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Premature ejaculation (PE) is one of the most common male sexual dysfunctions, often resistant to conventional pharmacological and behavioral treatments. This randomized clinical trial aims to compare the safety and efficacy of two minimally invasive treatment options - hyaluronic acid (HA) injection into the glans penis versus botulinum toxin type A injection into the bulbospongiosus muscle - in men with lifelong drug-resistant premature ejaculation. Eighty participants will be randomly assigned in a 1:1 ratio to receive either HA or botulinum toxin injection. The primary outcome is change in intravaginal ejaculatory latency time (IELT). Secondary outcomes include changes in Premature Ejaculation Diagnostic Tool (PEDT), Arabic Index of Premature Ejaculation (AIPE) scores, Premature Ejaculation Profile (PEP), patient satisfaction, and treatment-related adverse events during a 12-month follow-up period.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Botulinum Toxin Injection Group | Experimental | Participants in this group will receive intramuscular injection of botulinum toxin type A into the bulbospongiosus muscle. A total dose of 100 units of botulinum toxin type A, diluted in 10 milliliters of normal saline, will be administered under ultrasound guidance. The injection will be divided equally, with 5 milliliters injected on each side of the muscle to ensure even distribution across most muscle fibers. The procedure will be performed under aseptic conditions with patients in the lithotomy position. |
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| Hyaluronic Acid Injection Group | Experimental | Participants in this group will receive injection of hyaluronic acid into the glans penis using the Fanning Technique. Two milliliters of 3.5 percent micronized hyaluronic acid gel will be injected through a single puncture site using a 27-gauge needle. The injection will start from the tip of the glans and proceed toward the coronal sulcus to achieve uniform distribution of the gel. The procedure will be performed under local anesthesia with application of topical lidocaine and prilocaine cream for 30 minutes prior to injection. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Botulinum toxin type A | Drug | Botulinum toxin type A will be reconstituted by diluting 100 units in 10 milliliters of sterile normal saline. Using ultrasound guidance, 5 milliliters will be injected into each side of the bulbospongiosus muscle through a single puncture site while the patient is in the lithotomy position. The aim is to achieve even distribution of the toxin within the muscle fibers to reduce muscular contractions associated with ejaculation. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in intravaginal ejaculatory latency time | The duration from vaginal penetration to ejaculation will be recorded using a stopwatch by the patient's partner. The median intravaginal ejaculatory latency time will be calculated for each participant from several intercourse attempts. The change in latency time after treatment compared with baseline will be used to assess treatment efficacy. | Baseline, 1 month, 3 months, 6 months, and 12 months after intervention |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Premature Ejaculation Diagnostic Tool (PEDT) score | The Premature Ejaculation Diagnostic Tool questionnaire will be used to evaluate changes in ejaculatory control and distress levels. Higher scores indicate greater severity. | Baseline, 1 month, 3 months, 6 months, and 12 months after intervention |
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Inclusion Criteria:
Exclusion Criteria:
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De-identified individual participant data that underlie the results reported in this study will be made available to qualified researchers upon reasonable request. Shared data will include demographic characteristics, intervention details, and outcome measures related to intravaginal ejaculatory latency time, questionnaire scores, and adverse events. No information that could identify participants will be released.
De-identified data will be available beginning six months after publication of the primary results and will remain accessible for up to three years.
Researchers may submit a formal request to the principal investigator describing the intended analyses and data use. Requests will be reviewed by the study steering committee. Data will be shared electronically in compliance with institutional and ethical guidelines.
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| ID | Term |
|---|---|
| D061686 | Premature Ejaculation |
| ID | Term |
|---|---|
| D000097910 | Ejaculatory Dysfunction |
| D005832 | Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
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| ID | Term |
|---|---|
| D019274 | Botulinum Toxins, Type A |
| D006820 | Hyaluronic Acid |
| ID | Term |
|---|---|
| D001905 | Botulinum Toxins |
| D008666 | Metalloendopeptidases |
| D010450 | Endopeptidases |
| D010447 | Peptide Hydrolases |
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Two-arm randomized trial comparing botulinum toxin A injection into the bulbospongiosus muscle vs hyaluronic acid injection into the glans (Fanning Technique) in lifelong drug-resistant premature ejaculation (PE).
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| Hyaluronic acid | Drug | Two milliliters of 3.5 percent micronized hyaluronic acid gel will be injected into the dermis of the glans penis using the Fanning Technique. The injection will be performed through a single puncture site with a 27-gauge needle, advancing from the tip of the glans toward the coronal sulcus to distribute the gel evenly. Topical anesthetic cream containing lidocaine and prilocaine will be applied for 30 minutes before the procedure. |
|
| Change in Arabic Index of Premature Ejaculation (AIPE) score |
The Arabic Index of Premature Ejaculation questionnaire will assess subjective improvement in control, satisfaction, and distress related to ejaculation. Higher scores reflect better control and lower distress. |
| Baseline, 1 month, 3 months, 6 months, and 12 months after intervention |
| Change in Premature Ejaculation Profile (PEP) score | The Premature Ejaculation Profile will be used to evaluate treatment-related improvement across four domains: perceived control, personal distress, interpersonal difficulty, and sexual satisfaction. | Baseline, 1 month, 3 months, 6 months, and 12 months after intervention |
| Patient satisfaction score | Participants will rate overall satisfaction with the procedure using a four-point scale (0 = dissatisfied, 1 = slightly satisfied, 2 = satisfied, 3 = very satisfied). | 1 month, 3 months, 6 months, and 12 months after intervention |
| D012735 | Sexual Dysfunction, Physiological |
| D052801 | Male Urogenital Diseases |
| D020018 | Sexual Dysfunctions, Psychological |
| D001523 | Mental Disorders |
| D006867 |
| Hydrolases |
| D004798 | Enzymes |
| D045762 | Enzymes and Coenzymes |
| D045726 | Metalloproteases |
| D001426 | Bacterial Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D001427 | Bacterial Toxins |
| D014118 | Toxins, Biological |
| D001685 | Biological Factors |
| D006025 | Glycosaminoglycans |
| D011134 | Polysaccharides |
| D002241 | Carbohydrates |