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Address correspondence to: Parviz K. Kavoussi, M.D., F.A.C.S., Department of Reproductive Urology and Andrology Laboratory, Austin Fertility & Reproductive Medicine/Westlake IVF, 300 Beardsley Lane, Building B, Suite 200, Austin, TX 78746.
To assess the impact of Promescent, a commonly used topical medication for premature ejaculation (PE), on human sperm motility, forward progression (FP), viability, and sperm DNA fragmentation (SDF) in vitro.
Materials and Methods
Aliquots from specimens for diagnostic semen analyses from patients (n = 20) presenting to a couple's fertility center andrology laboratory for fertility testing were included after the full diagnostic semen analyses were performed. Samples that met the World Health Organization's fifth edition criteria as “normal” had Promescent applied to an aliquot of the sample and motility, FP, viability, and SDF were compared with an aliquot that was not treated with Promescent. Institutional review board exemption was obtained. Statistical analysis was performed by Student t test with a P value of <.05 considered as statistically significant.
Results
Promescent had a cytotoxic effect on sperm, which resulted in a statistically significant decrease in mean motility, FP, and viability as compared with corresponding control group samples, which did not have Promescent applied. There was no statistically significant difference in SDF between the 2 groups.
Conclusion
PE is estimated to affect up to 39% of men and is one of the most common self-reported male sexual disorders. There is an overlap among men with PE and those trying to achieve a pregnancy, and Promescent is a commonly used topical treatment for PE. Although there was no difference in SDF between the 2 groups, Promescent had a cytotoxic impact on sperm.
is one of the most common forms of sexual dysfunction in men and affects between 20% and 30% of the male population. Although the definition of PE has been debated over the years, the International Society for Sexual Medicine defines PE as ejaculation that always, or almost always, occurs before or within 1 minute of penetration and results in negative personal consequences such as frustration and avoidance of sexual intimacy.
PE can be classified as either a lifelong condition where the male has had symptoms since the onset of sexual maturity, an acquired condition where there was a time of normal intimacy with satisfactory intravaginal ejaculatory latency time (IELT) before the development of PE, or natural variable PE, which is situation specific.
The etiology of PE is uncertain and, consequently, there are proposed hypotheses relating to the patient's mental or behavioral state when pertaining to sexual intimacy, as well as physical factors such as heightened sensitivity.
Many medical treatments have been utilized, including selective serotonin reuptake inhibitors, hormonal treatments, phosphodiesterase type 5 inhibitors, and local topical desensitizing formulations. Topical desensitizing formulations are common treatments for PE that vary in their compositions but utilize a similar approach to penile hypersensitivity, a hypoesthesia effect to desensitize the penis with the goal of prolonging IELT.
Promescent is a commonly used, over-the-counter localized desensitizing spray for the treatment of PE. Promescent has a 2-phase melt system using binary eutectic technology and has an independent effect of ethanol to further increase absorption across the stratum corneum of the skin. This binary eutectic mixture of components, at certain ratios, results in a reduction of the melting point temperature of the active ingredients. By reducing the active melting point temperature of its active ingredients, an oil-aqueous 2-phase melt system is created with a high concentration of active ingredient in the oil phase. The use of 2 different melting point depressive compounds (thymol and ethanol) minimizes the relative volumes of these compounds in the system and enables the concentration of lidocaine to be maximized in the oil phase of the 2-phase melt system up to 87%. Promescent is applied to the penile skin 10 minutes before intercourse. Each metered dose contains 130 µL and 10 mg of lidocaine. The components of Promescent include lidocaine, acrylates-C10-30 alkyl acrylate crosspolymer, ceteareth-20, cetearyl alcohol, citric acid, dimethicone, farnesol, fragrance, glycerin, hydrogenated polyisobutene, macademia ternifiola seed oil, panthenol, phenoxyethanol, purified water, SD alcohol 40-B, sodium hydroxide, soy, lecithin, stearoxytrimethylsilane, stearyl alcohol, thymol, and tocopheryl acetate (vitamin E).
Approximately 15% of couples trying to conceive have difficulty doing so and are considered subfertile.
With the prevalence of male infertility and the high prevalence of PE, there is a high propensity for subfertile men to have PE and to potentially use treatments for PE when trying to conceive. We sought to investigate whether or not Promescent affects human semen parameters among subfertile and fertile men. The present study aimed to evaluate the impact of Promescent on fresh sperm motility, forward progression (FP), viability, and sperm DNA fragmentation (SDF) in vitro.
Materials and Methods
Semen specimens collected by male patients at a couple's fertility center andrology laboratory for routine semen analysis (n = 20) were selected after samples were determined to meet “normal” semen analysis parameters per World Health Organization (WHO) fifth edition criteria (Table 1). The samples were collected after a minimum of 2 days and a maximum of 5 days of abstinence from ejaculation. The samples were collected on-site at the fertility center by masturbation in wide-mouthed, sterile specimen cups, and were placed on the bench in the andrology laboratory and kept at room temperature until the semen liquified, at which time diagnostic semen analysis was performed. After diagnostic semen analysis was performed, the remainder of each sample's volume was divided in half; one-half remained untreated and the other half was treated with the Promescent topical spray. After the sample liquified, the treated aliquot was exposed to 2 sprays of Promescent, consistent with the starting clinical dose, and allowed to incubate for 10 minutes at room temperature per Promescent's protocol for clinical use after application to the penile skin. After the 10-minute incubation period, a diagnostic semen analysis was performed on the treated sample using the WHO fifth edition diagnostic criteria. An eosin-nigrosin viability stain was performed on both the Promescent-treated and untreated aliquots per the WHO fifth protocol. One hundred cells were counted per aliquot and the percent viable was calculated. SDF testing was then performed by sperm chromatin dispersion test using Spectrum Technology's second-generation Halosperm Kit (Madrid, Spain). Three hundred cells were counted per aliquot and the percent of SDF was calculated per the Halosperm guidelines. Institutional review board exemption was obtained. Statistical analysis was performed by the Student t test with a P value of <.05 considered as statistically significant.
Table 1The World Health Organization fifth edition normal semen parameter reference range
A total of 20 men's semen samples were included. Sperm motility, FP, viability, and SDF of Promescent-treated aliquots were compared with untreated aliquots of the 20 samples at 10 minutes after the application of Promescent. Promescent-treated aliquots revealed a statistically significant decrease in mean motility, FP, and viability as compared with the untreated aliquots of the same samples examined at the same time interval. These effects were clearly due to the cytotoxic impact of Promescent on sperm viability and therefore the motility and FP. The untreated portions of the samples had a mean motility of 50% (standard deviation [SD] 11.6, range 30%-61%), a mean FP of 31% (SD 11.9, range 11%-63%), and a mean viability of 70% (SD 9.5, range 53%-87%), all of which were 0% in the Promescent-treated aliquots. There were no motile, forward progressive, or viable sperm cells identified in the aliquots exposed to Promescent (Table 2, Fig. 1). The mean SDF index in the untreated group was 27% (SD 11.6, range 14%-57%) The mean SDF index in the Promescent-treated group was 29% (SD 11.4, range 19%-59%). There was no statistically significant difference in SDF between the 2 groups at 10 minutes after the application of Promescent (Table 2).
Table 2Promescent-treated semen samples vs untreated semen samples: motility, forward progression, viability, and DNA fragmentation index
Ejaculation is the final phase of the sexual response cycle in men. Ejaculation is a reflex comprising sensory stimuli, cerebral and spinal cord centers, and efferent neural pathways. PE is a very common form of male sexual dysfunction occurring in up to 39% of men in the general population and causes a negative impact in the quality of life of couples. The definition of PE has evolved over time. In the 1950s, PE was defined as the inability to control ejaculation to satisfy the partner at least 50% of the time. In 2000, PE was redefined as ejaculation with minimal stimulation before or shortly after penetration. The 2014 definition of PE by the International Society for Sexual Medicine was described as ejaculation that always or nearly always occurs before or within 1 minute of vaginal penetration or a clinically significant and bothersome reduction in IELT, often to ≤3 minutes, the inability to delay ejaculation on all or nearly all vaginal penetrations, and negative personal consequences, such as distress, bother, frustration, and the avoidance of sexual intimacy.
The exact pathology of PE is not perfectly understood and multiple modalities of treatment are used to treat PE, including behavioral modifications, selective serotonin reuptake inhibitors, hormonal treatments, phosphodiesterase type 5 inhibitors, and local topical desensitizing formulations. Topical desensitizing formulations have gained favor as they are simple to use, can be used on demand, and do not have systemic side effects.
Promescent is an over-the-counter, topical spray desensitizing treatment for PE in a metered dose delivery system, which is an appealing treatment option, as it is an on-demand drug and does not result in systemic side effects. Promescent has become a commonly used treatment option for PE, and as it is sold over the counter, there is the potential of recreational use as well. To our knowledge, the impact of Promescent on human sperm, and potentially on male fertility, has not been assessed until now. Data from this proof-of-concept study reveal a severely harmful impact of Promescent on human sperm motility, FP, and viability in vitro. Although the mechanism of the cytotoxic impact of Promescent on sperm in vitro, or which component of Promescent is responsible for this effect, is not elicitable from these data, clearly it is severe. Regardless of the chemical component in Promescent that has this deleterious impact on human sperm, these data raise questions about the use of this formulation in men desiring to achieve a pregnancy.
A limitation of the present study is that the impact on human sperm was assessed with direct application of Promescent to sperm in vitro, which may not be equivalent to the impact it would have on sperm after being applied to penile skin. This likely represents a higher dose of Promescent directly to sperm than would be in a clinical scenario. However, this is a proof-of-concept study as an initial evaluation of the impact of Promescent on human sperm in vitro, much as the initial study evaluating the impact of vaginal lubricants on human sperm was performed in vitro, which led to further studies that led to the clinical understanding of vaginal lubricants impact on conception at the time of ovulation. Our Promescent study evaluated the same number of samples as the data on lubricants impact on sperm in vitro.
Further study including assessing sperm after applying Promescent to the penis, as would be done for clinical use, and collecting a specimen 10 minutes after the application of the product would help elucidate the cytotoxic impact of Promescent on sperm in the clinical scenario. Postcoital testing may also be helpful to assess the impact.
Conclusion
Promescent has a cytotoxic impact on sperm when applied directly to the semen in vitro. Further clinical studies are needed to further evaluate the findings in this in vitro proof-of-concept study, as in vitro analysis may not be equivalent to the impact clinically, but based on this preliminary data, caution should be used with the use of Promescent in couples trying to conceive.
Financial Disclosure:The authors declare that they have no relevant financial interests.
Funding Support:There was no external source of funding for this work. The materials and work were provided by the practice with the in-house laboratory.
Author Contributions: Melissa Sutton, M.S., and Caitlin Hunn, M.S.: substantial contributions to research design; acquisition, analysis, and interpretation of data; drafting; and critical revision of the paper. Roxanne B. Summers-Colquitt, M.Sc., Keikhosrow M. Kavoussi, M.D., and Shu-Hung Chen, M.S.: substantial contributions to research design, and acquisition, analysis, and interpretation of data. Shahryar K. Kavoussi, M.D., M.P.H., and Parviz K. Kavoussi, M.D.: substantial contributions to research design; the acquisition, analysis, and interpretation of data; drafting and critical revision of the paper; approval of the submitted and final versions.
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