Lack of associations between female hormone levels and visuospatial working memory, divided attention and cognitive bias across two consecutive menstrual cycles

Background: Interpretation of observational studies on associations between prefrontal cognitive functioning and hormone levels across the female menstrual cycle is complicated due to small sample sizes and poor replicability. Methods: This observational multisite study comprised data of n = 88 menstruating women from Hannover, Germany, and Zurich, Switzerland, assessed during a first cycle and n = 68 re-assessed during a second cycle to rule out practice effects and false-positive chance findings. We assessed visuospatial working memory, attention, cognitive bias and hormone levels at four consecutive time-points across both cycles. In addition to inter-individual differences we examined intra-individual change over time (i.e., within-subject effects). Results: Estrogen, progesterone and testosterone did not relate to inter-individual differences in cognitive functioning. There was a significant negative association between intra-individual change in progesterone and change in working memory from pre-ovulatory to mid-luteal phase during the first cycle, but that association did not replicate in the second cycle. Intra-individual change in testosterone related negatively to change in cognitive bias from menstrual to pre-ovulatory as well as from pre-ovulatory to mid-luteal phase in the first cycle, but these associations did not replicate in the second cycle. Conclusions: There is no consistent association between women’s hormone levels, in particular estrogen and progesterone, and attention, working memory and cognitive bias. That is, anecdotal findings observed during the first cycle did not replicate in the second cycle, suggesting that these are false-positives attributable to random variation and systematic biases such as practice effects. Due to methodological limitations, positive findings in the published literature must be interpreted with reservation

Living with endometriosis: Comorbid pain disorders, characteristics of pain and relevance for daily life

BACKGROUND: Pain plays a central role in endometriosis. The complex relationship among pain characteristics, comorbid pain disorders and daily life represents a challenge for medical support. This multicentre cross‐sectional case–control study analysed the association between endometriosis‐related chronic pain and functions of daily life in 510 women with endometriosis, 265 (52%) who experienced chronic pain, either from endometriosis alone (N = 134, 26.3%) or in association with additional pain disorders (N = 131, 25.7%). METHODS: Self‐administered questionnaires from the Brief Pain Inventory and the Pain Disability Index were used to investigate associations between pain characteristics (frequency, duration, intensity) and daily life. Also, associations between different endometriosis characteristics (rASRM stage, presence of adhesions, localisation of lesions) and pain were evaluated. RESULTS: Chronic pain is negatively associated with almost all (12/14) aspects of daily life investigated, including standing, walking, sitting, defaecation, sleep, sports activities, family and domestic responsibilities, sexuality, social functioning, professional life, mood, and joy of life. Altogether, 33.7% of women with chronic pain reported moderate and 27.5% severe limitations. Comorbid pain disorders resulted in significantly more limitations. The length of pain episodes showed a particularly important influence, especially for family/domestic responsibilities (OR 22.94, p < 0.001), professional life (OR 16.56, p < 0.001) and social functioning (OR 41.03, p < 0.001). CONCLUSIONS: Our data confirm that despite treatment, about 50% of women experience pain. Pain was associated with at least moderate negative effects on almost all areas of daily life; additional pain comorbidities increased limitations. Improving pain management is essential for improving quality of life in women with endometriosis. SIGNIFICANCE: The study provides an accurate overview of the impact of endometriosis‐associated pain on daily life. This is important because pain plays a central role in women living with endometriosis, and despite modern therapies, many women continue to suffer from chronic pain. The detailed analysis of its impact with a comprehensive survey of all aspects of daily life in a very large study population is unique. We expect an improved understanding of consequences of pain to significantly advance medical support in these patients

Does endometriosis affect professional life? A matched case-control study in Switzerland, Germany and Austria.

OBJECTIVES Endometriosis is a gynaecological disease most commonly causing severe and chronic pelvic pain as well as an impaired quality of life. The aim of this study was to investigate if and how endometriosis affects choices regarding professional life as well as the quality of daily working life. DESIGN, SETTING AND PARTICIPANTS In the context of a multicentre case-control study, we collected data from 505 women with surgically/histologically confirmed diagnosis of endometriosis and 505 matched controls. Study participants were recruited prospectively in hospitals and doctors' practices in Switzerland, Germany and Austria. Using a detailed questionnaire, the study investigated work-life and career choices of study participants. MAIN OUTCOME MEASURES Associations between endometriosis/disease symptoms and limitations in career development as well as ability to work. RESULTS Women with endometriosis were less often able to work in their desired profession than women from the control group (adjusted OR=1.84, 95% CI: 1.15 to 2.94, R2=0.029, p=0.001) and they had to take health-related limitations into consideration in their career decisions to a significantly higher degree than women in the control group (OR=4.79, 95% CI: 2.30 to 9.96, R2=0.063, p<0.001). Among women with endometriosis, chronic pain was significantly associated with increased sick leave (OR=3.52, 95% CI: 2.02 to 6.13, R2=0.072, p<0.001) as well as with loss of productivity at work (OR=3.08, 95% CI: 2.11 to 4.50, R2=0.087, p<0.001). CONCLUSIONS Endometriosis is associated with impairment of professional life, in particular with regard to career choices. Further research to develop strategies to support endometriosis-affected women in realising professional opportunities is recommended. TRIAL REGISTRATION NUMBER NCT02511626; Pre-results

The association between adverse childhood experiences and quality of partnership in adult women

Background Adverse childhood experiences (ACE) have a significant effect on psychological and physical child development and represent a risk factor for interpersonal difficulties. Objective This study aims to investigate the association between ACE, in particular physical, sexual, emotional abuse and neglect, and partnership quality during adulthood in women. Participants and setting This study is a secondary analysis of a retrospective multi-center study evaluating risk factors and quality of life in women with and without endometriosis, a chronic, disabling gynecological disease. The investigation includes 533 consenting adult women (159 with ACE and 374 women without) recruited from various hospitals in Switzerland, Austria and Germany. Methods To evaluate the association between ACE and partnership, a questionnaire including the Childhood Trauma Questionnaire and a validated partnership questionnaire were used. Results Altogether, 29.8 % (N = 159) women experienced maltreatment in childhood, 9.7 % (N = 52) of them more than one type. Women who went through ACE showed a lower level of happiness (P = 0.013) and of quality of partnership (P = 0.001) as well as a higher number of conflict areas (P < 0.001). Emotional (P = 0.03; 95 % CI=-1.27,-0.070) and sexual abuse (P = 0.01; 95 % CI=-1.765,-0.197) had the strongest association with reduced partnership quality. Conclusion Our study showed a significant association between ACE, in particular sexual and emotional abuse, and reduced partnership quality. As the quality of partnership is a key factor in the quality of life, improvement in social support with a special focus on intimate relationships should be part of the strategy to address the consequences of ACE already during childhood/adolescence

The relevance of age in female human reproduction – Current situation in Switzerland and pathophysiological background from a comparative perspective

During recent years women tend to postpone childbirth to ages when fertility declines. Consequently, an increasing number of women experiences reproductive difficulties and seeks help by assisted reproductive techniques (ART). To investigate the dynamics of age-related fertility in Switzerland we evaluated data from the nationwide FIVNAT-CH statistics on ART as well as from a subsample receiving ART at the Division of Reproductive Endocrinology, University Hospital Zurich. Since 2000 the average age of women receiving ART increased from 34.9 to 36.3 years in Switzerland and since 2006 numbers of annual ART cycles augmented steadily. The percentage of women ⩾40 increased from 17.2% in 2007 to 19.6% in 2011. In the Zurich cohort AMH, the number of oocytes retrieved, the number of fertilized oocytes with two pronuclei, the number of embryos with an adequate cell number, clinical pregnancy rates as well as life birth/ongoing pregnancy rates were lower in the age group ⩾40 years, especially when compared to 33 year-old women. In the nationwide sample pregnancy rates decreased from about 45% at the age of 30 to less than 3% at the age of 45; delivery rates declined from about 38% to nearly 0%. In the Zurich cohort percentages of clinical pregnancies declined from 46% in women ⩽34 years to 21% in women ⩾40 years. In the national sample as well as in the Zurich cohort the percentage of miscarriages increased dramatically from 15.4% and 22% in women ⩽34 years to 38.6% and 33% in women ⩾40 years, respectively. Even in a country with high health standards such as Switzerland fertility is declining with age and ART does not succeed to improve reduced fertility. Rodent and primate models enrich our knowledge on the pathophysiological mechanisms underlying reproductive senescence. As non-infertility specialist physicians as well as the general public are not sufficiently aware of the dramatic reduction of chances for life births in women ⩾40 years, medical counseling as well as schools and media should support the distribution of information future parents need for successful family planning

Associations between natural physiological and supraphysiological estradiol levels and stress perception

Stress is a risk factor for impaired general, mental, and reproductive health. The role of physiological and supraphysiological estradiol concentrations in stress perception and stress processing is less well understood. We, therefore, conducted a prospective observational study to investigate the association between estradiol, stress perception, and stress-related cognitive performance within serial measurements either during the natural menstrual cycle or during fertility treatment, where estradiol levels are strongly above the physiological level of a natural cycle, and consequently, represent a good model to study dose-dependent effects of estradiol. Data from 44 women receiving in vitro fertilization (IVF) at the Department of Reproductive Endocrinology in Zurich, Switzerland was compared to data from 88 women with measurements during their natural menstrual cycle. The German version of the Perceived Stress Questionnaire (PSQ) and the Cognitive Bias Test (CBT), in which cognitive performance is tested under time stress were used to evaluate subjective and functional aspects of stress. Estradiol levels were investigated at four different time points during the menstrual cycle and at two different time points during a fertility treatment. Cycle phases were associated with PSQ worry and cognitive bias in normally cycling women, but different phases of fertility treatment were not associated with subjectively perceived stress and stress-related cognitive bias. PSQ lack of joy and PSQ demands related to CBT in women receiving fertility treatment but not in women with a normal menstrual cycle. Only strong changes of the estradiol level during fertility treatment were weakly associated with CBT, but not with subjectively experienced stress. Our research emphasizes the multidimensional character of stress and the necessity to adjust stress research to the complex nature of stress perception and processing. Infertility is associated with an increased psychological burden in patients. However, not all phases of the process to overcome infertility do significantly increase patient stress levels. Also, research on the psychological burden of infertility should consider that stress may vary during the different phases of fertility treatment. Clinical trial registration: ClinicalTrials.gov # NCT02098668

Fatigue - a symptom in endometriosis

STUDY QUESTION: Is fatigue a frequent symptom of endometriosis? SUMMARY ANSWER: Fatigue is an underestimated symptom of endometriosis as it affects the majority of women with endometriosis, but it is not widely discussed in literature. WHAT IS KNOWN ALREADY: Fatigue can be a symptom of endometriosis causing major distress impacting the daily activities and quality of life of women with endometriosis. However, few studies with large sample sizes have investigated fatigue as a symptom of endometriosis. STUDY DESIGN, SIZE, DURATION: The study was designed as a multi-center matched case-control study. Recruitment took place at hospitals and private practices in Switzerland, Germany and Austria between 2010 and 2016. Data was collected from 1120 women, 560 of them with endometriosis. The women with endometriosis were matched to 560 control women in regard to age ±3 years and ethnic background. PARTICIPANTS/MATERIALS, SETTING, METHODS: Diagnosis of women with endometriosis had to be surgically and histologically confirmed. Surgical exclusion or absence of any endometriosis-identifying symptoms was required for control subjects. Materials included surgical and histological reports as well as data retrieved from a self-administered questionnaire. This study focused on the symptom fatigue in endometriosis. Relationships of variables were established by regression analysis and associations were quantified as odds ratios. MAIN RESULTS AND THE ROLE OF CHANCE: Frequent fatigue was experienced by a majority of women diagnosed with endometriosis (50.7% versus 22.4% in control women, P < 0.001). Fatigue in endometriosis was associated with insomnia (OR: 7.31, CI: 4.62-11.56, P < 0.001), depression (OR: 4.45, CI: 2.76-7.19, P < 0.001), pain (OR: 2.22, CI: 1.52-3.23, P < 0.001), and occupational stress (OR: 1.45, CI: 1.02-2.07, P = 0.037), but was independent of age, time since first diagnosis and stage of the disease. LIMITATIONS, REASONS FOR CAUTION: Women with asymptomatic endometriosis cannot be excluded in the control group which would lead to underestimation of our results. The study's design allows no evaluation of causal effects. WIDER IMPLICATIONS OF THE FINDINGS: As fatigue is experienced by numerous women with endometriosis, it needs to be addressed in the discussion of management and treatment of the disease. In addition to treating endometriosis, it would be beneficial to reduce insomnia, depression, pain and occupational stress in order to better manage fatigue. STUDY FUNDING/COMPETING INTEREST(s): There was no additional funding received for this study and no conflict of interest. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT 02511626

Living with endometriosis: Comorbid pain disorders, characteristics of pain and relevance for daily life

Background: Pain plays a central role in endometriosis. The complex relationship among pain characteristics, comorbid pain disorders and daily life represents a challenge for medical support. This multicentre cross-sectional case-control study analysed the association between endometriosis-related chronic pain and functions of daily life in 510 women with endometriosis, 265 (52%) who experienced chronic pain, either from endometriosis alone (N = 134, 26.3%) or in association with additional pain disorders (N = 131, 25.7%). Methods: Self-administered questionnaires from the Brief Pain Inventory and the Pain Disability Index were used to investigate associations between pain characteristics (frequency, duration, intensity) and daily life. Also, associations between different endometriosis characteristics (rASRM stage, presence of adhesions, localisation of lesions) and pain were evaluated. Results: Chronic pain is negatively associated with almost all (12/14) aspects of daily life investigated, including standing, walking, sitting, defaecation, sleep, sports activities, family and domestic responsibilities, sexuality, social functioning, professional life, mood, and joy of life. Altogether, 33.7% of women with chronic pain reported moderate and 27.5% severe limitations. Comorbid pain disorders resulted in significantly more limitations. The length of pain episodes showed a particularly important influence, especially for family/domestic responsibilities (OR 22.94, p < 0.001), professional life (OR 16.56, p < 0.001) and social functioning (OR 41.03, p < 0.001). Conclusions: Our data confirm that despite treatment, about 50% of women experience pain. Pain was associated with at least moderate negative effects on almost all areas of daily life; additional pain comorbidities increased limitations. Improving pain management is essential for improving quality of life in women with endometriosis. Significance: The study provides an accurate overview of the impact of endometriosis-associated pain on daily life. This is important because pain plays a central role in women living with endometriosis, and despite modern therapies, many women continue to suffer from chronic pain. The detailed analysis of its impact with a comprehensive survey of all aspects of daily life in a very large study population is unique. We expect an improved understanding of consequences of pain to significantly advance medical support in these patients

Cognitive function in association with high estradiol levels resulting from fertility treatment

The putative association between hormones and cognitive performance is controversial. While there is evidence that estradiol plays a neuroprotective role, hormone treatment has not been shown to improve cognitive performance. Current research is flawed by the evaluation of combined hormonal effects throughout the menstrual cycle or in the menopausal transition. The stimulation phase of a fertility treatment offers a unique model to study the effect of estradiol on cognitive function. This quasi-experimental observational study is based on data from 44 women receiving IVF in Zurich, Switzerland. We assessed visuospatial working memory, attention, cognitive bias, and hormone levels at the beginning and at the end of the stimulation phase of ovarian superstimulation as part of a fertility treatment. In addition to inter-individual differences, we examined intra-individual change over time (within-subject effects). The substantial increases in estradiol levels resulting from fertility treatment did not relate to any considerable change in cognitive functioning. As the tests applied represent a broad variety of cognitive functions on different levels of complexity and with various brain regions involved, we can conclude that estradiol does not show a significant short-term effect on cognitive function

Associations Between Natural Physiological and Supraphysiological Estradiol Levels and Stress Perception

Stress is a risk factor for impaired general, mental, and reproductive health. The role of physiological and supraphysiological estradiol concentrations in stress perception and stress processing is less well understood. We, therefore, conducted a prospective observational study to investigate the association between estradiol, stress perception, and stress-related cognitive performance within serial measurements either during the natural menstrual cycle or during fertility treatment, where estradiol levels are strongly above the physiological level of a natural cycle, and consequently, represent a good model to study dose-dependent effects of estradiol. Data from 44 women receiving in vitro fertilization (IVF) at the Department of Reproductive Endocrinology in Zurich, Switzerland was compared to data from 88 women with measurements during their natural menstrual cycle. The German version of the Perceived Stress Questionnaire (PSQ) and the Cognitive Bias Test (CBT), in which cognitive performance is tested under time stress were used to evaluate subjective and functional aspects of stress. Estradiol levels were investigated at four different time points during the menstrual cycle and at two different time points during a fertility treatment. Cycle phases were associated with PSQ worry and cognitive bias in normally cycling women, but different phases of fertility treatment were not associated with subjectively perceived stress and stress-related cognitive bias. PSQ lack of joy and PSQ demands related to CBT in women receiving fertility treatment but not in women with a normal menstrual cycle. Only strong changes of the estradiol level during fertility treatment were weakly associated with CBT, but not with subjectively experienced stress. Our research emphasizes the multidimensional character of stress and the necessity to adjust stress research to the complex nature of stress perception and processing. Infertility is associated with an increased psychological burden in patients. However, not all phases of the process to overcome infertility do significantly increase patient stress levels. Also, research on the psychological burden of infertility should consider that stress may vary during the different phases of fertility treatment