Change of the 5α/5β ratio of urinary steroid metabolites in benign prostatic hyperplasia patients treated with dutasteride

Takahiro Maeda, Eiji Kikuchi, Masanori Hasegawa, Keiko Homma, Yota Yasumizu, Seiya Hattori, Takeo Kosaka, Kazunobu Shinoda, Akira Miyajima, Mototsugu Oya

Research output: Contribution to journalArticle

Abstract

Background: The effects of the administration of dutasteride (DUT) on steroid metabolite pathways in BPH patients have not been examined. Methods: Urine and blood samples as well as clinical parameters were prospectively collected after the administration of DUT to 60 BPH patients, and after its withdrawal in another set of 25 BPH patients. Urine samples were assessed using gas chromatography/mass spectrometry for the urinary steroid profile (USP), which simultaneously measures 63 steroid metabolites. We examined pharmacological changes in the 5α/5β ratio of urinary metabolites and their relationships with clinical parameters in patients treated with DUT. Results: The mean urinary androsterone/etiocholanolone (An/Et) ratio in sex-steroid pathways significantly decreased from 1.39 to 0.02 (p < 0.01). Urinary metabolites in other steroid pathways such as 5αTHF/5βTHF in the glucocorticoid pathway and 5αTHB/5βTHB in the mineralocorticoid pathway also significant decreased after the DUT treatment. As compared to baseline level, the mean An/Et ratios in patients with the withdrawal of DUT were 0.7%, 1.4%, 12.6%, and 82.4% at just before, one month, 3 months, and 6 months after the withdrawal of DUT, respectively. All other steroid pathways changed in a similar manner without the aggravation of urinary symptoms. The recovery ratio of An/Et in USP before and 3 months after the withdrawal of DUT correlated with the recovery ratio of serum PSA levels (ρ = 0.61, p < 0.01). Conclusion: Urinary 5α/5β metabolites in all pathways were strongly suppressed after the administration of DUT for one month and the pharmacological effect of DUT prolonged even after withdrawal of DUT.

Original languageEnglish
JournalClinical Biochemistry
DOIs
Publication statusAccepted/In press - 2018 Jan 1

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Prostatic Hyperplasia
Metabolites
Steroids
Etiocholanolone
Androsterone
Dutasteride
Urine
Pharmacology
Recovery
Mineralocorticoids
Sex Ratio
Gas chromatography
Gas Chromatography-Mass Spectrometry
Glucocorticoids
Mass spectrometry
Blood

ASJC Scopus subject areas

  • Clinical Biochemistry

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Change of the 5α/5β ratio of urinary steroid metabolites in benign prostatic hyperplasia patients treated with dutasteride. / Maeda, Takahiro; Kikuchi, Eiji; Hasegawa, Masanori; Homma, Keiko; Yasumizu, Yota; Hattori, Seiya; Kosaka, Takeo; Shinoda, Kazunobu; Miyajima, Akira; Oya, Mototsugu.

In: Clinical Biochemistry, 01.01.2018.

Research output: Contribution to journalArticle

Maeda, Takahiro ; Kikuchi, Eiji ; Hasegawa, Masanori ; Homma, Keiko ; Yasumizu, Yota ; Hattori, Seiya ; Kosaka, Takeo ; Shinoda, Kazunobu ; Miyajima, Akira ; Oya, Mototsugu. / Change of the 5α/5β ratio of urinary steroid metabolites in benign prostatic hyperplasia patients treated with dutasteride. In: Clinical Biochemistry. 2018.
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abstract = "Background: The effects of the administration of dutasteride (DUT) on steroid metabolite pathways in BPH patients have not been examined. Methods: Urine and blood samples as well as clinical parameters were prospectively collected after the administration of DUT to 60 BPH patients, and after its withdrawal in another set of 25 BPH patients. Urine samples were assessed using gas chromatography/mass spectrometry for the urinary steroid profile (USP), which simultaneously measures 63 steroid metabolites. We examined pharmacological changes in the 5α/5β ratio of urinary metabolites and their relationships with clinical parameters in patients treated with DUT. Results: The mean urinary androsterone/etiocholanolone (An/Et) ratio in sex-steroid pathways significantly decreased from 1.39 to 0.02 (p < 0.01). Urinary metabolites in other steroid pathways such as 5αTHF/5βTHF in the glucocorticoid pathway and 5αTHB/5βTHB in the mineralocorticoid pathway also significant decreased after the DUT treatment. As compared to baseline level, the mean An/Et ratios in patients with the withdrawal of DUT were 0.7{\%}, 1.4{\%}, 12.6{\%}, and 82.4{\%} at just before, one month, 3 months, and 6 months after the withdrawal of DUT, respectively. All other steroid pathways changed in a similar manner without the aggravation of urinary symptoms. The recovery ratio of An/Et in USP before and 3 months after the withdrawal of DUT correlated with the recovery ratio of serum PSA levels (ρ = 0.61, p < 0.01). Conclusion: Urinary 5α/5β metabolites in all pathways were strongly suppressed after the administration of DUT for one month and the pharmacological effect of DUT prolonged even after withdrawal of DUT.",
author = "Takahiro Maeda and Eiji Kikuchi and Masanori Hasegawa and Keiko Homma and Yota Yasumizu and Seiya Hattori and Takeo Kosaka and Kazunobu Shinoda and Akira Miyajima and Mototsugu Oya",
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T1 - Change of the 5α/5β ratio of urinary steroid metabolites in benign prostatic hyperplasia patients treated with dutasteride

AU - Maeda, Takahiro

AU - Kikuchi, Eiji

AU - Hasegawa, Masanori

AU - Homma, Keiko

AU - Yasumizu, Yota

AU - Hattori, Seiya

AU - Kosaka, Takeo

AU - Shinoda, Kazunobu

AU - Miyajima, Akira

AU - Oya, Mototsugu

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background: The effects of the administration of dutasteride (DUT) on steroid metabolite pathways in BPH patients have not been examined. Methods: Urine and blood samples as well as clinical parameters were prospectively collected after the administration of DUT to 60 BPH patients, and after its withdrawal in another set of 25 BPH patients. Urine samples were assessed using gas chromatography/mass spectrometry for the urinary steroid profile (USP), which simultaneously measures 63 steroid metabolites. We examined pharmacological changes in the 5α/5β ratio of urinary metabolites and their relationships with clinical parameters in patients treated with DUT. Results: The mean urinary androsterone/etiocholanolone (An/Et) ratio in sex-steroid pathways significantly decreased from 1.39 to 0.02 (p < 0.01). Urinary metabolites in other steroid pathways such as 5αTHF/5βTHF in the glucocorticoid pathway and 5αTHB/5βTHB in the mineralocorticoid pathway also significant decreased after the DUT treatment. As compared to baseline level, the mean An/Et ratios in patients with the withdrawal of DUT were 0.7%, 1.4%, 12.6%, and 82.4% at just before, one month, 3 months, and 6 months after the withdrawal of DUT, respectively. All other steroid pathways changed in a similar manner without the aggravation of urinary symptoms. The recovery ratio of An/Et in USP before and 3 months after the withdrawal of DUT correlated with the recovery ratio of serum PSA levels (ρ = 0.61, p < 0.01). Conclusion: Urinary 5α/5β metabolites in all pathways were strongly suppressed after the administration of DUT for one month and the pharmacological effect of DUT prolonged even after withdrawal of DUT.

AB - Background: The effects of the administration of dutasteride (DUT) on steroid metabolite pathways in BPH patients have not been examined. Methods: Urine and blood samples as well as clinical parameters were prospectively collected after the administration of DUT to 60 BPH patients, and after its withdrawal in another set of 25 BPH patients. Urine samples were assessed using gas chromatography/mass spectrometry for the urinary steroid profile (USP), which simultaneously measures 63 steroid metabolites. We examined pharmacological changes in the 5α/5β ratio of urinary metabolites and their relationships with clinical parameters in patients treated with DUT. Results: The mean urinary androsterone/etiocholanolone (An/Et) ratio in sex-steroid pathways significantly decreased from 1.39 to 0.02 (p < 0.01). Urinary metabolites in other steroid pathways such as 5αTHF/5βTHF in the glucocorticoid pathway and 5αTHB/5βTHB in the mineralocorticoid pathway also significant decreased after the DUT treatment. As compared to baseline level, the mean An/Et ratios in patients with the withdrawal of DUT were 0.7%, 1.4%, 12.6%, and 82.4% at just before, one month, 3 months, and 6 months after the withdrawal of DUT, respectively. All other steroid pathways changed in a similar manner without the aggravation of urinary symptoms. The recovery ratio of An/Et in USP before and 3 months after the withdrawal of DUT correlated with the recovery ratio of serum PSA levels (ρ = 0.61, p < 0.01). Conclusion: Urinary 5α/5β metabolites in all pathways were strongly suppressed after the administration of DUT for one month and the pharmacological effect of DUT prolonged even after withdrawal of DUT.

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