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.

The control of prolactin secretion is a complex interaction of peptides and neurotransmitters acting either in an inhibitory or stimulating way to effect final secretion of this hormone from the lactotrope cell in the anterior hypothalamus. These factors may act either directly on the lactotrope cell or indirectly by changing either dopamine restraint of prolactin secretion or by modulating peptide substances or neurotransmitters higher up in the hypothalamus. Gonadal steroids may also modulate the effect of peptides or dopamine at the level of the lactotrope. Prolactin's major role in the female rat is one of milk production post - partum, nurturing the young. It probably also has other physiological functions and may play a part in the menstrual cycle although this is controversial. Certainly, pulsatile secretion of prolactin during the menstrual cycle is well established and in the luteal phase this is concomitant with the secretion of luteinizing hormone. Theories explaining the synchronous surges seen during this phase of the menstrual cycle have been proposed and GnRH has been implicated in the genesis of the concordance of these secretory spikes. Using a potent GnRH antagonist an experiment was undertaken to establish the role of GnRH by blocking this hypothalamic peptide and observing the effect that this had on luteinizing hormone, prolactin and follicle stimulating hormone. In the first part of the thesis the control of prolactin secretion is reviewed. In the following section, an experiment was performed using a potent GnRH antagonist. A dose response curve was established for the antagonist action on LH. Then a twice maximum dose of this peptide was administered to three subjects in the midluteal phase of the menstrual cycle and the response of LH, prolactin and FSH was measured. The results indicate that although the GnRH antagonist significantly blocked LH secretory peaks, this action was not observed for either prolactin or FSH. This result is perhaps at variance with previous data which suggested that GnRH was responsible for concordant secretory spikes of LH and prolactin in the midluteal phase of the menstrual cycle.

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Call number: LD2668 .T4 1985 T65 / Master of Science

Syfte - Studien avser att undersöka om prestation gällande maximalstyrka och explosivitet varierar under menstruationscykeln. Dessutom undersöks om den psykologiska motivationen eller känslan korrelerar med prestationen. Studiens syfte är att skapa en utgångspunkt för att se om periodisering av styrketräning i relation till menstruationscykeln faser är aktuell för kvinnor inom prestationsidrotter. Metod - Testerna genomfördes under en menstruationscykel, fyra veckor. Ett test genomfördes varje vecka för att täcka in fyra faser under menstruationscykeln och för att erhålla ett konsekvent veckomönster. Menstruationscykelns faser räknades ut i efterhand för att inte i förhand påverka testdeltagarnas motivation och prestation i förhållande till menstruationscykeln. Fas 1 menstruationsfas, fas 2 intermenstruation, fas 3 intermenstruation/ägglossning och fas 4 premenstruation. I testgruppen ingick fyra kvinnor, 32 år (± 10), längd 162,8 cm (± 7,32), vikt 57,4 kg (± 5,79). I kontrollgruppen ingick en man och två kvinnor utan menstruation, 26,67 år (± 9,02), längd 168,3 cm (± 8,96), vikt 71,7 kg (± 11,02). Fysiska tester, längdhopp och knäböj. En standardiserad uppvärmning genomfördes inför varje test, följdes av tre stycken jämfota längdhopp utan ansats med två minuter vila mellan hoppen. Bästa hoppet av tre dokumenterades. Längdhopp (CV 1,8 %) (Hopkins, Schabort & Hawley, 2001), knäböj, en repetition max [1RM] (CV 1,57 %) (Urquhart, Moir, Graham & Connaboy, 2015). En specifik uppvärmning genomfördes även inför 1RM knäböj därefter försök på en repetition på 1RM. Frågeformulär gällande hälsotillstånd och motivation “Snabbkollen” (Cross & Lyle, 1999) besvarades inför varje testtillfälle. Vid sista testtillfället fick alla testdeltagare fylla i ett frågeformulär om upplevda symptom och tillstånd under den gångna menstruationscykeln. Resultat och slutsats - Det är ur denna studie svårt att tyda om menstruationscykelns olika faser skulle ha någon relevant effekt värd att ta hänsyn till när det gäller prestationen hos idrottande kvinnor. Dock visar resultaten att menstruationscykeln påverkar motivationen. / Purpose - This study aimed to examine how maximum strength and explosivity varies during the menstrual cycle and how this relates to psychological motivation or feelings over the same time period. The study's purpose was to create a starting point to see if there are changes in strength in relation to the menstrual cycle phases with relevance for women in sports performance. Method - The tests were carried out over one menstrual cycle, four weeks. One test was conducted every week to cover the four phases of the cycle and to obtain a consistent weekly pattern. Menstrual cycle phases were calculated retrospectively so as to not preempt the test participants motivation and performance in relation to the menstrual cycle. (Phase 1 menstruation phase, phase 2 inter-menstrual, phase 3 inter-menstrual/ovulation and phase 4 premenstruation). The test group included four women, aged 32 (± 10), length 162.8 cm (± 7.32), weight 57.4 kg (± 5.79). The control group included one man and two women without menstruation, 26.67 years (± 9.02), length 168.3 cm (± 8.96), weight 71.7 kg (± 11.02). Strength and explosivity were assessed by long jump and squat. A standardized preparation was carried out before each test, followed by three long jumps performed with both feet together without effort, with two minutes rest between jumps. The best jump of three was documented. An individualized warm-up was then performed to attain 1RM squat performance. A questionnaire focusing on health status and motivation of "Snabb Kollen" (Cross & Lyle, 1999) was answered before each test date. At the end of the last test session all test participants completed a questionnaire on perceived symptoms, motivation and conditions specific to the duration of the test period, which for the females, corresponded to their last menstrual cycle. Results and Conclusion - Results from this study show that it is difficult to interpret if the menstrual cycle phase would have any relevant effect worth taking into account when it comes to the strength and explosivity performance of sportswomen. However, the results show that menstrual cycle does affect motivation.

Although prostaglandins (PG) and oxytocin are crucial mediators of uterine contractility, their receptor-mediated effects during the menstrual cycle, pregnancy and labour are not fully understood. The aim of this thesis was to elucidate the functional expression of EP, FP, TP and oxytocin receptors in isolated human myometrium relative to myocyte mRNA and signal transduction pathways. Myometrial samples were obtained from consenting non-pregnant and pregnant donors. Functional techniques were used to determine isometric muscle contractions. Primary uterine myocytes and fibroblasts were cultured at term to identify stimulated changes in calcium (Ca2+), cyclic adenosine monophosphate (cAMP) and mRNA. Myometrial strips exhibited spontaneous contractions, which were most active midcycle under oestrogenic conditions. At this time intrinsic contractility and responsiveness to uterotonins decreased towards the fundus. PGE2 produced bellshaped responses with predominant utero-relaxant effects mediated via the EP2 subtype. Although activity was partially restored by PGE2 through EP3/1 receptors, tissue excitation was more pronounced at FP, TP and oxytocin receptors. Despite high FP mRNA expression, the lower segment uterus was particularly responsive to U46619 and oxytocin at term pregnancy. Even so, Ca2+ mobilisation by oxytocin was greater via principal release from intracellular stores. Incubations with atosiban, progesterone and a rho-kinase inhibitor reduced oxytocin-stimulated Ca2+ transients. EP2 also attenuated oxytocic effects but this appeared to be mediated through cAMP rather than Ca2+ signalling pathways. With advancing labour, intrinsic myogenic activity declined in parallel with oxytocin desensitisation. However, TP-induced contractions were continued in the lower parturient uterus. These findings demonstrate that PG and oxytocin receptor expression are regulated in a hormone-dependent temporal and spatial manner. EP2-mediated cAMP formation appears to promote uterine quiescence, whilst TP receptors may control muscle tonus during parturition. These receptors and their messenger systems represent effective tocolytic targets for uterine hypercontractile disorders, such as dysmenorrhoea and preterm labour.

Title The influence of muscle tonus with hormonal contraception Objective The thesis aims to determine whether and to what extent the use of hormonal contraception affects muscle tension, which can vary depending on the current phase of the menstrual cycle in women. Method The thesis is divided into theoretical part where there is a summary of information on this topic from the literature Czech and world, a special part that is treated as research using noninvasive myotonometer. The measurement is performed in 12 probands four times in four weeks, always at some stage of their menstrual cycle. The measurement results are compared between the two groups by probands and is found to influence hormonal contraceptives on muscle tension during the menstrual cycle. Results Measurement myotonometer shows that hormonal contraceptive use affects muscle tension. The measurement results show a stable and predictable changes in fluctuating muscle tension in probands who use hormonal contraceptives, but the rate changes are subject to interpersonal differences, and these results can not give a general opinion. Key words Menstrual cycle, hormonal contraception, muscle tension, myotonometer

Primary dysmenorrhoea, or painful menstruation in the absence of pelvic pathology, is a common, and often debilitating, gynaecological condition that affects between 45 to 95% of menstruating women. Despite the high prevalence, dysmenorrhoea is often poorly treated, and even disregarded, by health professionals, pain researchers, and the women themselves, who may accept it as a normal part of the menstrual cycle. The overall purpose of this thesis is two-fold: first, to contribute knowledge about the impact and consequences of recurrent severe menstrual pain on pain sensitivity, mood, quality of life and sleep in women with primary dysmenorrhoea, and secondly, to investigate day-time and night-time treatment of recurrent primary dysmenorrhoeic pain. For this thesis, I completed five separate studies on three different groups of young, otherwise healthy women with a history of severe primary dysmenorrhoea, and age-matched controls without dysmenorrhoea. The first two studies, presented in Chapter 2, addressed the question of whether women with primary dysmenorrhoea are hypersensitive to experimental pain. I used clinically-relevant experimentally-induced muscle pain stimuli (intramuscular injection of hypertonic saline and ischaemia) in referred and non-referred sites of menstrual pain, at different phases of the menstrual cycle. Women with dysmenorrhoea, compared to women without dysmenorrhoea, had increased sensitivity to deep-muscle pain both within the area of referred menstrual pain and at a remote pain-free site. Further, the increased muscle pain sensitivity was evident even in phases of the menstrual cycle when women did not have menstrual pain, illustrating that the changes in pain perception extend outside of the painful menstruation phase. These findings suggest that women with dysmenorrhoea show long-lasting changes in pain processing possibly because of the recurrent dysmenorrhoeic pain. A secondary aim of the study presented in Chapter 2a, was to determine the impact of menstrual cycle phase on experimentally-induced muscle pain sensitivity in women with and without primary dysmenorrhoea. My results suggest that menstrual cycle phase has no effect on pain sensitivity in either group of women. As part of my studies, I investigated the impact of dysmenorrhoeic pain on quality of life and mood. I found that women with dysmenorrhoea had a significantly reduced quality of life (Chapter 3) and poorer mood (Chapter 2a and Chapter 5), during menstruation compared to their pain-free follicular phase, and compared to the menstruation phase of the pain-free control women. These data highlight the negative impact that primary dysmenorrhoea has on young women, for up to a few days every month. Non-steroidal anti-inflammatory drugs (NSAIDs) are often prescribed as the first-line therapy for menstrual pain. Yet, severe dysmenorrhoeic pain is often poorly managed, especially at night, when the pain likely disrupts sleep. I conducted two studies investigating the effectiveness of diclofenac potassium, a readily-available NSAID with a low side-effect profile, compared to placebo, in alleviating severe primary dysmenorrhoeic pain across the day (Chapter 4), and during the night (Chapter 5). I also investigated the effectiveness of diclofenac potassium in improving subjective and objective sleep quality (Chapter 5). I found that the daily recommended dose (150 mg) of diclofenac potassium, administered at three timepoints across the first 24 hours of menstruation, significantly reduced perceived menstrual pain, compared to placebo. I confirmed that dysmenorrhoeic pain reduces polysomnographic and subjective measures of sleep quality compared with the pain-free follicular phase. I also showed, for the first time, that diclofenac potassium is effective, compared to placebo, in alleviating nocturnal pain, along with restoring subjective sleep quality and polysomnographic measures of objective sleep quality in women with severe primary dysmenorrhoea. My studies have addressed several gaps in the knowledge about primary dysmenorrhoea. I have shown that women with primary dysmenorrhoea are hypersensitive to deep muscle pain, supporting the hypothesis of other researchers that the recurrent menstrual pain experienced by these women is associated with central sensitisation, and may predispose women with primary dysmenorrhoea to other chronic painful conditions. Therefore, limiting the monthly noxious input into the central nervous systems of these women, by means of effective treatment of dysmenorrhoea, may improve their long-term health. The research presented in this thesis further highlights the efficacy of diclofenac potassium in relieving not only day-time and night-time dysmenorrhoeic pain, but also in restoring objective and subjective pain-induced sleep disturbances in women with dysmenorrhoea. Further, my research has shown that dysmenorrhoeic pain has an immediate negative impact on quality of life and mood during menstruation. The results of this thesis show the multi-factorial impact of dysmenorrhoea and should stimulate further research about the long-term benefits of effective treatment of menstrual pain.