Preliminary Evidence for an Association Between Variants of the Catechol-O-Methyltransferase (COMT) Gene and Premature Ejaculation.

BACKGROUND: Studies have suggested that dopamine plays a role in the neurobiological mechanism that triggers ejaculation, leading scientists to hypothesize that dopamine-related genetic polymorphisms could contribute to symptoms of premature ejaculation (PE). AIM: To investigate associations between dopamine receptor and catechol-O-methyltransferase (COMT; an enzyme involved in the catabolism of dopamine) gene-linked polymorphisms and PE. METHODS: PE status in patient groups was determined by clinical diagnosis performed by a physician specializing in sexual medicine. Self-reported PE symptoms from a validated questionnaire also were reported. Saliva samples were collected from 149 patients with PE and 1,022 controls from a population-based sample. In total, we tested associations between PE and 11 single-nucleotide polymorphisms in the dopamine receptor D1, D2, and D3 genes and in the COMT gene. OUTCOMES: We found no associations between dopamine receptor gene polymorphisms and PE, but 2 COMT-linked loci (rs4680 and rs4818) had significant associations after correction for multiple testing. RESULTS: 1 COMT gene-linked locus that was associated with PE symptoms in the present study, rs4680, is a well-documented functional polymorphism that causes a valine-to-methionine substitution. The other polymorphism, rs4818, is in high linkage disequilibrium with the rs4680 locus, indicating that they capture the same effect. Surprisingly, the rs4680 variant that was statistically significantly more prevalent in the PE group (ie, the valine-encoding allele) has been associated with higher enzymatic activity and therefore lower synaptic dopamine levels. CLINICAL TRANSLATION: Drugs targeting the dopaminergic system could affect PE symptoms. STRENGTHS AND LIMITATIONS: No replication sample was available for the present study; thus, our findings should be interpreted with caution. Moreover, a limitation of our study is the small sample in the context of genetic association studies (although it should be mentioned that genetically informative samples with phenotypic information about PE symptoms are scarce, and most previous genetic association studies of PE have used samples of similar or smaller size). However, our results are plausible: we report an association between one of the most extensively studied and understood genetic polymorphisms in psychiatric research and PE, and our results are in line with the long-standing hypothesis that dopamine influences human ejaculatory function. CONCLUSIONS: We report an association between 2 COMT gene-linked loci and PE symptoms, but our results should be treated with caution until independently replicated. Jern P, Johansson A, Strohmaier J, et al. Preliminary Evidence for an Association Between Variants of the Catechol-O-Methyltransferase (COMT) Gene and Premature Ejaculation. J Sex Med 2017;14:1558-1565.

A Longitudinal Analysis of Premature Ejaculation Symptoms Raises Concern Regarding the Appropriateness of a "Lifelong" Subtype.

Premature ejaculation (PE) is divided into acquired and lifelong subtypes, with the implication that the latter is chronic. This longitudinal study included data for untreated respondents from a population-based sample (sample 1) and a sample of patients diagnosed with lifelong PE (sample 2). About half of the respondents who at time 1 fulfilled the most important diagnostic criterion for lifelong PE (≤1minute ejaculation latency) no longer did so at time 2. Standardised autoregressive coefficients for PE symptom measures were 0.58 for sample 1, 0.83 for sample 2, and 0.37 for individuals with ejaculatory latencies ≤1minute. A subjective perception of change in ejaculatory latency was reported by 47% (n=397) of sample 1 and 62% (n=10) of sample 2. PE symptoms were in general unstable over time, which raises concern regarding the appropriateness of the "lifelong" diagnosis. PATIENT SUMMARY: We looked at the stability of symptoms of premature ejaculation (PE) over time. We found that PE symptom severity varies considerably, and to a lesser but still considerable degree in patients diagnosed with lifelong PE. Our results suggest that there is reason to doubt the appropriateness of the term lifelong PE.

Validation of three early ejaculation diagnostic tools: a composite measure is accurate and more adequate for diagnosis by updated diagnostic criteria.

PURPOSE: To validate three early ejaculation diagnostic tools, and propose a new tool for diagnosis in line with proposed changes to diagnostic criteria. Significant changes to diagnostic criteria are expected in the near future. Available screening tools do not necessarily reflect proposed changes. MATERIALS AND METHODS: Data from 148 diagnosed early ejaculation patients (M age = 42.8) and 892 controls (M age = 33.1 years) from a population-based sample were used. Participants responded to three different questionnaires (Premature Ejaculation Profile; Premature Ejaculation Diagnostic Tool; Multiple Indicators of Premature Ejaculation). Stopwatch measured ejaculation latency times were collected from a subsample of early ejaculation patients. We used two types of responses to the questionnaires depending on the treatment status of the patients 1) responses regarding the situation before starting pharmacological treatment and 2) responses regarding current situation. Logistic regressions and Receiver Operating Characteristics were used to assess ability of both the instruments and individual items to differentiate between patients and controls. RESULTS: All instruments had very good precision (Areas under the Curve ranging from .93-.98). A new five-item instrument (named CHecklist for Early Ejaculation Symptoms - CHEES) consisting of high-performance variables selected from the three instruments had validity (Nagelkerke R (2) range .51-.79 for backwards/forwards logistic regression) equal to or slightly better than any individual instrument (i.e., had slightly higher validity statistics, but these differences did not achieve statistical significance). Importantly, however, this instrument was more in line with proposed changes to diagnostic criteria. CONCLUSIONS: All three screening tools had good validity. A new 5-item diagnostic tool (CHEES) based on the three instruments had equal or somewhat more favorable validity statistics compared to the other three tools, but is more in line with recently proposed diagnostic criteria.