Mechanism of Action: Vardenafil for PE

Lidocaine-prilocaine cream used for a period of 30–60 days significantly increases the mean IELT, especially when penile hypersensitivity is likely to be the cause. The main side-effects of topical anaesthetic application included retarded ejaculation of >30 min, decreased penile sensitivity, penile irritation, and decreased vaginal sensitivity [Citation102]. Topical anaesthetics are contraindicated for patients and/or their partners with allergies to any component of the product [Citation103]. Administration of 20 mg fluoxetine daily plus local application of lidocaine ointment was found to be more effective than fluoxetine alone [Citation104]. The SS-cream is formed from nine natural substances including ginseng and cinnamon and has local desensitising and vasoactive effects differing from the local anaesthetics in the fact that it persists for up to 2 h. It promises to be an effective and safe therapeutic modality for patients with PE [Citation105]. Applying SS-cream on the glans penis 1 h before planned sexual intercourse, lead to prolongation of ejaculatory latency time and improvement of sexual satisfaction for both partners with no adverse effect [Citation105,Citation106]. A study assessed penile vibratory threshold change using a bio-thesiometer using various doses of SS-cream and found that SS-cream increased the penile sensory threshold in a dose-dependent manner [Citation107]. Topical eutectic mixture for PE (TEMPE or PSD502) is a formulation of lidocaine and prilocaine in a metered dose aerosol-delivery system.

Other treatments against premature ejaculation

Lidocaine-prilocaine cream used for a period of 30–60 days significantly increases the mean IELT, especially when penile hypersensitivity is likely to be the cause. The main side-effects of topical anaesthetic application included retarded ejaculation of >30 min, decreased penile sensitivity, penile irritation, and decreased vaginal sensitivity [Citation102]. Topical anaesthetics are contraindicated for patients and/or their partners with allergies to any component of the product [Citation103]. Administration of 20 mg fluoxetine daily plus local application of lidocaine ointment was found to be more effective than fluoxetine alone [Citation104]. The SS-cream is formed from nine natural substances including ginseng and cinnamon and has local desensitising and vasoactive effects differing from the local anaesthetics in the fact that it persists for up to 2 h.

Premature Ejaculation Medication

It promises to be an effective and safe therapeutic modality for patients with PE [Citation105]. Applying SS-cream on the glans penis 1 h before planned sexual intercourse, lead to prolongation of ejaculatory latency time and improvement of sexual satisfaction for both partners with no adverse effect [Citation105,Citation106]. A study assessed penile vibratory threshold change using a bio-thesiometer using various doses of SS-cream and found that SS-cream increased the penile sensory threshold in a dose-dependent manner [Citation107]. Topical eutectic mixture for PE (TEMPE or PSD502) is a formulation of lidocaine and prilocaine in a metered dose aerosol-delivery system. Each spray delivers 7.5 mg lidocaine and 2.5 mg prilocaine.

On average, how long does a man last?

It is fast acting (within 5 min) and appears to be effective in improving the IELT and sexual satisfaction in patients with PE. It does not penetrate keratinised epithelium, and so only anaesthetises the glans, with no systemic side-effects and a low incidence of local side-effects [Citation108,Citation109]. Dyclonine is a local anaesthetic usually used in the field of dentistry. It has been combined with the vasodilator alprostadil and used to treat PE. The product is applied 5–20 min before intercourse to the tip of the penis in the region of the meatus. Each spray delivers 7.5 mg lidocaine and 2.5 mg prilocaine. It is fast acting (within 5 min) and appears to be effective in improving the IELT and sexual satisfaction in patients with PE.

It does not penetrate keratinised epithelium, and so only anaesthetises the glans, with no systemic side-effects and a low incidence of local side-effects [Citation108,Citation109]. Dyclonine is a local anaesthetic usually used in the field of dentistry. It has been combined with the vasodilator alprostadil and used to treat PE. The product is applied 5–20 min before intercourse to the tip of the penis in the region of the meatus. One pilot study claimed positive results with it; however, the data were limited and further studies are warranted before conclusions can be made [Citation110]. Several clinical trials have examined the potential effectiveness of the PDE5 inhibitor, sildenafil, in the treatment of PE. The rationale for the use of PDE5 inhibitors in the treatment of PE may be due to peripheral and/or central mechanisms. Ejaculation retarding by peripheral actions may include modulation of contractile response of vas deferens, seminal vesicles, prostate and urethra, induction of a state of peripheral analgesia, and prolongation of the total duration of erection. Central mechanisms may involve lessening of the central sympathetic output [Citation111].

Medication Summary

The on-demand administration of 50–100 mg sildenafil citrate for 1–3 months, in patients with PE complicated by ED, was found to safely and effectively improve erectile function and prolong ejaculation [Citation112]. In addition, sildenafil citrate increased confidence, perception of ejaculatory control, and overall sexual satisfaction, and decreased the refractory time to achieve a second erection after ejaculation in men with PE [Citation113].

It has also been shown that sildenafil combined with behavioural therapy produced more prolongation of the IELT and better male and female satisfaction than behavioural therapy alone in the treatment of patients with PE [Citation114]. On-demand administration of 50 mg sildenafil 1 h before planned sexual activity combined with 10 mg paroxetine daily for 3 weeks and then 20 mg on demand, for 6 months provided significant increases in the ILET and intercourse satisfaction than paroxetine alone in potent patients with PE. However, combined treatment is associated with a mild increase in drug-related side-effects (headache and flushing episodes) [Citation115]. Sildenafil citrate combined with paroxetine and psychological and behavioural counselling alleviated PE in patients in whom other treatments failed [Citation116]. Administration of 50 mg sildenafil on-demand 1 h before planned sexual activity combined with 50 mg sertraline daily, for 12 weeks produced more prolongation of the IELT, and better male and female satisfaction than sertraline alone in patients with PE [Citation117]. Furthermore, the on-demand administration of 50 mg sildenafil citrate 1 h before planned sexual activity for 6 months in patients with PE provided significant increases in the IELT and intercourse satisfaction than 20 mg paroxetine daily and the squeeze technique. However, adverse effects were more frequent in the sildenafil and paroxetine groups compared male enhancement pill to the squeeze technique group. The most frequent adverse effects for sildenafil were headache and nasal congestion [Citation118]. Other forms of PDE5 inhibitors have been used for the treatment of PE. The administration tadalafil 20 mg within 36 h before planned sexual intercourse combined with fluoxetine 90 mg once per week for 12 weeks in patients with lifelong PE resulted in significant increase in the IELT when compared to fluoxetine or tadalafil alone [Citation51].

The on-demand administration of 10 mg vardenafil for 16 weeks provided significant increase of IELT and reduced post-ejaculatory refractory time in men with lifelong PE [Citation119]. Improvement in confidence, perception of ejaculatory control and overall sexual satisfaction were reported. The use of 5 mg tadalafil once daily plus lidocaine anaesthetic spray in treatment of lifelong PE was more effective than tadalafil alone or lidocaine anaesthetic spray alone [Citation120]. In a single- blind placebo-controlled clinical study, the combined use of on-demand dapoxetine (30 mg) with sildenafil (50 mg) for patients with PE for 6 weeks had the best values of IELT and satisfaction scores in comparison with dapoxetine alone or sildenafil alone [Citation88]. Tramadol is a centrally acting analgesic with two mechanisms of action.

Surgical Intervention

Long-term studies are needed to determine the verifiable risk of opioid addiction [Citation9,Citation124]. Glans augmentation has been a technique proposed to desensitise the glans penis and slow the ejaculatory reflex. It is a method in which hyaluronic acid is injected into the glans at the coronal edge to provide analgesia of the penis. Hyaluronic acid is a glycosaminoglycan and bulking agent that has been used to insulate the nerve endings and provide long-term (>1 year) local anaesthesia. It was reported to increase the IELT and satisfaction in patients with PE [Citation125,Citation126].

What are common premature ejaculation medications?

Dorsal neurectomy with or without glandular augmentation with hyaluronic acid gel has been reported for treatment of refractory PE. It showed a significant increase in the IELT and patient satisfaction but associated with significant side-effects, including penile numbness, paraesthesia and pain [Citation125]. It has been reported that selective neurotomy of the dorsal penile nerve preserved potency and decreased sensitivity [Citation127]. Pulsed radiofrequency neuromodulation has been used for treatment of PE by desensitisation of the dorsal penile nerves. It showed a significant increase in the IELT in patients with PE.

More Information

There were no reported side-effects post-procedure such as pain, penile hypoesthesia, or ED [Citation128]. Frenectomy has been studied as a possible surgical therapy for PE because of the association of PE with a short frenulum, or frenulum breve [Citation129]. This condition can be congenital resulting from defects during sexual development or acquired secondary to excessive scarring occurring after rupture of a normal frenulum [Citation130]. It hinders complete retraction of the prepuce during erection causing a ventral curvature of the glans. It is thought that a short frenulum may illicit PE through two plausible premises: (1) an uncomfortable sense of traction during intercourse that may trigger the end of coitus, (2) being a reservoir of nerve endings that are directly exposed to the tactile stimulation during intercourse [Citation129]. It exerts an effect on the μ-opioid receptor, but also inhibits noradrenaline and serotonin reuptake. Its mechanism of action in PE is poorly understood; however, it is thought to be related to its action on the μ-opioid receptor, which may reduce sensitivity, as well as the inhibition of serotonin reuptake, which may delay ejaculation.

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Other forms of PDE5 inhibitors have been used for the treatment of PE. The administration tadalafil 20 mg within 36 h before planned sexual intercourse combined with fluoxetine 90 mg once per week for 12 weeks in patients with lifelong PE resulted in significant increase in the IELT when compared to fluoxetine or tadalafil alone [Citation51]. The on-demand administration of 10 mg vardenafil for 16 weeks provided significant increase of IELT and reduced post-ejaculatory refractory time in men with lifelong PE [Citation119]. Improvement in confidence, perception of ejaculatory control and overall sexual satisfaction were reported. The use of 5 mg tadalafil once daily plus lidocaine anaesthetic spray in treatment of lifelong PE was more effective than tadalafil alone or lidocaine anaesthetic spray alone [Citation120].

Corresponding author

In a single- blind placebo-controlled clinical study, the combined use of on-demand dapoxetine (30 mg) with sildenafil (50 mg) for patients with PE for 6 weeks had the best values of IELT and satisfaction scores in comparison with dapoxetine alone or sildenafil alone [Citation88]. Tramadol is a centrally acting analgesic with two mechanisms of action. It exerts an effect on the μ-opioid receptor, but also inhibits noradrenaline and serotonin reuptake. Its mechanism of action in PE is poorly understood; however, it is thought to be related to its action on the μ-opioid receptor, which may reduce sensitivity, as well as the inhibition of serotonin reuptake, which may delay ejaculation. It has a safety profile that is well tolerated with few side-effects [Citation121].

Tadalafil (Cialis)

Administration of 50 mg tramadol HCl 2 h before planned sexual activity for 8 weeks, resulted in a significant increase of IELT and intercourse satisfaction vs placebo [Citation55]. Administration of 25 mg tramadol, 1–2 h before planned sexual activity for 8 weeks, significantly increased the IELT and intercourse satisfaction [Citation121]. Administration of 50 mg tramadol with behavioural modification, 2 h before planned sexual activity for 8 weeks resulted in significant improvement in the IELT and overall sexual satisfaction [Citation122]. On-demand administration of 62 mg tramadol (oral disintegrating tablet), 2–8 h before planned sexual intercourse for 12 weeks in patients with mild to severe PE resulted in significant increase in the IELT, improvement in overall sexual satisfaction and control over ejaculation, and decreased ejaculation-related personal distress and interpersonal difficulty [Citation123]. As tramadol is an opioid, with weak µ-opioid activity, there are concerns about its abuse and dependence. It has a safety profile that is well tolerated with few side-effects [Citation121].

• Vardenafil is marketed under various brand names.
• Its use for PE is based on anecdotal success stories.
• Some men combine Vardenafil with other PE strategies.
• Non-medical use is discouraged due to health risks.
• Regular medical check-ups are recommended during use.
• Vardenafil has a rapid onset time for many users.
• It may affect blood pressure temporarily.
• Not recommended for recreational use.
• Its impact on PE varies widely.
• Men should disclose all health data to their doctor.
• Overdose symptoms include dizziness and prolonged erection.
• Financial costs may vary depending on brand and pharmacy.

Administration of 50 mg tramadol HCl 2 h before planned sexual activity for 8 weeks, resulted in a significant increase of IELT and intercourse satisfaction vs placebo [Citation55]. Administration of 25 mg tramadol, 1–2 h before planned sexual activity for 8 weeks, significantly increased the IELT and intercourse satisfaction [Citation121]. Administration of 50 mg tramadol with behavioural modification, 2 h before planned sexual activity for 8 weeks resulted in significant improvement in the IELT and overall sexual satisfaction [Citation122]. On-demand administration of 62 mg tramadol (oral disintegrating tablet), 2–8 h before planned sexual intercourse for 12 weeks in patients with mild to severe PE resulted in significant increase in the IELT, improvement in overall sexual satisfaction and control over ejaculation, and decreased ejaculation-related personal distress and interpersonal difficulty [Citation123]. As tramadol is an opioid, with weak µ-opioid activity, there are concerns about its abuse and dependence.

Treating Premature Ejaculation

Long-term studies are needed to determine the verifiable risk of opioid addiction [Citation9,Citation124].

Class Summary

One pilot study claimed positive results with it; however, the data were limited and further studies are warranted before conclusions can be made [Citation110]. Several clinical trials have examined the potential effectiveness of the PDE5 inhibitor, sildenafil, in the treatment of PE. The rationale for the use of PDE5 inhibitors in the treatment of PE may be due to peripheral and/or central mechanisms. Ejaculation retarding by peripheral actions may include modulation of contractile response of vas deferens, seminal vesicles, prostate and urethra, induction of a state of peripheral analgesia, and prolongation of the total duration of erection. Central mechanisms may involve lessening of the central sympathetic output [Citation111].

Authors and Affiliations

The on-demand administration of 50–100 mg sildenafil citrate for 1–3 months, in patients with PE complicated by ED, was found to safely and effectively improve erectile function and prolong ejaculation [Citation112]. In addition, sildenafil citrate increased confidence, perception of ejaculatory control, and overall sexual satisfaction, and decreased the refractory time to achieve a second erection after ejaculation in men with PE [Citation113]. It has also been shown that sildenafil combined with behavioural therapy produced more prolongation of the IELT and better male and female satisfaction than behavioural therapy alone in the treatment of patients with PE [Citation114]. On-demand administration of 50 mg sildenafil 1 h before planned sexual activity combined with 10 mg paroxetine daily for 3 weeks and then 20 mg on demand, for 6 months provided significant increases in the ILET and intercourse satisfaction than paroxetine alone in potent patients with PE. However, combined treatment is associated with a mild increase in drug-related side-effects (headache and flushing episodes) [Citation115].

Vardenafil (Levitra®) for PE

Sildenafil citrate combined with paroxetine and psychological and behavioural counselling alleviated PE in patients in whom other treatments failed [Citation116]. Administration of 50 mg sildenafil on-demand 1 h before planned sexual activity combined with 50 mg sertraline daily, for 12 weeks produced more prolongation of the IELT, and better male and female satisfaction than sertraline alone in patients with PE [Citation117]. Furthermore, the on-demand administration of 50 mg sildenafil citrate 1 h before planned sexual activity for 6 months in patients with PE provided significant increases in the IELT and intercourse satisfaction than 20 mg paroxetine daily and the squeeze technique. However, adverse effects were more frequent in the sildenafil and paroxetine groups compared male enhancement pill to the squeeze technique group. The most frequent adverse effects for sildenafil were headache and nasal congestion [Citation118]. Glans augmentation has been a technique proposed to desensitise the glans penis and slow the ejaculatory reflex. It is a method in which hyaluronic acid is injected into the glans at the coronal edge to provide analgesia of the penis.

• Vardenafil may improve overall sexual satisfaction.
• Men should report any adverse effects to their doctor.
• Taking Vardenafil 1 hour before sex is common.
• It can assist men with PE but is not a standalone solution.
• Lifestyle changes may also help manage PE symptoms.
• Combining medication with therapy increases effectiveness.
• Vardenafil's efficacy varies among individuals.
• Medical advice is crucial before starting Vardenafil for PE.
• Not recommended for men with certain cardiovascular conditions.
• Dose adjustments may be needed based on response.
• Vardenafil can be used with other ED treatments.
• Store Vardenafil at room temperature, away from moisture.

Hyaluronic acid is a glycosaminoglycan and bulking agent that has been used to insulate the nerve endings and provide long-term (>1 year) local anaesthesia. It was reported to increase the IELT and satisfaction in patients with PE [Citation125,Citation126]. Dorsal neurectomy with or without glandular augmentation with hyaluronic acid gel has been reported for treatment of refractory PE.

• Men should discuss their PE history before use.
• Patience is key; effects may not be immediate.
• Vardenafil is sometimes used alongside other medications.
• Combining therapy and medication often yields better results.
• Side effects are generally mild but should be monitored.
• It is not recommended for use by women.
• Alcohol can diminish the effectiveness of Vardenafil.
• The medication should be stored away from children.
• Follow dosing instructions carefully.
• Consulting a urologist can optimize treatment plans.
• Vardenafil can improve sexual confidence.
• Men should be aware of potential interactions.

It showed a significant increase in the IELT and patient satisfaction but associated with significant side-effects, including penile numbness, paraesthesia and pain [Citation125]. It has been reported that selective neurotomy of the dorsal penile nerve preserved potency and decreased sensitivity [Citation127].

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Surgical removal of foreskin remnants in incomplete circumcised adult patients with PE resulted in a significant increase in the IELT, overall sexual satisfaction, and control over ejaculation because it significantly decreased hypersensitivity of penis [Citation131]. A higher prevalence of PE has been reported in men with varicocele for unclear reasons [Citation132,Citation133]. Pulsed radiofrequency neuromodulation has been used for treatment of PE by desensitisation of the dorsal penile nerves. It showed a significant increase in the IELT in patients with PE.

• Vardenafil may cause a sensation of visual flickering.
• It can assist in cases of PE linked to performance anxiety.
• Proper hydration supports medication effectiveness.
• Combining Vardenafil with counseling may help extend benefits.
• Men should avoid excessive alcohol consumption.
• The recommended dose varies based on individual health.
• Some men notice a delay in ejaculation within 30 minutes.
• Not all men respond equally to Vardenafil.
• Safe use requires medical supervision.
• Vardenafil should not be mixed with other PDE5 inhibitors.
• Monitoring blood pressure is important during use.
• Use caution to prevent interactions with other drugs.

There were no reported side-effects post-procedure such as pain, penile hypoesthesia, or ED [Citation128]. Frenectomy has been studied as a possible surgical therapy for PE because of the association of PE with a short frenulum, or frenulum breve [Citation129]. This condition can be congenital resulting from defects during sexual development or acquired secondary to excessive scarring occurring after rupture of a normal frenulum [Citation130]. It hinders complete retraction of the prepuce during erection causing a ventral curvature of the glans. It is thought that a short frenulum may illicit PE through two plausible premises: (1) an uncomfortable sense of traction during intercourse that may trigger the end of coitus, (2) being a reservoir of nerve endings that are directly exposed to the tactile stimulation during intercourse [Citation129]. Surgical removal of foreskin remnants in incomplete circumcised adult patients with PE resulted in a significant increase in the IELT, overall sexual satisfaction, and control over ejaculation because it significantly decreased hypersensitivity of penis [Citation131]. A higher prevalence of PE has been reported in men with varicocele for unclear reasons [Citation132,Citation133].