Premature ejaculation (PE) is a common condition that can impact a man’s confidence and intimate relationships. Fortunately, medical treatments such as oral tablets and topical creams offer effective solutions. Tablets, including selective serotonin reuptake inhibitors (SSRIs) and phosphodiesterase inhibitors, help delay ejaculation by altering neurotransmitter activity. Topical creams, often containing numbing agents like lidocaine or prilocaine, reduce sensitivity and prolong performance.

This article explores how these treatments work, their effectiveness, and potential side effects to help you make an informed decision.

Which Tablets are used for Treatment of PE?

Several types of tablets are used to medically treat PE. These medications primarily work by altering neurotransmitter activity to delay ejaculation. The most commonly used tablets include:

Selective Serotonin Reuptake Inhibitors (SSRIs)

Originally developed as antidepressants, SSRIs are effective in delaying ejaculation by increasing serotonin levels in the brain. Common SSRIs used for PE include:

• Dapoxetine (Priligy) – The only SSRI specifically approved for PE, offering fast action and short half-life.
• Paroxetine – Used off-label, but may take several weeks to show effects.
• Sertraline – Another off-label SSRI, sometimes prescribed for PE.
• Fluoxetine – Can also be used, but has a longer onset of action.

Phosphodiesterase Type 5 Inhibitors (PDE5 Inhibitors)

These medications are primarily used for erectile dysfunction but may help with PE, especially in men who also experience erection issues. Examples include:

• Sildenafil (Viagra)
• Tadalafil (Cialis)
• Vardenafil (Levitra, Staxyn)

Tricyclic Antidepressants (TCAs)

Although less common, some tricyclic antidepressants can help delay ejaculation:

• Clomipramine – A TCA that has been shown to prolong ejaculation time.

Alpha-Adrenergic Receptor Blockers

These medications, usually used for hypertension or prostate conditions, may help some men with PE:

• Tamsulosin (Flomax) – Can reduce ejaculation urgency.

Dopamine Receptor Antagonists

• Tramadol – A pain reliever with off-label use for delaying ejaculation.

While these medications can be effective, they may have side effects such as nausea, dizziness, or changes in libido. Always consult a doctor before starting treatment.

Mechanisms of action and side effects of tablets used for the medical treatment of PE

Different types of tablets are used to treat premature ejaculation (PE), each with distinct mechanisms of action and potential side effects.

1. Selective Serotonin Reuptake Inhibitors (SSRIs)

Examples: Dapoxetine, Paroxetine, Sertraline, Fluoxetine
Mechanism of Action:

• Increase serotonin levels in the brain, which helps delay ejaculation by reducing sensitivity to sexual stimulation.
• Dapoxetine is the only SSRI specifically approved for PE, with a rapid onset of action.

Side Effects:

• Nausea, dizziness, headache
• Insomnia or drowsiness
• Decreased libido or erectile dysfunction in some cases

2. Phosphodiesterase Type 5 (PDE5) Inhibitors

Examples: Sildenafil (Viagra), Tadalafil (Cialis), Vardenafil (Levitra)
Mechanism of Action:

• Improve blood flow to the penis, enhancing erection quality and reducing performance anxiety, which indirectly helps with PE.
• May also modulate neurotransmitters that influence ejaculation control.

Side Effects:

• Headache, flushing, nasal congestion
• Indigestion, dizziness
• Low blood pressure (rare)

3. Tricyclic Antidepressants (TCAs)

Example: Clomipramine
Mechanism of Action:

• Acts on serotonin and norepinephrine receptors, delaying ejaculation similarly to SSRIs.
• Used off-label for PE treatment.

Side Effects:

• Dry mouth, constipation
• Drowsiness, dizziness
• Increased heart rate (tachycardia)

4. Opioid Analgesics (Tramadol)

Example: Tramadol (low-dose)
Mechanism of Action:

• Binds to opioid receptors and increases serotonin and norepinephrine levels, delaying ejaculation.
• Used off-label but can be effective for short-term management of PE.

Side Effects:

• Drowsiness, dizziness
• Nausea, constipation
• Risk of dependence with prolonged use

5. Alpha-Adrenergic Receptor Blockers

Example: Tamsulosin (Flomax)
Mechanism of Action:

• Relaxes smooth muscles in the reproductive tract, delaying ejaculation.
• More commonly used for prostate conditions but may help some men with PE.

Side Effects:

• Dizziness, fatigue
• Low blood pressure
• Retrograde ejaculation (semen enters the bladder instead of exiting the penis)

Combination medical treatment of PE

Combining different medical treatments can enhance the effectiveness of premature ejaculation (PE) therapy by targeting multiple mechanisms. Here are some common combination approaches:

SSRIs + PDE5 Inhibitors

• Example: Dapoxetine + Sildenafil (Priligy + Viagra)
• How it Works: SSRIs increase serotonin levels to delay ejaculation, while PDE5 inhibitors improve erection quality and reduce performance anxiety.
• Effectiveness: Studies suggest this combination provides better results for men with both PE and erectile dysfunction.

Topical Anesthetics + Oral Medications

• Example: Lidocaine-Prilocaine Cream + Dapoxetine
• How it Works: Topical anesthetics reduce penile sensitivity, while SSRIs work on the central nervous system to delay ejaculation.
• Effectiveness: This combination helps men who don’t fully respond to SSRIs alone.

Tramadol + SSRIs

• Example: Tramadol + Paroxetine
• How it Works: Tramadol, an opioid analgesic, delays ejaculation, and SSRIs enhance the effect by modulating serotonin levels.
• Effectiveness: Some studies suggest this combination is useful for men who don’t respond well to SSRIs alone.

Behavioral Therapy + Medications

• Example: Dapoxetine + Pelvic Floor Exercises
• How it Works: Medications delay ejaculation, while exercises strengthen pelvic muscles, improving ejaculatory control.
• Effectiveness: A long-term solution that improves natural ejaculation control.

Hormonal Therapy + SSRIs

• Example: Testosterone Therapy + Dapoxetine (for low testosterone patients)
• How it Works: Treating testosterone deficiency can improve sexual function, while SSRIs directly address PE.
• Effectiveness: Beneficial for men with PE linked to hormonal imbalances.

Considerations

• Combining treatments should be done under medical supervision to avoid interactions or side effects.
• Some combinations may work better for certain types of PE (lifelong vs. acquired).
• Lifestyle changes, such as stress management and regular exercise, can enhance treatment results.

Topical creams for the medical treatment of PE

Topical creams are a common treatment for PE, as they work by reducing penile sensitivity, thereby delaying ejaculation. These creams typically contain local anesthetics that temporarily numb the area without significantly affecting sexual pleasure.

Lidocaine-Based Creams

• Lidocaine 5% Cream
• Promescent (Lidocaine Spray) – A desensitizing spray that absorbs quickly and offers precise control over sensitivity.

Prilocaine-Based Creams

• Prilocaine 2.5% Cream
• Often combined with lidocaine for enhanced effect.

Lidocaine-Prilocaine Combination Creams

• EMLA Cream (Lidocaine 2.5% + Prilocaine 2.5%)
• One of the most commonly prescribed topical anesthetics for PE.

Benzocaine-Based Creams

• Benzocaine 4-10% Creams/Gels
• Works similarly to lidocaine but is milder in effect.

Herbal & Natural Desensitizing Creams

• Some creams contain herbal extracts with mild numbing effects, such as menthol or clove oil.

Mecghanisms and side effects of creams

We can summarised the mechanisms of action and side effects as follows;

How These Creams Work

• They reduce penile sensitivity, allowing for longer intercourse before ejaculation.
• Most are applied 10-30 minutes before intercourse and wiped off before penetration to prevent partner numbness.

Potential Side Effects

• Temporary numbness or loss of sensitivity.
• Partner transfer, causing reduced pleasure for the partner.
• Allergic reactions (itching, redness, burning).

Summary

PE can be effectively managed with medical treatments, including oral tablets and topical creams. Tablets such as SSRIs (e.g., Dapoxetine, Paroxetine) and PDE5 inhibitors (e.g., Sildenafil, Tadalafil) help delay ejaculation by altering neurotransmitter activity or improving erectile function. Topical creams like Lidocaine-Prilocaine work by reducing penile sensitivity, prolonging intercourse. Combination treatments, including behavioral therapy, can enhance results. While these treatments are effective, potential side effects and individual suitability should be considered under medical supervision.

Prof. Dr. Emin ÖZBEK

Urologist

Istanbul- TURKIYE