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Protective effects of peri menopausal oestrogen replacement
Name: Protective effects of peri menopausal oestrogen replacement
Pages: 321
Year: 2013
Language: English
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II Author's Declaration At no time during the registration for the degree of Doctor of Philosophy has the author been registered for any other University award without prior agreement of the Graduate Committee. This study was self financed with the aid of a £3,000 research award from the University of Plymouth to help finance the supplements needed for the completion of study two. This study was completed part time from October 2008 until the submission of March 2013. Relevant scientific seminars and conferences were regularly attended at which work was often presented and one paper is being prepared for publication. Papers Jacobs, P., & Pettit, S. (2009). What determines declines in working memory and attention during pregnancy: Mood or oestrogen? Psychology and Health, 24(1), 216. Papers in preparation Pettit, S., Jacobs, P., & Andrade, J. (2011). Hormone replacement therapy benefits working memory when taken during the peri menopause: Evidence to support the critical period hypothesis. (in preparation) Oral presentations Pettit, S. (2012). Time is critical for beneficial effects of hormone replacement therapy on working memory above other cognitive functions. 9th European congress on menopause and andropause, Athens, Greece 28 31st March


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III Pettit, S. (2010). Hormone replacement therapy, soya, and their time of initiation, what we have found so far. PsyPAG 25th Annual Conference, the University of Sheffield, UK Pettit, S. (2009). How realistic is soya for replacement of hormone replacement therapy to relieve menopausal symptoms. The Vice Chancellors Research and Enterprise Conference, The University of Plymouth, 22nd April Pettit, S. (2009). Does time of initiation of hormone replacement therapy (relative to menopausal symptoms) have an effect on cognition? Staff Postgraduate Psychology Conference, The University of Plymouth, 26th May Pettit, S. (2009). Does hormone replacement therapy have a protective role in cognition? University of Plymouth Postgraduate Short Conference Series, The University of Plymouth, 17th November Poster presentations Pettit, S., Jacobs, P. (2010). The effect of hormone replacement therapy on working memory and sustained attention, evidence for a right and wrong time of initiation. Staff Postgraduate Psychology Conference, The University of Plymouth, 19th May Pettit, S. (2009). Effects of oestrogen on the human female brain. 7th Annual London Evolutionary Research Network Conference, The Natural History Museum, London, 14th September Pettit, S. & Jacobs, P. (2009). Working memory decline in the third trimester of pregnancy evidence for the role of oestrogen or simply baby on the brain? Psychology Postgraduate Affairs Group Annual Conference, 29th August 2009, University of Cardiff, Cardiff, UK Word count for the main body of this thesis: 64,599 Signed: Date .....


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IV Table of Contents Table of Contents .............................................................................................. IV List of figures ..................................................................................................VIII List of appendices ............................................................................................ X Acknowledgments ..........................................................................................XIII Summary ........................................................................................................ XVI Oestrogen action in the body and brain ......................................................... 1 1.1 Oestrogen action ................................................................................. 1 1.2 Oestrogen creates differences in female brain structure, mechanisms and activity ............................................................................... 4 1.2.1 Exposure to oestrogen creates differences in female brain activity and function ................................................................................... 8 1.3 Oestrogen affects neurotransmitter production, duration and destruction .................................................................................................... 13 1.3.1 Dopaminergic terminals innervate pyramid cell spines in the PFC 13 1.3.2 Oestrogen change affects the cholinergic system and memory 14 1.3.3 Serotonin in the PFC is oestrogen responsive, influencing verbal memory and executive function .................................................. 15 1.4 Oestrogen affects brain mechanisms which impact on memory systems ......................................................................................................... 16 1.4.1 Explicit, implicit and episodic memory ..................................... 17 1.4.2 Verbal memory .......................................................................... 20 1.4.3 Executive function .................................................................... 21 1.5 Hormone therapy is used to reduce menopausal symptoms in menopausal women ..................................................................................... 25


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V 1.5.1 HRT can reduce osteoporosis when initiated within 3 years of completion of the menopause ................................................................. 28 1.5.2 HRT can reduce cardiovascular disease in younger menopausal women ................................................................................. 29 1.6 HRT can protect natural cognitive declines experienced during the menopause ............................................................................................ 30 1.6.1 The potential for HRT to protect against dementia ................ 32 1.6.2 HRT enhances Verbal, episodic and explicit memory in menopausal women ................................................................................. 35 1.6.3 HRT can target executive function systems in the PFC ........ 40 1.6.4 HRT maintains neurotransmitter activity in the PFC and hippocampus and this improves mood .................................................. 48 1.6.5 Neuroprotection against toxic insults ...................................... 51 1.6.6 Detrimental, or no effects of the therapy................................. 52 1.7 Summary ............................................................................................ 54 Critical period ..................................................................................................... 59 2.1 HRT can protect cognition in peri menopausal women ................ 59 2.2 Evidence for the critical period hypothesis from RCTs and Observational studies ................................................................................. 61 2.3 HRT alleviates disrupted cognition as experienced with induced menopause; indications of more than just an aging effect ..................... 66 2.4 The neuroprotective role of oestrogen replacement is limited to the critical period ......................................................................................... 71 2.5 Early initiation of HRT can protect different aspects of cognition 75 2.5.1 Executive function, attention and working memory................ 76 2.6 Summary ............................................................................................ 82 2.7 The interaction of time of initiation of HRT will affect executive function performance; rational for the present study design .................. 84 2.8 Method for study one ......................................................................... 100 2.9 Results and Analysis ......................................................................... 110 2.10 One year follow up ...................................................................... 135 2.11 Discussion .................................................................................... 147 Phytoestrogens as an alternative to HRT ......................................................... 179 4.1 A history of Hormone Replacement Therapy ................................... 179 4.2 Natural Solutions................................................................................. 184 4.3 Metabolism, hormonal action and brain plasticity of phytoestrogens .......................................................................................... 186 4.4 The effect of Isoflavones on menopausal symptoms ...................... 190


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VI 4.5 The effect of Isoflavones on cognition .............................................. 193 4.6 Isoflavones and the critical period hypothesis ................................. 197 4.7 Summary and study design ................................................................ 202 4.8 Method ................................................................................................. 209 4.9 Results ................................................................................................. 215 4. 10 Discussion ........................................................................................... 231 General discussion .......................................................................................... 246 References ...................................................................................................... 253 Appendix A .................................................................................................... 295 Appendix B .................................................................................................... 299


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