Background: HSV-2 was estimated to infect 491 million people worldwide, with women disproportionately affected by HSV-2. Understanding factors that influence susceptibility to HSV-2 in women is important in preventing infections. Through various studies, the progestin-based contraceptive DMPA exhibited immunosuppressive effects, and has shown increased susceptibility to HIV and HSV-2. Studies comparing DMPA to other contraceptives like NET suggest that NET may be safer. In vivo NET effects have not been characterized thoroughly to better understand the effect of NET on susceptibility to HSV-2. Therefore, this study aimed to compare the effects of NET and DMPA in mouse models that affect susceptibility to HSV-2. We hypothesized that NET treated mice will have decreased susceptibility to HSV-2 compared to DMPA but elevated compared to normal mice. Method of study: Ovariectomized mice were treated with DMPA (2mg) and NET (2 mg injections, 2.5 mg pellets or 5 mg pellets) for 10 days and intravaginally immunized with HSV-2 TK-, then intravaginally challenged with WT HSV-2 ~4-7 weeks later. Primary intravaginal WT HSV-2 challenges were conducted in ovariectomized and normal mice after 10 days of DMPA and NET treatment. Viral titers, pathology and survival were examined. Mucus production in the vagina was investigated through immunohistology. Effects of hormones on immune cells were explored in the lymph nodes, spleens, and vaginal tracts through flow cytometry. Results: Increased mucus was consistently observed in the vaginal tracts of mice after treatment with NET 2.5 mg and 5 mg treated mice, but not with DMPA Therefore, NET treated mice displayed reduced viral shedding and delayed pathology compared to DMPA treated mice. No significant changes occurred in immune cells analyzed post DMPA and NET treatment, although there were trends of increased T cells in progestin treated mice. However, more experiments need to be conducted to confirm observed trends. Conclusion: NET treatment in mice results in mucus production in the vaginal tract, a potential mechanism impeding intravaginal HSV-2 infection and could be applied to other STIs. This provides insight into protective effects of NET compared to DMPA allowing women to make informed decisions regarding hormonal contraceptives. / Thesis / Master of Science in Medical Sciences (MSMS)

Orientador: Sarah Monte Alegre / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-26T08:26:23Z (GMT). No. of bitstreams: 1 Batista_GiseleAlmeida_M.pdf: 1859346 bytes, checksum: 3cb1bc28cbd20d9ddb7e8e3a58874a1e (MD5) Previous issue date: 2014 / Resumo: Introdução: O acetato de medroxiprogesterona de depósito (AMPD, Depoprovera®) é um método contraceptivo de alta eficácia e segurança; seu uso tem se difundido amplamente e vem sendo utilizado por milhões de mulheres. Existem poucos estudos na literatura sobre o gasto energético em repouso nas usuárias de Depoprovera®, e é possível que existam variações especialmente naquelas que ganham peso em uso do método. Objetivo: Avaliar as alterações no peso, composição corporal e gasto energético em repouso de mulheres em uso de acetato de medroxiprogesterona de depósito e DIU TCu 380 no período de 12 meses. Métodos: Estudo prospectivo com 20 usuárias de Depoprovera® e 17 usuárias de DIU TCu380, como controle, no período de um ano. Mulheres atendidas no ambulatório de Planejamento Familiar do CAISM/UNICAMP em idade fértil, que optaram como método contraceptivo o injetável Depoprovera®, sem uso prévio deste método, e que apresentavam Índice de Massa Corporal (IMC) < 30 kg/m², além de mulheres que utilizavam o método contraceptivo não hormonal DIU TCu 380A foram convidadas a participar do estudo. Resultados: Os grupos foram pareados no período basal, tornando-se um grupo homogêneo em relação a peso, idade e IMC. Após 12 meses de avaliação, pode-se observar aumento de peso, IMC e superfície corporal de forma significativa no grupo Depo. Em relação ao gasto energético em repouso e quociente respiratório, houve aumento significativo da taxa metabólica basal nos dois grupos. O quociente respiratório reduziu de forma significante nos dois grupos. Quando o grupo Depo foi subdividido por ganho de peso, o subgrupo que ganhou < 3 kg após 12 meses teve aumento significativo de peso, IMC, superfície corporal e quociente respiratório, já o subgrupo que ganhou > 3 kg aumentou significativamente peso, IMC, superfície corporal, peso de massa magra, peso de massa gorda, taxa metabólica basal, Leptina, HOMA-IR e circunferência da cintura e reduziu quociente respiratório após os 12 meses de acompanhamento. Conclusão: Nosso estudo encontrou alterações relevantes no peso, composição corporal e perfil metabólico da população estudada nos primeiros 12 meses de uso do contraceptivo. Essas alterações principalmente o aumento de peso corporal, aumento dos níveis de leptina e HOMA-IR, podem contribuir para o desenvolvimento de algumas complicações crônicas, entre elas a obesidade, resistência à insulina e diabetes mellitus / Abstract: Introduction: Depot Medroxyprogesterone Acetate (DMPA, Depoprovera®) is an high contraceptive efficacy and safety; its use has spread broadly and has been used by millions of women. There are few studies on the resting energy expenditure in Depoprovera® users, and it is possible that there are variations especially those who gain weight using the method. Objective: To evaluate the changes in weight, body composition and resting energy expenditure in women using depot medroxyprogesterone acetate and IUD TCu 380 in 12 months. Methods: This was a prospective study with 20 Depoprovera® users and 17 IUD users TCu380 as a control within one year. Women attending the outpatient clinic of CAISM / UNICAMP of childbearing age who chose the injectable contraceptive Depoprovera ® without previous use of this method, Body Mass Index (BMI) < 30kg / m², and women using non-hormonal contraception IUD TCu 380, were invited to participate in the study. Results: The groups were paired at baseline, becoming a homogeneous group in relation to age (± 1 year), and BMI (+1 kg/m²). After 12 months of evaluation, we could observe a significant increase in the DMPA group in weight, BMI and body surface. Relative to resting energy expenditure and respiratory quotient, there was an increase of baseline metabolic rate in both groups after one year. The respiratory quotient was significantly reduced after 12 months in groups DMPA and IUD. The sub-group DMPA that gained < 3kg had increased significant weight, BMI and body surface with respiratory quotient reduction, while the sub-group that gained > 3kg had a significant increase in weight, BMI, body surface, free fat mass, fat mass, baseline metabolic rate, Leptin, HOMA-IR and waist circumference, with respiratory quotient significantly reduced. Conclusion: Our study found significant changes in weight, body composition and metabolic profile of the population studied in the first 12 months of contraceptive use. These changes mainly increased body weight, leptin levels and HOMA-IR which can contribute to the development of some chronic complications, including obesity, insulin resistance and diabetes mellitus / Mestrado / Clinica Medica / Mestra em Clínica Médica