The Cape ground squirrel, Xerus inauris, is a highly social cooperative breeder that forms groups containing multiple breeding females. While the distribution of reproduction among group members is fairly even (i.e. exhibits low reproductive skew), previous studies of Cape ground squirrels suggest the reproductive development of sub-adult females is inhibited by the presence of adult breeding female group mates. As reproductive delay is known to be influenced by a number of different parameters, my goal was to determine if other factors affected the timing of sexual maturity, and if so, which factors are the most influential. In this study, I simultaneously test the relative power of seven different social and environmental parameters at explaining the variation in the female age of sexual maturity in two populations of Cape ground squirrels. Field work was conducted at two study sites in southern Africa, where trapping, behavioral and hormonal data were collected to determine the timing of reproductive development. Hormonal data was analyzed through the use of steroid enzyme immunoassay analysis to quantify the concentration of gonadal hormone in fecal samples which indicate the onset of sexual maturity. Prior to the start of the field season, I conducted an initial experiment to determine the best alternative form of fecal storage if freezing was unavailable. I found that drying feces provides a more reliable method for long-term preservation of fecal steroid concentrations when compared to storing fecal samples in alcohol. Data associated with each of the seven parameters was analyzed using model selection to simultaneously measure the ability of different combinations of parameters to explain the observed variation in female age of sexual maturity. I found that an increase in the number of adult breeding female group mates and related adult male group mates resulted in a substantial inhibition of female reproductive maturity. I concluded that a female Cape ground squirrel's age of sexual maturity is principally a result of the interaction between adult breeding females' capacity for reproductive suppression and sub-adults' ability to maximize lifetime reproductive success while minimizing inbreeding. The overall reproductive dynamics of each social group results from the tug-of-war between the adult and sub-adult female group mates to control breeding within the group, with minimal direct influence on sexual maturity by environmental factors.

Background: Numerous studies have shown that estrogen replacement therapy (ERT) is an effective treatment for vasomotor symptoms, insomnia and vaginal dryness. Beneficial effects have also been shown on lipid patterns and on the incidence of osteoporotic fractures. As ERT increases the risk of endometrial adenocarcinoma, combinations with various progestogens have been developed in order to protect the endometrium. However, the addition of progestogens tends to reduce the beneficial effects of estrogens on mood, cognition and lipid metabolism. The added progestogen often causes side effects such as irritability and depression. There is evidence that the effect on wellbeing varies between women and with the type of progestogen used. Women who prefer to avoid withdrawal bleedings can be given continuous combined hormone replacement therapy (HRT). Unfortunately, irregular bleedings are common at the beginning of treatment and reduces compliance. Recently, several studies have reported an increased risk of breast cancer and venous thrombosis, and therefore long-term treatment with HRT for women without climacteric symptoms is no longer recommended. The ongoing debate has, for the time being, resulted in a recommendation that improving quality of life (QoL) by treatment of climacteric symptoms should be the only indication for prescribing HRT. Aims and methods: The aims of the study were to investigate bleeding patterns, changes in wellbeing at onset and during long-term treatment, and lipid and lipoprotein profiles with two different types of continuous combined HRT. In addition, women starting, and women switching from mainly sequential HRT were compared. The design was a randomised, double-blind, one year, prospective, multicentre study including 249 healthy postmenopausal women who were given continuous daily oral treatment with either combined 0.625mg conjugated estrogen (CE) and 5mg medroxyprogesterone acetate (MPA) or combined 2mg 17β - estradiol (E2) and 1mg norethisterone acetate (NETA). Bleedings, if any, were recorded daily throughout the study. The main outcome measures (changes in wellbeing and climacteric symptoms) consisted of daily ratings of 12 items on a validated symptom scale. Serum concentrations of lipids and lipoproteins were measured at baseline and after one year of treatment. Results and conclusions: The majority of drop-outs were confined to the first three months, and the main reasons were bleedings and/or decreased wellbeing. Drop-outs were three times more common in the E2/NETA group. During the first month, 67% of the women reported irregular bleedings. The number of bleeding days decreased on both treatments during the first four months. Treatment with CE/MPA resulted in less irregular bleedings and a shorter time to amenorrhoea compared to E2/NETA. As expected, "starters" experienced more sweats than "switchers" at the onset of treatment, but both groups improved significantly. Side effects such as breast tenderness, swelling, depression and irritability appeared during the first treatment week in both groups. The side effects of HRT appeared much more quickly than the benefits and were more frequent in women with a history of premenstrual syndrome (PMS). Breast tenderness was more common in the E2/NETA group throughout the whole study period. Apart from that, there were no differences between the two treatment regimens as regards effects on well-being at the end of the study. Lipoprotein(a) levels, an important risk factor for cardiovascular disease, decreased in both treatment groups. Triglyceride levels increased in women treated with CE/MPA, and levels of total cholesterol, high density lipoprotein and low density lipoprotein fell in the E2/NETA group. In conclusion, treatment with E2/NETA caused more bleeding problems than treatment with CE/MPA. CE/MPA was better tolerated than E2/NETA at the beginning of the study, but among the women remaining in the study there was no difference in QoL between the two treatment groups. HRT counselling should take into account that a history of PMS increases the likelihood of side effects and that these may precede any beneficial effects. Both treatments produced beneficial effects on lipid and lipoprotein levels, and neither of the regimens was superior in this respect.

O climatério afeta significativamente a vida de milhares de mulheres ao redor do mundo. A evolução do conhecimento em relação à segurança das opções medicamentosas utilizadas para manejo de seus sintomas se faz essencial no atual momento. A terapia hormonal usando estrógeno e progestágeno (TEP) tem sido amplamente prescrita para o manejo dos sintomas climatéricos. O uso da TEP foi recomendado no passado também com o objetivo de prevenção de doença cardiovascular. Porém, ensaios clínicos randomizados recentes falharam em comprovar os benefícios cardiovasculares do regime de TEP mais comumente utilizado (EEC 0.625mg + AMP 2.5mg /dia), tendo também sugerido que este regime está associado a significativo aumento de risco cardiovascular. A doença cardiovascular é a principal causa de mortalidade em países ditos desenvolvidos e em desenvolvimento, como o Brasil. Atualmente, mulheres brasileiras com faixa etária entre 50-59 anos apresentam taxa de mortalidade por DCV de 36%, aumentando este percentual gradativamente nas décadas que se seguem (60-69 anos = 40%, ≥70 anos = 46%). A população de mulheres pós-menopáusicas com Diabete Melito Tipo 2 (DM2) também vem crescendo significativamente em todo o mundo. O Brasil é um dos 10 países do mundo que apresentará o maior número de pessoas com diagnóstico de DM em 2025. A maioria desta população será de mulheres, moradoras de áreas urbanas, com idade entre 45-64 anos. Desta forma, mulheres pós-menopáusicas com DM2 representam um percentual significativo da população, e sabidamente apresentam risco cardiovascular aumentado. Além de ser um grupo de alto risco cardiovascular, estas mulheres freqüentemente necessitam manejo medicamentoso dos sintomas climatéricos. Este estudo visa revisar a literatura existente sobre o uso de TEP em mulheres pósmenopáusicas com DM2, analisando o impacto das diversas combinações sobre marcadores de risco de doença cardiovascular clássicos e não-clássicos. / The menopause has significant impact on thousands of women worldwide. The safety of pharmacological options in the management of menopause symptoms is an essential area of research and development. The hormonal therapy by means of estrogen and progestogen (EPT) has been widely prescribed to manage menopausal symptoms. The use of EPT had been also recommended in the past to prevent cardiovascular disease. However, recent large-scale randomized clinical trials have not only shown no cardiovascular benefit, but also have demonstrated that it is associated with significant increase in cardiovascular risk, at least with the most used regimen (CEE 0.625mg+MPA 2.5mg/day). Cardiovascular diseases (CVD) are the leading cause of death in developed world and in developing countries such as Brazil. Brazilian women, who are currently in the 50-59 age range, are expected to have a CVD mortality rate of 36%, with gradual increase in risk in the following decades (60-69 years-old = 40%, ≥ 70 years-old = 46%). The postmenopausal diabetic women population has also grown significantly worldwide. Brazil is one of the 10 countries in the world that will have the largest population of diabetics by 2025. The majority of this population will be female, living in urban areas and between 45 and 64 years-old. Therefore, post-menopausal diabetic women will represent a significant percentage of people, who knowingly have increased cardiovascular risk, these women frequently need medical management of their menopause symptoms. The aim of this study is to review the existing literature on EPT in post-menopausal diabetic women, analyzing the impact of several regimens over classic and non-classic CVD risk factors.

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Agradecemos a compreensão. on 2016-08-23T20:00:38Z (GMT) / Submitted by LINCY LISETH CAMACHO ORJUELA null (lincy55@hotmail.com) on 2016-08-23T20:19:59Z No. of bitstreams: 1 DissertacaoMsLincy.camacho Pronta.pdf: 1931933 bytes, checksum: 69a9c72283cf115cef6d6c040765b13a (MD5) / Approved for entry into archive by Ana Paula Grisoto (grisotoana@reitoria.unesp.br) on 2016-08-24T16:18:58Z (GMT) No. of bitstreams: 1 orjuela_llc_me_jabo.pdf: 1931933 bytes, checksum: 69a9c72283cf115cef6d6c040765b13a (MD5) / Made available in DSpace on 2016-08-24T16:18:58Z (GMT). No. of bitstreams: 1 orjuela_llc_me_jabo.pdf: 1931933 bytes, checksum: 69a9c72283cf115cef6d6c040765b13a (MD5) Previous issue date: 2016-07-11 / A região neotropical passa por um período critico em termos de perda da biodiversidade e as biotécnicas reprodutivas podem auxiliar na conservação de recursos neste processo. Entretanto, a aplicação dessas tecnologias para conservação de ungulados não-domésticos reúne muitas limitações, como o pouco conhecimento de sua fisiologia reprodutiva e a necessidade de manejo intensivo dos animais. O uso de protocolos menos invasivos para sincronização do ciclo estral pode trazer vantagens e torná-los aplicáveis a uma gama maior de situações práticas. Visando estabelecer protocolos hormonais não invasivos para realização desta biotécnicas, este trabalho teve por objetivo avaliar alguns aspectos do metabolismo do acetato de melengestrol (MGA) (Experimento 1), administrado pela via oral em fêmeas de veado catingueiro (Mazama gouazoubira) por meio de dosagens dos progestágenos fecais e urinários, e avaliar o seu efeito na manipulação do ciclo estral (Experimento 2 e 3). Para o experimento 1, após a administração do fármaco em dose única as fezes e urina foram coletadas a cada 4 horas por 72 horas. Os resultados mostraram concentrações hormonais, em média, para o pré-tratamento para as fêmeas FMG1; FMG2; FMG3; FMG4; FMG5 em fezes foram respectivamente, de 606,15±291,10; 313,96 ± 95,25; 628,94 ± 382,04; 295,11 ± 95,15; 454,53 ± 140,88,e para urina as medias foram 0,31 ± 0,13; 0,23 ± 0,08; 0,31 ± 0,18; 0,59 ± 0,32; 0,26 ± 0,10. As concentrações médias do pós-tratamento para as fêmeas FMG1; FMG2; FMG3; FMG4; FMG5 em fezes foram respectivamente, de 706,17± 194,35; 257,13±69,88; 373,85±108,69; 503,13 ± 194,46; 970,16± 322, 28, e para urina 0,38 ± 0,12; 0,10± 0,056; 0,49 ± 0,14; 0,89 ± 0,31; 0,17± 0,08, respectivamente. Não foi evidente a ocorrência de picos nos perfis endócrinos após administração de MGA, no entanto foi possível visualizar um pequeno aumento dos níveis em 4 das 5 fêmeas, 16 a 24 horas após ingestão do fármaco. No experimento 2, o medicamento foi oferecido uma vez por dia durante 8 dias e no final do 8o dia foi realizada uma aplicação de cloprostenol sódico. As fêmeas tiveram estro monitorado, sendo possível observar estro comportamental em 3 das 6 fêmeas (50%), Já para o experimento 3, o medicamento foi administrado uma vez por dia durante 7 dias sendo que no final do 2° dia foi feita uma aplicação intramuscular de cloprostenol sódico, o estro foi monitorado duas vezes por dia. Três das 5 fêmeas (60%) apresentaram estro após aplicação do cloprostenol, mostrando a ineficiência do MGA, na dose testada, em inibir o crescimento folicular e ovulação após a luteólise. / The neotropical region is experiencing a critical period in terms of loss of biodiversity, and the development of new reproductive biotechnologies might assist to moderate this reality. However, the application of these technologies for non-domestic ungulates conservation presents important limitations, like the lack of knowledge of their reproductive physiology as well as the need for an intensive handling of the animals. The use of less invasive protocols for the oestrous cycle synchronization could be more advantageous and applicable in a wide variety of practical situations. Therefore, the establishment of new non-invasive hormonal protocols to performing this biotechnology is necessary. The aims of this study were, on the one hand, to assess some aspects of Melengestrol Acetate (MGA) metabolism (Experiment 1) administered orally in brocket deer females (Mazama gouazoubira) through the analysis of faecal and urinary progestagens. For the experiment 1, after the drug administration in a single dose, faeces and urine were collected every 4 hours for 72 hours. The faecal mean hormonal concentrations in the pre-treatment for the females FMG1; FMG2; FMG3; FMG4; FMG5 were 606,15±291,10; 313,96 ± 95,25; 628,94 ± 382,04; 295,11 ± 95,15; 454,53 ± 140,88 respectively, and 0,31 ± 0,13; 0,23 ± 0,08; 0,31 ± 0,18; 0,59 ± 0,32; 0,26 ± 0,10 for urine. With regard to the post-treatment, the faecal mean hormonal concentrations for the females FMG1; FMG2; FMG3; FMG4; FMG5 were 706,17± 194,35; 257,13±69,88; 373,85±108,69; 503,13 ± 194,46; 970,16± 322, 28 respectively, and 0,38 ± 0,12; 0,10± 0,056; 0,49 ± 0,14; 0,89 ± 0,31; 0,17± 0,08 for urine. I was not observed the presence of progestagens peaks in the endocrine profiles after the MGA administration; however, it was possible to visualize a small increase in its levels in 4 of the 5 females from 16 to 24 hours after the drug ingestion. In the experiment 2, the MGA was administered once a day for eight consecutive days, and on the last day, an application of Sodium Cloprostenol was performed. Females were monitored daily and an oestrus behavioural was observed in 3 of the 6 animals (50%).In the experiment 3, the MGA was administered once a day for seven consecutive days, and at the end of the second day, an intramuscular application of Sodium Cloprostenol was performed. Females were monitored twice daily and three of the five females (60%) showed an oestrus behavioural after the cloprostenol application showing the inefficiency of MGA on the initial tested dose to inhibe the follicular growth, anterior ovulation and luteolysis.

O climatério afeta significativamente a vida de milhares de mulheres ao redor do mundo. A evolução do conhecimento em relação à segurança das opções medicamentosas utilizadas para manejo de seus sintomas se faz essencial no atual momento. A terapia hormonal usando estrógeno e progestágeno (TEP) tem sido amplamente prescrita para o manejo dos sintomas climatéricos. O uso da TEP foi recomendado no passado também com o objetivo de prevenção de doença cardiovascular. Porém, ensaios clínicos randomizados recentes falharam em comprovar os benefícios cardiovasculares do regime de TEP mais comumente utilizado (EEC 0.625mg + AMP 2.5mg /dia), tendo também sugerido que este regime está associado a significativo aumento de risco cardiovascular. A doença cardiovascular é a principal causa de mortalidade em países ditos desenvolvidos e em desenvolvimento, como o Brasil. Atualmente, mulheres brasileiras com faixa etária entre 50-59 anos apresentam taxa de mortalidade por DCV de 36%, aumentando este percentual gradativamente nas décadas que se seguem (60-69 anos = 40%, ≥70 anos = 46%). A população de mulheres pós-menopáusicas com Diabete Melito Tipo 2 (DM2) também vem crescendo significativamente em todo o mundo. O Brasil é um dos 10 países do mundo que apresentará o maior número de pessoas com diagnóstico de DM em 2025. A maioria desta população será de mulheres, moradoras de áreas urbanas, com idade entre 45-64 anos. Desta forma, mulheres pós-menopáusicas com DM2 representam um percentual significativo da população, e sabidamente apresentam risco cardiovascular aumentado. Além de ser um grupo de alto risco cardiovascular, estas mulheres freqüentemente necessitam manejo medicamentoso dos sintomas climatéricos. Este estudo visa revisar a literatura existente sobre o uso de TEP em mulheres pósmenopáusicas com DM2, analisando o impacto das diversas combinações sobre marcadores de risco de doença cardiovascular clássicos e não-clássicos. / The menopause has significant impact on thousands of women worldwide. The safety of pharmacological options in the management of menopause symptoms is an essential area of research and development. The hormonal therapy by means of estrogen and progestogen (EPT) has been widely prescribed to manage menopausal symptoms. The use of EPT had been also recommended in the past to prevent cardiovascular disease. However, recent large-scale randomized clinical trials have not only shown no cardiovascular benefit, but also have demonstrated that it is associated with significant increase in cardiovascular risk, at least with the most used regimen (CEE 0.625mg+MPA 2.5mg/day). Cardiovascular diseases (CVD) are the leading cause of death in developed world and in developing countries such as Brazil. Brazilian women, who are currently in the 50-59 age range, are expected to have a CVD mortality rate of 36%, with gradual increase in risk in the following decades (60-69 years-old = 40%, ≥ 70 years-old = 46%). The postmenopausal diabetic women population has also grown significantly worldwide. Brazil is one of the 10 countries in the world that will have the largest population of diabetics by 2025. The majority of this population will be female, living in urban areas and between 45 and 64 years-old. Therefore, post-menopausal diabetic women will represent a significant percentage of people, who knowingly have increased cardiovascular risk, these women frequently need medical management of their menopause symptoms. The aim of this study is to review the existing literature on EPT in post-menopausal diabetic women, analyzing the impact of several regimens over classic and non-classic CVD risk factors.

O climatério afeta significativamente a vida de milhares de mulheres ao redor do mundo. A evolução do conhecimento em relação à segurança das opções medicamentosas utilizadas para manejo de seus sintomas se faz essencial no atual momento. A terapia hormonal usando estrógeno e progestágeno (TEP) tem sido amplamente prescrita para o manejo dos sintomas climatéricos. O uso da TEP foi recomendado no passado também com o objetivo de prevenção de doença cardiovascular. Porém, ensaios clínicos randomizados recentes falharam em comprovar os benefícios cardiovasculares do regime de TEP mais comumente utilizado (EEC 0.625mg + AMP 2.5mg /dia), tendo também sugerido que este regime está associado a significativo aumento de risco cardiovascular. A doença cardiovascular é a principal causa de mortalidade em países ditos desenvolvidos e em desenvolvimento, como o Brasil. Atualmente, mulheres brasileiras com faixa etária entre 50-59 anos apresentam taxa de mortalidade por DCV de 36%, aumentando este percentual gradativamente nas décadas que se seguem (60-69 anos = 40%, ≥70 anos = 46%). A população de mulheres pós-menopáusicas com Diabete Melito Tipo 2 (DM2) também vem crescendo significativamente em todo o mundo. O Brasil é um dos 10 países do mundo que apresentará o maior número de pessoas com diagnóstico de DM em 2025. A maioria desta população será de mulheres, moradoras de áreas urbanas, com idade entre 45-64 anos. Desta forma, mulheres pós-menopáusicas com DM2 representam um percentual significativo da população, e sabidamente apresentam risco cardiovascular aumentado. Além de ser um grupo de alto risco cardiovascular, estas mulheres freqüentemente necessitam manejo medicamentoso dos sintomas climatéricos. Este estudo visa revisar a literatura existente sobre o uso de TEP em mulheres pósmenopáusicas com DM2, analisando o impacto das diversas combinações sobre marcadores de risco de doença cardiovascular clássicos e não-clássicos. / The menopause has significant impact on thousands of women worldwide. The safety of pharmacological options in the management of menopause symptoms is an essential area of research and development. The hormonal therapy by means of estrogen and progestogen (EPT) has been widely prescribed to manage menopausal symptoms. The use of EPT had been also recommended in the past to prevent cardiovascular disease. However, recent large-scale randomized clinical trials have not only shown no cardiovascular benefit, but also have demonstrated that it is associated with significant increase in cardiovascular risk, at least with the most used regimen (CEE 0.625mg+MPA 2.5mg/day). Cardiovascular diseases (CVD) are the leading cause of death in developed world and in developing countries such as Brazil. Brazilian women, who are currently in the 50-59 age range, are expected to have a CVD mortality rate of 36%, with gradual increase in risk in the following decades (60-69 years-old = 40%, ≥ 70 years-old = 46%). The postmenopausal diabetic women population has also grown significantly worldwide. Brazil is one of the 10 countries in the world that will have the largest population of diabetics by 2025. The majority of this population will be female, living in urban areas and between 45 and 64 years-old. Therefore, post-menopausal diabetic women will represent a significant percentage of people, who knowingly have increased cardiovascular risk, these women frequently need medical management of their menopause symptoms. The aim of this study is to review the existing literature on EPT in post-menopausal diabetic women, analyzing the impact of several regimens over classic and non-classic CVD risk factors.