The uterine endometrium undergoes cyclical phases of cell proliferation, cell differentiation, and menstruation under the influence of the ovarian hormones, estrogen and progesterone. Since the data necessary to create a classical kinetic model of these signaling pathways is lacking, we used a Boolean network approach that includes the influences of various growth factors and the differential expression of their receptors under the influence of estrogen and progesterone. Results show a gain in endometrial tissue and loss of tissue during menstruation that mirrors what can be expected over the course of a normal menstrual cycle in women, where the endometrium typically reaches a thickness of approximately 10 mm. We utilized an existing model of the normal menstrual cycle that was used to predict hormonal changes following administration of GnRH analogues. We adapted this model to provide the hormonal and ovarian compartments that would interact with our model of the endometrial cycle.

No description available.

Kilocalorie, protein, fat and carbohydrate intakes of five women were examined during the period of at least one menstrual cycle. Kilocalorie intake was significantly lower in the periovulatory phase of the cycle compared to the midluteal phase (t=2.10, p <.05). Carbohydrate and fat intakes were higher, although not significantly, during the midluteal phase compared to the periovulatory phase. Mean intake was 85 kilocalories higher in the postovulatory phase compared to preovulatory, but the difference was not significant. Mean carbohydrate and fat intakes were also increased, but not significantly, in the postovulatory phase. Protein intakes remained relatively stable when phases of the cycle were compared. A spectral analysis of variance produced two cycles showing monophasic sine component variations. Protein intake had a significant monophasic variation in two cycles; fat and carbohydrate had significant monophasic variation in one cycle each. The period of two to four days contained the most often significant sine components (10) and the period of five to seven days was next with five significant values. / Master of Science

Sex-differences in cardiometabolic physiology are evident; however, the inclusion of female participants in research studies for the purposes of exploration of sex-specific physiological responses is limited by the perceived complexity due to hormonal cycles. This dissertation examined the prevalence of sex-specific inclusion in human vascular exercise physiology research, investigate the influence of endogenous and exogenous sex hormones on cardiovascular, respiratory, and skeletal muscle metabolism, and consider sex- and gender-differences in peripheral vascular outcomes. The first study confirmed a sex-specific bias towards male inclusion in vascular exercise physiology research, with perceived hormonal complexity noted as one rationale for sex-specific exclusion. To address this perception, we reviewed the literature and identified a small effect of the menstrual cycle, and a more robust influence of oral contraceptive pills, on macrovascular endothelial function, with no influence on smooth muscle function or arterial stiffness. Our next set of studies objectively evaluated the influence of the natural menstrual and two generations of oral contraceptive pills on a comprehensive suite of cardiovascular, respiratory, and metabolic outcomes, and found largely no influence on these outcomes or the underlying vascular cellular regulation, apart from a small effect elevated endogenous and exogenous sex hormones on brachial artery endothelial function. Another area identified in our initial sex-inclusion review was the absence of gender-based research in vascular exercise physiology. Our final study found that biological sex aligned with gender identity, but not gender expression and influenced cardiovascular markers by including elevating systolic blood pressure, central arterial stiffness and endothelial function in males and men compared to females and women. Altogether, this dissertation provides substantial evidence for the lack of hormonal cycle influence of endogenous and exogenous sex hormones on three organ systems, which will open further incorporating females into research study design. / Dissertation / Doctor of Philosophy (PhD) / Females have been historically understudied in basic science and clinical research. This dissertation set out to explore sex-specific prevalence of research participants in human vascular exercise physiology studies and examined how sex hormones (through the menstrual cycle and oral contraceptive pill use) impact the cardiovascular, respiratory, and skeletal muscle metabolism systems. We found that there is an evident male-bias in vascular exercise physiology research, due in part to the perceived complexity of how sex hormones may impact the cardiovascular system. We also found that the menstrual cycle and oral contraceptive pill cycle have minimal influence on the biological systems examined. While there are evident sex-differences in cardiovascular outcomes, gender expression does not appear to have an impact in young adults. This research is foundational to further the inclusion of female participants in human physiology research and encourage future considerations of how sex/gender may influence physiological outcomes.

Interest in women's reproductive variation within the subfield of Physical Anthropology known as Human Reproductive Ecology is dominated by energetic models for fecundity that disregard genetic variation as a potential cause of differences in reproduction. Further, a strong correlation between ovarian and uterine markers of fecundity is assumed, although this assumption is not supported by the available data. A polymorphism in the progesterone receptor gene, called PROGINS, shows diminished progesterone response in vitro and is associated with a number of uterine disorders in women. To elucidate the discrepancy between ovarian and uterine markers of fecundity, carriers of the PROGINS variant were compared to non-carriers with regard to endometrial thickness and menstrual cycle characteristics. Gene-environment interactions between PROGINS and life history, lifestyle factors, progesterone levels, anthropometric measures, and physical activity were also considered. The PROGINS polymorphism was found to impact both luteal phase length and menses duration, as well as to modify endometrial sensitivity to life history factors, progesterone levels, anthropometric measures, and physical activity. These results support the notion that PROGINS diminishes progesterone response, and indicate that the polymorphism also alters endometrial sensitivity to acute and chronic energetic stress. The findings of this study indicate that Human Reproductive Ecologists must consider genetically-based variation in sensitivity to energetic stress in future adaptive models of women's reproduction. / Anthropology

Introduction: Women with bipolar disorder (BD) have higher rates of premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD). The primary goal of this thesis was to examine the neural correlates of bipolar disorder and comorbid PMDD and identify changes in brain structure or function that may mediate emotional and cognitive dysregulation in the late luteal phase. Results: In healthy women with no history of PMDD, absolute levels of estradiol, progesterone, allopregnanolone and dehydroepiandrosterone sulfate (DHEAS) were correlated with patterns of functional coupling in multiple regions associated with emotional and cognitive processes, in the mid-follicular and late luteal menstrual phases. A systematic review of the literature on resting state functional connectivity (Rs-FC) in BD during euthymia highlighted consistent patterns of resting state functional connectivity (Rs-FC) using ICA and SBA; including stability of the default mode network (DMN), salience network (SN) and fronto-parietal network (FPN) relative to controls. Available literature largely failed to control for sex, menstrual cycle phase or menstrual cycle disorders. Thus, we conducted the first fMRI studies to control for menstrual cycle phase in BD. During the mid-follicular phase, we found increased Rs-FC between critical nodes of the default mode and frontoparietal networks in BD compared to controls and increased functional connectivity between the somatosensory cortex and the insular cortex, inferior prefrontal gyrus and frontal orbital cortex in BD compared to controls. Voxel based morphometry analysis showed decreased gray matter in the somatosensory cortex in the same population compared to controls. Finally, women with BD and co-morbid PMDD displayed different patterns of Rs-FC using the right and left hippocampi as seed regions than women with BD without comorbid PMDD and controls with PMDD. Differences in cortical thickness between controls with and without PMDD and with and without BD were also found in regions central to emotional regulation and cognitive processing. Conclusions: Results highlight the influence of sex hormones on Rs-FC and support the need to control for menstrual phase and PMDD diagnosis. Differences in structural and functional connectivity, and the clinical profile of women with BD and those with BD and co-morbid PMDD highlights the impact of PMDD on BD and the need for future research in this area. / Thesis / Doctor of Philosophy (PhD)

Introduction: Sleep and biological rhythms have not been investigated in women with comorbid Bipolar and Premenstrual Dysphoric Disorder in the context of the menstrual cycle. We explored whether menstrual cycle phase causes increased disturbances in sleep, biological rhythms and mood symptoms. Additionally, we explored whether these women have worse illness outcome than women diagnosed with either Bipolar or Premenstrual Dysphoric Disorder, and healthy women. Methods: In this post-hoc analysis, participants were split into four groups: those with a Bipolar and comorbid Premenstrual Dysphoric Disorder diagnosis (n = 17, BDPMDD), those with a Bipolar Disorder diagnosis (n = 16, BD), those with a Premenstrual Dysphoric Disorder diagnosis (n = 19, PMDD), and women with no history of psychiatric diagnosis (n = 25, HC). The primary outcome variable was biological rhythm disruption as measured by the Biological Rhythms Interview and Assessment in Neuropsychiatry (BRIAN). The secondary outcome variables were depressive symptoms (Montgomery-Asberg Depression Scale, MADRS; Hamilton Depression Rating Scale, HAMD), manic symptoms (Young Mania Rating Scale, YMRS), and sleep quality (Pittsburgh Sleep Quality Index, PSQI). All variables were collected at both mid-follicular and late-luteal stages of the menstrual cycle. Results: The BDPMDD group did not have significantly higher disruptions in biological rhythms than the BD or PMDD groups at the luteal phase; however, there were significant disruptions and mood symptoms in comparison to the HC group, especially at the follicular stage, which point to markedly higher disruptions in these areas that seem to persist beyond the symptomatic luteal phase. Conclusion and Future Directions: Women diagnosed with a BD and PMDD comorbidity experience a higher illness burden then women diagnosed with either BD or PMDD. A relatively small sample size, not excluding for participants who were taking medications that affect sleep and relying solely on subjective measures of biological rhythms may explain some of the null results. Future studies should employ objective measures of sleep such as actigraphy to complement subjective measures like the BRIAN, as well as recruit a larger sample of participants. More importantly, more studies surrounding this topic must be done in order to create a robust body of evidence that can be used to compare results across studies and identify specific biological rhythms domains that can be targets for treatment. / Thesis / Master of Science (MSc) / Sleep disruptions are common in women diagnosed with Bipolar Disorder and in those diagnosed with Premenstrual Dysphoric Disorder. Illness burden has been shown to be greater in women diagnosed with a comorbidity of the above disorders in terms of clinical variables such as number of comorbidities, episode relapse, rapid cycling and mixed mood states. This thesis aims to investigate whether women diagnosed with Bipolar and comorbid Premenstrual Dysphoric Disorder have greater biological rhythms disruptions than women diagnosed with either disorder. Biological rhythms will be evaluated at both the follicular and late-luteal stages. The overall goal of this work is to add to the currently scant literature on the clinical presentation of a Bipolar and Premenstrual Dysphoric Disorder comorbidity.

The effects of menstrual cycle (MC) phases (post-menses, premenses, and menses) and dietary behavior (Normal (N), Restrainer (R), and Restrainer/Disinhibitor (RD)) on women's thresholds and preferences for sucrose solutions was investigated. MC phase was determined using both daily temperature readings and days of menses. Dietary group was assigned on the basis of women's responses to the Three Factor Eating Questionnaire (Stunkard and Messick, 1985). Women reported for sensory testing every third day for five weeks following a two-week training phase. Each evening subjects filled out a questionnaire to assess their overall daily fluctuations in total consumption; cravings for sweets; mood (feeling good, happy, and tired); pain (menstrual and other discomfort); metabolic need for energy (hunger, and fatigue); and stress. The results indicated that threshold did not vary due to MC phase (p = 0.9118), dietary behavior (p = 0.4037), or the interaction of these two variables (p = 0.2940). Preference for sucrose fluctuated as a result of MC phase only (p = 0.0441). Of the variables assessed daily, only "other discomfort" (p = 0.0486), "feeling good" (p = 0.0091), and "feeling hungry" (p = 0.0944) correlated with preference for sucrose. However, these correlations did not relate with MC phase clearly, indicating preference is not the manifestation of these theorized causes of MC distress. In general this study does not support the negative mood, or increased metabolic need for energy theory of MC distress. The theory of a decreased pain threshold found some support. The theory implicating dietary behavior in the development of MC distress symptoms was significantly supported. The fact MC phases have been implicated in the perpetuation of eating disorders implies the need for a counseling approach for the women most significantly affected, i.e. the R/D group. / Master of Science

Yes / Introduction: Investigate the effectiveness of short-term heat acclimation (STHA), over 5-days (permissive dehydration), on an intermittent sprint exercise protocol (HST) with females. Controlling for menstrual cycle phase. Materials and Methods: Ten, moderately trained, females (Mean [SD]; age 22.6 [2.7] y; stature 165.3 [6.2] cm; body mass 61.5 [8.7] kg; VO˙ 2 peak 43.9 [8.6] mL·kg−1 ·min−1 ) participated. The HST (31.0◦C; 50%RH) was 9 × 5 min (45-min) of intermittent exercise, based on exercise intensities of female soccer players, using a motorized treadmill and Wattbike. Participants completed HST1 vs. HST2 as a control (C) trial. Followed by 90 min, STHA (no fluid intake), for five consecutive days in 39.5◦C; 60%RH, using controlled-hyperthermia (∼rectal temperature [Tre] 38.5◦C). The HST3 occurred within 1 week after STHA. The HST2 vs HST3 trials were in the luteal phase, using self-reported menstrual questionnaire and plasma 17β-estradiol. Results: Pre (HST2) vs post (HST3) STHA there was a reduction at 45-min in Tre by 0.20◦C (95%CI −0.30 to −0.10◦C; d = 0.77); Tsk (−0.50; −0.90 to −0.10◦C; d = 0.80); and Tb (−0.25; −0.35 to −0.15◦C; d = 0.92). Cardiac frequency reduced at 45-min (−8; −16 to −1 b·min−1 ; d = 1.11) and %PV increased (7.0; −0.4 to 14.5%: d = 1.27). Mean power output increased across all nine maximal sprints by 56W (−26 to 139W; d = 0.69; n = 9). There was limited difference (P > 0.05) for these measures in HST1 vs HST2 C trial. Discussion: Short-term heat acclimation (5-days) using controlled-hyperthermia, leads to physiological adaptation during intermittent exercise in the heat, in moderately trained females when controlling for menstrual cycle phase.

A visibilidade da etapa fértil na mulher é uma questão polêmica e tem sido muito discutida nas últimas décadas. Alguns autores argumentam que no transcorrer da evolução a ovulação ficou oculta. Em paralelo, outros pesquisadores afirmam que a ovulação na mulher não se manifesta de forma tão visível como em alguns primatas que apresentam sinais muito notórios da ovulação, por exemplo, a tumefação vaginal. Mas diversas pesquisas têm fornecido evidência que mostram que o período fértil na mulher é perceptível de maneira sutil, sem que se tenha consciência do processo perceptual envolvido. Os achados destas pesquisas apontam para o fato de diversas características (como a face, a proporção cintura quadril, a simetria de tecidos brandos pareados e o cheiro) serem percebidas como mais atraentes na etapa fértil. O presente estudo teve por objetivo investigar se em alguma etapa (folicular tardia ou lútea) do ciclo menstrual a face da mulher se torna mais atraente para o sexo oposto devido a mudanças morfológicas induzidas pelos níveis hormonais. Foram apresentados, apenas para participantes masculinos, 36 slides com fotografias de faces frontais de mulheres em idade reprodutiva. Em cada slide foram mostradas simultaneamente duas fotos da mesma mulher, uma das fotos obtida na Fase Folicular Tardia (FFT) do ciclo e a outra obtida na Fase Lútea (FL). Os participantes escolheram a face mais atraente e posteriormente avaliaram o grau de atratividade mediante uma escala analógica visual (VAS), cujo extremo esquerdo e direito da escala foram rotulados respectivamente por: nem um pouco atraente e muito atraente. Os resultados mostraram que a atratividade facial feminina muda em função da etapa do ciclo menstrual. As faces das mulheres que não tomavam anticoncepcionais foram julgadas como mais atraentes na etapa fértil do que na etapa infértil do ciclo. E o julgamento de atratividade feito para as faces das mulheres que tomavam anticoncepcionais não diferiram significativamente entre a FFT e a FL. Os resultados obtidos nesta pesquisa e nos estudos realizados previamente proporcionam evidências que demonstram que o período fértil nos humanos não está oculto, pois ocorrem mudanças na face que são detectáveis, mesmo quando o processo de percepção não é ciente. / Visibility of fertile period in women is a controversial topic that has been broadly discussed during the last decades. Some authors argue that ovulation became hidden in the course of evolution. In contrast, some other researchers state that ovulation in woman is not manifested as visibly as in other primates, which present very evident signals of ovulation like, e.g., vaginal tumefaction. However, several studies have provided evidence showing that fertile period in women is perceptible in a subtle way, without being aware of the perceptual process involved. Findings of those works points to the fact that some characteristics such as face, waist hip ratio, paired soft tissues symmetry and smell are perceived as more attractive in the fertile stage. The present work aimed to find out whether in any stage (late follicular or luteal) of menstrual cycle woman face appears more attractive to opposite sex, due to morphological changes induced by hormonal levels. 36 slides with frontal face photographs of woman in reproductive age were shown to male participants. In each slide two pictures of the same woman, one obtained in the late follicular phase and the other obtained in the luteal phase were exposed. Participants chose the more attractive picture and then they assessed the attractiveness through a visual analogical scale (VAS), in whose left and right extremes the legends not attractive at all and very attractive were marked, respectively. Results showed that female facial attractiveness changes as a function of the menstrual cycle stage. Faces of women who did not take contraceptives did not differ significantly between FFT and FL. The results obtained in this research and previous studies provide evidence to demonstrate that the fertile period in humans is not hidden, because on the face occur changes that are detectable even when the process of perception is not aware of.