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Background: Reproductive and menstrual factors have been evaluated as surrogates for long-term hormonal exposures in several prospective studies of colorectal cancer, yet findings have been conflicting. Methods: The relation of reproductive and menstrual factors (self-reported via a reproductive history questionnaire) with incident colorectal cancer was investigated among women enrolled in the Women's Health Initiative Observational Study (WHI-OS), a longitudinal cohort of 93 676 postmenopausal women (aged 50-79 years at enrolment) in which 1149 incident cases of colorectal cancer occurred over a median follow-up of 11.9 years. Multivariable Cox proportional hazards models that included established colorectal cancer risk factors were constructed to examine the association of colorectal cancer incidence with reproductive and menstrual factors. Results: Having had two children (vs nulliparous: hazard ratio (HR) = 0.80, 95% confidence interval (CD: 0.64-0.99) was inversely associated with colorectal cancer risk. Compared with never users, ever use of oral contraceptives was associated with lower colorectal cancer risk (HR = 0.74, 95% CI: 0.63-0.86); however, no relationship was observed for duration of oral contraceptives use (4 years vs 1 year: HR = 0.94, 95% CI: 0.67-1.32). None of the remaining reproductive and menstrual factors was associated with colorectal cancer incidence. Conclusions: Parity and prior use of oral contraceptives were associated with lower colorectal cancer risk in this cohort of postmenopausal women.

Antropóloga Social / A lo largo de la historia de diferentes culturas y sociedades la menstruación se ha encontrado siempre envuelta en una serie de normas que delimitan el comportamiento tanto de las mujeres menstruantes, como de aquellos sujetos que las rodean y que pertenecen al resto de la sociedad. Esta situación ha sido abordada por la antropología de manera directa o indirecta en sus investigaciones. Ahora bien, las características socioculturales del menstruo y de las mujeres que lo vivencian mes a mes, se explica en buena medida a partir de las estructuras hegemónicas de género y biomedicina. En este contexto, a nivel de la sociedad contemporánea ha predominado una visión higienista y medicalizada respecto de la menstruación, en donde se le considera un fluido contaminante, desagradable y poco deseable. En búsqueda de abarcar tanto la dimensión estructural como agencial de esta problemática de estudio desarrollamos las experiencias encarnadas de las mujeres, trazando sus itinerarios corporales menstruales desde el enfoque de embodiment. Esta perspectiva nos permitirá tanto un acceso privilegiado a esta vivencia que tiene una índole muy privada y personal, pero que a su vez remite a las conformaciones de género dominantes. En Chile esta temática ha sido poco estudiada y las investigaciones que se han realizado en torno a ella necesitan ser actualizadas. Se ha escogido a ocho mujeres con visiones muy diversas en torno a su menstruación, algunas que hacen totalmente propio el discurso y práctica de tipo biomédico e higienista, otras que cuestionan esta forma prevaleciente o hegemónica que indica cómo relacionarse con la propia sangre menstrual. Y finalmente un grupo que si bien es minoritario en nuestro país, es del interés de este estudio puesto que ha generado un proceso de ritualización importante en torno a la menstruación. Es así que a través de los itinerarios corporales de estos tres grupos de mujeres, logramos dar cuenta de algunos de los factores socioculturales que se vinculan y median las experiencias menstruales encarnadas de nuestras entrevistadas

O mecanismo de ação dos esteróides sexuais sobre a proliferação e diferenciação do endométrio envolve a participação de fatores de crescimento e protooncogenes, cuja regulação é pouco conhecida. O objetivo deste trabalho foi investigar a influência do ciclo menstrual e os efeitos do acetado de medroxiprogesterona (MP A) sobre a expressão de prolactina (PRL), do protooncogene c-los e do fator de crescimento TGF~ no endométrio humano in vivo. Quarenta e seis mulheres com ciclos regulares receberam, de forma randomizada, placebo ou MP A (10mg/ dia, 10 dias). Em seguida foram submetidas a biópsia do endométrio e as amostras foram classificadas em 3 grupos de acordo com a fase do ciclo/tratamento: Proliferativo/Placebo (grupo 1, N=ll), Secretor/Placebo (grupo 2, N=18) e Secretor/MPA (grupo 3, N=8). Parte do material foi fixada em formol e incluída em parafina, sendo posteriormente submetida a coloração por imuno-histoquímica. O restante foi congelado a -70°C para posterior análise do RNA mensageiro (mRNA) pela técnica de RT-PCR. Encontrou-se PRL imunorreativa no epitélio glandular de 9,1% das amostras do grupo 1, em 55,6% das amostras do grupo 2 e em 100% das amostras do grupo 3 (p<0,05; teste de Fisher). No estroma endometriat observou-se imunocoloração para PRL em 9)% , 66,7% e 87,5% das biópsias dos grupos 1, 2 e 3, respectivamente (p<0,01). Os níveis médios de mRNA da PRL foram maiores na fase secretora (grupo 2) e significativamente maiores no grupo 3 em relação ao grupo 1 (p<0,05). Observou-se imunocoloração para c-los (predominando no núcleo das células estremais) em 54,5% das biópsias do grupo 1, em 7,1% das do grupo 2 e em nenhuma do grupo 3 (p<0,05, grupo 1 vs 2 e 3). Os níveis de mRNA do c-los foram substancialmente menores nos grupos 2 e 3 comparados ao grupo 1 (p<0,05) e apresentaram correlação direta com os níveis séricos de estradiol (r= 0,56; p<0,02). Não houve diferença entre os grupos quanto à expressão de TGF~l. Entretanto, a freqüência de amostras com imunocoloração positiva para TGFB3 e os níveis de mRNA do TGFB3 foram sucessivamente maiores nos grupos 2 e 3 em comparação com o grupo 1. Os dados demonstram aumento da expressão de PRL e TGF~3 e inibição da expressão de c-los no endométrio durante a fase secretora do ciclo menstrual, bem como no endométrio estimulado por MPA. A inibição de c-los e o aumento na expressão de TGFB3 poderiam participar do mecanismo antiproliferativo da progesterona e dos progestogênios sobre o endométrio humano in vivo. / Growth factors anci protooncogenes are involveci in the mechanism of sex steroicistirnulateci growth anci ciifferentiation of the enciometriurn, but their precise regulation remains unclear. The aim of the present stuciy was to evaluate the influence of menstrual cycle anci the effects of meciroxyprogesterone acetate (MP A) on the expression of prolactin (PRL), c-los anci transforrning growth factor beta (TGFI3) in the hurnan enciometriurn in vivo. Forty-six cycling women were ranciomizeci to receive either 10 mg MPA or placebo, once a ciay ciuring 10 ciays. Enciometrial specirnens were obtaineci about 8-12 hours following the last tablet intake anci patients were classifieci into three groups accorciing to biopsy ciating anci treatment: Proliferative/Placebo (group 1, N=ll), Secretory /Piacebo (group 2, N=18) anci Secretory /MP A (group 3, N=8). Enciometrial sampies were partially snap-frozen in liquici nitrogen anci partially fixeci in formalin, embecicieci in paraffin anci staineci by irnrnunohistochemistry. Messenger ribonucleic acici (rnRNA) leveis were assessed by reverse transcriptidase polymerase chain reaction (RT-PCR). Irnmunoreactive PRL was found in the epithelium of 9.1% of the specirnens from group 1, in 55.6% of group 2, anci in 100% of group 3 (p<0.05, Fisher's exact test). In the enciometrial stroma, immunopositive PRL was present in 9.1%, 66.7% anci 87.5% of the specirnens from groups 1, 2 anci 3, respectively (p<0.01). The average leveis of PRL mRNA were slightiy increaseci in group 2 anci markecily increaseci in group 3 compareci to group 1 (p<0.05). Irnrnunoreactive c-los was concentrateci in the nucleus of stromal cells in 54.5% of the biopsies from group 1, in 7.1% of group 2, and in 0% of group 3 (p<0.05, group 1 vs 2 and 3). The leveis of c-los mRNA were greatly reciuceci in groups 2 anci 3 compareci to group 1 (p<0.05) anci correlateci positiveiy with serum estraciiollevels (r=0.56, p<0.02). There were no ciifferences between groups conceming to the enciometrial expression of TGFI31. However, the frequency of immunopositive samples for TGFB3 anci the leveis of TGFB3 rnRNA were higher in groups 2 anci 3 compareci to group 1. 1t is conclucieci that MP A induces PRL anci TGFB3 and inhibits c-los expression in endometrial cells in vivo, resembling what occurs ciuring the secretory phase of spontaneous ovulatory cycles. The inhibition of c-los and the increase of TGFB3 expression may contribute to the antiproliferative effect of progestins on the endometriurn.

The objective of the research comprising this thesis was to characterize ovarian follicular development in healthy women of reproductive age undergoing natural menstrual cycles and oral contraception (OC) cycles. We quantified changes in the numbers and diameters of follicles, detected ovulation and assessed changes in the growth and regression of corpora lutea using high-resolution transvaginal ultrasonography. Changes in follicular and luteal development were then correlated with changes in concentrations of reproductively-active hormones and endometrial growth to provide a comprehensive approach to ovarian and uterine function.<p>We documented, for the first time, that women exhibited waves of antral follicular development during the menstrual cycle. Two and three waves of follicle growth were observed. Major and minor waves of follicle development were characterized. Major waves were those in which a dominant follicle was selected for preferential growth; minor waves were those in which dominance was not manifest. Luteal progesterone production appeared to have a negative effect on the emergence and development of follicle waves in women. The ovarian follicular wave phenomenon has provided a new model for studying the growth and regression of ovarian follicles during the human menstrual cycle. Documentation of ovarian follicular waves in women has implications for the development of new strategies to manipulate ovarian follicular development, in particular hormonal contraceptive regimens and infertility therapies. <P>We further documented that ovarian follicular development occurred during the compliant use of oral contraception. Follicles developed to ostensibly ovulatory diameters and either regressed, ovulated, or formed follicular cysts under the suppressive effects of OC. The majority of follicles that developed during OC use emerged during the hormone-free interval (HFI). We interpreted our findings to mean that ovarian follicular development during OC use was associated with loss of endocrine suppression during the HFI, rather than user non-compliance as previously speculated. The number and maximum diameter of follicles that developed during OC use were greater in women administered OC containing 20 g versus 30--35 g Ethinyl -- Estradiol formulations. Our results provided rationale for a reduction or complete elimination of the HFI in OC regimens, and the judicious use of low EE dose OC regimens (i.e., ? 20 g EE). Ovarian follicular development and circulating concentrations of estradiol and LH were not suppressed effectively when OC use was initiated at mid to late stages of follicle development (i.e., ? 10 mm). Our findings demonstrated that dominant follicles secrete estradiol and become increasingly responsive to LH as they acquire functional dominance after becoming physiologically selected for preferential growth during the follicular phase of the menstrual cycle.

The objective of the research comprising this thesis was to characterize ovarian follicular development in healthy women of reproductive age undergoing natural menstrual cycles and oral contraception (OC) cycles. We quantified changes in the numbers and diameters of follicles, detected ovulation and assessed changes in the growth and regression of corpora lutea using high-resolution transvaginal ultrasonography. Changes in follicular and luteal development were then correlated with changes in concentrations of reproductively-active hormones and endometrial growth to provide a comprehensive approach to ovarian and uterine function.<p>We documented, for the first time, that women exhibited waves of antral follicular development during the menstrual cycle. Two and three waves of follicle growth were observed. Major and minor waves of follicle development were characterized. Major waves were those in which a dominant follicle was selected for preferential growth; minor waves were those in which dominance was not manifest. Luteal progesterone production appeared to have a negative effect on the emergence and development of follicle waves in women. The ovarian follicular wave phenomenon has provided a new model for studying the growth and regression of ovarian follicles during the human menstrual cycle. Documentation of ovarian follicular waves in women has implications for the development of new strategies to manipulate ovarian follicular development, in particular hormonal contraceptive regimens and infertility therapies. <P>We further documented that ovarian follicular development occurred during the compliant use of oral contraception. Follicles developed to ostensibly ovulatory diameters and either regressed, ovulated, or formed follicular cysts under the suppressive effects of OC. The majority of follicles that developed during OC use emerged during the hormone-free interval (HFI). We interpreted our findings to mean that ovarian follicular development during OC use was associated with loss of endocrine suppression during the HFI, rather than user non-compliance as previously speculated. The number and maximum diameter of follicles that developed during OC use were greater in women administered OC containing 20 g versus 30--35 g Ethinyl -- Estradiol formulations. Our results provided rationale for a reduction or complete elimination of the HFI in OC regimens, and the judicious use of low EE dose OC regimens (i.e., ? 20 g EE). Ovarian follicular development and circulating concentrations of estradiol and LH were not suppressed effectively when OC use was initiated at mid to late stages of follicle development (i.e., ? 10 mm). Our findings demonstrated that dominant follicles secrete estradiol and become increasingly responsive to LH as they acquire functional dominance after becoming physiologically selected for preferential growth during the follicular phase of the menstrual cycle.

Thesis (M.S.)--Brigham Young University. Dept. of Psychology, 2009. / Includes bibliographical references (p. 65-72).

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