Peer Review History
Original SubmissionFebruary 3, 2020 |
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PONE-D-20-03178 Short-term outcomes of pubertal suppression in a selected cohort of 12 to 15 year old young people with persistent gender dysphoria in the UK PLOS ONE Dear Prof. Viner, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. We would appreciate receiving your revised manuscript by May 14 2020 11:59PM. When you are ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols Please include the following items when submitting your revised manuscript:
Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out. We look forward to receiving your revised manuscript. Kind regards, Geilson Lima Santana, M.D., Ph.D. Academic Editor PLOS ONE Journal Requirements: When submitting your revision, we need you to address these additional requirements: 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at http://www.plosone.org/attachments/PLOSOne_formatting_sample_main_body.pdf and http://www.plosone.org/attachments/PLOSOne_formatting_sample_title_authors_affiliations.pdf 2. We note that you have indicated that data from this study are available upon request. 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Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Partly Reviewer #2: Yes ********** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ********** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: No Reviewer #2: No ********** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ********** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: This is a prospective observational uncontrolled study of a cohort of 44 adolescents with gender dysphoria treated with GnRH analogues, reporting both physical and psychological outcomes. The lack of a control group is an important limitation which the authors acknowledge and discuss. The use of z-scores for various measures does allow some comparison with expected changes with age. The sample size is small (n=44), and even smaller for data beyond 12 months of follow-up, but given the fact that very limited outcome data of GnRHa treatment in adolescents with gender dysphoria are available, the study is a valuable addition nonetheless. However, the authors do need to clarify if any data from this cohort have been included in previous reports, for example in the studies by Costa et al. (ref 39) and by Joseph et al. (ref 48). The authors provide a clear and detailed description of the methodology. Because of the small sample size the statistical analysis was limited to a small set of key outcomes that had been pre-specified in an analysis plan provided as supplemental material. Data are not being made available because of concerns about disclosure. The manuscript generally reads well. Of the three aims of the study described in lines 129-134 the third receives relatively little attention. I have the following questions and comments: Introduction Line 105: >20 years of follow-up is available on a single case only (ref 12) rather than on a cohort. Methods Lines 178-179: Why was pubic hair stage >2/3 a requirement in addition to breast/genital stage >2/3? (this is not the case in the Endocrine Society guideline for example) Line 247: were options to store gametes available to all, for example, were birth-registered females aged <16 years eligible for cryopreservation of oocytes? Line 251: was consent from one parent sufficient even if both parents held parental responsibility? Line 281: ‘based predominantly on the breast/genital stage’ is unclear. Were Tanner stages evaluated by the clinician or self-reported? Lines 286-290: was a short synacthen test performed in all birth-assigned females, irrespective of symptoms/baseline adrenal steroid levels? Routinely performing a synacthen test and pelvic ultrasound is not recommended by the Endocrine Society guideline. Lines 475: please clarify that ‘sexuality’ refers to sexual orientation rather than sexual activity Results Line 500: The median time between intake and study entry is 2.0 years. Does the diagnostic process typically take this long? Or did many adolescents have psychiatric disorders, for example autism spectrum disorder, which complicated the diagnostic assessment? This is also relevant in relation to the psychological outcomes. Lines 506-507: most clinics report seeing more birth registered females than males in recent years. What might explain this difference in sex ratio with other clinics? Lines 545-546: was the attempt to store sperm successful? Did it take 9 months for sperm production to resume? Lines 563: the difference in lumbar spine BMD z-score does seem to be larger between 36 months and baseline (-1.5 - -0.2= -1.3) than between 24 months and baseline (-1.5 - -0.5= -1.0) which suggests they the z-score may further decrease between 24 and 36 months. The same is true for the height-adjust z-scores for the spine. Line 594: The group at 24 months is not the same as the group at baseline. Were the scores within the subgroup with data at 24 months also higher at 24 months compared to baseline? Lines 652-654: but one person eventually decided to stop GnRHa treatment. Could the authors describe the reasons for this decision? Did this person no longer experience gender dysphoria (this is suggested later on in line 889) or were there other reasons to decide against cross-sex hormone treatment? Lines 662-663: could the authors provide some more detail on the add-back oestradiol therapy. What dose was prescribed, for what period and how effective was this in reducing symptoms? Table 3. Why is the n different for BMC (42) and BMD (43) at the lumbar spine at 12 months follow-up? Table 6. It would be helpful to mention in the table or legend that BMD is BMD at the lumber spine. Table 7. Why are headaches and hot flushes reported together rather than separately? Discussion Lines 698-700: could the authors look at baseline BMI z-score of the 14 individuals from whom data are available at 36 months to assess which of the two explanations offered is more likely (true trend towards greater adiposity or effect of different subgroup at 36 months compared to baseline)? Lines 714-715: why were side effects reported during interviews not included in table 7? (percentage fatigue at 13-24 months in the table is much lower (8%) than the percentage mentioned here (38%)). Lines 715-717: headaches are very common among adolescents too so isn’t it difficult to conclude that they are due to GnRHa treatment, just as it is for fatigue? For example, a Norwegian study reports that the one-year prevalence of any headache type was 88% among 493 adolescents aged 12-18 years, and the point prevalence 38% (Cephalalgia. 2015 Nov;35(13):1181-91. doi: 10.1177/0333102415573512). Line 813: ‘consistent with the fall in height z-score’ suggests that the fall in BMD z-score can be explained by the reduced growth rate but height-adjust z-scores also decreased. Lines 850-851: see comments above about the headaches (lines 715-717) Lines 851-853: perhaps the authors could add something about the potential influence of the treatment on gender identity development. In lines 888-892 they indicate that the fact that one person did not start cross-sex hormones provides evidence that gender identity can change during treatment but it is unknown if this number would have been different if the adolescents had not been treated with GnRHa. One of the aims of the study was to assess the persistence and desistence of GD so this could be discussed in some more detail. In lines 194-204 the authors describe low baseline BMD as an exclusion criterion for treatment, although from lines 257-260 it seems that no one was actually excluded because of this. Do the authors still consider low BMD z-scores a contra-indication for GnRHa treatment based on the findings of the current study? References Reference 9 – author line is incorrect Comments relating to language Line 77: please remove parentheses Line 164: change ‘stresses medical treatment’ into ‘stresses associated with medical treatment’ Lin 246: change ‘was’ to ‘were’ Reviewer #2: General; This manuscript on the ‘early intervention study’ of the UK Gender Identity Development Service is long awaited and the results are extremely topical. At present, despite the fact that blockers are widely used in increasing numbers of transgender adolescents and recommended according to the Endocrine’s Society and WPATH’s guidelines, a replication of the first longitudinal Dutch study on the outcomes of this intervention is lacking. The current manuscript analyses Psychological Functioning (PF) and Body Image / Gender Dysphoria (GD) in addition to Physical outcomes after 12, 24 (and 36) months of the first 44 adolescents with gender dysphoria receiving blockers in the UK. The manuscript extensively describes the background, aims, methods and results of the study concluded by a detailed discussion of the findings. It refers to much relevant literature. It is sometimes too lengthly and not enough to the point. Below some comments and suggestions for further improvement and clarification. Title; I think a title like ‘Physical, Psychological And Body Image Outcomes Of Pubertal Suppression In 12 To 15 Years Old Young People With Persistent Gender Dysphoria In The UK’ better represents the study For clarity, in every part of the study (intro, methods, results and discussion) the order should be the same; first physical (including side effects), than psychological, followed by body image (and gender dysphoria). And then follow the same order of sub-subjects again within these main subjects. Abstract: - ‘semistructured interviews’ ; this part of the study is least explained and vague, also in the complete manuscript. Asks for some further explanation - Tanner stages could be added here already - ‘most participants reported positive or mixed positive-and-negative life changes’ unclear what this means, looking at the figure representing the outcomes, interview results seem more positive - Conclusions; physical outcomes are missing, the results put in international perspective and a concluding message for clinicians is missing Introduction: - Introduction is rather detailed, especially about the UK situation and the Tavistock clinic, could be more general and shorter - Terminology; persistence and desistence are introduced; these terms are under debate, especially since they are in the literature primarily used regarding the persistence or desistence of pre-pubertal GD; I suggest to stick to the ‘continuing or discontinued wish for puberty suppression’ - On p 3, when describing the guidelines, the criteria for puberty suppression should be added, like they are described in the SOC’s and the Endocrine guidelines, these are extensively described - P. 4 when referring to a meta-analysis of over 500 young people, what were the conclusions in the review? - Long term follow up data, again, what are the conclusions or outcomes of the referred papers? The 20 year plus follow up is just one case. - Aims; change persistence and desistence in ‘continuation’ and ‘discontination’ - P. 5, last paragraph of the Introduction, ‘many of the … to assess the effects of treatment’; this is a limitation that better belongs in the Discussion - Tables; add ‘sex’ to primary characteristics, secondary characteristics Methods - Methods are lengthy described and a bit diffuse, could be more to the point and shorter - Participants; recruited from clinical cohorts…; which cohorts are referred to? - ‘potentially eligible’ ; when was an adolescent considered ‘potentially eligible’? what were eligibility criteria? - ‘fulfils standard readiness criteria’ ; what were these and weren’t these the same as the eligibility criteria? - It might be helpful to provide the eligibility criteria of the SOC and how these were adapted in the GIDS, e.g. the SOC do not ask for ‘6 months of and at least 4 interviews assessment’; it are four criteria (persisting and intensifying GD, no interfering mental health comorbities, family / social support, capacity for informed consent), in addition to Tanner stage 2-3 (and age 12 in the case of the Dutch clinic where suppression was introduced, de Vries 2012, etc) - P 6; exclusion criteria; how many adolescents were excluded? Due to what reason? Exclusion criteria overlap with ‘not fulfilling eligibility criteria’ (e.g interfering comorbidties; an example would be needle phobia). BMI < 2nd centile, what about BMI in higher range/ overweight?, 5 ii, iii, and iv; ‘able to give informed consent’ - P 8, first para; how many families were no longer interested 3 months after the first visit? - P.8 third para; how many adolescents stored gametes? - P. 8 fifth para; ‘a small number’ ; how many? - P. 8 last para; participants were ‘followed up’; how? - P. 10; when were questionnaires collected? What was the procedure? - P. 11: ‘self harm’, change into ‘suicidal thoughts and self-harm’ - P 12; 5 participant experience and satisfaction o This is an interesting part, what sort of questions were asked and how were they analysed? - P 13, third para; ‘note that……a future paper’ doesn’t need to be here, can be deleted or part of the discussion Results - 7 tables and 1 figure is quite extensive, maybe some findings could be presented in a more compact way, Tables can maybe combined? Is the figure necessary? Could also be presented in text - P 20, the description of the individuals temporarily stopping blockers is very interesting; was the sperm storage successful? - Table 4; internalizing and externalizing scores are also provided but not discussed in the methods and discussion? Discussion - The discussion is very extensive and detailed with a lot of repetition of the results, could be more compact and to the point - Third para; …or reflect a higher baseline in this group; baseline BMI can be compared with norm reference values? - Finding of experiencing ‘fatigue or low energy’ as side effects that are unknown in GnRHanalogues deserve more discussion, might these be subjective attributions of the adolescents? - ‘comparison with the literature’ delete this heading, a discussion is always an comparison with the literature - After strengths and limitations, a concluding paragraph with clinical implications should be added as a final section ********** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No Reviewer #2: No [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files to be viewed.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at figures@plos.org. Please note that Supporting Information files do not need this step. |
Revision 1 |
PONE-D-20-03178R1 Short-term outcomes of pubertal suppression in a selected cohort of 12 to 15 year old young people with persistent gender dysphoria in the UK PLOS ONE Dear Dr. Viner, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by Sep 18 2020 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. Please include the following items when submitting your revised manuscript:
If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols We look forward to receiving your revised manuscript. Kind regards, Geilson Lima Santana, M.D., Ph.D. Academic Editor PLOS ONE Additional Editor Comments (if provided): Thank you for addressing reviewer's considerations. Some minor aspects still need to be addressed, though. Please, take into consideration the reviewer's orientations, and, please, follow PlosOne's Guideline about the three levels of heading. https://journals.plos.org/plosone/s/file?id=80c1/PLOSOne_formatting_sample_main_body.pdf [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation. Reviewer #2: All comments have been addressed ********** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #2: Yes ********** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #2: Yes ********** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #2: (No Response) ********** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #2: (No Response) ********** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #2: This revised manuscript addressed most of my previous reviewer comments and deserves publication. The collected data have long been waited for publication, and the findings deserve an open scientific discussion. I have just some minor comments that should be addressed before publication. First, while revising the manuscript, two papers have been published that should be incorporated and referred to and discussed. Second, some suggestions to interpret the outcomes in a slighty different way. 1) The two studies that are published in between revising the manuscript and reviewing are: - Kuper LE, Stewart S, Preston S, et al. Body Dissatisfaction and Mental Health Outcomes of Youth on Gender-Affirming Hormone Therapy. Pediatrics. 2020; 145(4):e20193006 This is another proper follow up study, the first apart from the Dutch studies referred to in the Introduction (line 95, references 14-16), it is an important paper that shows improvement of psychological functioning and body dissatisfaction, although it did not evaluate effects of puberty suppression only but combined with affirming sex hormones - Biggs, M, Gender Dysphoria and Psychological Funtioning in Adolescents Treated with GnRHa: comparing Dutch and English Prospective Studies, Arch Sex Beh, 2020 - This is a letter to the editor presenting the preliminary presented results of the data of the current study in comparison with the published Dutch results; although a detailed discussion of this letter deserves a separate commentary, some sentences should be included in the Discussion or Introduction of the present paper. 2) The findings of the semi structured interviews showed that the majority reported improved mood, family, friendship and gender role quality, although a smaller minority had more mixed experiences. These qualitative findings received just one sentence in the Discussion (678-681), but seem to me probably the most important finding, given that the numbers were further possibly too small to show improvements in quantitative measures! These more positive (and a bit mixed) results deserve therefor more positive attention in the Discussion and conclusion. ********** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #2: No [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. |
Revision 2 |
Short-term outcomes of pubertal suppression in a selected cohort of 12 to 15 year old young people with persistent gender dysphoria in the UK PONE-D-20-03178R2 Dear Dr. Viner, We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Geilson Lima Santana, M.D., Ph.D. Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation. Reviewer #2: All comments have been addressed ********** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #2: Yes ********** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #2: Yes ********** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #2: Yes ********** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #2: Yes ********** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #2: Authors addressed all my comments on the first revision and even more, which makes the current version up to date and important and relevant for transgender care for adolescents. ********** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #2: No |
Formally Accepted |
PONE-D-20-03178R2 Short-term outcomes of pubertal suppression in a selected cohort of 12 to 15 year old young people with persistent gender dysphoria in the UK Dear Dr. Viner: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Geilson Lima Santana Academic Editor PLOS ONE |
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