madman
Super Moderator
Abstract
Introduction
Lifelong premature ejaculation (LPE) is a subtype of premature ejaculation. Genetic research on LPE has primarily focused on neurotransmitters such as serotonin, dopamine, and norepinephrine, whereas LPE treatment studies have focused on drugs such as selective serotonin reuptake inhibitors. However, findings from genetic association and pharmacotherapeutic studies have been inconsistent.
Objectives
To provide a quality overview of neurobiological targets that are potentially associated with LPE by investigating genetic association and pharmacotherapeutic studies.
Methods
This scoping review was conducted per the PRISMA-ScR tool (Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension for Scoping Reviews). Five databases were searched in March 2023 without timeline- or language-related restrictions.
Results
After deduplication, 3949 records were obtained for review. Following screening and full-text review with citation tracking, 52 studies were included: 18 genetic and 34 pharmacotherapy studies. Serotonergic targets, such as the serotonin transporter and pre- and post synaptic serotonergic receptors, were most often associated with LPE in genetic and pharmacotherapeutic studies. Mixed results were found among polymorphisms within genetic studies. This mechanism is in accordance with pharmacotherapeutic studies, as the highest efficacy was found for potent serotonergic antidepressants. Successful treatment was also observed with medication acting on phosphodiesterase-5 enzyme, such as tadalafil and vardenafil. Analyses of other genetic association studies did not yield any further evidence for associated targets.
Conclusions
This review is the first comprehensive scoping review on LPE. We found that serotonergic targets are most often associated with LPE, suggesting that the serotonergic pathway is a predisposing factor in LPE. Furthermore, there is some evidence for phosphodiesterase 5 inhibitors, which should be investigated. Other previously investigated neurobiological targets appear less likely to contribute to LPE. Future studies should focus on multiple targets, ideally in a genome-wide association study design. This review has been registered with the Open Science Framework (doi:10.17605/OSF.IO/JUQSD).
Discussion
*Serotonergic targets
*Nitric oxide synthase
*Noradrenergic targets
*Dopaminergic targets
*Other targets
*Pharmacokinetic influences
Limitations
Current review
This review has some limitations. First, some studies used factors based on geometric means while others used those based on arithmetic means. Comparing these 2 types of fold increases may lead to overestimation of effects in favor of studies using an arithmetic mean.33
Conclusion
Performance of this scoping review led to the selection of the highest-quality studies on genetic and pharmacotherapeutic LPE research. The 5-HTTLPR, all pre- and postsynaptic 5-HT receptors, and NOS have been identified as suspected targets in the pathophysiology of LPE. These targets should be investigated in future GWASs.
Introduction
Lifelong premature ejaculation (LPE) is a subtype of premature ejaculation. Genetic research on LPE has primarily focused on neurotransmitters such as serotonin, dopamine, and norepinephrine, whereas LPE treatment studies have focused on drugs such as selective serotonin reuptake inhibitors. However, findings from genetic association and pharmacotherapeutic studies have been inconsistent.
Objectives
To provide a quality overview of neurobiological targets that are potentially associated with LPE by investigating genetic association and pharmacotherapeutic studies.
Methods
This scoping review was conducted per the PRISMA-ScR tool (Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension for Scoping Reviews). Five databases were searched in March 2023 without timeline- or language-related restrictions.
Results
After deduplication, 3949 records were obtained for review. Following screening and full-text review with citation tracking, 52 studies were included: 18 genetic and 34 pharmacotherapy studies. Serotonergic targets, such as the serotonin transporter and pre- and post synaptic serotonergic receptors, were most often associated with LPE in genetic and pharmacotherapeutic studies. Mixed results were found among polymorphisms within genetic studies. This mechanism is in accordance with pharmacotherapeutic studies, as the highest efficacy was found for potent serotonergic antidepressants. Successful treatment was also observed with medication acting on phosphodiesterase-5 enzyme, such as tadalafil and vardenafil. Analyses of other genetic association studies did not yield any further evidence for associated targets.
Conclusions
This review is the first comprehensive scoping review on LPE. We found that serotonergic targets are most often associated with LPE, suggesting that the serotonergic pathway is a predisposing factor in LPE. Furthermore, there is some evidence for phosphodiesterase 5 inhibitors, which should be investigated. Other previously investigated neurobiological targets appear less likely to contribute to LPE. Future studies should focus on multiple targets, ideally in a genome-wide association study design. This review has been registered with the Open Science Framework (doi:10.17605/OSF.IO/JUQSD).
Discussion
*Serotonergic targets
*Nitric oxide synthase
*Noradrenergic targets
*Dopaminergic targets
*Other targets
*Pharmacokinetic influences
Limitations
Current review
This review has some limitations. First, some studies used factors based on geometric means while others used those based on arithmetic means. Comparing these 2 types of fold increases may lead to overestimation of effects in favor of studies using an arithmetic mean.33
Conclusion
Performance of this scoping review led to the selection of the highest-quality studies on genetic and pharmacotherapeutic LPE research. The 5-HTTLPR, all pre- and postsynaptic 5-HT receptors, and NOS have been identified as suspected targets in the pathophysiology of LPE. These targets should be investigated in future GWASs.
