remains to be precisely determined, as now a days the concept of BPH as the disease is changing fast. BPH is no longer considered as a simple benign enlargement of the prostate gland, but is a chronic, complex disease, which may need more than one agent to take care of the different symptomatologies i.e., LUT, BOO, PSA and sex health.
The data from our study gives some rational and convincing results in favour of the use of a combined treatment for BPH (Tamsulosin and Dutasteride), as this combination is not only safe, well- tolerated with low adverse effects, but also results in much earlier relief of LUTS due to better improvement of IPSS obstructive symptoms, UFR and reduction in PVRU, than observed with the Tamsulosin and Finasteride combination.
| Acknowledgment|| |
We acknowledge M/s Cipla Ltd. for supporting this study, by supplying free medicines to the patients, necessary stationeries and statistical data analysis.
| References|| |
|1.||Rochborn CG, McConnell JD. Etiology, pathophysiology, epidemiology and natural history of BPH. Campbell Urology 8th ed, 2002. p. 1297-330. |
|2.||Brukewitz R, Girman CJ, Fowler J. The effect of Finasteride on bother and other health related quality of life aspects associated with benign prostate hyperplasia. Urology 1999;546:670-8. |
|3.||Mc Connell JD, Roechrhorn CG, Bautista OM, Gerald L Andriole Jr, Christopher H, et al . The long term effect of Doxazosin, Finasteride and combination therapy on clinical progression of benign prostatic hyperplasia. N Engl J Med 2003;349:2387-98. |
|4.||McConnell JD, Bruskewitz R, Walsh P. The effect of Finasteride on the risk of acute urinary retention and the need for surgical treatment among men with BPH. N Engl J Med 1998;338:557-63. |
|5.||Bartsch G, Rittmaster RS, Klocker H. Dihydrotestosterone and the concept of 5 a-reductase inhibition in human benign Prostatic hyperplasia. Eur Urol 2000;37:367-80. [PUBMED] [FULLTEXT]|
|6.||Andriole GL, Kirby R. Safety and tolerability of the dual 5a-reductase inhibitor Dutasteride in the treatment of BPH. Eur Urol 2003;44:82-8. [PUBMED] [FULLTEXT]|
|7.||Rosen RC, Catania J, Pollack L, Althrof S. Male sexual health questionnaire (MSHQ) scale and psychometric validation. Urology 2004;64:777-82. |
|8.||Rochborn CG, Marks LS, Tom F, Freedman S, Tuttle J, Gittleman M, et al . Efficacy and safety of Dutasteride in the four year treatment of men with benign prostatic hyperplasia. Urology 2004;63:709-15. |
|9.||McConnell JD. The long term effects of medical therapy on the progression of BPH results from the MTOPS trial. J Urol 2002;167:1042. |
|10.||Rochborn CG, Boyle P, Nickel JC, Hoefiner K, Andriole G. Efficacy and safety of a dual inhibitor of 5-a reductase type 1 and 2 (Dutasteride) in men with BPH. Urology 2002;60:434-41. |
|11.||Marberger MJ. Long term effects of Finasteride in patients with benign Prostatic hyperplasia - A double blind, placebo controlled multi center study. Urology 1998;51:677-86. [PUBMED] [FULLTEXT]|
[Figure - 1], [Figure - 2]
[Table - 1], [Table - 2], [Table - 3], [Table - 4]