Correlation between serum tryptophan metabolism and treatment efficacy of dapoxetine in patients with premature ejaculation : A pilot study
© 2024 American Society of Andrology and European Academy of Andrology..
INTRODUCTION: Primary premature ejaculation (PPE) is a common male neurobiological disorder. Currently, there is consensus that the impairment in central serotonin (5-HT) neurotransmission constitutes a key pathogenic factor in PPE. Selective serotonin reuptake inhibitors (SSRIs) serve as the primary pharmacological intervention; however, a comprehensive elucidation of their mechanism of action remains incomplete. Owing to significant individual variability in efficacy, SSRIs exhibit a high discontinuation rate. Hence, there is an urgent need to address the selection of SSRIs for PPE treatment.
OBJECTIVE: This study aims to investigate the characteristics of tryptophan (TRP) metabolism in patients with PPE and to assess its influence on the efficacy of SSRIs.
METHODS: The exploratory study included a total of 16 patients with PPE and 16 control subjects who were healthy men without any sexual dysfunction. Upon enrollment in the study, all participants underwent a thorough medical history review and physical examination. Subsequently, their serum levels of TRP, its metabolites, large neutral amino acids (LNAAs), and metabolite ratios were assessed using a liquid chromatography-mass spectrometry (LC-MS) assay. After a period of 4 weeks of dapoxetine treatment, all patients with PPE underwent reassessment using the Premature Ejaculation Diagnostic Tool (PEDT) score and intravaginal ejaculatory latency time (IELT) test.
RESULTS: The ratio of serum TRP to other LNAAs (TRP/LNAAs) in patients with PPE was found to be significantly lower compared to the control group (P < 0.05). Conversely, the ratio of kynurenine to TRP (KYN/TRP) was observed to be significantly higher in the PPE patients compared to the control group (P < 0.05). Including the serum TRP/LNAAs ratio and KYN/TRP ratio in the prediction model yielded the highest prediction efficiency for PPE. There was a significant negative correlation between the ratio of TRP/LNAAs before the treatment and the IELT after 4 weeks of the treatment. Additionally, there was a significant positive correlation observed between the ratio of TRP/LNAAs before the treatment and the PEDT score after 4 weeks of the treatment.
CONCLUSIONS: This study demonstrates that the reduction in the TRP/LNAAs ratio and the elevation of the KYN/TRP ratio are significant characteristics associated with PPE. These findings suggest that diminished tryptophan availability in the brain and the activation of the kynurenine (KYN) pathway may play a role in the pathogenesis of PPE. The TRP/LNAAs ratio has potential as a reliable indicator of central serotonin (5-HT) levels. Considering the TRP/LNAAs ratio when selecting SSRIs for the treatment of PPE may enhance the response rate of this medication.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Andrology - (2024) vom: 21. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wu, Chenglun [VerfasserIn] |
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| Links: |
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| Themen: |
Journal Article |
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| Anmerkungen: |
Date Revised 21.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1111/andr.13632 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM370014278 |
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| 100 | 1 | |a Wu, Chenglun |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Correlation between serum tryptophan metabolism and treatment efficacy of dapoxetine in patients with premature ejaculation |b A pilot study |
| 264 | 1 | |c 2024 | |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a © 2024 American Society of Andrology and European Academy of Andrology. | ||
| 520 | |a INTRODUCTION: Primary premature ejaculation (PPE) is a common male neurobiological disorder. Currently, there is consensus that the impairment in central serotonin (5-HT) neurotransmission constitutes a key pathogenic factor in PPE. Selective serotonin reuptake inhibitors (SSRIs) serve as the primary pharmacological intervention; however, a comprehensive elucidation of their mechanism of action remains incomplete. Owing to significant individual variability in efficacy, SSRIs exhibit a high discontinuation rate. Hence, there is an urgent need to address the selection of SSRIs for PPE treatment | ||
| 520 | |a OBJECTIVE: This study aims to investigate the characteristics of tryptophan (TRP) metabolism in patients with PPE and to assess its influence on the efficacy of SSRIs | ||
| 520 | |a METHODS: The exploratory study included a total of 16 patients with PPE and 16 control subjects who were healthy men without any sexual dysfunction. Upon enrollment in the study, all participants underwent a thorough medical history review and physical examination. Subsequently, their serum levels of TRP, its metabolites, large neutral amino acids (LNAAs), and metabolite ratios were assessed using a liquid chromatography-mass spectrometry (LC-MS) assay. After a period of 4 weeks of dapoxetine treatment, all patients with PPE underwent reassessment using the Premature Ejaculation Diagnostic Tool (PEDT) score and intravaginal ejaculatory latency time (IELT) test | ||
| 520 | |a RESULTS: The ratio of serum TRP to other LNAAs (TRP/LNAAs) in patients with PPE was found to be significantly lower compared to the control group (P < 0.05). Conversely, the ratio of kynurenine to TRP (KYN/TRP) was observed to be significantly higher in the PPE patients compared to the control group (P < 0.05). Including the serum TRP/LNAAs ratio and KYN/TRP ratio in the prediction model yielded the highest prediction efficiency for PPE. There was a significant negative correlation between the ratio of TRP/LNAAs before the treatment and the IELT after 4 weeks of the treatment. Additionally, there was a significant positive correlation observed between the ratio of TRP/LNAAs before the treatment and the PEDT score after 4 weeks of the treatment | ||
| 520 | |a CONCLUSIONS: This study demonstrates that the reduction in the TRP/LNAAs ratio and the elevation of the KYN/TRP ratio are significant characteristics associated with PPE. These findings suggest that diminished tryptophan availability in the brain and the activation of the kynurenine (KYN) pathway may play a role in the pathogenesis of PPE. The TRP/LNAAs ratio has potential as a reliable indicator of central serotonin (5-HT) levels. Considering the TRP/LNAAs ratio when selecting SSRIs for the treatment of PPE may enhance the response rate of this medication | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a kynurenine pathway | |
| 650 | 4 | |a pathogenesis | |
| 650 | 4 | |a primary premature ejaculation | |
| 650 | 4 | |a treatment | |
| 650 | 4 | |a tryptophan availability | |
| 700 | 1 | |a Huang, Shengyu |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Zhuojie |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yixin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Yuanqiang |e verfasserin |4 aut | |
| 700 | 1 | |a Zang, Zhi-Jun |e verfasserin |4 aut | |
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