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Twenty-nine college females, aged 18-29, participated in a six month boron supplementation protocol to evaluate mineral and hormone status of athletes and non-athletes. All subjects were classified into activity and oral contraceptive groups as follows: athletes (n=16), non-athletes (n=13), oral contraceptives (n=12), and no oral contraceptives (n=17). Subjects were randomly assigned to receive a placebo or 3 mg of boron per day. Subjects' maximal oxygen consumption (VO₂max) was assessed as a baseline measurement and was used to confirm a difference between activity groups. Body fat, height, bone mineral density, and serum calcitonin and parathyroid also were baseline measurements. Subjects were measured at baseline and six months for the following: dietary intake, body weight, serum levels of 17-f-estradiol, progesterone, and testosterone, and plasma and urine levels of calcium, phosphorus, magnesium, and boron. Athletes had a Significantly greater VO₂max (p < 0.01) than did non-athletes. Subjects taking oral contraceptives had significantly lower serum estradiol (p < 0.05) as compared to subjects not taking oral contraceptives. Boron supplemented non-athletes had a significantly greater change in plasma calcium levels (p < 0.05) as compared to boron supplemented athletes, although the athletes had a significantly higher plasma calcium level (p < 0.05) at the baseline measurement. Control subjects (n=6) had a significantly greater change in dietary carbohydrate (p < 0.01) and protein intake (p < 0.05) as compared to subjects taking boron (n=23). Boron supplementation did not appear to significantly influence any of the parameters measured. However, boron supplementation combined with activity appeared to influence plasma calcium, while serum estradiol may be influenced by oral contraceptives. / Master of Science

Endometrial cancer is the most common gynecologic cancer with 54,870 cases occurring in the United States in 2015 and causing 10,170 deaths, an 18.5% mortality rate (Elit and Reade, 2015). Ovarian cancer, while less common, is much more fatal. In 2015 in the United States, 21,290 cases occurred and resulted in 14,180 deaths, a 66.6% mortality rate. This mortality rate makes ovarian cancer the fifth most deadly cancer for women in the United States, which is largely explained by ineffective screening strategies and limited treatment possibilities (Cramer, 2012). Thus, developing effective prevention strategies is especially important to saving the lives of women who will develop ovarian or endometrial cancer. Women taking combined oral contraceptives (COCs), a type of hormonal birth control, have shown a significant reduced risk of developing ovarian and endometrial cancer. However, the Centers for Disease Control and Prevention (CDC) does not currently recommend taking COCs for the prevention gynecologic cancer (CDC, 2014a). Since the efficacy of COCs for reducing risk of ovarian and endometrial cancer is well established, guidelines need to be determined for populations of women that should take hormonal birth control to minimize cancer risk. This paper highlights the current understanding of ovarian and endometrial cancer, populations of women at highest risk for developing either of these two cancers, and then proposes a case-control study to help determine which populations of women should take hormonal birth control to reduce their gynecologic cancer risk.

RESUMO STOCCO, B. Avaliação do efeito de contraceptivos hormonais sobre a hemostasia. 2011. 92f. Dissertação (Mestrado). Faculdade de Ciências Farmacêuticas de Ribeirão Preto Universidade de São Paulo, Ribeirão Preto, 2011. Introdução: Mais de 100 milhões de mulheres no mundo fazem uso de métodos contraceptivos hormonais. Apesar de seu desejado efeito na contracepção, sua metabolização ocorre no fígado estimulando a síntese de proteínas plasmáticas, dentre elas, as que controlam os sistemas de coagulação e fibrinólise, conferindo um estado de hipercoagulabilidade em suas usuárias. A literatura aponta também alterações no metabolismo dos lipídios e carboidratos, além de modular a expressão de moléculas de adesão presentes no endotélio. Para combater os efeitos indesejáveis destes medicamentos, baixas concentrações de estrógenos e diferentes progestágenos foram introduzidos, pois, a estes últimos é conferida a atividade anti estrogênica destas formulações. Estudos independentes sugerem que progesteronas de terceira e quarta geração possuem atividade anti-estrogênica menor em relação as de segunda geração. Objetivos: avaliar a ocorrência de alterações hemostáticas, analisar o perfil lipídico e quantificar moléculas de adesão no soro ou plasma da população feminina brasileira usuária de contraceptivos orais de segunda e quarta gerações. Materiais e Métodos: 70 participantes distribuídas em quatro grupos a saber : grupo I (controle- 20 pacientes); grupo II (DRSP/30EE- 20 pacientes); grupo III (DRSP/20EE- 16 pacientes) e grupo IV (LNG/30EE-14 pacientes). Foram avaliados os seguintes parâmetros: TP, Fator VII, TTPA, Fator XII, Fibrinogênio, Fator 1+2, Proteína C, Proteína S, Antitrombina, D dímeros, PAI 1, VCAM, ICAM, E- selectina, HDL, LDL,VLDL, Colesterol total e Triglicérides. Resultados e discussões: grupo II promoveu diminuição em TP e Prot. S; e aumento em HDL,VLDL,Col. total e TG; grupo III diminuiu TP, TTPA, Prot.S, ICAM e VCAM ; e aumentou Fibrinogênio, D-dímeros, HDL,VLDL,Col. total e TG e grupo IV diminuiu TP, Prot.C e aumentou ICAM e VCAM. Conclusões: Dos medicamentos estudados apontamos que: o grupo II promoveu alterações significativas no perfil lipídico caracterizando um estado pró-trombótico, apesar de apresentar o maior aumento nos valores de HDL e poucas alterações associadas à hipercoagulabilidade; o grupo III promoveu o maior número de alterações hipercoagulantes, alterou também perfil lipídico contribuindo para um estado pró- trombótico, embora tenha apresentado proteção endotelial e o grupo IV foi o medicamento que promoveu melhor proteção endotelial, não alterou perfil lipídico e ocasionou poucas alterações associadas à hipercoagulabilidade / Introduction: More than 100 million women in the world make use of hormonal contraceptives. In spite of its desired effect on contraception, its metabolization occurs at liver, estimulating the synthesis of the plasmatic proteins, among them, the ones that control the coagulation system and fibrinolysis, confering a hypercoagulability state in their users. The literature also points changes in the metabolism of lipids and carbohydrates, besides modulate the expression of adhesion molecules present in the endothelium. Trying to combat undesirable effects of these drugs, low concentrations of estrogen and different progestogens were introduced, because, the antiestrogenic activity of these drugs is assigned to the progesterone used. Independent papers suggest that third and fourth generation progesterones have a smaller antiestrogenic activity in relation to the second generation one. Objectives: evaluate the occurrence of hemostatic alterations, analyze the lipid profile and quantify adhesion molecules in serum or plasma on the Brazilian female population who is user of contraceptives from second and fourth generation. Material and Methods: 70 participants were distributed into four groups: group I (control- 20 patients); group II (DRSP/30EE- 20 patients); group III (DRSP/20EE- 16 patients) and group IV (LNG/30EE- 14 patients). From these were assessed the following parameters: PT, Factor VII, APTT, Factor XII, Fibrinogen, Factor 1+2, Protein C, Protein S, Antithrombin, Ddimmers, PAI 1,VCAM, ICAM, E- selectin, HDL, LDL, VLDL, Total Cholesterol and Triglycerides.Results and discussion: group II promoted a decrease in PT and Prot.S; and an increase in HDL,VLDL, Total cholesterol and TG; group III decreased PT, APTT, Prot.S, ICAM and VCAM ; and increased Fribrinogen, D- dimers, HDL,VLDL,Total Cholesterol and TG and group IV decreased PT, Prot.C and increased ICAM and VCAM.Conclusions: among the drugs studied we aim that: the group II promoted significant changes in lipid profile featuring a pro- thrombotic state, in spite of presented the highest increase in the levels of HDL and few alterations associated to hypercoagulability; group III promoted the biggest number of hypercoagulability alterations, this drug also changed the lipid profile contributing to a pro-thrombotic state, although it has presented endothelial protection and the group IV it was the drug that promoted the best endothelial protection, did not change lipid profile and caused few alterations associated with hypercoagulability

Introdução: O crescimento do número de idosos no Brasil tem aumentado o interesse em identificar os determinantes da sua sobrevida e da incidência de doenças crônicas. A menopausa é definida como a cessação permanente da menstruação e está associada à diminuição da secreção de estrógenos por perda da função folicular, marcando o fim da fase reprodutiva na vida feminina. A idade da menopausa tem sido associada em alguns estudos internacionais com a mortalidade e algumas causas de morbidade, mas faltam estudos sobre o tema no Brasil. Esta tese será apresentada por meio de 3 artigos. O primeiro analisou os fatores associados à idade da menopausa natural em mulheres do estudo SABE (Saúde, Bem-estar e Envelhecimento). O tabagismo e a escolaridade estiveram estatisticamente associados com uma menopausa mais cedo nas três coortes analisadas: 2000, 2006 e 2010. Mulheres fumantes atuais tiveram 35% maior risco de ter menopausa precoce (HR=1.35, 95% CI: 1.12, 1.62) e as ex-fumantes 27% maior risco (HR=1.27, 95% CI: 1.09, 1.50), em comparação com as mulheres que nunca fumaram. Em relação à escolaridade, as mulheres com 8 anos ou mais de estudos tiveram 33% menor risco de menopausa precoce (HR=0.67, 95% CI: 0.50, 0.89) comparadas às mulheres sem escolaridade. Estado civil e número de filhos estiveram associados a uma menopausa mais tardia na coorte 2006. No segundo artigo, foi realizada uma análise de sobrevida segundo a idade da menopausa natural das mulheres pertencentes à coorte 2000. Foram identificados 444 óbitos de mulheres até 2016. Mulheres com menopausa precoce tiveram 48% de maior risco de mortalidade geral (HR=1.48, 95% IC: 1.03, 2.14) comparadas às mulheres com idade de menopausa entre os 50 e 54 anos (referência). Em relação à mortalidade específica, mulheres entre 41 e 49 anos apresentaram o dobro de risco de mortalidade por neoplasias em comparação com o grupo de referência. No terceiro artigo, foi realizada uma revisão sistemática e meta-análise dos fatores reprodutivos associados à menopausa natural. Os três fatores estudados apresentaram uma associação com a menopausa tardia. As mulheres com uso de anticoncepcionais orais em relação àquelas que não relataram uso de anticoncepcionais orais (HR=0.86, CI=0.79, 0.92), as com idade da menarca >=13 anos comparadas àquelas com idade da menarca <13 anos (HR=0.88, CI=0.84, 0.93) e aquelas que relataram ter um filho ou mais comparadas com as que não tiveram filhos (HR=0.80, CI=0.76, 0.85). / Introduction: The increase of the elderly population in Brazil has raised concerns about their care and the determinants of survival and incidence of chronic diseases. Menopause is defined as the permanent end of a woman\'s menstruation and is associated with the decline of the release of estrogens due to loss of follicular function, indicating the end of the reproductive phase of a woman\'s life. Age at menopause has been linked with mortality and morbidity in international studies. The first article of this thesis analyzed the factors associated with age at natural menopause among women of the SABE study cohort (Health, Well-Being, Aging). Smoking and education were associated with earlier menopause for the three waves analyzed: 2000, 2006 and 2010. Current smokers had 35% higher risk of earlier natural menopause (HR=1.35, 95% CI: 1.12, 1.62) and former smokers had 27% higher risk of earlier natural menopause (HR=1.27, 95% CI: 1.09, 1.50), in comparison with never smokers. Regarding education, women with 8 years or more of formal education had 33% lower risk of earlier natural menopause (HR=0.67, 95% CI: 0.50, 0.89) than women with no education. Marital status and parity were associated with later age at natural menopause only in 2006. In the second article, a survival analysis was performed according to age at natural menopause in women from SABE 2000. We found a total of 444 deaths from 2000 to 2016. Women with earlier menopause had 48% increased risk of all-cause mortality (HR=1.48, 95% IC: 1.03, 2.14) compared to women with age at menopause between 50 and 54 years (reference group). Regarding cause-specific mortality, women with ages at natural menopause between 41 and 49 had twice the risk of cancer mortality compared to the reference group. In the third article, we performed a systematic review and meta-analysis of the reproductive factors associated with natural menopause. The three factors analyzed were statistically associated with later menopause: women with use of oral contraceptives before menopause compared to women with no use of oral contraceptive (HR=0.86, CI=0.79, 0.92), women with age at menarche >=13 compared to women with age at menarche <13 years (HR=0.88, CI=0.84, 0.93) and those with one or more live births compared to nulliparous women (HR=0.80, CI=0.76, 0.85).

RESUMO STOCCO, B. Avaliação do efeito de contraceptivos hormonais sobre a hemostasia. 2011. 92f. Dissertação (Mestrado). Faculdade de Ciências Farmacêuticas de Ribeirão Preto Universidade de São Paulo, Ribeirão Preto, 2011. Introdução: Mais de 100 milhões de mulheres no mundo fazem uso de métodos contraceptivos hormonais. Apesar de seu desejado efeito na contracepção, sua metabolização ocorre no fígado estimulando a síntese de proteínas plasmáticas, dentre elas, as que controlam os sistemas de coagulação e fibrinólise, conferindo um estado de hipercoagulabilidade em suas usuárias. A literatura aponta também alterações no metabolismo dos lipídios e carboidratos, além de modular a expressão de moléculas de adesão presentes no endotélio. Para combater os efeitos indesejáveis destes medicamentos, baixas concentrações de estrógenos e diferentes progestágenos foram introduzidos, pois, a estes últimos é conferida a atividade anti estrogênica destas formulações. Estudos independentes sugerem que progesteronas de terceira e quarta geração possuem atividade anti-estrogênica menor em relação as de segunda geração. Objetivos: avaliar a ocorrência de alterações hemostáticas, analisar o perfil lipídico e quantificar moléculas de adesão no soro ou plasma da população feminina brasileira usuária de contraceptivos orais de segunda e quarta gerações. Materiais e Métodos: 70 participantes distribuídas em quatro grupos a saber : grupo I (controle- 20 pacientes); grupo II (DRSP/30EE- 20 pacientes); grupo III (DRSP/20EE- 16 pacientes) e grupo IV (LNG/30EE-14 pacientes). Foram avaliados os seguintes parâmetros: TP, Fator VII, TTPA, Fator XII, Fibrinogênio, Fator 1+2, Proteína C, Proteína S, Antitrombina, D dímeros, PAI 1, VCAM, ICAM, E- selectina, HDL, LDL,VLDL, Colesterol total e Triglicérides. Resultados e discussões: grupo II promoveu diminuição em TP e Prot. S; e aumento em HDL,VLDL,Col. total e TG; grupo III diminuiu TP, TTPA, Prot.S, ICAM e VCAM ; e aumentou Fibrinogênio, D-dímeros, HDL,VLDL,Col. total e TG e grupo IV diminuiu TP, Prot.C e aumentou ICAM e VCAM. Conclusões: Dos medicamentos estudados apontamos que: o grupo II promoveu alterações significativas no perfil lipídico caracterizando um estado pró-trombótico, apesar de apresentar o maior aumento nos valores de HDL e poucas alterações associadas à hipercoagulabilidade; o grupo III promoveu o maior número de alterações hipercoagulantes, alterou também perfil lipídico contribuindo para um estado pró- trombótico, embora tenha apresentado proteção endotelial e o grupo IV foi o medicamento que promoveu melhor proteção endotelial, não alterou perfil lipídico e ocasionou poucas alterações associadas à hipercoagulabilidade / Introduction: More than 100 million women in the world make use of hormonal contraceptives. In spite of its desired effect on contraception, its metabolization occurs at liver, estimulating the synthesis of the plasmatic proteins, among them, the ones that control the coagulation system and fibrinolysis, confering a hypercoagulability state in their users. The literature also points changes in the metabolism of lipids and carbohydrates, besides modulate the expression of adhesion molecules present in the endothelium. Trying to combat undesirable effects of these drugs, low concentrations of estrogen and different progestogens were introduced, because, the antiestrogenic activity of these drugs is assigned to the progesterone used. Independent papers suggest that third and fourth generation progesterones have a smaller antiestrogenic activity in relation to the second generation one. Objectives: evaluate the occurrence of hemostatic alterations, analyze the lipid profile and quantify adhesion molecules in serum or plasma on the Brazilian female population who is user of contraceptives from second and fourth generation. Material and Methods: 70 participants were distributed into four groups: group I (control- 20 patients); group II (DRSP/30EE- 20 patients); group III (DRSP/20EE- 16 patients) and group IV (LNG/30EE- 14 patients). From these were assessed the following parameters: PT, Factor VII, APTT, Factor XII, Fibrinogen, Factor 1+2, Protein C, Protein S, Antithrombin, Ddimmers, PAI 1,VCAM, ICAM, E- selectin, HDL, LDL, VLDL, Total Cholesterol and Triglycerides.Results and discussion: group II promoted a decrease in PT and Prot.S; and an increase in HDL,VLDL, Total cholesterol and TG; group III decreased PT, APTT, Prot.S, ICAM and VCAM ; and increased Fribrinogen, D- dimers, HDL,VLDL,Total Cholesterol and TG and group IV decreased PT, Prot.C and increased ICAM and VCAM.Conclusions: among the drugs studied we aim that: the group II promoted significant changes in lipid profile featuring a pro- thrombotic state, in spite of presented the highest increase in the levels of HDL and few alterations associated to hypercoagulability; group III promoted the biggest number of hypercoagulability alterations, this drug also changed the lipid profile contributing to a pro-thrombotic state, although it has presented endothelial protection and the group IV it was the drug that promoted the best endothelial protection, did not change lipid profile and caused few alterations associated with hypercoagulability

The use of a new, more sensitive immunoassay for growth hormone (GH) revealed that the serum levels in men were lower than expected in sera drawn ambulatory in the morning after an overnight fast and that the gender difference was more than 10 times greater than reported. These observations led to a more thorough study on the impact of gender and sex steroids on the levels of GH and other hormones in ambulatory morning samples and over a 24-hour period. Furthermore, the impact of gender was studied in GH deficient (GHD) patients and healthy young adults treated with GH, and in patients with acromegaly treated with octreotide. An 80-fold gender difference in the morning GH levels was observed in young individuals as a reaction to ambulation, with decreased levels in men and increased in women. Oral contraceptives (OCs) given to women further increased the morning GH levels. During the day, higher outputs of epinephrine and lower levels of GH were seen in the men, while no gender differences were seen at night. The gender difference in morning GH levels decreased with age due to opposite changes in men and women. Administration of 17β-estradiol (E2) via subcutaneous implants in postmenopausal women, which increased the E2-concentrations to luteal phase levels, had no effect on the morning GH levels, indicating that the different reactions to ambulation do not appear to result from a direct sex steroid effect alone. Short-term administration of GH to young, healthy adults resulted in larger effects on insulin-like growth factor I (IGF-I) and other key metabolic parameters in men than in women. The smallest response was noted in women taking OCs. The clinical studies involving long-term GH treatment of patients with GHD demonstrate a gender difference in GH responsiveness, with women being less sensitive than men, a fact which should have a therapeutic impact in patients with GH disorders. A further gender difference of therapeutic importance was observed in men and women with acromegaly. Long-term treatment with a slow-release formulation of octreotide resulted in higher IGF-I levels in the men, despite equal doses of the drug and similar levels of GH.

It is known that some psychiatric disorders may deteriorate in relation to the menstrual cycle. However, in some conditions, such as premenstrual dysphoric disorder (PMDD), symptomatology is triggered mainly by the variations in ovarian steroid hormones. Although symptoms induced by fluctuations in ovarian steroids often are affective, little is known about how emotion processing in women is influenced by variations, or actual levels, of ovarian steroid hormones. The general aim of this thesis was to evaluate menstrual cycle effects on reactivity in emotion generating and controlling areas in the corticolimbic system to emotional stimulation and anticipation, in healthy controls and women with PMDD. A second aim was to evaluate corticolimbic reactivity during long-term administration of exogenous ovarian steroids. In study I, III and IV effects of the menstrual cycle on emotional reactivity in women with PMDD was studied. In study I, women with PMDD in displayed higher amygdala reactivity than healthy controls to emotional faces, not in the luteal phase as was hypothesised, but in the follicular phase. No difference between menstrual cycle phases was obtained in women with PMDD, while healthy controls had an increased reactivity in the luteal phase. The results of study I was further elaborated in study III, where women with PMDD were observed to have an increased anticipatory reactivity to negative emotional stimuli. However, no differences in amygdala reactivity to emotional stimuli were obtained across the menstrual cycle. Finally, in study IV the hypothesis that amygdala reactivity increase in the luteal phase in women with PMDD is linked to social stimuli rather than generally arousing stimuli was suggested, tested and supported. In study II, re-exposure to COC induced mood symptoms de novo in women with a previous history of COC-induced adverse mood. Women treated with COC reported increased levels of mood symptoms both as compared to before treatment, and as compared to the placebo group. There was a relatively strong correlation between depressive scores before and during treatment. The effects of repeated COC administration on subjective measures and brain function were however dissociated with increased aversive experiences accompanied by reduced reactivity in the insular cortex.

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Bibliography: v. 2, leaves [410]-464 / 2 v. : ill ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Community Medicine, 1986?