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Novel Ways of Assessing Puberty

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NOVEL WAYS OF ASSESSING PUBERTY Findings from the Adolescent Rural Cohort Study of Hormones, Health, Education, Environments and Relationships Ben W.R. Balzer B.Med.Sc., M.B., B.S. (Syd.) A thesis submitted in fulfilment of the requirements for the degree of Doctor of Philosophy Discipline of Child and Adolescent Health, Sydney Medical School, Faculty of Medicine and Health, The University of Sydney Primary Supervisor: Professor Katharine S. Steinbeck Medical Foundation Chair in Adolescent Medicine, The University of Sydney 2019 STATEMENT OF AUTHENTICATION This thesis is submitted to the University of Sydney in fulfilment of the requirement is for the Degree of Doctor of Philosophy. The work presented in this thesis is, to the best of my knowledge and belief, original except as acknowledged in the text. I hereby declare that I have not submitted this material, either in full or in part, for a degree at this or any other institution. Signature: Ben W.R. Balzer Date: 3 June 2019 i ACKNOWLEDGEMENTS I would like to thank Professor Kate Steinbeck for her role as my primary supervisor. I have worked with Kate since 2010, when I first joined the Academic Department of Adolescent Medicine as a Summer Research Scholar. Her expertise, supervision and support have been inspiring and have brought this thesis to fruition. Thank you also to my associate supervisors, Professor David Handelsman and Associate Professor Catherine Hawke, whose time and input have benefitted me greatly and been vital to this project’s success. I wish to acknowledge the National Health and Medical Research Council Project Grant awarded to Professor SteinbecK and I am grateful for personal support from the University of Sydney Faculty of Medicine through the Postgraduate Research Support Scheme and the Dean’s Scholarship Fund Conference Grant. Additionally, I am thankful for the assistance of Tina Cunningham, Dr. Hoi Lun (Helen) Cheng, Karen Paxton and Mazen Amatoury, as well as the contributions of my co-authors: Associate Professor Patrick Kelly, Professor Philip Hazell, Dr. Gurmeet Surindar Singh, Dr. Frances Garden and Dr. Georgina Luscombe. I would also like to acknowledge the participants of the Adolescent Rural Cohort, Hormones and Health, Education, Environments and Relationships (ARCHER) study. Finally, to my parents Ben and Sandra, sisters Bianca and Isabella, my grandparents and extended family for their unwavering love and continual encouragement. Also, Con and Maria James for their support and originally suggesting I apply to work with Kate in 2010. Above all to my wife Anthea – without your love, patience and support, none of this would have been possible. ii ETHICS APPROVAL The Adolescent Rural Cohort study of Hormones, health, Education, environments and Relationships (ARCHER) has ethical approval from the Human Research Ethics Committee, University of Sydney (HREC 13094) within the National Health and Medical Research Council Guidelines for Human Experimentation, which is consistent with the Declaration of Helsinki. Prior to commencing the study, all participants assented, and a parent/guardian provided written informed consent. iii AUTHORSHIP ATTRIBUTION STATEMENT Chapter 3 of this thesis is published as Balzer B.W.R., Duke SA., Hawke C.I., Steinbeck K.S.. The effects of estradiol on mood and behavior in human female adolescents: a systematic review. Eur J Pediatr. 2015 Mar;174(3):289-98. I designed and performed the literature search, extracted the data and wrote the drafts of the manuscript. Dr Duke and A/Prof Hawke provided critical revisions of the manuscript. Prof Steinbeck also assisted with data analysis and providing critical revision of the manuscript. Chapter 4 of this thesis is published as Duke SA., Balzer B.W.R., Steinbeck K.S.. Testosterone and its effects on human male adolescent mood and behavior: a systematic review. J Adolesc Health. 2014;55(3):315-22. I assisted with data analysis, study data extraction and writing the drafts of the manuscript. Dr Duke was the lead author and responsible for the literature search and principal data extraction. Prof Steinbeck also assisted with data analysis and providing critical revision of the manuscript. Chapter 5 of this thesis is published as Balzer B.W.R., Kelly P.J., Hazell P., Paxton K., Hawke C.I., Steinbeck K.S.. Text messaging is a useful reminder tool. Arch Dis Child. 2014 July 1, 2014;99(7):666-7. I designed the analysis plan, analysed the collected data and wrote the drafts of the manuscript. A/Prof Kelly assisted with data analysis. Prof Hazell, Ms Paxton and A/Prof Hawke made substantial contributions to the overall ARCHER study. Prof iv Steinbeck is the principal investigator of the ARCHER study and has overseen its conception, design and progress. I wrote the drafts of the manuscript and all authors provided critical reviews of the drafts prior to submission A poster based on this work was also presented at the National Youth Health Conference, Fremantle, Australia in November 2013. Chapter 6 of this thesis is published as Singh G.K., Balzer B.W.R., Kelly P.J., Paxton K., Hawke C.I., Handelsman D.J., Steinbeck, K.S.. Urinary sex steroids and anthropometric markers of puberty - a novel approach to characterising within- person changes of puberty hormones. PLoS One. 2015;10(11):e0143555. Dr Singh and I are equal first authors on this manuscript. Dr Singh designed and performed the hormone assays and assisted with drafting the manuscript. I was responsible for data analysis and was the principal author of the manuscript. I conducted the data analysis with the help of A/Prof Kelly. Ms Paxton and A/Prof Hawke made substantial contributions to the overall ARCHER study. Prof Handelsman was substantially involved in the conception and design of the ARCHER study and designed and performed steroid hormone assays with Dr Singh. Prof Steinbeck is the principal investigator of the ARCHER study and has overseen its conception, design and progress. I wrote the drafts of the manuscript and all authors provided critical reviews of the drafts prior to submission. A poster based on this work was also presented at the International Congress of Endocrinology/Endocrine Society of America Annual Meeting, Chicago, USA in June 2014. v Chapter 7 of this thesis is published as Balzer B.W.R., Garden F.L., Amatoury M., Luscombe G.M., Paxton K., Hawke C.I., Handelsman D.J., Steinbeck K.S.. Self- rated Tanner stage and subjective measures of puberty are associated with longitudinal gonadal hormone changes. J Pediatr Endocrinol Metab. 2019. 32(6):569-76. I co-designed the study with the co-authors, interpreted the analysis done with Dr Garden and Dr Luscombe. Mr Amatoury helped with data collection by overseeing specimen transport and storage and provided reviews of manuscript drafts. Ms Paxton and A/Prof Hawke made substantial contributions to the overall ARCHER study. Prof Handelsman was substantially involved in the conception and design of the ARCHER study and designed and performed steroid hormone assays. Prof Steinbeck is the principal investigator of the ARCHER study and has overseen its conception, design and progress. I wrote the drafts of the manuscript and all authors provided critical reviews of the drafts prior to submission. Part of this research was presented as an oral presentation at the National Youth Health Conference, Melbourne, Australia, in November 2015. Chapter 8 of this thesis is Balzer, B.W.R., Cheng, H.L., Garden, F.L., Luscombe, G.M., Paxton, K., Hawke, C.I., Handelsman, D.J., Steinbeck, K.S.. Foot length growth as a novel marker of early puberty. Clin Pediatr. 2019;58(13):1429-35. I designed the analysis plan and performed the data analysis with Dr Cheng, Dr Garden and Dr Luscombe. Ms Paxton and A/Prof Hawke made substantial contributions to the overall ARCHER study. Prof Handelsman was substantially involved in the conception and design of the ARCHER study and designed and vi performed steroid hormone assays. Prof Steinbeck is the principal investigator of the ARCHER study and has overseen its conception, design and progress. I wrote the drafts of the manuscript and all authors provided critical reviews. A poster based on this work was also presented at the European Society for Paediatric Endocrinology Annual Meeting, Athens, Greece, in September 2018. Ben William Robert Balzer Date: 3 June 2019 As supervisor for the candidature upon which this thesis is based, I can confirm that the authorship attribution statements above are correct. Professor Katharine S. Steinbeck Date: 3 June 2019 In addition to the statements above, in cases where I am not the corresponding author of a published item, permission to include the published material has been granted by the corresponding author. vii TABLE OF CONTENTS Statement of Authentication ...................................................................................... i Acknowledgments ...................................................................................................... ii Ethics Clearance ....................................................................................................... iii Authorship Attribution Statement .......................................................................... iv Contents ................................................................................................................... viii List of Tables ............................................................................................................ xii List of Figures ........................................................................................................
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