Comparison of the Efficacy and Safety of Dapoxetine, Kegel Exercises, and Acupuncture in the Treatment of Premature Ejaculation: A Randomized, Double-Blind, Placebo-Controlled Trial

Study OverviewPremature ejaculation (PE) is one of the most prevalent male sexual dysfunctions, affecting approximately 20-30% of men worldwide. It is defined by the International Society of Sexual Medicine (ISSM) as ejaculation occurring within one minute of vaginal penetration, accompanied by a lack of control over ejaculation and resultant distress or interpersonal difficulties (Althof et al., 2014). PE significantly impacts quality of life, self-esteem, and relationship satisfaction. Current treatment options include pharmacological interventions (e.g., dapoxetine, a selective serotonin reuptake inhibitor), behavioral therapies (e.g., Kegel exercises targeting pelvic floor muscles), and complementary approaches (e.g., acupuncture). However, there is a lack of comprehensive studies comparing the efficacy and safety of these interventions in a single trial. This study aims to address this gap by evaluating the efficacy and safety of dapoxetine, Kegel exercises, acupuncture, and their respective placebo controls in a randomized, double-blind, placebo-controlled trial.Study ObjectivesThe primary objective is to compare the efficacy of dapoxetine, Kegel exercises, and acupuncture in increasing intravaginal ejaculation latency time (IELT) in men with PE, relative to placebo and sham controls. Secondary objectives include assessing improvements in PE severity, sexual quality of life, and the safety profile of each intervention. The study hypothesizes that:Dapoxetine, Kegel exercises, and acupuncture will significantly increase IELT compared to their respective placebo/sham groups.

Differences in efficacy will be observed among the active treatment groups. All interventions will demonstrate acceptable safety profiles with minimal adverse effects.

Study DesignThis is a multi-center, randomized, double-blind, placebo-controlled, parallel-group clinical trial. A total of 250 male participants will be enrolled and randomly assigned to one of five groups (50 participants per group) in a 1:1:1:1:1 ratio. The study duration is 24 months, including 6 months for preparation and recruitment, 12 months for intervention and data collection, and 6 months for data analysis and dissemination. The intervention phase lasts 12 weeks, followed by a 4-week follow-up period to assess sustained effects.Randomization and Blinding:Randomization will be performed using a computer-generated random number sequence to ensure balanced allocation across groups.

Double-blinding will be maintained by ensuring that participants and outcome assessors are unaware of group assignments. Dapoxetine and placebo tablets will be identical in appearance and packaging. Acupuncture and sham acupuncture procedures will use standardized needles to maintain blinding, with sham acupuncture involving superficial needle insertion at non-active points.

Study PopulationThe study will recruit 250 men aged 18-50 years diagnosed with PE according to ISSM criteria. Participants will be enrolled from university hospitals and private clinics across multiple centers (specific sites to be determined).Inclusion Criteria:Male, aged 18-50 years.

Diagnosed with lifelong or acquired PE per ISSM criteria (IELT \< 2 minutes, lack of ejaculatory control, and associated distress or interpersonal difficulties).

In a stable sexual relationship with a partner for at least 6 months. Willing to provide written informed consent and comply with study procedures.

Exclusion Criteria:Presence of erectile dysfunction (diagnosed via International Index of Erectile Function score \< 21).

Severe psychiatric disorders (e.g., major depression, bipolar disorder) or neurological conditions (e.g., multiple sclerosis, Parkinson's disease).

Current use of selective serotonin reuptake inhibitors (SSRIs) or other psychotropic medications.

History of alcohol or substance dependence. Known contraindications to dapoxetine (e.g., hepatic impairment) or acupuncture (e.g., bleeding disorders).

Previous pelvic floor surgery or trauma affecting pelvic floor muscles.

Sample Size Justification:

The sample size of 250 participants (50 per group) was calculated based on a power analysis (α=0.05, power=0.80) to detect a clinically meaningful 30% increase in IELT, assuming a standard deviation derived from prior studies (McMahon et al., 2011). This accounts for an estimated 10% dropout rate.InterventionsParticipants will be assigned to one of the following five groups for a 12-week intervention period:Dapoxetine Group:Dosage: 30 mg dapoxetine, taken orally 1-3 hours before anticipated sexual activity, with a maximum of 3 doses per week.

Administration: Provided in blister packs to ensure compliance. Reference: McMahon et al., 2011.

Placebo Group:Dosage: Placebo tablets identical in appearance and taste to dapoxetine, administered on the same schedule (1-3 hours before sexual activity, maximum 3 doses per week).

Administration: Provided in identical blister packs.

Kegel Exercises Group:Protocol: Participants will perform pelvic floor muscle exercises consisting of three sets of 10-15 contractions daily, each held for 5-10 seconds followed by relaxation.

Training: Participants will receive initial training from a licensed physiotherapist, with weekly follow-up sessions to ensure proper technique and adherence.

Reference: Pastore et al., 2014.

Acupuncture Group:Protocol: Two 30-minute acupuncture sessions per week, targeting standardized points (e.g., CV4, SP6, ST36) known to influence sexual function and autonomic nervous system regulation.

Administration: Performed by licensed acupuncturists following a standardized protocol.

Reference: Sunay et al., 2011.

Sham Acupuncture Group:Protocol: Two 30-minute sessions per week using superficial needle insertion at non-active points to minimize therapeutic effects while maintaining the placebo effect.

Administration: Performed by licensed acupuncturists to ensure consistency with the active acupuncture group.

Outcome MeasuresPrimary Outcome Measure:Intravaginal Ejaculation Latency Time (IELT): Measured by stopwatch during sexual intercourse, reported as the weekly average. Participants will record IELT for each sexual encounter. Time points: Baseline, Week 4, Week 8, Week 12, and Follow-up (Week 16).

Secondary Outcome Measures:Premature Ejaculation Diagnostic Tool (PEDT): A validated 5-item questionnaire assessing PE severity, including control, frequency, and distress (Symonds et al., 2007). Time points: Baseline, Week 4, Week 8, Week 12, and Follow-up (Week 16).

Sexual Quality of Life-Male (SQoL-M): A validated scale measuring the impact of sexual dysfunction on quality of life (Abraham et al., 2008). Time points: Baseline, Week 4, Week 8, Week 12, and Follow-up (Week 16).

Adverse Effects: Any adverse events (e.g., nausea, headache, skin irritation) will be systematically recorded using a standardized adverse event reporting form throughout the study.

Data Collection and ManagementIELT Measurement: Participants will use a stopwatch to record IELT during sexual intercourse and report weekly averages via a secure electronic diary.

Questionnaires: PEDT and SQoL-M will be administered electronically or on paper at specified time points.

Adverse Events: Participants will report adverse effects at each study visit, with additional spontaneous reporting encouraged via a dedicated contact line.

Data Management: Data will be stored in a secure, anonymized database compliant with data protection regulations (e.g., GDPR). Regular audits will ensure data integrity.

Statistical AnalysisPrimary Outcome (IELT): Analyzed using repeated-measures ANOVA with post-hoc tests to compare changes in IELT across groups and time points.

Secondary Outcomes (PEDT, SQoL-M): Analyzed using the Kruskal-Wallis test for non-parametric data, with pairwise comparisons as needed.

Adverse Effects: Analyzed using Chi-square tests to compare the frequency and severity of adverse events across groups.

Significance Level: p\<0.05. Software: Statistical analysis will be conducted using SPSS (version 28) or R (version 4.3 or higher).

Handling Missing Data: Intention-to-treat analysis will be used, with last observation carried forward (LOCF) for missing data points.

Ethical ConsiderationsThe study will adhere to the principles of the Declaration of Helsinki and Good Clinical Practice (GCP) guidelines.

Approval will be obtained from local Institutional Review Boards (IRBs) at each participating site.

• Premature Ejaculation Diagnostic Tool (PEDT): [Срок оценки: Time points: Baseline, Week 4, Week 8, Week 12, and Follow-up (Week 16).]