To determine the effect of estrogen on weight changes in women, eight adult females were followed for a period of six months subsequent to hysterectomy or ovariohysterectomy. Three groups comprised the study: 1) a hysterectomy or control group, 2) an ovariohysterectomy group with estrogen replacement therapy, and 3) an ovariohysterectomy without estrogen treatment group. Body weight, caloric intake, and activity level were recorded for the eight prospective subjects over the six month period. Weight data were gathered from past medical records on an additional 19 patients meeting the treatment criteria. Weight changes between groups were not statistically significant. A trend in weight changes among the groups was noted. The hysterectomy group lost five pounds, ovariohysterectomy treated group lost one pound and the untreated group, 0.2 pound. The same trend in weight changes was noted when data from prospective and retrospective subjects were combined. Caloric intake and activity levels did not explain all changes noted. Detailed information on subjects was presented as case studies. The results supported the concept that endogenous estrogen protects against weight gain; evidence did not support the comparable action of exogenous estrogen. Subjects having ovariohysterectomy stated that they experienced appetite changes such as cravings for sweets, undesirable muscle tone and body contour changes, and difficulty in ability to control weight. Further research with a larger sample size is needed to determine direct relationships between female hormones and suppression of weight gain in women. / Master of Science

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.

OBJETIVO: Analisar a sintomatologia climatérica, a função hepática e a hemostasia das pacientes com hepatite crônica pelo vírus C, durante o uso da terapia hormonal. METODOLOGIA: As pacientes foram divididas em dois grupos: Grupo TH (Grupo caso) - 25 pacientes com terapia hormonal transdérmica (50mcg de estradiol e 170 mcg de noretisterona/dia) por 9 meses, e Grupo NT (Grupo controle) - 25 pacientes sem terapia hormonal, ambos com sintomas climatéricos. A menopausa foi confirmada pela dosagem do FSH, LH e estradiol, e a hepatite C foi diagnosticada pela sorologia, PCR (reação em cadeia de polimerase) e biópsia hepática (grau histológico variando de I-IV). Os dois grupos foram avaliados no mês 0, 1,4,7 e 9; sendo a sintomatologia climatérica mensurada através do Índice Menopausal de Kupperman, a função hepática e a hemostasia pelos exames: alanina aminotransferase, aspartato aminotransferase, gama glutamiltransferase, fosfatase alcalina, bilirrubinas, albumina, tempo de protrombina, fator V, fibrinogênio e plaquetas. ANÁLISE ESTATÍSTICA: realizada através do teste t de Student, teste de Mann Whitney e análises de variâncias com medidas repetidas com dois fatores. Após a realização das análises de variâncias, para os efeitos estatisticamente significantes foram realizadas comparações múltiplas através de contrastes ou do método de Dunnett. RESULTADOS: A média da idade das pacientes foi de 53,72 e a da menopausa foi de 47,3 anos. Os escores médios dos sintomas vasomotores, fraqueza, palpitação e a somatória dos valores atribuídos ao índice menopausal de Kupperman sofreram alteração no comportamento ao longo do tempo (p<0,05). Os valores da fosfatase alcalina apresentaram alteração no comportamento ao longo do tempo (p<0,05), entretanto, as demais medidas da função hepática e hemostasia, não apresentaram diferença entre os grupos. CONCLUSÕES: Houve melhora da sintomatologia climatérica. Não houve alteração na hemostasia e na função hepática, exceção feita à fosfatase alcalina que apresentou melhora significativa no Grupo TH a partir do 4º mês; portanto, houve melhora na qualidade de vida, sem interferência na função hepática e na hemostasia. / OBJECTIVE: To analize climacteric symptoms, liver function, hemostasis in patients with chronic viral hepatitis C, during hormone therapy. DESIGN: Patients were divided in two groups: Group TH (Case Group) - 25 patients on transdermal hormone therapy (50mcg of estradiol and 170 mcg of norethisterone/day) for 9 months, and Group NT (Control Group) - 25 hormone-untreated patients, both with climacteric symptoms. Menopause was confirmed by measuring FSH, LH and estradiol, and hepatitis C was diagnosed by serology, PCR (Polymerase Chain Reaction) and liver biopsy (histological type stages I to IV). Both groups were evaluated in the months 0, 1, 4, 7 and 9; and the climacteric symptoms measured by using Kupperman menopausal index, liver function and hemostasis by the following laboratory tests: alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase, alkaline phosphatase, bilirubin, albumin, prothrombin time (PT), factor V, fibrinogen and platelets. STATISTICAL ANALYSIS: Student\'s t test, Mann-Whitney test and two-factor analysis of variance with repeated measures were applied. After analysis of variance, multi-factor analysis of variance was applied for the statistically significant effects using contrasts or Dunnett?s test. RESULTS: The mean age of patients was 53.72 and the mean age of menopause was 47.3 years. The total mean scores for vasomotor symptoms, fatigue, palpitations and the sum of the values attributed to Kupperman menopausal index do change throughout time (p<0.05). Levels of alkaline phosphatase show alteration throughout time (p<0.05), although, other measures for liver function and hemostasis present no mean difference between the groups. CONCLUSION: There was an improvement in climacteric symptoms. No change was found in hemostasis levels or liver function. However, alkaline phosphatase levels significantly improved in Group TH starting in month 4; therefore, an increase in quality of life was observed.

RESUME Introduction: Le cancer du sein (CS) est le cancer le plus fréquent chez la femme. Le risque de CS est influencé par de nombreux facteurs. Le traitement hormonal de la ménopause (THM) est l’un d’entre eux. Le risque de CS associé au THM varie probablement en fonction de la population traitée, du type de traitement utilisé, de la durée du traitement et du moment où il est instauré par rapport au début de la ménopause. Il existe des alternatives au THM pour soulager les symptômes de la ménopause. Quelques traitements ont montré une certaine efficacité mais présentent des effets secondaires. D’autres traitements doivent faire l’objet d’études plus approfondies. Objectifs: 1) Contribuer à l’analyse de l’influence du THM sur le CS. 2) Contribuer à l’amélioration de la qualité de vie des patientes ayant eu un CS. Résultats: 1) Nous avons analysé l’évolution de l’incidence du CS et des ventes de THM en Belgique et montré une corrélation entre ces deux paramètres. Nous avons réalisé une revue systématique des études analysant l’association entre l’incidence du CS et l’utilisation de THM. Toutes présentaient des limitations et leur hétérogénéité les rendait difficilement comparables. Nous avons analysé l’évolution des ventes de THM en Europe et montré une diminution importante au cours de la dernière décennie dans l’ensemble des pays étudiés. Nous avons analysé l’évolution de l’incidence du CS et de l’utilisation des THM dans différents pays européens et n’avons pas trouvé d’association entre ces deux paramètres. Nous avons réalisé une revue systématique des études évaluant l’influence du THM sur les caractéristiques du CS et montré que les CS développés sous THM n’étaient pas de meilleur pronostic. 2) Nous avons réalisé deux revues systématiques sur la sécurité d’emploi des THM et des traitements non hormonaux de la ménopause chez les femmes ayant eu un CS. Nous avons montré que le CS représentait une contre-indication au THM et que peu de données existaient concernant les traitements alternatifs. Nous avons mené deux études concernant l’utilisation de traitements de la ménopause chez les femmes ayant eu un CS et montré qu’une proportion importante des femmes ayant eu un CS présentait des symptômes de la ménopause mais que peu d’entre elles utilisaient un traitement. Certains de ces traitements pouvaient potentiellement réduire l’efficacité de leur traitement contre le CS. Conclusions: 1) L’influence exacte du THM sur l’incidence du CS reste difficile à déterminer. D’autres facteurs interviennent également. Nous avons montré l’importance du temps lorsqu’on observe l’évolution de deux paramètres. 2) Les traitements sûrs et efficaces des symptômes de la ménopause chez les femmes ayant eu un CS sont limités. La qualité de vie des patientes ménopausées, ayant souffert d’un CS, peut cependant être nettement améliorée. / ABSTRACT Introduction: Breast cancer (BC) is the most common cancer in women. BC risk is influenced by many factors. Menopausal hormone therapy (MHT) is one of them. BC risk associated with MHT may vary depending on the treated population, the type of MHT used, the treatment duration and the delay between the beginning of the treatment and the onset of the menopause. There are alternatives to MHT for the treatment of menopausal symptoms. Some of them have shown some efficacy but have side-effects. Others need further research. Objectives: (1) To contribute to the analysis of the influence of MHT on BC; (2) to contribute to the improvement of the quality of life of BC patients. Results: (1) We analysed changes in BC incidence and MHT sales in Belgium and showed a correlation between these two parameters. We made a systematic review of studies analysing the association between BC incidence and MHT use. All the studies had limitations and were heterogeneous, making them difficult to compare. We analysed changes in MHT sales in Europe and showed an important decrease during the last decade in all the studied countries. We analysed changes in BC incidence and MHT sales in several European countries and found no association between these two parameters. We made a systematic review of studies assessing the influence of MHT on BC characteristics and showed that cases of BC developed under MHT did not have a better prognosis. (2) We made two systematic reviews on the safety of MHT and non-hormonal treatments in BC patients. We showed that BC was a contra-indication to MHT and that few data on alternative treatments were available. We conducted two studies on the use of treatments to alleviate menopausal symptoms in BC patients and showed that an important proportion of these women suffered menopausal symptoms but that few of them were using a treatment. Some of these treatments could reduce the efficacy of their BC treatment. Conclusions: (1) The exact influence of MHT on BC incidence is difficult to evaluate. Other factors are also involved. We showed that long follow-ups are needed when analysing time trends. (2) Efficient and safe treatments for menopausal symptoms in BC patients are limited. However, the quality of life of BC patients may be improved. / Doctorat en Sciences biomédicales et pharmaceutiques (Médecine) / info:eu-repo/semantics/nonPublished

Indiana University-Purdue University Indianapolis (IUPUI) / Menopausal symptoms, primarily hot flashes, are a pressing clinical problem for both naturally menopausal women and breast and ovarian cancer patients, with a high societal and personal cost. Hot flashes are poorly understood, and animal modeling has been scarce, which has substantially hindered the development of non-hormonal treatments. An emerging factor in the hot flash experience is the role of anxiety and stress-related stimuli, which have repeatedly been shown to influence the bother, frequency, and severity of hot flashes. Causal relationships are difficult to determine in a clinical setting, and the use of animal models offers the ability to elucidate causality and mechanisms. The first part of this work details the development and validation of novel animal models of hot flashes using clinically relevant triggers (i.e., compounds or stimuli that cause hot flashes in clinical settings), which also increase anxiety symptoms. These studies revealed that these triggers elicited strong (7-9 °C) and rapid hot flash-associated increases in tail skin temperature in rats. In a surgical ovariectomy rat model of menopause, which typically exhibit anxiety-like behavior, hot flash provocation revealed an ovariectomy-dependent vulnerability, which was attenuated by estrogen replacement in tested models. An examination of the neural circuitry in response to the most robust flushing compound revealed increased cellular activity in key thermoregulatory and emotionally relevant areas. The orexin neuropeptide system was hyperactive and presented as a novel target; pretreatment with selective and dual orexin receptor antagonists significantly diminished or eliminated, respectively, the response to a hot flash provocation in ovariectomized rats. The insertion/deletion polymorphism of the serotonin transporter has been linked to increased anxiety-associated traits in humans, and subsequent studies prolonged hot flashes in SERT+/- rats, which also caused hot flashes in highly symptomatic women. These studies indicate the orexin system may be a novel non-hormonal treatment target, and future studies will determine the therapeutic importance of orexin receptor antagonists for menopausal symptoms.

Thesis (MA)--Stellenbosch University, 2004. / ENGLISH ABSTRACT: The popular media ("Media" here referring to newspapers, magazines. television, internet) adds to confusion and panic when reporting on the risks and benefits of Hormone Replacement Therapy for women (HRT). Most reports show bias, cast scientists as villains, or leave the reader more confused than before about terminology. The Southern African media does in general aspire to objectivity towards both the pharmaceutical and natural health industry. However, shallow or inept reporting, the need to generalise complicated findings and dramatise what's regarded as cold scientific news, create this bias and confusion. Misleading health reporting, in South Africa as much as anywhere else in the world, can change health behaviour and can even cost lives. Ethical health reporting can therefore be described as a matter of life and death. This paper aims to analyse the media for biased, confusing and alarmist reporting. It then aims to explain reasons for the bias or confusion. Fourteen reports are analysed. One Time magazine report, and 13 reports selected from the Southern African media. / AFRIKAANSE OPSOMMING: Berigte oor Hormoonvervangingsterapie (HVT) vir vroue in die media ("Media") hier verwys na koerante, tydskrifte, televisie, internet) dra by tot verwarring en paniek. Die meerderheid berigte is bevooroordeeld, in die sin dat medici as booswigte uitgebeeld word. Indien hulle nie bevooroordeeld is nie, is berigte verwarrend, soms juis in 'n poging om konsepte te vereenvoudig. Die media in Suider Afrika aspireer wel tot objektiwiteit, teenoor beide die farmaseutiese sowel as die holistiese (kruie) industrie. Nietemin, oppervlakkige/oningeligte verslaggewing en die behoefte om ingewikkelde navorsing te vereenvoudig/interessant te maak, dra by tot vooroordeel en verwarring. Misleidende mediese beriggewing in Suid Afrika, net soos in die res van die wêreld, kan mense hoop om besluite te neem wat hul gesondheid kan skaad. Die belang van etiese verslaggewing kan dus as 'n kwessie van lewe en dood beskryf word. Hierdie studie ontleed berigte en ondersoek vooroordeel, verwarring of sensasionalisering. Redes vir bogenoemde word dan bespreek. Veertien berigte word ontleed. (een berig uit die Amerikaanse tydskrif Time, en 13 uit die Suider Afrikaanse media)

Estrogen therapy (ET) is most effective to reduce menopausal symptoms and prevent other disorders associated with estrogen deficiency. However, Women's Health Initiative studies found that hormone therapy (HT) containing estrogen plus progestogen, but not estrogen-alone increases breast cancer (BC) risk. To prevent the increase in BC risk and yet relieve menopausal symptoms, a novel HT with 17β-estradiol (E2) for symptom relief, progesterone (P4) for uterine protection and melatonin (Mel) for both BC and uterine protection was designed. Inclusion of Mel was postulated to offer uterine protection with lower P4 dose and protect against BC. The goal of this study was to assess the efficacy of E2, P4 and Mel Therapy (EPMT) on mammary cancer (MC) and uterine protection in MMTV-Neu mouse model that mimics HER2 BC. Starting at 2 months age, female mice received Mel in drinking water at night to supplement endogenous Mel surge; while E2 and P4 Therapy (EPT) was provided continuously in diet until 14 months with weekly MC onset and growth monitoring. Normal mammary, uterus and mammary tumors harvested by month 14 were analyzed for potential mechanisms. The results from this study revealed that EPMT delayed tumor onset leading to a decrease in MC incidence. In addition, mice in the EPMT group had no increase in relative uterine weight as opposite to an increase of this parameter in EPT group versus control. The percent tumor-bearing mice with gross metastatic lung lesions were reduced in Mel, EPT and EPMT groups. Mel receptor, estrogen receptor (ER) and progesterone receptor (PR) expression revealed that all tissues examined have Mel receptors. However, ER and PR expression varied. In normal mammary tissue, both ERα and PR were detected by immunohistochemistry. However, no ERα and PR were detected in mammary tumors of same mice. In uterus, mice given Mel or EPMT had significant decreases in PR expression but no change in ERα expression compared to control suggesting that Mel-mediated inhibition of ER binding to estrogen response elements may be involved in the down regulation of uterine PRs. Overall, this study reveal that EPMT prevents mammary cancer and may protect against uterotrophy. / Mylan School of Pharmacy and the Graduate School of Pharmaceutical Sciences; / Pharmacology / PhD; / Dissertation;

Bakgrund: Prostatacancer är den vanligaste cancerformen i Sverige där det finns olika behandlingsalternativ. Behandlingarna medför olika biverkningar och effekter för männen. Under behandlingen är det oftast en sjuksköterska männen träffar innan, under och efter behandlingen. Syfte: Syftet var att beskriva mäns upplevelser av livskvalitet under behandling av prostatacancer. Metod: En litteraturöversikt av aktuell forskning med kvalitativ och kvantitativ ansats där 12 artiklar har analyserats. Resultat: Många män upplevde en förändrad livsrytm och att det var viktigt att försöka leva så normalt och hälsosamt som möjligt. Männen upplevde förändringar av kroppen vilket ledde till att en del män kände skam och upplevde sig mindre manliga. Männen upplevde en förändrad syn på livet. Flera av männen upplevde att relationen till deras partner kunde bli påverkad både positivt och negativt. För att kunna hantera sjukdomen upplevde männen att det var viktigt med stöd och information från sjukvården för att behålla sin livskvalitet. Konklusion: Studien visar att män under behandling av prostatacancer upplever flera olika förändringar som påverkar deras livskvalitet. Män upplever en förändrad livsrytm, en förändring av kroppen, en förändrad syn på livet, ett förändrat samliv och ett behov av information och stöd från sjukvården. Som sjuksköterska är det därför viktigt att ha kunskap om förändringarna för att kunna vara ett stöd för patienten och därmed minska lidande.

When Y-1 mouse adrenal tumor cells were treated with sodium orthovanadate, an intermediate filament (IF) inhibitor in BHK21-F cells, there was no change in the amount of 20α-dihydroprogesterone produced. A neurofilament inhibitor, β, β'-iminodipropionitrile (IDPN), enhanced the ability of Y-1 cells to produce steroid in response to ACTH by acting on the plasma membrane. Electron microscopy of Y-1 cells extracted with Triton X-100 revealed that both vanadate and IDPN caused the aggregation of cytoskeletal and granular structures in the perinuclear area. The steroidogenic effects of IDPN suggest that the perinuclear aggrergation of cytoskeletal structures may result from the detachment of IF from the plasma membrane, while the reason for the cytoskeletal changes by vanadate is unknown.