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Ovarian Steroid Hormones and Auditory Function

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Ovarian Steroid Hormones and Auditory Function Title page Ovarian Steroid Hormones and Auditory Function Deena Al-Mana The Ear Institute University College London A thesis presented to UCL for the degree of Doctor of Philosophy 2013 1 Statement of Originality I, Deena Al-Mana, confirm that the work presented in this thesis is my own. Where information has been derived from other sources, I confirm that this has been indicated in the thesis. 2 Abstract Considerable anecdotal evidence and information from previous studies suggest that auditory function may be influenced by hormones. This thesis reviews in detail the potential role of hormones in modulating the auditory system and in the development of pathological conditions in the auditory system with an emphasis on the effect of the ovarian hormones. Ovarian steroids may influence auditory function directly through their receptors, which have been detected in the auditory system, or indirectly through their effects on the blood supply, the fluid electrolyte balance of the cochlea, and the neurotransmitters of the auditory system. Effects on other parts of the central nervous system connected to the auditory system may also be of importance. The aim of the study was to investigate whether physiological alterations in ovarian hormones in women with normal hearing, during the natural ovarian cycle and assisted conception treatment were associated with changes in auditory function at the cochlear and brain stem level, and whether these variations were not seen in men over a similar period of time. The auditory tests evaluated auditory function from the outer ear to the brainstem in both the afferent and efferent system. Hormone levels were assayed only in the female subjects at the same time as the auditory testing, four times during the ovarian cycle, or three times during the assisted conception treatment. Auditory tests were undertaken in the male subjects once a week for four consecutive weeks to correspond with the ovarian cycle measurements. A number of changes in auditory function were observed during the ovarian cycle and assisted conception treatment, and gender differences were noted. The OAE results may suggest either excitation of the cochlea with higher levels of oestrogen, or suppression of the cochlea with higher level of progesterone. The longer ABR latency following ovarian stimulation and in the follicular phase of the ovarian cycle is consistent with the inhibitory effect of neurosteroids on ABR associated with higher levels of oestrogen. The variation in auditory function were not observed in men. 3 Acknowledgements I am so grateful to both my supervisors, Dr Borka Ceranic and Professor Linda Luxon for their support and guidance in the design and execution of this work. Their dedication to the field of audiovestibular medicine inspired me to undertake this research and hopefully to further my career in audiovestibular medicine. A huge thanks to Professor Ovrang Djahanbakhch for his help in the design of the project and acting as an external collaborator. His constructive feedback and guidance was greatly appreciated especially in the field of reproductive medicine which was new to me. I would like to thank Professor Djahanbakhch’s research assistants Dr Athanasios Papathanasiou and Dr Essam El Mahdi for their help in recruiting the patients. A special thanks to all my volunteers that took part in my study, especially the women who were undergoing assisted conception treatment even though it may have been inconvenient for some. A special thanks to the staff at the neuro-otology clinic in Queen square for their support and patience with me performing my tests and helping me if I got stuck. Huge thanks to my husband Abdulaziz for his support and love, I could not have finished this research without his love and support. A big thanks to my son Ryan who entered my life during my study and for being a good boy with his mother being so busy. And finally, a huge thanks to my parents and my sister and brothers for their unconditional love and support. 4 Publications and Presentation Publications Al-Mana, D., Ceranic, B., Djahanbakhch, O., & Luxon, L. M. (2008). Hormones and the auditory system: A review of physiology and pathophysiology. Neuroscience, 153(4), 881-900. Al-Mana, D., Ceranic, B., Djahanbakhch, O., & Luxon, L. M. (2010). Alteration in auditory function during the ovarian cycle. Hear Res, 268(1-2), 114-122. (Copies in Appendix IV) Published abstract Al-Mana, D., Ceranic, B., Djahanbakhch, O., & Luxon, L. M. (2007). Ovarian steroids influence the gender differences in auditory function. In Furness D. (ed): Abstracts of the British Society of Audiology Short Papers Meeting on Experimental Studies of Hearing and Deafness. September 2006, Cambridge University, UK. Int J Audiol, 46, 619-658. Presentations “The effect of reproductive hormones on auditory system: Modulation of cochlear function during the hormone replacement therapy.” • Oral presentation at 3rd Meeting of the British Society of Neuro-Otology, 22 September 2003. Charing Cross Hospital, London. “The Influence of Ovarian Hormones on Auditory Function” • Poster presentation at British Society of Audiology Short Papers Meeting on Experimental Studies of Hearing and Deafness, 16-17 September 2004. University College London, London. • Poster and Oral presentation at Annual Research Forum 2004: 'Chronic Disease Research: addressing the challenges', 11 November 2004. Academic Centre, Newham University Hospital, London. 5 • Oral presentation at Neuro-Otology Scientific Meeting, 28 January 2005. The National Hospital for Neurology and Neurosurgery, London. • Oral presentation at XVIII International Federation of Oto-Rhino- Laryngological Societies (IFOS) World Congress, 25-30 June 2005, Rome, Italy “Ovarian Steroids Influence the Gender Differences in Auditory Function” • Poster presentation at British Society of Audiology Short Papers Meeting on Experimental Studies of Hearing and Deafness, 14-15 September 2006. Cambridge University, Cambridge. • Oral presentation at Annual Research Forum 2006: 'The Next Generation - Junior Researchers', 16 November 2006. Academic Centre, Newham University Hospital, London. • Oral and poster presentation at Bart’s International Conference in Reproductive Medicine, 14-16 May 2008. St. Bartholomew’s Hospital, London. • Oral presentation at IAPA 2008- XIV International Symposium in Audiological Medicine, 18-21 September 2008. Ferrara, Italy. 6 Table of contents Title page............................................................................................................1 Statement of Originality ....................................................................................2 Abstract..............................................................................................................3 Acknowledgements ............................................................................................4 Publications and Presentation...........................................................................5 List of Figures .................................................................................................. 13 List of Tables.................................................................................................... 17 List of abbreviations ........................................................................................ 20 Chapter 1 : General Introduction ................................................................... 21 1.1 Review of auditory system: structure and physiology ............................. 22 1.1.1 The external and middle ears............................................................ 22 1.1.2 The internal ear................................................................................ 24 1.1.2.1 The cochlear fluids .................................................................... 25 1.1.2.2 The organ of Corti ..................................................................... 25 1.1.2.3 Cochlear innervation and blood supply ...................................... 26 1.1.3 Afferent auditory pathway ............................................................... 29 1.1.4 The efferent auditory pathway.......................................................... 31 1.1.5 Summary of auditory system............................................................ 35 1.1.6 Links between the auditory and other parts of the central nervous system........................................................................................................ 36 1.2 Functional assessment of the auditory system......................................... 38 1.2.1 Pure tone audiometry ....................................................................... 38 1.2.2 Tympanometry................................................................................. 39 1.2.3 Otoacoustic emissions...................................................................... 40 1.2.3.1 Spontaneous otoacoustic emissions............................................ 41 7 1.2.3.2 Transient evoked otoacousic emissions...................................... 42 1.2.4 Medial olivocochlear reflex (MOC suppression) .............................. 43 1.2.5 Auditory brainstem evoked responses .............................................. 44 Chapter 2 : The Endocrine System and Potential Effects of Hormones on the Auditory System .............................................................................................. 46 2.1 Endocrine system structure....................................................................
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