Author's response to reviews Title:Herbal medicine for the management of polycystic ovary syndrome (PCOS) and associated oligo/amenorrhoea and hyperandrogenism; a review of the laboratory evidence for effects with corroborative clinical findings. Authors: Susan G Arentz (s.arentz@uws.edu.au) Jason A Abbott (j.abbott@unsw.edu.au) Caroline A Smith (caroline.smith@uws.edu.au) Alan Bensoussan (a.bensoussan@uws.edu.au) Version:7Date:15 October 2014 Author's response to reviews: see over
47 Knight Street Arncliffe, NSW 2205, Australia s.arentz@uws.edu.au 7 October 2014 BMC Journal of Complementary and Alternative Medicine, Dear Madam/Sir, Please find attached our revised paper titled: Herbal medicine for the management of polycystic ovary syndrome (PCOS) and associated oligo/amenorrhoea, hyperandrogenism; a review of the laboratory evidence for effects with corroborative clinical findings. Thank you for reviewing our article, your comments were indeed valuable. The objectives of the review have been clarified following the incorporation of compulsory and discretionary revisions. Thank you for your advice, we believe revision has improved the clarity of the article. Following is an overview of the major compulsory revisions indicated by reviewer Jon Wardle followed by the description of how each point was addressed within the text of the article. It was apparent that we had not clearly presented the purpose of the review, our rationale for the study methodology and reasons for not including some studies. The aim of the review was to contribute new information by presenting the mechanisms of reproductive endocrinological effects for herbal medicines in PCOS and associated oligo/amenorrhoea and hyperandrogenism based on the scientific literature. There is current literature describing the range of herbal treatments available including Raja Khan [1] Kasim Karis [2] and Hywood [3] as well as chapters in books including Wardle in Sarris [4] and Tricky [5]. We wanted to provide further information in relation to the mechanism of reproductive endocrinological effects for herbal medicine based on laboratory and clinical studies. We hoped that providing this information would inform clinicians of the strength of evidence regarding hormonal effects of herbal treatment, contribute to inter-professional collaboration for herbalists practicing in integrative settings and meet the needs of clinicians and clients seeking a pragmatic approach to herbal management of PCOS, oligo/amenorrhoea and hyperandrogenism. We have substantially edited the introduction and explicitly stated the purpose of the article. We have elaborated the argument for the methodology used and revised the article title to overtly state the purpose of the review. Thank you again for your valuable revision of the article. We hope the revisions meet your requirements prior to publication and any further feedback or required amendments are most welcome.
Reviewers report Lily Lai 1. We have reframed the introduction explicitly describing the value for reviewing the WHM in PCOS and drawing earlier attention to the reproductive endocrinology characteristics associated with oligo/amenorrhoea, hyperandrogenism and PCOS. Sentences focussed on the long term health implications were omitted. The first paragraph articulates the clinical gap in the medical management of PCOS and presents herbal medicine as a potential alternative treatment. The second paragraph is focussed on herbal medicine within the context of increasing prevalence for use of CM by women and the third paragraph describes PCOS in terms of its complexity including reproductive endocrinopathy. 2. This review was specifically aimed at WHM in reproductive endocrinology associated with PCOS, oligo/amenorrhoea and hyperandrogenism. We have redescribed the conditions as PCOS and associated oligo/amenorrhoea and hyperandrogenism. 3. The definition of PCOS, oligo/amenorrhoea and hyperandrogenism were moved to introduce the methods section. 4. The methods of the search were understood correctly. We have clarified why the six herbal medicines were selected and moved into the methods section following an explanation for the rationale behind the methods used. 5. Removed apostrophes. 6. Consistent terminology of herbal medicines. 7. A short sentence describing the discussion of the pre-clinical and clinical evidence will be summarised together was inserted. 8. Described camp in full. 9. The outcomes of the Vitex agnus-castus and Bromocriptine study was presented and outcomes from all clinical trials for Vitex agnus-castus and Cimicifuga racemosa have been presented in the text to improve consistency. 10. Inserted full stop 11. Removed full stop.
12. Added comment regarding side-effects into the discussion and into the conclusion. 13. Reference to no studies comparing herbal medicine with OCP line 333 14. Paragraph in discussion referring to limitations of review and non-inclusion of other potentially effective herbal medicines (line 387-391). Reviewers report Jon Wardle Major essential revisions 1. There was substantial revision regarding the clarification of the aims of the review and the methods of the review. The argument for the methodology was expanded and we have elaborated on the rationale for the methodology. We have aimed to openly focus from the outset on studies with both preclinical and clinical evidence with the aim to clear misunderstanding of the articles potential contribution to the current knowledge base. 2. Changed Glycyrrizza glabra to Glycorrhizza spp in the sub-heading and identified the two species used in the studies. 3. We included herbal medicines based on the availability of pre-clinical evidence describing the mechanisms for effect. We avoided identifying herbal medicine selected based on traditional discipline but rather on basis of appropriate pre-clinical and clinical evidence explaining their effects. 4. Yes spearmint was excluded based on the exclusion criteria. We have added to the discussion, limitations of the study, and detailed why spearmint and green tea were excluded from the study. We have included supplementary tables 3, 4 and 5 which present the studies investigating western herbal medicines excluded (with reasons) from the review. We have highlighted that the the review does not presentation all herbal medicines that may be effective treatment for PCOS, oligo/amenorrhoea and hyperandrogenism. Minor essential revisions 1. The title has been changed from Herbal medicine for the treatment of oligo/amenorrhoea, hyperandrogenism and polycystic ovary syndrome (PCOS); a review of the laboratory and clinical evidence to Herbal medicine for the management of polycystic ovary syndrome (PCOS) and associated oligo/amenorrhoea, hyperandrogenism; a review of the laboratory evidence for
effects with corroborative clinical findings. We believe that the revised title connects hyperandrogenism and oligo/amenorrhoea with PCOS rather than presenting them as standalone signs and symptoms. 2. Changed from genetic to epigenetic. According to a wide range of literature and research findings, PCOS has genetic origins however the particular genes have not yet been identified. 3. Changed to all aspects of PCOS. We rearranged the context of oligo/amenorrhoea, hyperandrogenism and polycystic ovary syndrome to read polycystic ovary syndrome and associated oligo/amenorrhoea and hyperandrogenism. 4. Changed to conventionally prescribed pharmaceuticals and inserted and appear to be 5. Reproductive endocrinology in PCOS, and associated oligo/amenorrhoea and hyperandrogenism overtly stated in the introduction and methods. 6. Pharmaceutical names clarified. 7. Consistent presentation of herbal names. 8. We have clarified why the six herbal medicines were selected in the methods and results sections. 9. Completed sentence (line 136) 10. Changed usual to often, clarified context of herbal selection approach and provided references. Discretionary revisions 1. Clarified that that studies into isolated constituents were not included in discussion paragraph. 2. Referred to the tables more frequently 3. Removed western countries. 4. Correct the name of the late Dr Gruner, (many apologies). Once again, thank you for your revision and advice. Yours Sincerely Susan Arentz
1. Raja-Khan, N., et al., The physiological basis of complementary and alternative medicines for polycystic ovary syndrome. American Journal of Physiology-Endocrinology And Metabolism, 2011. 301(1): p. E1-E10. 2. Kasim-Karakas, S.E. and S. Mishra, Botanical Treatment for Polycystic Ovary Syndrome, in Complementary and Alternative Therapies and the Aging Population, W. Ronald Ross, Editor. 2009, Academic Press: San Diego. p. 317-332. 3. Hywood, A., Phytotherapy for polycystic ovarian syndrome. Australian Journal of Herbal Medicine, 2012. 24(3): p. 81. 3. Sarris, J. and J. Wardle, Clinical naturopathy: an evidence-based guide to practice. 2010: Elsevier Australia. 4. Trickey, R., Women, hormones and the menstrual cycle: Herbal and medical solutions from adolescence to menopause. 2004: Allen & Unwin. 1.