The effects of exogenous estrogen administration on aspects of memory and cognition in women were examined in two studies. In Study 1, women receiving estrogen replacement therapy were compared to untreated women on four measures of verbal memory. Those receiving estrogen had significantly better scores on a measure of delayed memory for propositional material. In Study 2, women in the early stages of Alzheimer's Disease (AD) were administered either estrogen or placebo on a double-blind basis for six months. Women given estrogen showed improvement on a measure of verbal memory and spatial attention compared to the placebo controls. The combined results of these studies provide evidence that estrogen enhances aspects of verbal memory in both healthy postmenopausal women and in postmenopausal women in the early stages of AD as measured by neuropsychological tests. These effects might be mediated by actions of estrogen on neuronal morphology and physiology in brain areas important for memory and cognition.

Memory function was examined in association with sex hormone levels in women. The results of the first study suggest that self-reports of memory problems were especially prevalent among women attending a menopause clinic compared to a nonpatient sample. In the following investigation, women given placebo after undergoing a bilateral oophorectomy showed decreases in memory performance, specifically on a paired-associate learning task, coincident with declines in estrogen levels. Significant improvements were found in estrogen-treated women pre- to postoperatively in the immediate recall of paragraphs, in association with supraphysiological estrogen levels. A final study on naturally-cycling women found a decline in visual memory performance during the menstrual compared to the luteal phase of the cycle. Visual memory scores were positively correlated with progesterone levels whereas paired-associate recall scores were positively associated with estradiol levels during the luteal phase. These results suggest that certain aspects of memory covary with changes in sex steroid levels in some women.

Graduation date: 2000

Context: The Women’s Health Initiative (WHI) study, published in July 2002, had a significant impact on the prescribing of hormone replacement therapy (HRT). The controversy surrounding the findings, however, has led to much uncertainty regarding the prescription of HRT. Aims and Objectives: The aim of this study is to determine both the initial and the continued impact of the WHI study on the prescribing of HRT in a defined South African population and to determine whether HRT was appropriately individualised based on recommendations published subsequent to the WHI study. Setting: Claims data from a Managed Healthcare Organisation (MHO) that administers for a number of medical aid schemes in South Africa. Method: A retrospective drug utilisation review (DUR) was conducted to identify HRT-related prescribing patterns in the defined populations. The time-frame of the dataset included January 2002, to assess prescribing patterns prior to the publication of the WHI study, January 2003 to determine the initial impact of the WHI study, and January 2005 to assess the continued impact. An extensive, additional dataset of all the HRT users in the defined populations was utilised to conduct a sub-group analysis and determine whether HRT had been appropriately individualised. Key Findings: The percentage of patients in the dataset using HRT decreased from 30.05 percent in January 2002 to 28.30 percent in January 2003 and to 23.24 percent in January 2005, with the latter decrease reaching statistical significance. Although sex hormones and modulators (G03) of the genital system were the most frequently prescribed drug class in all three years of the study period, the prescribing frequency decreased significantly from 10.40 percent in January 2002 to 9.32 percent in January 2003 and 7.44 percent in January 2005. The most noteworthy change in the prescribing of HRT was a 3.95 percent decrease in the prescribing of conjugated equine estrogen (CEE), with a corresponding 2.53 percent increase in the prescribing of estradiol between January 2002 and January 2003. However, less pronounced changes were observed in the prescribing frequencies of other types of HRT, including medroxyprogesterone and estrogen (the HRT type investigated in the estrogen plus progestin phase of the WHI study). Patients initiating HRT post-WHI publication were generally found to be in the younger menopausal age categories (40 to 49 years). These patients were more likely to have been initiated on HRT types other than those investigated in the WHI study and were at a higher risk for disease states for which HRT use is beneficial, such as osteoporosis. Patients discontinuing HRT post-WHI publication were generally found to be in the older menopausal age categories (60 to 69 years), were more likely to have been combined HRT users (although not necessarily the type investigated in the WHI study) and were at a higher risk for disease states for which HRT use is considered harmful or has an uncertain effect, such as diseases affecting the cardiovascular system. Conclusion: It can be concluded that the WHI study did have an impact on the prescribing of HRT in the defined South African population of this study, but that the impact was considerably less than the impact reported in global studies. It was also determined that HRT was appropriately individualised according to recommendations made subsequent to publication of the WHI study.

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Conclusion 1. The results of the research partly supported hypothesis 1a. There was a significant reduction in both endothelium-dependent arterial relaxation following a surgical menopause. The results of the research partly supported hypothesis 1b. There was a significant reduction in endothelium-dependent arterial relaxation but no significant effect on endothelium-independent arterial relaxation. / Conclusion 2. The results of the research partly supported hypothesis 2a. The addition of unopposed oestrogen significantly improved endothelium-dependent but not endothelium-independent arterial relaxation. The results of the research supported hypothesis 2b. The addition of oestradiol combined with progestogen (norethisterone acetate) reversed the reduction in arterial relaxation caused by a surgical menopause. The results of the research partly supported hypothesis 2c. The addition of tibolone reversed the reduction endothelium-dependent but not endothelium-independent arterial relaxation. The results of the research partly supported hypothesis 2d. The addition of oestradiol combined with a progestogen (norethisterone acetate) reversed the reduction in endothelium-dependent but not endothelium-independent arterial relaxation. / Conclusion 3. The results of the research partly supported hypothesis 3a. Endothelium-dependent arterial relaxation but no endothelium-independent arterial relaxation was improved after the addition of menopausal hormone therapy using oestrogen combined with a progestogen in a continuous manner. The results of the research did not support hypothesis 3b. Neither endothelium-dependent arterial relaxation nor the endothelium-independent arterial relaxation was improved by cyclical menopausal HT. / Conclusion 4. The results of the research did not support hypothesis 4. The addition of menopausal hormone therapy using combined oestrogen with progestogen did not improve arterial relaxation in postmenopausal women with established coronary heart disease. / Hypothesis 2. This hypothesis examined three different types of commonly used menopausal HT. That unopposed oestrogen (2a), oestrogen combined with a progestogen (2b and 2d) or a synthetic steriod that has oestrogenic, progestogenic as well as androgenic activity (tibolone, 2c), reverse the reduction in arterial relaxation following menopause in Hong Kong Chinese women. / Hypothesis 3. That menopausal hormone therapy using oestrogen combined with progestogen given in either continuous (3a) or cyclical (3b) regimens improves arterial relaxation in postmenopausal Hong Kong Chinese women. / Hypothesis 4. That menopausal hormone therapy using combined oestrogen with progestogen improves arterial relaxation in postmenopausal Hong Kong Chinese women with established coronary heart disease. / Menopausal HT can in general at least partially reverse changes in arterial relaxation in postmenopausal women. Different types of menopausal HT exhibit different effects on arterial relaxation. In healthy vessels, menopause HT mainly reverses the endothelium-dependent vascular effect, but it remains unclear how menopausal HT affects the endothelium-independent vascular effect. However, with established coronary heart disease, menopausal HT cannot reverse the changes in vascular reactivity. / Summary. Menopause results in a reduction in arterial relaxation. However, GnRHa temporarily induced menopause in young women, the endothelium-independent vasodilatation was not impaired. This difference can be partly explained by the difference in age as vascular reactivity is age dependent. Secondly, GnRHa works with an initial phase of increase in oestrogen production resulting in a shorter duration of hypo-oestrogenism resulting in the lack of impairment on endothelium-independent vasodilatation. / This thesis tested the following hypotheses: Hypothesis 1. That vascular reactivity decreases after the menopause as shown in premenopausal Hong Kong Chinese women with either a surgical (1a) or a medically induced (1b) menopause. / This thesis will examine the effects of menopause and menopausal HT on arterial reactivity which is an indirect measurement of vascular function. Previous studies have shown that oestrogen is a potent coronary artery vasodilator, and this effect may be mediated via both endothelium-dependent and endothelium-independent mechanisms. One method of assessing vascular reactivity is to use ultrasound measurement of changes in brachial artery diameter in response to certain stimuli. Using this technique, changes in both endothelium-dependent and endothelium-independent vasodilatation can be measured. Increased rather than decreased arterial relaxation after stimulus can be viewed as a favourable response. / Yim, So-fan. / Adviser: C. J. Haines. / Source: Dissertation Abstracts International, Volume: 68-09, Section: B, page: 5873. / Thesis (M.D.)--Chinese University of Hong Kong, 2006. / Includes bibliographical references (p. 159-194). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / School code: 1307.

Postmenopausat women on hormone replacement therapy (HRT) have been reported to be stronger when compared to women who are not using HRT. The first goal of this study was to investigate whether muscle morphology was altered in women who use HRT when compared to women who do not use HAT. In addition, this study examined the combined effects of a 6-month moderate-intensity strength training (ST) routine and HRT on the neuromuscular system of early postmenopausal women. Because not all the women completed the ST, this study was separated into two separate analyses, baseline (n=17; 7 HRT, 10 non-HRT) and training (n=14; 6 HRT, 8 non-HRT). ST consisted of two exercises (squat and dead lift), two days a week, for 6-months. Vastus lateralis muscle biopsies were taken at baseline and 6-months after exercise training. Biopsy samples were sectioned and analyzed histochemically for muscle fiber type and fiber cross-sectional area (CSA). In addition, voluntary knee extension strength was assessed at 30��/sec using an isokinetic dynamometer at these two time points. At baseline there were no significant differences in knee extensor strength between groups (HRT: 443 �� 121 N, non-HRT: 490 �� 106 N). Regardless of hormone status, Type I fibers were significantly larger (p=.005) in GSA (Type I=3705 �� 877��m��; Type II=2790 �� 756��m��). However, there were significantly more Type II fibers (p<.0001) (61.5 �� 7.9% of total) and consequently, Type II fibers occupied significantly more total fiber area p=.00l2) (Type I=45.3 �� 7.4%; Type II=54.7 �� 7.4%). No significant differences were found in the fiber type distributions of the HAT (37.9 �� 2.5% Type I, 62.1 �� 2.5% Type II) and non-HRT (38.9 �� 2.9% Type I, 61.1 �� 2.9% Type II) groups. There were no significant differences in fiber CSA of Type I fibers (HRT: 3615 �� 886 ��m��, non-HRT: 3769 �� 912 ��m��) or Type II fibers (HRT: 2770 �� 722 ��m��, non-HRT: 2849 �� 804 ��m��) obtained from the two groups. Six months of ST had no effect on the strength, fiber CSA, and fiber type distribution for HRT and non-HRT subjects. These results suggest that HRT does not alter muscle strength, fiber type distribution, and fiber CSA in early postmenopausal women. / Graduation date: 2003

[Truncated abstract] Alzheimer’s disease (AD) is a progressive neurodegenerative disease which manifests clinically as personality changes and global cognitive decline resulting in a loss of function, ultimately leading to death. Whilst causal genetic mutations have been identified, accounting for a small proportion of familial cases, the vast majority of all AD cases are late onset and idiopathic. However, a number of risk factors have been identified, including age associated changes in the reproductive hormones – estrogen and the gonadotropins. Previous in vitro and in vivo studies have implicated both estrogen and the gonadotropins in the regulation of the neurotoxic beta amyloid (Aß) peptide, accumulation of which is thought to be a key pathogenic event in the development of AD, but the role of these hormones in the etiology and pathogenesis of AD remains contentious. The aim of this thesis was to further understanding of the role of female reproductive hormones in modulating susceptibility to AD. The role of menopausal hormone dysregulation in behavior, cognitive decline and Aß-related neuropathology was examined in vivo in 4 studies using animal models of AD and menopause. The first two studies used a mouse model of AD expressing a human PS1 mutation (PS1KI) to examine the effects of ovariectomy as a model of menopause on cognition and neuropathology. Ovariectomy was found to selectively impair learning on a spatial working memory task without affecting working memory recall or reference memory performance. However, this cognitive impairment was not associated with any changes in Aß accumulation or oxidative stress. ... However, these findings cannot explain the lack of effect of estrogen supplementation on Aß levels. It is possible that supra-physiological doses of estrogen are necessary to yield anti-amyloidogenic and anti-oxidative benefits in ovariectomized sheep. It is becoming clear that the relationship between hormone changes at menopause and risk of AD may be more complicated than previously conceived. This study has begun to tease apart the relative contributions of estrogen and the gonadotropin hormones in the modulation of Aß, accumulation of which may confer susceptibility to AD. The findings presented indicate that the gonadotropins may play an important role in the regulation of AD-related behavior and cognition. The observed functional effects of the gonadotropins may also have implications for our understanding of behavioral and cognitive changes occurring during reproductive events. Based on the evidence presented here, combined with previous literature, it is clear that both estrogen and the gonadotropins are involved in the modulation of Aß accumulation, however, elucidation of the circumstances necessary to elicit these effects and their clinical relevance to humans will require further investigation. These findings contribute to a more sophisticated understanding of the post-menopausal hormonal milieu, recognizing the role of the gonadotropin hormones and that gonadal estrogen depletion does not necessarily result in brain estrogen depletion.

Includes bibliographical references (leaves 254-288). Examines language used by general practitioners and in mass media to ask 'what are the implications of constructions of menopause for health care practice and public health for women at menopause?'. Presents the findings of qualitative analysis of semi-structured interviews with nine general practitioners working in rural South Australia and qualitative and quantitative analyses of 345 south Australian newspaper articles from 1986 to 1998.

Includes bibliographical references (leaves 254-288). / x, 288 leaves ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Examines language used by general practitioners and in mass media to ask 'what are the implications of constructions of menopause for health care practice and public health for women at menopause?'. Presents the findings of qualitative analysis of semi-structured interviews with nine general practitioners working in rural South Australia and qualitative and quantitative analyses of 345 south Australian newspaper articles from 1986 to 1998. / Thesis (Ph.D.)--University of Adelaide, Dept. of Public Health, 2001?