Topical Treatment of Premature Ejaculation: The Rise of Anesthetic Spray Formulations?
, Carolina Bebi 3, Andrea Salonia 1,2 and Luca Boeri 1,3,*Round 1
Reviewer 1 Report
This narrative review from Pozzi and colleagues highlights some important findings regarding the use of topical anesthetics in the treatment of premature ejaculation. The review is not deep and exhaustive but it covers some important aspects of anesthetic use in PE. Overall most of my suggestions refer to minor typos/grammatical issues specifically pinpointed below. I also suggest widening the introduction section covering more data suggestive of increased penile hypersensitivity in PE and also the conflicting data suggesting normal penile sensitivity of patients with PE. In fact, the only cited study investigating penile sensitivity in patients with PE is that of Salonia et al (JSM, 2009). In addition, briefly discussing the surgical penile denervation in PE as an emerging therapeutic option to PE would also be interesting as it gives some support to an increased penile sensitivity as an organic cause of PE (please see the interesting paper of Liu et al JSM 16:522, 2019 suggesting increased penile innervation in patients with PE).
Bellow my minor issues:
Page 2, line 45: correct “inteconnectedetiologies”
Page 2, line 49: correct “patients on commonly report SSRI...” to “patients commonly report SSRI...”
Page 2, line 51: correct “In the light of this findings...” to “In the light of these findings...”aesthetics to anesthetic.
Page 2, line 52-54: please add references to the “hypersensitivity hypothesis”.
Page 2, line 54: correct aesthetics to anesthetics.
Page 2, lines 53-56: please add references of studies showing the beneficial effect of topical anesthetics to both patients and partners.
Page 2, Materials and Methods section: I did not understand the statement that reviews were an exclusion criteria for retrievered studies (line 64).
Page 2, Results section, lines 87-98: “Subsequently, Atikeler et al. investigated the efficacy of this preparation in a larger cohort of patients, observing a statistically significant increase in ejaculation time, with an average pre-ejaculation period increasing from 6.7 minutes to 8.7 minutes [18].”
Please correct this statement. Actually, the authors show the IELT from the patients with PE (IELT < 1min at baseline according to the medical history) increased to 6-8 min depending on the total time of anesthetic application, i.e. the IELTs increased from around 1 min to 6-8 min and not from 6.7min to 8.7 minutes as stated in the present manuscript. In fact, men with a 6.7 min IELT are not considered PE patients and would not be recruited in the study of Atikeler et al.
Page 3, line 93: change “anaesthetics” to “anesthetics” to keep consistency in the chosen English.
Page 3, line 105: correct “lidocaine only spray” to “lidocaine-only spray”
Page 3, line 106: correct “over the counter” to “over-the-counter”
Page 3, line 11: correct “results were shown to significantly better” to “results were shown to be significantly better”
Page 3, line 118: please correct “Despite being is oil-free...” to “Despite being oil-free...”.
Page4, line 156: please correct “on demand” to “on-demand”
Page 5, line 190: on-demand use can not to be cited as an advantage of topical treatments over systemic treatments to PE as dapoxetine, a systemic drug, is used on-demand.
Page 5, line 197: change “has to be applied” to “have to be applied”
As stated by the authors “Only a limited number of studies investigated the efficacy of combination therapy of local anesthetics and phosphodiesterase type 5 inhibitors (PDE5i) for PE.” (Page 4, lines 172-173). Therefore, there is no place to the authors’ speculation that “Based on recent literature and emerging data we could speculate that the combination of PDE5i with topical lidocaine/prilocaine could possibly increase the efficacy of any kind of monotherapy and could become an established second-line therapy severe PE.” (Page 5, lines 205-207). The analysis of PDE5i/local anesthetics combination therapy on PE therapeutic arena needs much more studies yet to be done. Please remove the Page 5, lines 205-207 final discussion.
Author Response
"This narrative review from Pozzi and colleagues highlights some important findings regarding the use of topical anesthetics in the treatment of premature ejaculation. The review is not deep and exhaustive but it covers some important aspects of anesthetic use in PE. Overall most of my suggestions refer to minor typos/grammatical issues specifically pinpointed below. I also suggest widening the introduction section covering more data suggestive of increased penile hypersensitivity in PE and also the conflicting data suggesting normal penile sensitivity of patients with PE. In fact, the only cited study investigating penile sensitivity in patients with PE is that of Salonia et al (JSM, 2009). In addition, briefly discussing the surgical penile denervation in PE as an emerging therapeutic option to PE would also be interesting as it gives some support to an increased penile sensitivity as an organic cause of PE (please see the interesting paper of Liu et al JSM 16:522, 2019 suggesting increased penile innervation in patients with PE)."
Answer: The introduction section has been revised accordingly.
"
Page 2, line 45: correct “inteconnectedetiologies”
Page 2, line 49: correct “patients on commonly report SSRI...” to “patients commonly report SSRI...”
Page 2, line 51: correct “In the light of this findings...” to “In the light of these findings...”aesthetics to anesthetic.
Page 2, line 52-54: please add references to the “hypersensitivity hypothesis”.
Page 2, line 54: correct aesthetics to anesthetics.
Page 2, lines 53-56: please add references of studies showing the beneficial effect of topical anesthetics to both patients and partners.
Page 2, Materials and Methods section: I did not understand the statement that reviews were an exclusion criteria for retrievered studies (line 64).
Page 2, Results section, lines 87-98: “Subsequently, Atikeler et al. investigated the efficacy of this preparation in a larger cohort of patients, observing a statistically significant increase in ejaculation time, with an average pre-ejaculation period increasing from 6.7 minutes to 8.7 minutes [18].”
Please correct this statement. Actually, the authors show the IELT from the patients with PE (IELT < 1min at baseline according to the medical history) increased to 6-8 min depending on the total time of anesthetic application, i.e. the IELTs increased from around 1 min to 6-8 min and not from 6.7min to 8.7 minutes as stated in the present manuscript. In fact, men with a 6.7 min IELT are not considered PE patients and would not be recruited in the study of Atikeler et al.
Page 3, line 93: change “anaesthetics” to “anesthetics” to keep consistency in the chosen English.
Page 3, line 105: correct “lidocaine only spray” to “lidocaine-only spray”
Page 3, line 106: correct “over the counter” to “over-the-counter”
Page 3, line 11: correct “results were shown to significantly better” to “results were shown to be significantly better”
Page 3, line 118: please correct “Despite being is oil-free...” to “Despite being oil-free...”.
Page4, line 156: please correct “on demand” to “on-demand”
Page 5, line 190: on-demand use can not to be cited as an advantage of topical treatments over systemic treatments to PE as dapoxetine, a systemic drug, is used on-demand.
Page 5, line 197: change “has to be applied” to “have to be applied”
Answer: each typo has been corrected. Methods & Results have been revised according to Reviewer's comments.
"As stated by the authors “Only a limited number of studies investigated the efficacy of combination therapy of local anesthetics and phosphodiesterase type 5 inhibitors (PDE5i) for PE.” (Page 4, lines 172-173). Therefore, there is no place to the authors’ speculation that “Based on recent literature and emerging data we could speculate that the combination of PDE5i with topical lidocaine/prilocaine could possibly increase the efficacy of any kind of monotherapy and could become an established second-line therapy severe PE.” (Page 5, lines 205-207). The analysis of PDE5i/local anesthetics combination therapy on PE therapeutic arena needs much more studies yet to be done. Please remove the Page 5, lines 205-207 final discussion."
Answer: We totally agree with Reviewer1 that data are insufficient to draw general conclusions. The text has been revised accordingly.
Reviewer 2 Report
Overall, the manuscript is well-written and it is interesting. However, there are few comments to be addressed:
- It seems the authors are performing a systematic search, in this case it would be interesting to describe the number of articles included, the number of articles excluded and the reasons. Include a flow chart.
- It would help the reader to include some tables summarising the information about which formulation is better with pros and cons.
- It would be useful to include some schematics or diagrams in the manuscript to make it easeir to read.
Author Response
We thank the Reviewer 2 for these precise comments
"1-It seems the authors are performing a systematic search, in this case it would be interesting to describe the number of articles included, the number of articles excluded and the reasons. Include a flow chart.
2- It would help the reader to include some tables summarising the information about which formulation is better with pros and cons.
3- It would be useful to include some schematics or diagrams in the manuscript to make it easeir to read"
Answer: we have included the PRISMA diagram and a summary table of advantages/disadvantages for each topical preparation
