Objetivo - Estimar a incidência dos distúrbios do sono e identificar seus fatores de risco em mulheres livres de problemas com o sono na primeira fase do Projeto de Saúde de Pindamonhangaba (PROSAPIN) realizado em 2007. Metodologia - Consiste da segunda etapa do PROSAPIN, realizada em 21 Unidades da Estratégia de Saúde da Família com 1.200 mulheres de 35 a 72 anos divididas entre participantes novas (sorteadas em 2014) e antigas (participantes do PROSAPIN 2007). Foram pesquisados por meio de questionários os seguintes distúrbios do sono: 1) sono ruim, pelo Índice de Qualidade do Sono de Pittsburgh; 2) insônia, também pelo questionário de Pittsburgh; 3) sonolência diurna excessiva, pela Escala de Sonolência de Epworth e 4) apnéia obstrutiva do sono, pelo Questionário de Berlin. Como variáveis independentes foram investigadas características sócio demográficas; história ginecológica; presença de morbidades; sintomas emocionais, climatéricos e musculoesqueléticos; hábitos de vida; uso de medicamentos; medidas antropométricas e exames de sangue. As análises, realizadas no Programa Stata versão 11.0, consistiram em: a) estimativa da prevalência de distúrbios do sono em geral e separada por tipos em 2014; b) comparação das prevalências entre os estudos de 2007 e 2014; c) identificação dos fatores associados a prevalência de distúrbios do sono em 2014; e d) estimativa da incidência dos distúrbios do sono em 2014 e seus fatores de risco. Resultados- A incidência de distúrbios do sono em sete anos foi de 75,0 por cento e os fatores de risco foram o triglicerídeo 150 mg/dl e a circunferência abdominal 100,5 cm; como proteção, o HDL 50 mg/dl e a escolaridade 1°colegial. As prevalências em 2007 e 2014 foram respectivamente: distúrbios do sono em geral 63,4 por cento e 82,7 por cento ; sono ruim 45,1 por cento e 54,9 por cento ; insônia 13,3 por cento e 19,0 por cento ; sonolência diurna excessiva 23,1 por cento e 24,1 por cento e apnéia obstrutiva do sono 25,1 por cento e 60,5 por cento . Os fatores associados a prevalência de distúrbios do sono em 2014 foram como risco a ansiedade intensa, o estresse relatado, o uso de antidepressivos e a glicose > 100mg/dl, como fatores de proteção, ser aposentada e considerada fisicamente muito ativa. Conclusão- A incidência dos distúrbios do sono em sete anos foi alta e seus fatores de risco foram metabólicos. A comparação das prevalências em dois pontos, 2007 e 2014, demonstrou aumento expressivo nos distúrbios do sono. / Objective - Estimate the incidence of sleep disorders and identify theirs risk factors in women without trouble sleeping this was the first step Pindamonhangaba Health Project (PROSAPIN) conducted in 2007. Methodology It was consist of in the second stage of PROSAPIN project realized on 21 units of the Family Health Strategy 1,200 women between 35 to 72 age was divided with brand new volunteers (chosen in 2014) and old (volunteers PROSAPIN 2007). They were surveyed by questionnaire the following sleep disorders:1) poor sleep by the Pittsburgh Sleep Quality Index; 2) insomnia, by the questionnaire Pittsburgh;3) excessive daytime sleepiness, the Epworth Sleepiness Scale and 4) obstructive sleep apnea, by Berlin Questionnaire. As independent socio demographic characteristics were investigated; gynecological history; presence of comorbidities; emotional symptoms, climatic and musculoskeletal; lifestyle; use of medications; anthropometric measurements and blood tests. These analysis, were performed for Stata version 11.0, were a)estimate the prevalence of sleep disorders separate for type during the year of 2014b) compare the prevalence studies between 2007 and 2014 c) identification of factors associated with prevalence of sleep disorders in 2014; d) estimate the incidence of sleep disorders during the year of 2014 and their risks factors. Results- The incidence of sleep disorders in seven years was 75.0 per cent and the risk factors were the triglycerides 150 mg / dl and waist circumference 100.5 cm; as protection, HDL 50 mg / dl and schooling 1 high school. The prevalence rates in 2007 and 2014 were as follows: sleep disorders in general 63.4 per cent and 82.7 per cent ; poor sleep 45.1 per cent and 54.9 per cent ; insomnia 13.3 per cent and 19.0 per cent ; EDS 23.1 per cent and 24.1 per cent and obstructive sleep apnea 25.1 per cent and 60.5 per cent . Factors associated with the prevalence of sleep disorders in 2014 were a risk to intense anxiety, stress reported, the use of antidepressants and glucose> 100 mg / dl, as protective factors be considered retired and physically very active. Conclusion - The incidence of sleep disorders in seven years was high and their risk factors were metabolic. Comparison of the prevalence of two points, 2007 and 2014 Showed a significant Increase in sleep disorders.

Objetivo do estudo: Estimar a prevalência de lesões malignas e prémalignas nos pólipos endometriais e correlacionar com fatores associados com risco de neoplasia de endométrio. Métodos: Revisados dados sobre características clínicas e resultado anatomopatológico dos pólipos ressecados em histeroscopias cirúrgicas com polipectomia realizados entre janeiro de 2005 e julho de 2013 no Hospital de Clínicas de Porto Alegre (HCPA). Resultados: Incluídas 359 pacientes submetidas a polipectomias histeroscópicas. 87,2% das pacientes apresentaram pólipos benignos e 9,9% apresentaram hiperplasia sem atipias. Pólipos com hiperplasia atýpica corresponderam a 2,6% da amostra, enquanto que adenocarcinoma de endométrio foi encontrado de 0,3% dos casos. Verificou-se correlação de resultado maligno/pré-maligno dos pólipos com idade da paciente, seu status menopausal e a presença de sangramento uterino anormal. Todas as mulheres com resultados malignos/pré-malignos apresentaram sangramento uterino anormal. Observou-se maior frequência de malignidade dos pólipos entre usuárias de tamoxifeno, porém sem significância estatística (p 0,059%). Não houve correlação com hipertensão arterial, diabetes mellitus, obesidade, uso de terapia hormonal, espessura endometrial ou diâmetro do pólipo. Conclusão: A prevalência de lesões malignas/pré-malignas nos pólipos endometriais é baixa, tendo sido nula nas pacientes sem sangramento. Não se recomenda a exérese rotineira dos pólipos em pacientes assintomáticas. / Objective: To estimate the prevalence of malignant and premalignant lesions among endometrial polyps and correlate this prevalence with risk factors for endometrial neoplasms. Methods: Review of clinical and histopathological data on polyps resected during hysteroscopic polypectomies performed from January 2005 through July 2013 at Hospital de Clínicas de Porto Alegre (HCPA), Brazil. Results: The sample comprised 359 patients who underwent hysteroscopic polypectomy. Overall, 87.2% of patients had benign polyps and 9.9% had hyperplasia without atypia. Polyps with atypical hyperplasia were found in 2.6% of patients, and endometrial adenocarcinoma, in 0.3%. Polyp malignancy/premalignancy correlated with patient age, menopausal status, and presence of abnormal uterine bleeding. All women with malignant/premalignant lesions had abnormal uterine bleeding.The rate of polyp malignancy was higher among tamoxifen users, although the difference did not reach statistical significance (p=0.059). There was no correlation with hypertension, diabetes mellitus, obesity, hormone replacement therapy, endometrial thickness, or polyp diameter. Conclusion: The prevalence of malignancy/premalignancy among endometrial polyps is low; no cases were identified in patients without uterine bleeding. Routine excision of asymptomatic polyps cannot be recommended.

Introdução: Durante a transição menopausal, as mulheres podem sofrer alterações na atividade sexual, devido à diminuição dos níveis plasmáticos de estrogênio e androgênio. Além disso, fatores como a idade, o tempo de relacionamento e o aumento de morbidades que causam diminuição do bemestar podem levar à redução da atividade sexual. Objetivo: Estimar a prevalência da disfunção sexual em mulheres no período da transição menopausal e pós-menopausa e identificar potenciais fatores de risco. Método: estudo transversal que incluiu 756 mulheres de 35 a 65 anos cadastradas na Saúde da Família de Pindamonhangaba. Para avaliar a função sexual, foi utilizado o Female Sexual Function Index (FSFI), questionário composto por 19 perguntas referentes às últimas quatro semanas, que abrange seis domínios: desejo, excitação, lubrificação, satisfação, orgasmo e dor. Foi realizado um modelo de regressão múltipla de Poisson, no programa Stata 11. Resultados: A prevalência de disfunção sexual foi de 57,7 por cento (IC95 por cento : 54,0 por cento 61,4 por cento). Quando consideradas apenas as mulheres sexualmente ativas, foi de 39,8 por cento (IC95 por cento : 35,4 por cento 44,2 por cento). A disfunção sexual associou-se positivamente a idade (p<0,001), ao estado civil (p<0,001), a religião (p=0,003), a depressão (p<0,001) e a diabetes (p=0,013). Dentre as mulheres sexualmente ativas, a disfunção sexual associou-se positivamente também com a idade (p<0,001), a depressão (p<0,001) além do uso de medicamento ansiolítico (p=0,011). Conclusão: Houve alta prevalência de disfunção sexual entre as mulheres participantes do PROSAPIN, e os fatores associados foram: idade, o estado civil, a religião, a depressão, diabetes e uso de medicamento ansiolítico / Introduction: During the menopausal transition women may experience changes in sexual activity due to decreased plasma levels of estrogen and androgen. Beyond that, factors such as age, length of relationship and increased morbidities that cause decreased well-being can lead to reduced sexual activity. Objective: To estimate the prevalence of sexual dysfunction in women during the menopausal transition and postmenopausal women and to identify potential risk factors. Method: A cross-sectional study that included 756 women from 35 to 65 years indexed in the program Saúde da Família in Pindamonhangaba. To evaluate sexual function, we used the Female Sexual Function Index (FSFI) questionnaire consisting of 19 questions concerning the last four weeks, covering six domains: desire, arousal, lubrication, satisfaction, orgasm and pain. We performed a multiple regression model the Poisson in the Stata 11. Results: The prevalence of sexual dysfunction was 57.7 per cent (95 per cent CI: 54.0 per cent - 61.4 per cent). When considered only sexually active women, was 39.8 per cent (95 per cent CI: 35.4 per cent - 44.2 per cent). Sexual dysfunction was positively associated with age (p <0.001), marital status (p <0.001), religion (p = 0.003), depression (p <0.001) and diabetes (p = 0.013). Among sexually active women, sexual dysfunction also was positively associated with age (p <0.001), depression (p <0.001) and the use of anxiolytic medication (p = 0.011). Conclusion: there is a high prevalence of sexual dysfunction among women participants PROSAPIN, and associated factors were: age, marital status, religion, depression, diabetes and use of anxiolytic medication

Menopause is a biological change that affects the aging woman at some point in her life. Hormone replacement therapy (HRT) has been a primary medical intervention for decades, and this study explores how HRT products are marketed to women experiencing menopause through direct-to-consumer (DTC) drug ads. Through a qualitative analysis of DTC ads and interviews with women experiencing menopause symptoms, this research investigated their perspective on HRT drug ads to understand if women respond to this type of advertising. Women’s understanding and experiences concerning menopause are influenced by a number of factors and can vary depending on the meanings that are associated with menopause. In U.S. culture, physical appearance is emphasized above other characteristics, so menopause and other signs of aging chge the beauty ideal. Media portrayals of women too often value youth and ideal beauty, with direct-to-consumer (DTC) ads reinforcing this notion by emphasizing how women can remain young, fight the signs of aging, and maintain their vitality by using HRT products. Women also feel conflicted about their bodies as they age because of these dominant standards that can then lead to negative body image. Social comparisons are an inherent process guiding behavior and experiences that affect how people understand themselves (Corcoran, Crusius, & Mussweiler, 2011). People look at others and to media images of others, relating that information to themselves as a way to measure what they are and aren’t capable of. When advertisements construct menopause as a deficiency that women need to treat with medications, women compare themselves to mediated images as they try to understand their menopause experience. Ads analyzed for this study presented messages that women need medication to maintain healthy activities during and after menopause. Most of the ads focused on painful sex that can happen with menopause but nearly all of the participants agreed that these ads did not relate to their experiences. This research found that women don’t believe menopause is a disease to be treated but if medications are used, it should be for the shortest time possible and only if the symptoms drastically interfere with a woman’s quality of life. Through these interviews with menopausal women and analysis of HRT ads, this study adds to limited current research on DTC ads for hormone replacement therapies and menopause.

Although Hormone Therapy (HT) is the most effective treatment for alleviating menopausal vasomotor symptoms and reducing bone loss, many women are reluctant to take this treatment due to side effects and concerns about safety. Epidemiological studies suggest that a significant proportion of women use Complementary and Alternative Medicine (CAM) therapies to alleviate vasomotor symptoms and improve quality of life. Anecdotal and clinical evidence indicate a number of CAM therapies, such as herbal medicine, may be effective in alleviating symptoms and modulating bone metabolism. Hence, in the context of concerns over the safety of HT and the extensive history of the clinical use of herbal medicine, this thesis investigated issues pertinent to CAM use and the menopausal transition. The aims of this thesis were to: • Examine the nature and extent of CAM use by women transitioning through menopause • Evaluate the effectiveness of a herbal formula containing Chinese herbs and Cimicifuga racemosa for alleviating vasomotor symptoms, improving quality of life and modulating bone turnover markers. From July 2003 until July 2004 the Women’s Health during Midlife Survey recruited 1,296 women aged 45-65 who were symptomatic when transitioning through menopause or asymptomatic but taking menopause specific treatments. A validated 19-item survey instrument assessed the use of CAM modalities and menopause specific products. The instrument was completed voluntarily and anonymously by women recruited from three strata; menopause clinics, clinics of general practice and government agencies. Approximately 54% of respondents had visited a CAM practitioner and/or used a CAM product during the previous 12 months. The most popular practitioners were the naturopath (7.2%) and acupuncturist (4.8%), while soy (25.4%) and evening primrose oil (EPO, 18.4%) were the most popular products. Massage and chiropractic were considered the most effective therapies, while phytoestrogen tablets and EPO were the most efficacious products. Although 26.4% of respondents indicated their doctor asked about CAM use, 71% of CAM users said they informed their physician about using CAM. Of the 60% of women using pharmaceutical medicines, 62.5% reported using a CAM product during the preceding 12 months. The survey results confirm the continued popularity of CAM use amongst women transitioning through menopause. A number of treatments were perceived to be effective in relieving symptoms. However, communication between medical practitioners and patients about CAM use is inadequate, and given the high use of pharmaceutical medicines this oversight may unnecessarily expose women to drugherb interactions. A randomised, double-blind, placebo controlled clinical trial was conducted to evaluate the effectiveness of a herbal formula derived from two traditional Chinese herbal formulae with the addition of Cimicifuga in alleviating vasomotor symptoms. The trial recruited 93 healthy women who reported at least six vasomotor symptoms per day. After a four week baseline period, women were randomly allocated to receive either herbal treatment or identical looking placebo tablets for 16 weeks. During the trial women recorded the number and severity of their flushes on a Daily Flush Diary, and at each monthly consultation two quality of life scales were completed. Forty nine eligible trial women were entered into a pilot study to assess the effect of the formula on bone turnover markers; bone specific alkaline phosphatase and deoxypyridinoline (corrected for creatinine). The herbal formula was found to be no more effective than placebo in reducing the frequency of flushing and the composite hot flush score or in improving quality of life. The pilot study found the formula had no effect on bone turnover markers after 16 weeks of treatment. Therefore, this formula cannot be recommended as a treatment for vasomotor symptoms and is unlikely to have any long term effect on bone. The use of CAM during the menopausal transition is very popular. Although this thesis found the current herbal formula to be an ineffective treatment, the scientific evaluation of potential CAM therapies is imperative so that health care professionals and consumers can make informed decisions concerning treatment options for the alleviation of symptoms. / Doctor of Philosophy (PhD)

Background: The use of chemotherapy and endocrine therapies in the treatment of pre-menopausal women with breast cancer may result in menopausal symptoms, permanent infertility or the need to delay pregnancy. This series of studies investigates the fertility- and menopause-related information needs of pre-menopausal women with a diagnosis of early breast cancer (Studies 1 and 2) and the benefits women need to make undergoing adjuvant endocrine therapies worthwhile (Study 3). Method: Study 1 is a qualitative study of 24 women and Study 2 a survey study amongst 228 women. Study 3 included a subset of 102 women from the sample involved in Study 2 who had been treated with endocrine therapies for a minimum of three months. To be eligible, women had to be aged 40 years or younger (Study 2 and 3) when diagnosed with early stage breast cancer, and be 6-60 months post-diagnosis at the time of participation. For Study 2, participants completed a mailed self-report questionnaire that included a fertility- and menopause-related information needs survey, and standardized measures of distress, quality-of-life, menopausal symptoms and information preferences. For Study 3, participants were asked to complete a face-to-face interview. Results: Study 1 showed that many women thought that the information they had received in the past about fertility and menopausal symptoms was either insufficient or unavailable. Some women felt that, while information on fertility and menopause issues had not been paramount at the time of diagnosis, it became increasingly important after diagnosis. Study 2 showed that 71% of participants discussed fertility-related issues with a health professional as part of their breast cancer treatment and 86% discussed menopause-related issues. Consultation with a fertility or menopause specialist was the most preferred method of obtaining this information. Study 3 demonstrated that the majority of participants considered adjuvant endocrine therapy worthwhile for a 2% absolute gain in survival rates and for a 6-month gain in life expectancy. Conclusions: The results of this series of studies suggest that younger women have unmet needs for fertility- and menopause-related information. Women with early breast cancer who had received adjuvant endocrine therapies judged modest survival gains sufficient to make adjuvant endocrine therapy worthwhile.

This thesis examines the menopausal experiences of a non-clinical sample of lesbians living in Australia. Research on menopause to date has largely been conducted from a medicalised and heterosexual perspective: thus lesbians’ experiences remain unknown and invisible. Using a qualitative feminist multiple method research methodology combining content analysis and questionnaire/interview research, two hundred questionnaires were posted upon request to self-identified lesbians living in every Australian state and territory. Follow up in-depth interviews were conducted with twenty lesbians. Responses were grouped into four major themes: body image, sex and sexuality, hormone replacement therapy and health services and homophobia. The findings show that lesbians at menopause face some different and additional issues from those experienced by heterosexual midlife women. For many of the study participants, commonly discussed concerns at menopause such as weight gain and other physical signs of ageing, decreased fertility, lack of libido, sexual difficulties and hormone replacement therapy were of little relevance and importance. Lesbians in this study frequently raised other issues such as the universal assumption of heterosexuality and homophobia experienced when interacting with health professionals, which led to less than satisfactory health care and reinforced feelings of invisibility. In the Conclusion I argue that the study participants' views and experiences challenge negative, stereotypical views of both lesbians and menopause. The data thus add a new dimension to the presently narrow, heterosexist and medicalised view of women at midlife and contribute new knowledge to the body of literature on menopause. This thesis is a first important step in recording the experiences of lesbians regarding menopause in Australia. I include recommendations for further research in the area of lesbian health and improved practice, and discuss old and new obstacles lesbians face in a heteropatriarchal society in which lesbians continue to be invisible.

This is a study of a generation of women who are about to enter the climacteric period of their life, the menopause. Born between the years 1946 and 1956 they have been the object of continuous scrutiny by various interest groups. Because they are seen to be unique, many acronyms and titles, the most noted being the 'Baby Boomers' have been attached to them. The women of this generation have been classed as a Very active' generation, leaving a clear mark on society and the re-emerging women's movement. As they near menopause they are approaching a stage that could be seen as their last reproductive transition. For many women there is no cultural ritual, nor a single story to guide them through this period They are however not without advice. The 'big voices' of the drug companies, the medical system and the media, all tender their guidance as the dominant voice. These women have been told what to do by experts throughout their whole lives. It seems 'expert advice' on their reproductive phases have been penned mostly by men in the interests of treating, controlling and saving them. Control of their body remains a key struggle, both physically and linguistically. The purpose of the research was to study the expectations of this post-war, Baby Boom generation of menopause. The study shows that some women have made decisions to embrace non-medical help and accept menopause as an inevitable transition, while others are willing to consider medical help to enhance their 'quality of life '. Believing it is time to look after themselves, it seems many women will take a pragmatic view and accept medical opinion that the menopause is a deficiency disease, even if this requires them to become part of the consumer driven/drug company push for a 'symptom free' menopause. They wish to remain untroubled and express a willingness to do whatever they need to fulfil this. Their fervent hope is that the menopause will not upset their career, family or 'life'. Consequently a large majority of these women will think about or actively pursue hormone replacement therapy.

Extensive research and clinical observations in the past 20 years confirmed that the cessation of ovarian function at menopause does not stop the process of sex steroid hormone synthesis in females. Indeed, multiple extra-ovarian tissues contain the same enzymatic machinery the ovary uses which can maintain a significant rate of local hormonal synthesis sufficient to cause pathological outcomes. This is commonly termed “intracrine”. However, two obstacles face intracrinology. Firstly, wide clinical appreciation of this mechanism in causing disease and in targeting it with therapy does not currently exist. Secondly, blood hormonal assays are used in the clinic to diagnose and manage intracrine based disorders. This could be entirely misleading, since hormonal synthesis, action and metabolism occur within the tissue and, therefore, measuring blood levels is not reflective of the actual disease environment. This thesis presents evidence of significant intracrine based disorders in menopausal women that could be effectively managed by tackling the core intracrine mechanism. Three protocols are investigated emphasizing the usefulness of menopausal intracrine estrogen inhibition. The first presents a joint objective of treating menopausal symptoms using estrogenic replacement therapy while reducing breast cancer risk using long-term aromatase inhibitors. Aromatase inhibition is used to suppress the local estrogen synthesis in the breast. The second protocol is a new method of acute inhibition of breast estrogens to improve the accuracy of breast imaging techniques. This method showed a benefit in reducing the benign parenchymal enhancement during breast MRI indicating a potential improvement in specificity. The third protocol involves using aromatase inhibitors in the treatment of severe endometriosis that did not respond to oophorectomy. The pathogenesis of breast cancer, endometriosis and fibroids are believed to involve intracrine estrogen activity. Another significant contribution presented in this thesis is the development of a new technique that enables minimally invasive tissue assays of hormones in their genuine site of synthesis rather than indirectly in the blood. The new assay requires only microliter volumes of sample and employs a novel digital microfluidics technology. Estrogen and other sex steroids were extracted from droplet-scale breast tissue and blood samples.

Extensive research and clinical observations in the past 20 years confirmed that the cessation of ovarian function at menopause does not stop the process of sex steroid hormone synthesis in females. Indeed, multiple extra-ovarian tissues contain the same enzymatic machinery the ovary uses which can maintain a significant rate of local hormonal synthesis sufficient to cause pathological outcomes. This is commonly termed “intracrine”. However, two obstacles face intracrinology. Firstly, wide clinical appreciation of this mechanism in causing disease and in targeting it with therapy does not currently exist. Secondly, blood hormonal assays are used in the clinic to diagnose and manage intracrine based disorders. This could be entirely misleading, since hormonal synthesis, action and metabolism occur within the tissue and, therefore, measuring blood levels is not reflective of the actual disease environment. This thesis presents evidence of significant intracrine based disorders in menopausal women that could be effectively managed by tackling the core intracrine mechanism. Three protocols are investigated emphasizing the usefulness of menopausal intracrine estrogen inhibition. The first presents a joint objective of treating menopausal symptoms using estrogenic replacement therapy while reducing breast cancer risk using long-term aromatase inhibitors. Aromatase inhibition is used to suppress the local estrogen synthesis in the breast. The second protocol is a new method of acute inhibition of breast estrogens to improve the accuracy of breast imaging techniques. This method showed a benefit in reducing the benign parenchymal enhancement during breast MRI indicating a potential improvement in specificity. The third protocol involves using aromatase inhibitors in the treatment of severe endometriosis that did not respond to oophorectomy. The pathogenesis of breast cancer, endometriosis and fibroids are believed to involve intracrine estrogen activity. Another significant contribution presented in this thesis is the development of a new technique that enables minimally invasive tissue assays of hormones in their genuine site of synthesis rather than indirectly in the blood. The new assay requires only microliter volumes of sample and employs a novel digital microfluidics technology. Estrogen and other sex steroids were extracted from droplet-scale breast tissue and blood samples.