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RE: Effect of finasteride on serum levels of androstenedione, testosterone and their 5α-reduced metabolites in men at risk for prostate cancer
Journal of Steroid Biochemistry & Molecular Biology 138 (2013) 462
Contents lists available at ScienceDirect
Journal of Steroid Biochemistry and Molecular Biology journal homepage: www.elsevier.com/locate/jsbmb
Commentary
RE: Effect of finasteride on serum levels of androstenedione, testosterone and their 5␣-reduced metabolites in men at risk for prostate cancer Abdulmaged M. Traish a,b,∗ , Abraham Morgentaler c a
Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA Department of Urology, Boston University School of Medicine, Boston, MA, USA c Division of Urology, Men’s Health Boston, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA b
a r t i c l e
i n f o
Article history: Received 11 April 2013 Accepted 23 June 2013 Keywords: 5␣-reductase Finasteride Testosterone 5␣-DHT Prostate cancer Diagnostic marker
Stanczyk et al. [1] investigated the effects of finasteride on the plasma levels of androgen metabolites in men suspected to be at risk for prostate cancer (PCa). Based on the data from the placebo arm of the Reduce Trial [2] neither testosterone nor ␣-DHT plasma levels correlated with development of PCa. Thus for the authors to suggest that peripheral circulating levels of 3␣-diol G or ␣-DHT-S may serve as a diagnostic markers in PCa is, at best, unsupported if not unwarranted. Moreover, unlike other studies [3], this study did not measure intra-prostatic tissue levels of these androgen metabolites. Furthermore, there was no evidence to support the suggestion that ␣-DHT sulphate in the periphery is readily converted to ␣-DHT by sulfatases in the prostate. Since plasma levels of ␣-DHT are significantly lower than intraprostatic tissue and free (unbound) ␣-DHT is very low, it is unlikely that plasma ␣-DHTS will contribute significantly to the physiology of the prostate. More importantly, the premise that DHT sulphate is analogous to the pool of inactive estrone sulphate, which can be readily converted to estrone by sulfatase, and subsequently converted to the more potent estrogen, estradiol, is unlikely comparison due to binding of ␣-DHT to SHBG in plasma with very high affinity compared to other steroids, resulting in little or no free available fraction of ␣-DHT to reach the prostate. The recent work of Olsson et al. [3]
∗ Corresponding author at: Department of Biochemistry, Boston University School of Medicine, Laboratories for Sexual Medicine, Institute for Sexual Medicine, 715 Albany Street, W607, Boston, MA 02118, USA. Tel.: +1 617 638 4578. E-mail address: [email protected] (A.M. Traish). 0960-0760/$ – see front matter © 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jsbmb.2013.06.013
demonstrated that “there was no significant correlation between prostate weight and peripheral serum DHT” and for this reason the aforementioned premise remains unsupported. Since Stanczyk et al. [1] measured only peripheral metabolites, leaving much doubt regarding the conclusions made here in. Olsson et al. [3] noted that “No correlation was found between intra-prostatic tissue ␣DHT levels and the local prostatic or the peripheral serum DHT concentrations. The only significant correlation observed between intra-prostatic levels of androgen metabolites were between ADT and ADT-G and between 3␣-diol-3G and 3␣-diol-17G”. Since only peripheral levels of these derivatives were measured, the conclusions reached by Stanczyk et al. [1] are not well supported by the data presented. The authors suggestion that 3␣-diol G or ␣-DHT S may serve as a potential diagnostic marker of intraprostatic 5␣reductase activity during treatment of patients with 5␣-reductase inhibitors remains highly questionable. References [1] F.Z. Stanczyk, C.G. Azen, M.C. Pike, Effect of finasteride on serum levels of androstenedione, testosterone and their 5␣-reduced metabolites in men at risk for prostate cancer, Journal of Steroid Biochemistry and Molecular Biology 138C (March) (2013) 10–16. [2] R.L. Muller, L. Gerber, D.M. Moreira, G. Andriole, R. Castro-Santamaria, S.J. Freedland, Serum testosterone and dihydrotestosterone and prostate cancer risk in the placebo arm of the Reduction by Dutasteride of Prostate Cancer Events trial, European Urology 62 (November (5)) (2012) 757–764. [3] M. Olsson, L. Ekström, C. Guillemette, A. Belanger, A. Rane, O. Gustafsson, Correlation between circulatory, local prostatic, and intra-prostatic androgen levels, Prostate 71 (June (9)) (2011) 909–914.
Contents lists available at ScienceDirect
Journal of Steroid Biochemistry and Molecular Biology journal homepage: www.elsevier.com/locate/jsbmb
Commentary
RE: Effect of finasteride on serum levels of androstenedione, testosterone and their 5␣-reduced metabolites in men at risk for prostate cancer Abdulmaged M. Traish a,b,∗ , Abraham Morgentaler c a
Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA Department of Urology, Boston University School of Medicine, Boston, MA, USA c Division of Urology, Men’s Health Boston, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA b
a r t i c l e
i n f o
Article history: Received 11 April 2013 Accepted 23 June 2013 Keywords: 5␣-reductase Finasteride Testosterone 5␣-DHT Prostate cancer Diagnostic marker
Stanczyk et al. [1] investigated the effects of finasteride on the plasma levels of androgen metabolites in men suspected to be at risk for prostate cancer (PCa). Based on the data from the placebo arm of the Reduce Trial [2] neither testosterone nor ␣-DHT plasma levels correlated with development of PCa. Thus for the authors to suggest that peripheral circulating levels of 3␣-diol G or ␣-DHT-S may serve as a diagnostic markers in PCa is, at best, unsupported if not unwarranted. Moreover, unlike other studies [3], this study did not measure intra-prostatic tissue levels of these androgen metabolites. Furthermore, there was no evidence to support the suggestion that ␣-DHT sulphate in the periphery is readily converted to ␣-DHT by sulfatases in the prostate. Since plasma levels of ␣-DHT are significantly lower than intraprostatic tissue and free (unbound) ␣-DHT is very low, it is unlikely that plasma ␣-DHTS will contribute significantly to the physiology of the prostate. More importantly, the premise that DHT sulphate is analogous to the pool of inactive estrone sulphate, which can be readily converted to estrone by sulfatase, and subsequently converted to the more potent estrogen, estradiol, is unlikely comparison due to binding of ␣-DHT to SHBG in plasma with very high affinity compared to other steroids, resulting in little or no free available fraction of ␣-DHT to reach the prostate. The recent work of Olsson et al. [3]
∗ Corresponding author at: Department of Biochemistry, Boston University School of Medicine, Laboratories for Sexual Medicine, Institute for Sexual Medicine, 715 Albany Street, W607, Boston, MA 02118, USA. Tel.: +1 617 638 4578. E-mail address: [email protected] (A.M. Traish). 0960-0760/$ – see front matter © 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jsbmb.2013.06.013
demonstrated that “there was no significant correlation between prostate weight and peripheral serum DHT” and for this reason the aforementioned premise remains unsupported. Since Stanczyk et al. [1] measured only peripheral metabolites, leaving much doubt regarding the conclusions made here in. Olsson et al. [3] noted that “No correlation was found between intra-prostatic tissue ␣DHT levels and the local prostatic or the peripheral serum DHT concentrations. The only significant correlation observed between intra-prostatic levels of androgen metabolites were between ADT and ADT-G and between 3␣-diol-3G and 3␣-diol-17G”. Since only peripheral levels of these derivatives were measured, the conclusions reached by Stanczyk et al. [1] are not well supported by the data presented. The authors suggestion that 3␣-diol G or ␣-DHT S may serve as a potential diagnostic marker of intraprostatic 5␣reductase activity during treatment of patients with 5␣-reductase inhibitors remains highly questionable. References [1] F.Z. Stanczyk, C.G. Azen, M.C. Pike, Effect of finasteride on serum levels of androstenedione, testosterone and their 5␣-reduced metabolites in men at risk for prostate cancer, Journal of Steroid Biochemistry and Molecular Biology 138C (March) (2013) 10–16. [2] R.L. Muller, L. Gerber, D.M. Moreira, G. Andriole, R. Castro-Santamaria, S.J. Freedland, Serum testosterone and dihydrotestosterone and prostate cancer risk in the placebo arm of the Reduction by Dutasteride of Prostate Cancer Events trial, European Urology 62 (November (5)) (2012) 757–764. [3] M. Olsson, L. Ekström, C. Guillemette, A. Belanger, A. Rane, O. Gustafsson, Correlation between circulatory, local prostatic, and intra-prostatic androgen levels, Prostate 71 (June (9)) (2011) 909–914.