Abstract
Purpose: Androgens are essential for prostatic growth and development but they also have a significant role in prostate disease pathogenesis. Dihydrotestosterone, the primary prostatic androgen, is transformed from testosterone by types 1 and 2 5α-reductase and, thus, a potential therapeutic benefit could be achieved through the inhibition of 5α-reductase. Materials and Methods: A literature review was performed using PubMed®/MEDLINE® and congress abstracts to examine evidence supporting the potential of 5α-reductase inhibitors in the primary prevention of prostate cancer and in limiting the progression of diagnosed disease. Results: Prostate disease development is associated with increased expression of each 5α-reductase isoenzyme with over expression of type 1 of particular importance in prostate cancer development and progression. The 2 5α-reductase inhibitors currently clinically available are finasteride, a type 2 5α-reductase inhibitor, and dutasteride, a dual 5α-reductase inhibitor. Dual inhibition by dutasteride has been shown to translate into a greater degree and consistency of dihydrotestosterone suppression compared with finasteride. The Prostate Cancer Prevention Trial showed that finasteride significantly decreased the 7-year risk of prostate cancer in men with prostate specific antigen 3.0 ng/ml or less, while the ongoing Reduction by Dutasteride of Prostate Cancer Events study is assessing whether dutasteride decreases the risk of biopsy detectable prostate cancer in men with prostate specific antigen 2.5 to 10 ng/ml and a previous negative biopsy. Small-scale studies have demonstrated potential effects of 5α-reductase inhibition in prostate cancer treatment that warrant further investigation, while dutasteride use in men undergoing expectant treatment is also being examined. Conclusions: The inhibition of 5α-reductase represents a valid target for prostate cancer risk reduction and treatment strategies. The greater suppression of dihydrotestosterone observed with agents that inhibit each 5α-reductase isoenzyme may translate into enhanced outcomes and studies are under way to test this hypothesis.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1235-1242 |
| Number of pages | 8 |
| Journal | Journal of Urology |
| Volume | 179 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 2008 |
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Keywords
- androgens
- cholestenone 5 alpha-reductase
- dihydrotestosterone
- prostate
- prostatic neoplasms
ASJC Scopus subject areas
- Medicine(all)
- Urology
Cite this
The Rationale for Inhibiting 5α-Reductase Isoenzymes in the Prevention and Treatment of Prostate Cancer. / Tindall, Donald J.; Rittmaster, Roger S.
In: Journal of Urology, Vol. 179, No. 4, 04.2008, p. 1235-1242.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The Rationale for Inhibiting 5α-Reductase Isoenzymes in the Prevention and Treatment of Prostate Cancer
AU - Tindall, Donald J.
AU - Rittmaster, Roger S.
PY - 2008/4
Y1 - 2008/4
N2 - Purpose: Androgens are essential for prostatic growth and development but they also have a significant role in prostate disease pathogenesis. Dihydrotestosterone, the primary prostatic androgen, is transformed from testosterone by types 1 and 2 5α-reductase and, thus, a potential therapeutic benefit could be achieved through the inhibition of 5α-reductase. Materials and Methods: A literature review was performed using PubMed®/MEDLINE® and congress abstracts to examine evidence supporting the potential of 5α-reductase inhibitors in the primary prevention of prostate cancer and in limiting the progression of diagnosed disease. Results: Prostate disease development is associated with increased expression of each 5α-reductase isoenzyme with over expression of type 1 of particular importance in prostate cancer development and progression. The 2 5α-reductase inhibitors currently clinically available are finasteride, a type 2 5α-reductase inhibitor, and dutasteride, a dual 5α-reductase inhibitor. Dual inhibition by dutasteride has been shown to translate into a greater degree and consistency of dihydrotestosterone suppression compared with finasteride. The Prostate Cancer Prevention Trial showed that finasteride significantly decreased the 7-year risk of prostate cancer in men with prostate specific antigen 3.0 ng/ml or less, while the ongoing Reduction by Dutasteride of Prostate Cancer Events study is assessing whether dutasteride decreases the risk of biopsy detectable prostate cancer in men with prostate specific antigen 2.5 to 10 ng/ml and a previous negative biopsy. Small-scale studies have demonstrated potential effects of 5α-reductase inhibition in prostate cancer treatment that warrant further investigation, while dutasteride use in men undergoing expectant treatment is also being examined. Conclusions: The inhibition of 5α-reductase represents a valid target for prostate cancer risk reduction and treatment strategies. The greater suppression of dihydrotestosterone observed with agents that inhibit each 5α-reductase isoenzyme may translate into enhanced outcomes and studies are under way to test this hypothesis.
AB - Purpose: Androgens are essential for prostatic growth and development but they also have a significant role in prostate disease pathogenesis. Dihydrotestosterone, the primary prostatic androgen, is transformed from testosterone by types 1 and 2 5α-reductase and, thus, a potential therapeutic benefit could be achieved through the inhibition of 5α-reductase. Materials and Methods: A literature review was performed using PubMed®/MEDLINE® and congress abstracts to examine evidence supporting the potential of 5α-reductase inhibitors in the primary prevention of prostate cancer and in limiting the progression of diagnosed disease. Results: Prostate disease development is associated with increased expression of each 5α-reductase isoenzyme with over expression of type 1 of particular importance in prostate cancer development and progression. The 2 5α-reductase inhibitors currently clinically available are finasteride, a type 2 5α-reductase inhibitor, and dutasteride, a dual 5α-reductase inhibitor. Dual inhibition by dutasteride has been shown to translate into a greater degree and consistency of dihydrotestosterone suppression compared with finasteride. The Prostate Cancer Prevention Trial showed that finasteride significantly decreased the 7-year risk of prostate cancer in men with prostate specific antigen 3.0 ng/ml or less, while the ongoing Reduction by Dutasteride of Prostate Cancer Events study is assessing whether dutasteride decreases the risk of biopsy detectable prostate cancer in men with prostate specific antigen 2.5 to 10 ng/ml and a previous negative biopsy. Small-scale studies have demonstrated potential effects of 5α-reductase inhibition in prostate cancer treatment that warrant further investigation, while dutasteride use in men undergoing expectant treatment is also being examined. Conclusions: The inhibition of 5α-reductase represents a valid target for prostate cancer risk reduction and treatment strategies. The greater suppression of dihydrotestosterone observed with agents that inhibit each 5α-reductase isoenzyme may translate into enhanced outcomes and studies are under way to test this hypothesis.
KW - androgens
KW - cholestenone 5 alpha-reductase
KW - dihydrotestosterone
KW - prostate
KW - prostatic neoplasms
UR - http://www.scopus.com/inward/record.url?scp=40849135468&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=40849135468&partnerID=8YFLogxK
U2 - 10.1016/j.juro.2007.11.033
DO - 10.1016/j.juro.2007.11.033
M3 - Article
VL - 179
SP - 1235
EP - 1242
JO - Journal of Urology
JF - Journal of Urology
SN - 0022-5347
IS - 4
ER -