Abstract
Background
Situational delayed ejaculation (SD-DE, intravaginal anejaculation phenotype) is a clinically significant disorder marked by preserved masturbatory function but persistent coital anejaculation. This condition substantially impairs quality of life and causes significant distress. The underlying neurophysiology, particularly autonomic mechanisms, remains unclear. This study aimed to investigate sympathetic function in SD-DE using penile sympathetic skin response (PSSR) and assess its clinical correlates.
Methods
Sixty-seven SD-DE patients and 65 normal controls (NCs) were enrolled. PSSR latency and amplitude, penile sensory threshold (PST), and clinical characteristics (including psychological evaluations via the Self-Rating Anxiety Scale, SAS) were systematically analyzed to evaluate sympathetic nervous system function.
Results
SD-DE patients exhibited significantly shorter PSSR latency compared to NCs (P<0.001), indicating sympathetic hyperactivity. A significant negative correlation was observed between PSSR latency and anxiety scores (P<0.001), suggesting stress-mediated sympathetic overactivation. SD-DE patients also demonstrated higher PST (P=0.03), increased masturbation frequency (>2 times/week: 38.81% vs. 20.00%, P=0.02), and a higher prevalence of atypical masturbation (28.36% vs. 3.08%, P<0.001), reflecting compensatory sensorimotor adaptations.
Conclusions
These findings establish sympathetic dysfunction as a core feature of SD-DE [Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) 302.74], with PSSR serving as an objective biomarker. The intravaginal anejaculation phenotype represents a distinct clinical entity within DSM-5 302.74, informing targeted therapeutic strategies. In the future, it is necessary to further verify its pathological circuit mechanism by combining multimodal neuroimaging techniques.
Keywords: Delayed ejaculation, situational delayed ejaculation (SD-DE), intravaginal anejaculation, sympathetic skin response (SSR), anxiety
Highlight box.
Key findings
• Situational delayed ejaculation (SD-DE, intravaginal anejaculation phenotype) exhibits sympathetic hyperactivity, evidenced by significantly shortened penile sympathetic skin response (PSSR) latency (P<0.001).
• PSSR latency negatively correlates with anxiety severity (P<0.001), implicating stress-mediated autonomic dysregulation.
• SD-DE patients show compensatory sensorimotor adaptations: elevated penile sensory threshold (PST; P=0.03), increased masturbation frequency (>2/week: 38.81% vs. 20.0%, P=0.02), and prevalent atypical masturbation (28.36% vs. 3.08%, P<0.001).
What is known and what is new?
• SD-DE [Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) 302.74] is characterized by preserved masturbatory ejaculation but persistent coital anejaculation. Etiological models emphasize psychological factors and maladaptive masturbation habits, though neurophysiological mechanisms remain undefined.
• This study identifies sympathetic hyperactivity as a core neurophysiological feature of SD-DE using PSSR, establishing it as an objective biomarker. We further integrate autonomic dysregulation with peripheral sensory alterations (elevated PST) and behavioral adaptations (atypical masturbation), revealing a unified pathophysiological framework.
What is the implication, and what should change now?
• PSSR latency serves as a diagnostic biomarker for SD-DE, enabling objective assessment. Clinically, targeting sympathetic overactivity and addressing maladaptive masturbation may improve outcomes. Future research should validate these mechanisms using multimodal neuroimaging to guide precision therapies.
Introduction
Anejaculation is clinically defined as the complete absence of antegrade or retrograde semen emission, regardless of orgasmic attainment, resulting from failure of seminal fluid transport through the ejaculatory duct system (1).This condition accounts for approximately 2% of male infertility cases globally (2,3). Organic etiologies—including spinal cord injury (SCI), multiple sclerosis, diabetes mellitus, and iatrogenic retroperitoneal nerve damage—are well-established causes of complete anejaculation, characterized by persistent failure to achieve ejaculation through both masturbation and coital activity (4,5). In contrast, situational delayed ejaculation (intravaginal subtype; SD-DE) [Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) 302.74; International Classification of Diseases, Tenth Revision (ICD-10) N53.11] represents a well-defined clinical entity characterized by: (I) lifelong inability to achieve intravaginal ejaculation despite preserved masturbatory function; (II) occurrence in ≥75% of coital occasions for ≥6 months; (III) clinically significant distress (1,6). This phenotype corresponds to the ‘intravaginal ejaculatory dysfunction (IVEjD)’ classification in Japanese guideline (1), reflecting a severe form of delayed ejaculation (DE) rather than true anejaculation. In line with the European Association of Urology (EAU) Guideline, it is classified under DE internationally (7). In Chinese clinical practice, IVEjD is termed ‘functional anejaculation’ (8). Our cohort specifically represents this lifelong presentation. Elucidating its neurophysiological basis is critical for developing targeted interventions. Ejaculation constitutes a complex reflex process coordinated through integrated peripheral and central neural circuits (9). The supraspinal centers exert modulatory control over spinal reflex arcs via descending pathways that mediate both excitatory and inhibitory inputs (10). This bidirectional cortico-spinal communication is essential for maintaining homeostatic regulation of sexual responses. The sympathetic skin response (SSR), defined as a transient change in cutaneous electrical potential mediated by sudomotor C-fiber activity, serves as a sensitive indicator of autonomic nervous system function (11). Of particular diagnostic relevance is the penile sympathetic skin response (PSSR), a specialized SSR recording obtained from penile surface electrodes (12,13). Although electrical stimulation lacks ecological validity, PSSR remains a validated surrogate for sympathetic function (14). In the present study, we employed PSSR analysis to test the hypothesis that patients with SD-DE exhibit sympathetic nervous system dysregulation, potentially contributing to enhanced ejaculatory inhibition and subsequent coital anejaculation. We present this article in accordance with the STROBE reporting checklist (available at https://tau.amegroups.com/article/view/10.21037/tau-2025-348/rc).
Methods
Subjects
This study was carried out in accordance with the Declaration of Helsinki and its subsequent amendments, and was reported based on the Consolidated Standards for Reporting Trials statement. The study protocol was approved by the Ethics Committee of Nanjing Drum Tower Hospital (approval No. 2015-053-01), and all subjects provided written informed consent. Sample size was determined according to methodological standards in neurophysiological studies of ejaculatory dysfunction (12). With 67 SD-DE patients and 65 controls, our cohort exceeded the sample size of comparable PSSR investigations (12).
A retrospective analysis was conducted on 67 SD-DE patients meeting inclusion criteria at Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School (Nanjing, China), with data collected between January 2020 and January 2025. Inclusion criteria for SD-DE patients included: (I) meets DSM-5 diagnostic criteria for SD-DE (302.74): (i) persistent delay/absence of intravaginal ejaculation in ≥75% of coital occasions for ≥6 months, (ii) clinically significant distress; (II) preserved masturbation-induced ejaculation ability; (III) stable heterosexual partner ≥6 months; (IV) sexual intercourse frequency ≥1/week; (V) IIEF-5 score >21 [excluding erectile dysfunction (ED)]. Subjects in the normal controls (NCs) were selected from patients in the same department who were undergoing testing for semen quality and who had no complaints of ejaculation dysfunction or any other sexual dysfunction.
The exclusion criteria consisted of: subjects (I) have acquired SD-DE at some point during their sexual experiences (that is, they haven’t experienced it from their first sexual encounters); (II) have complications relating to or arising from central or peripheral nervous system dysfunction, sympathectomy, bladder neck or prostatic surgery, hypogonadism, sedative drug effects, chronic alcoholism, thyroid dysfunction, chronic pain syndrome, diabetes and hypertension, among others; (III) suffering from complications associated with ED, use of PDE5 inhibitors, or prostatitis, among other related conditions; or (IV) use drugs that interfere with ejaculation, including α and β blockers, antidopaminergics, tricyclic or serotoninergic antidepressants, and adrenergic neuron blockers.
Atypical masturbation
The definition of atypical masturbation is based on published literature and refers to the use of methods significantly different from typical masturbation for stimulation, including but not limited to speed, position, posture, pressure, and the source of stimulation (15). For instance, prone masturbation (PM) involves rubbing the penis against a pillow, mattress, or floor; squeezing legs masturbation (SLM) involves applying pressure by clamping the penis between the legs; and other types of masturbation (OM), such as using special devices for self-stimulation.
PSSR recording
The methods of PSSR tests have been previously described in detail (12,13). The Nicolet electromyography evoked potential instrument (VikingQuest®) was used for examination of the autonomic nervous systems. In brief, the ring electrode connected to the cathode was placed at penile crus, the ring electrode connected to the anode was placed on the coronal sulcus of the penis, the ground electrode was placed on the right forearm, and the stimulating electrode was placed at the median nerve of the right wrist. The electrode impedance was set at less than 10 kΩ, the duration of the rectangular current pulse was 1 ms, the stimulation intensity was 30 mA, and the interval between two tests was more than 30 s. The time of the first upward wave peak triggered by electrostimulation was the latency of PSSR, and the amplitude change was calculated according to the voltage difference between the wave peak and trough (Figure 1).
Figure 1.
Schematic diagram of PSSR recording setup. PSSR was recorded using a Nicolet VikingQuest® electromyography/evoked potential instrument. The stimulating electrode was positioned over the right median nerve at the wrist, delivering rectangular pulses (1 ms duration, 30 mA intensity, >30 s inter-stimulus interval). Recording ring electrodes were placed with the cathode at the penile crus and the anode on the coronal sulcus. A ground electrode was attached to the right forearm. Electrode impedance was maintained below 10 kΩ. PSSR latency was measured as the time from stimulus onset to the first upward peak deflection; amplitude was calculated as the peak-to-trough voltage difference of four averaged consecutive responses. PSSR, penile sympathetic skin response.
Clinical and psychological assessments
Erectile function assessment
International Index of Erectile Function-5 (IIEF-5), a validated self-report instrument (16). Scoring followed standardized criteria: ≥22: normal erectile function, 12–21: Mild ED, 8–11: moderate ED, 5–7: severe ED.
Premature ejaculation (PE) assessment
Premature Ejaculation Diagnostic Tool (PEDT): screens for PE; scores <9 exclude PE diagnosis (17).
Intravaginal ejaculation latency time (IELT): measured by stopwatch; >3 minute considered non-PE (lifelong PE or acquired PE) per International Society for Sexual Medicine standards (17).
Anxiety assessment
Anxiety levels were measured using the Self-Rating Anxiety Scale (SAS), a psychometrically validated tool (18,19). Scores were interpreted as: <50: no anxiety, 50–59: mild anxiety, 60–69: moderate anxiety, ≥70: severe anxiety.
Statistical analysis
All statistical analyses were performed using SPSS software (version 22.0; IBM Corp., Armonk, NY, USA). Continuous variables were assessed for normality via the Shapiro-Wilk test (α=0.05). Categorical variables were compared using Pearson’s Chi-squared test, with Yates’ continuity correction applied to 2×2 contingency tables when expected cell counts were <5. For parametric comparisons between independent groups, Student’s t-test (two-tailed) or one-way analysis of variance (ANOVA) was employed, following verification of homogeneity of variances using Levene’s test (median-centered). Post hoc pairwise comparisons following ANOVA were adjusted via the Bonferroni method. When normality or variance homogeneity assumptions were violated, non-parametric alternatives were applied: the Mann-Whitney U test for two-group comparisons and the Kruskal-Wallis test for multi-group analyses. Bivariate correlations between non-normally distributed continuous variables were evaluated using Spearman’s rank-order correlation coefficient. A two-sided P value <0.05 was considered statistically significant for all inferential analyses.
Results
Clinical characteristics
During the screening phase, seven SD-DE patients were excluded: five due to comorbid diabetes mellitus/hypertension (exclusion criterion II), and two due to the use of medications affecting ejaculation (exclusion criterion IV). In the NCs, five participants were excluded after being retrospectively diagnosed with ED (exclusion criterion III). Following screening exclusions, the analytical cohort comprised 67 patients with SD-DE and 65 NCs. All exclusions strictly adhered to the predefined criteria, ensuring no subjective bias in participant selection. The general clinical characteristics of all subjects are presented in Table 1. There was no statistical difference in terms of age, height, body weight, IIEF-5 score and educational level in SD-DE and NCs (Table 1). The number of subjects who masturbated more than 2 times per week (38.81% vs. 20.00%, P=0.02) and 1–2 times (47.76% vs. 26.15%, P=0.04) in the SD-DE group was higher than those in the NCs, while there were fewer patients who masturbated less than once a week in the SD-DE group than NCs (13.43% vs. 53.85%, P<0.001). In addition, PST of SD-DE group was higher than that of NCs (2.53±0.95 vs. 2.24±0.42 mA, P=0.03).
Table 1. Demographic, behavioral, and sensory profiles of SD-DE patients versus normal controls.
| Characteristics | NCs (n=65) | SD-DE (n=67) | P value |
|---|---|---|---|
| Age (years) | 29.66±6.33 | 28.11±6.84 | 0.18 |
| Height (cm) | 175.19±5.53 | 173.86±6.80 | 0.22 |
| Weight (kg) | 78.93±15.20 | 75.68±10.27 | 0.15 |
| Education (years) | 11.94±1.91 | 12.46±2.11 | 0.14 |
| IIEF-5 (score) | 23.43±0.80 | 23.57±1.13 | 0.43 |
| PEDT (score) | 3.92±2.46 | NA | NA |
| IELT (min) | 10.26±4.41 | NA | NA |
| SAS (score) | NA | 51.63±7.41 | NA |
| Frequency of masturbation | |||
| >2 weekly | 13 (20.00) | 26 (38.81) | 0.02† |
| 1–2 times per week | 17 (26.15) | 32 (47.76) | 0.04† |
| <1 a week | 35 (53.85) | 9 (13.43) | <0.001† |
| Atypical masturbation | 2 (3.08) | 19 (28.36) | <0.001† |
| PST (mA) | 2.24±0.42 | 2.53±0.95 | 0.03 |
Values are presented as mean ± standard deviation or n (%). P values were obtained through two-sample t-tests or Chi-squared tests. The significant level was set at P<0.05. IIEF-5 ≥22: normal erectile function; PEDT <9: excludes premature ejaculation; IELT >3 min: non-PE per ISSM criteria; SAS 50–59: mild anxiety. †, Chi-squared tests. IIEF-5, International Index of Erectile Function-5; IELT, intravaginal ejaculation latency time; ISSM, International Society for Sexual Medicine; NA, not applicable; NCs, normal controls; PE, premature ejaculation; PEDT, Premature Ejaculation Diagnostic Tool; PST, penile sensory threshold; SAS, Self-Rating Anxiety Scale; SD-DE, situational delayed ejaculation.
Of the 67 SD-DE patients, 14 patients (20.90%) achieved ejaculation only through atypical masturbation, including 4 cases reported masturbating without hands in lateral position, 1 case described masturbating with hands in lateral position, 5 cases described masturbating by rubbing their penis against the bed sheets, 2 cases reported masturbating with their legs rubbing against the penis in supine position and 2 cases described violently masturbating. The rest of the patients (79.10%) were able to ejaculate by regular masturbation with hand (not shown in the table). Thirty-eight patients (56.72%) considered masturbation to be more pleasurable than intercourse.
The latency of PSSR was shorter in SD-DE patients than NCs
The typical PSSR of the SD-DE patients and the NCs is shown in Figure 2A,2B. The mean latency of PSSR of SD-DE group was shorter than that of NCs (1,312.54±178.02 vs. 1,417.00±141.85 ms, P<0.001) (Figure 2C). There is no significantly difference of the median values of the amplitude between two groups (52.91±48.45 vs. 57.63±32.02 µV, P=0.51).
Figure 2.
Comparison of PSSR waveforms between the NCs and the SD-DE group. A representative PSSR waveform of NCs (A) and SD-DE group (B). The onset latency and peak-to-peak amplitude were shown in superimposed waveform of four consecutive responses. Neurophysiological assessment revealed significantly shortened PSSR latency in patients with SD-DE compared to NCs (C). P values were obtained through two-sample t-tests, *, P<0.001. A-A, peak-to-peak amplitude; L, latency; NCs, normal controls; PSSR, penile sympathetic skin response; SD-DE, situational delayed ejaculation.
To further explore the correlation between PSSR and the clinical characteristics of SD-DE patients, spearman correlation analysis was applied (Table 2). We found a significant negative correlation between the PSSR latency and the SAS score (P<0.001, r=−0.53) (Figure 3), while the PSSR latency was not correlated with age (P=0.63), disease history (P=0.40), having atypical masturbation habits (P=0.77), the age of first masturbation (P=0.40), weekly masturbation frequency (P=0.19), alcohol consumption (P=0.37), smoking status (P=0.33), or PST (P=0.95).
Table 2. Correlation of the latency of PSSR and clinical characteristics in SD-DE patients.
| Characteristics | SD-DE (n=67) | P value | r |
|---|---|---|---|
| Latency of PSSR (ms) | 1,312.54±178.02 | – | – |
| Age (years) | 29.66±6.33 | 0.63 | 0.06 |
| History (months) | 21.46±23.36 | 0.40 | −0.11 |
| Atypical masturbation (yes/no) | 1.72±0.45 | 0.77 | 0.04 |
| The time of the first masturbation (years) | 16.76±2.82 | 0.40 | −0.11 |
| Frequency of masturbation (0–7 times/per week) | 2.55±2.11 | 0.19 | −0.16 |
| Drinking or not (yes/no) | 1.76±0.43 | 0.37 | 0.11 |
| Smoking or not (yes/no) | 1.67±0.43 | 0.33 | −0.12 |
| PST (mA) | 2.53±0.95 | 0.95 | −0.01 |
| SAS (score) | 51.63±7.41 | <0.001 | −0.53 |
Values are presented as mean ± standard deviation. PSSR, penile sympathetic skin response; PST, penile sensory threshold; SAS, Self-Rating Anxiety Scale; SD-DE, situational delayed ejaculation.
Figure 3.
Correlation between PSSR latency and SAS score in SD-DE patients. PSSR, penile sympathetic skin response; SAS, Self-Rating Anxiety Scale; SD-DE, situational delayed ejaculation.
Discussion
This study delineates the autonomic neural substrate underlying SD-DE, yielding novel neurophysiological evidence of sympathetic hyperactivity in affected men. Xia et al. (20), reported prolonged dorsal penile nerve somatosensory evoked potential (DNSEP) latency (mean delay: 4.32 ms; reflecting impaired afferent pathways) in primary DE patients, yet their study lacked autonomic measures such as PSSR. Our neurophysiological assessments revealed significantly shortened PSSR latency in patients with SD-DE compared to NCs (P<0.001), indicative of sympathetic hyperactivity. The inverse correlation between PSSR latency and SAS scores (P<0.001) further implicates stress-mediated sympathetic overactivation as a potential pathophysiological mechanism, wherein heightened psychological stress may exacerbate autonomic dysregulation. These findings collectively establish PSSR latency as an objective neurophysiological biomarker for SD-DE, functionally linking sympathetic nervous system dysfunction to impaired ejaculatory reflexes.
Anejaculation shares common etiological factors with retrograde ejaculation, including diabetes mellitus, SCI, and pharmacological side effects (21). However, SD-DE is distinguished by the preserved capacity for masturbatory ejaculation despite persistent intravaginal failure. Current evidence suggests a non-organic pathogenesis with two predominant etiological frameworks: psychological factors and maladaptive (or inappropriate) masturbatory practices established during adolescence (7,22). Patients with DE frequently report preferential reliance on masturbation over partnered intercourse, as orgasmic ejaculation is achievable through self-stimulation but not coitally (23). This phenomenon often arise from idiosyncratic or inappropriate masturbatory patterns characterized by variations in stimulation intensity, duration, and focal penile regions—practices diverging markedly from typical partnered interactions. Our findings align with this model: the SD-DE cohort exhibited significantly elevated masturbation frequency (P=0.02) and a higher prevalence of atypical techniques (inappropriate practices) (P<0.001). Crucially, shortened PSSR latency (sympathetic hyperactivity) and elevated PST (sensory alteration) may represent neural mechanisms linking these maladaptive practices to ejaculatory inhibition. These observations suggest that entrenched inappropriate masturbatory behaviors may perpetuate sensory-motor incongruity, potentially contributing to SD-DE pathophysiology. Alternatively, chronic atypical masturbation may directly dysregulate sympathetic pathways, though causal mechanisms require longitudinal investigation.
The dynamic neurobiological theory of DE posits that neurobiological variations may elevate the ejaculatory threshold, requiring prolonged stimulation (24-26). This aligns with our findings of elevated PST in SD-DE patients, suggesting sensory hypoactivity as a potential contributor. Notably, selective serotonin reuptake inhibitors (SSRIs)—a first-line pharmacological intervention for PE—are hypothesized to exert therapeutic effects by elevating PST to prolong intravaginal latency, rather than modulating the amplitude or latency of sacral evoked potentials and cortical somatosensory evoked potentials (27,28). The elevated PST in SD-DE patients may stem from both peripheral and central mechanisms. Peripherally, chronic high-frequency masturbation likely induces adaptive desensitization of penile sensory nerve terminals through repetitive mechanical stimulation. This hypothesis aligns with Xia et al. (20), who reported significantly reduced conduction velocities in the dorsal penile nerves of DE patients, inversely correlating with masturbation frequency. Such desensitization could diminish sensory input during intercourse, raising the ejaculatory threshold (20). Centrally, compensatory hyperactivation of somatosensory processing may further exacerbate this phenomenon. Chen et al. (29) identified enhanced amplitude of low-frequency fluctuation (ALFF) in the postcentral gyrus—a primary cortical hub for genital sensation—in SD-DE patients, suggesting maladaptive sensory integration. Peripheral desensitization may drive central hyperactivation to compensate for diminished afferent signals (29). Compensatory sensorimotor adaptations refer to neuroplastic changes wherein chronic atypical masturbation induces peripheral desensitization and/or central hyperactivation, maintaining ejaculatory capacity during self-stimulation while impairing coital function. It is worth noting that no significant correlation was found between the increase in PST and the latency of PSSR (P=0.95), which may reflect the independence of their pathological mechanisms. This suggests that the pathogenesis of SD-DE involves multi-system dysregulation, and peripheral desensitization and central sympathetic hyperactivity may act as parallel pathological factors jointly leading to ejaculatory disorders.
PSSR is defined as a cutaneous potential reflecting sudomotor activity mediated by cerebral and spinal cord pathways, elicited by external stimuli (30). Crucially, the sympathetic fibers innervating genital sweat glands exhibit anatomical convergence with those regulating ejaculatory emission. These preganglionic fibers originate from the lumbar spinal cord, traverse sympathetic ganglia, and synapse with postganglionic neurons governing genital function. This neuroanatomical overlap supports the utility of PSSR as a functional biomarker of ejaculation-related sympathetic activity. Our data revealed that SD-DE patients exhibited significantly shorter PSSR latency compared to NC subjects (P<0.001), indicating sympathetic hyperactivity. In contrast, no significant difference was observed in median amplitude between groups (P=0.51). Given the substantial interindividual variability in evoked potential amplitudes influenced by stimulation parameters, recording conditions, and biological factors, amplitude measurements are considered diagnostically inferior to latency parameters according to Nikiforidis et al. (31). The observed autonomic dysfunction may arise through multiple mechanisms. First, psychological factors, such as anxiety or depression, play important roles in causing or sustaining DE. Prior research has indicated that sympathetic nervous system responsivity to stimuli with varying emotional significance is correlated with the severity of psychopathology (32). Second, the regulation of sexual response is coordinated by two centers in the brain and spinal cord (33). The brain center is located in the hypothalamus and midbrain, while the spinal cord center includes the sympathetic and parasympathetic nervous systems, which are controlled by the brain (34,35). Sensory sexual inputs are integrated in the temporal lobe, relayed via amygdala to hypothalamic nuclei, and modulated by prefrontal cortical regions. Dorsolateral prefrontal cortex (dlPFC) activity exhibits positive correlation with cutaneous sympathetic outflow (36), with left dlPFC stimulation enhancing sexual arousal responses (37) and right dlPFC inhibition ameliorating sexual dysfunction (38). This functional lateralization likely reflects dlPFC-amygdala connectivity mediating emotional processing (36). Although the PSSR tests the lower spinal cord center rather than the brain center, these centers are still regulated by the brain (34,35). Recent study has shown that targeted stimulation of the dlPFC in patients with anejaculation using repetitive transcranial magnetic stimulation (rTMS) can effectively improve anorgasmia and anxiety and depression symptoms (39). Furthermore, serotonergic dysregulation may compound autonomic imbalance. DE pathophysiology has been associated with diminished 5-HT1A receptor activity and/or enhanced 5-HT2C receptor signaling (25,40). Evidence from preclinical research demonstrates that 5-HT1A agonism accelerates ejaculation (40), while clinical data support buspirone’s efficacy in DE through 5-HT1A-mediated mechanisms. This neuropharmacological evidence suggests that affective dysregulation in SD-DE may perpetuate autonomic dysfunction via serotonin-autonomic interplay. Collectively, these findings posit PSSR as a critical interface marker, reflecting both pharmacological and neuromodulatory treatment effects on autonomic sexual circuitry.
To our knowledge, this represents the first investigation to characterize PSSR profiles in patients with SD-DE, systematically evaluating sympathetic nervous system functional status and its association with psychological comorbidity, thereby identifying a novel neurophysiological biomarker for therapeutic targeting. However, several methodological limitations warrant consideration. Firstly, the cohort size, while sufficient for primary outcome analysis, limits the capacity for comprehensive subgroup stratification and detection of subtle associations. Future studies with expanded samples are warranted to enhance generalizability and enable nuanced phenotyping of patient subpopulations. Secondly, cross-sectional study designs make it difficult to establish a causal relationship between anxiety and sympathetic hyperactivity. Future research could incorporate longitudinal follow-up designs or interventional study designs (for example, examining changes in PSSR after anti-anxiety treatment) to further validate the relevant hypotheses. Thirdly, while the study’s primary focus on anxiety-autonomic interactions provided mechanistic insights, the omission of depression assessment limits comprehensive evaluation of psychological comorbidities in SD-DE. Future investigations should integrate validated multidimensional instruments (e.g., depression inventories) to systematically examine potential interactions between depression, anxiety, and autonomic dysfunction. Fourthly, the retrospective self-report design carries inherent risks of recall bias and social desirability effects, particularly for sensitive behavioral data. Prospective studies incorporating real-time digital logging of sexual behaviors are needed to overcome this limitation.
Conclusions
This study identifies sympathetic hyperactivity in SD-DE, evidenced by shortened PSSR latency, which correlates inversely with anxiety levels. Patients with SD-DE exhibit higher PST, increased frequency of masturbation, and a high incidence of atypical masturbation patterns, all of which collectively reflect the existence of compensatory sensorimotor adaptation mechanisms. PSSR serves as a biomarker for autonomic dysregulation, implicating psychoneural interactions in SD-DE pathogenesis. Targeting sympathetic overactivity may offer therapeutic potential. Future studies should integrate multimodal neuroimaging to delineate central-peripheral neural circuit mechanisms.
Supplementary
The article’s supplementary files as
Acknowledgments
None.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was carried out in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by the Ethics Committee of Nanjing Drum Tower Hospital (approval No. 2015-053-01). Informed consent was obtained from all participants.
Footnotes
Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tau.amegroups.com/article/view/10.21037/tau-2025-348/rc
Funding: This work was supported by the Nanjing Medical Technology Development Project (No. YKK23071), and the Clinical Trials from the Affiliated Drum Tower Hospital, Medical School of Nanjing University (No. 2023-LCYJ-PY-41).
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-2025-348/coif). The authors have no conflicts of interest to declare.
Data Sharing Statement
Available at https://tau.amegroups.com/article/view/10.21037/tau-2025-348/dss
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