Within-person changes in reproductive hormones and cognition in the menopause transition.

OBJECTIVES: Most women complain of cognitive deficits in the menopause transition, though the cause is unclear. The current study investigated the role that within-person changes in reproductive hormones, particularly estradiol, may play in triggering such perimenopausal cognitive difficulties. STUDY DESIGN: Participants were 43 women aged 45-55 years and currently in the menopause transition. Once a week for 12 weeks, participants provided a urine sample for the measurement of estrone glucuronide (E1G), a urinary metabolite of estradiol. Every three weeks across the 12-week period, participants also underwent cognitive testing, including assessments of immediate and delayed memory, attention, and executive function, and completed questionnaires assessing subjective cognitive performance. Potential confounding variables including sleep quality, vasomotor symptoms, and depressive symptoms were also assessed. RESULTS: Within-person E1G was positively associated with objective measures of attention, particularly the ability to passively register auditory information on the first pass, as well as subjective measures of memory, specifically relating to a lower frequency of forgetting things in everyday life. Perimenopausal women with lower estimated levels of intellectual functioning furthermore exhibited a stronger relationship between E1G changes and objective cognitive performance. While depressive mood, poor sleep, and vasomotor symptoms were all negatively associated with at least one aspect of cognitive function, the E1G-cognition relationship was not explained by these factors. CONCLUSIONS: This study provides evidence that validates perimenopausal women's cognitive complaints but also suggests that cognitive deficits are generally mild and transient.

Menstrual cycle influences on cue-induced smoking cravings and heart rate variability.

Women experience greater difficulties in quitting smoking than men, though the hormonal factors contributing to this sex difference remain to be clarified. The current study aimed to examine menstrual cycle effects on smoking cue-induced cravings as well as examine dynamic reproductive hormone change as a potential mediator underlying any cycle effects observed. Twenty-one women who smoke underwent two laboratory sessions - one in the mid-follicular phase and the other in the late luteal phase - involving an in-vivo smoking cue task, administered before and after exposure to a psychosocial laboratory stressor. Heart rate variability (HRV) and subjective smoking cravings were assessed in response to the cue task. The degree of change in the urinary metabolites of estradiol and progesterone from 2 days before to the day of each laboratory session was measured. Results revealed that both before and following exposure to psychosocial stress, highly nicotine-dependent women exhibited smaller cue-induced increases in HRV relative to the follicular phase. In contrast, less nicotine-dependent women exhibit an increase in HRV in both menstrual cycle phases. Results furthermore suggest that menstrual cycle effects seen in highly nicotine-dependent women are driven by the decline in estradiol and progesterone occurring in the late luteal phase. Though limited by a small sample size, this study suggests that withdrawal from reproductive hormones in the late luteal phase may alter highly nicotine-dependent women's physiological response to smoking cues, which may reflect greater difficulty resisting temptation. These findings may provide some insight regarding women's greater difficulty in maintaining abstinence after quitting smoking.

Testosterone and depressive symptoms during the late menopause transition.

BACKGROUND: The menopause transition is associated with an increased risk of depression. While the mechanisms behind this increased risk are not well understood, the changing perimenopausal hormonal environment has been hypothesized to play a role. The current study examined the potential influence of testosterone and the ratio of testosterone to estradiol as a potential contributor to depressed mood in the menopause transition. METHODS: Fifty non-depressed perimenopausal women ages 45-55 were recruited for this study. Once every 3 weeks, for a total of four times, the women completed the Centre for Epidemiological Studies-Depression (CES-D) scale for the measurement of depressive symptoms and provided a first-morning urine sample for the measurement of urinary testosterone as well as estrone-3-glucuronide (E1G), a urinary metabolite of estradiol. The week-to-week and mean effects of testosterone, E1G, and the testosterone/E1G ratio on CES-D score were examined. Self-reported sleep quality and vasomotor symptoms were also assessed at each of the four time points. RESULTS: Testosterone levels rose with increasing months since last menstrual period associated with testosterone levels (ß(SE) = 175.3(63.2), p = .006), though this effect was moderated by body mass index (p for the interaction = .001) such that overweight women showed a less pronounced increase over time. Past and current smokers also had higher testosterone levels compared to never smokers. Week-to-week testosterone/E1G ratio was positively associated with CES-D score (ß(SE) = 1.57(0.76), p = .041) but not sleep quality or vasomotor symptoms (ps > .05). Mean testosterone/E1G ratio was also positively associated with vasomotor symptom bother (ß(SE) = 0.14(0.06), p = .018) and poorer sleep quality (ß(SE) = - 0.34(0.09), p = .0001). CONCLUSION: These results suggest that, within the context of the menopause transition, times that are characterized by a higher testosterone-to-estradiol ratio may be associated with higher depressive symptoms. Perimenopausal women with a higher average ratio of testosterone relative to estradiol may also experience more sleep difficulties and vasomotor symptom bother.

Mood sensitivity to estradiol predicts depressive symptoms in the menopause transition.

BACKGROUND: The risk for depression markedly rises during the 5-6 years leading up to the cessation of menstruation, known as the menopause transition. Exposure to extreme estradiol levels may help explain this increase but few studies have examined individual sensitivity to estradiol in predicting perimenopausal depression. METHOD: The current study recruited 101 perimenopausal women. During Phase 1, we quantified each woman's sensitivity to changes in estradiol using 12 weekly measures of estrone-3-glucuronide (E1G), a urinary metabolite of estradiol, and concurrent depressive symptoms. The weekly cortisol awakening response was measured to examine the hypothalamic-pituitary-adrenal (HPA) axis in mediating mood sensitivity to estradiol. In Phase 2, depressive symptoms and major depression diagnoses were assessed monthly for 9 months. The relationship between Phase 1 E1G sensitivity and Phase 2 depressive symptoms and major depressive episodes was examined. Several baseline characteristics were examined as potential moderators of this relationship. RESULTS: The within-person correlation between weekly E1G and mood varied greatly from woman to woman, both in strength and direction. Phase 1 E1G mood sensitivity predicted the occurrence of clinically significant depressive symptoms in Phase 2 among certain subsets of women: those without a prior history of depression, reporting a low number of baseline stressful life events, and reporting fewer months since their last menstrual period. HPA axis sensitivity to estradiol fluctuation did not predict Phase 2 outcomes. CONCLUSION: Mood sensitivity to estradiol predicts risk for perimenopausal depression, particularly among women who are otherwise at low risk and among those who are early in the transition.

Estradiol Fluctuation, Sensitivity to Stress, and Depressive Symptoms in the Menopause Transition: A Pilot Study.

The menopause transition is associated with an increased risk of depressed mood. Preliminary evidence suggests that increased sensitivity to psychosocial stress, triggered by exaggerated perimenopausal estradiol fluctuation, may play a role. However, accurately quantifying estradiol fluctuation while minimizing participant burden has posed a methodological challenge in the field. The current pilot project aimed to test the feasibility of capturing perimenopausal estradiol fluctuation via 12 weekly measurements of estrone-3-glucuronide (E1G), a urinary metabolite of estradiol, using participant-collected urine samples in 15 euthymic perimenopausal women ages 45-55 years. Furthermore, it aimed to correlate E1G fluctuation (standard deviation across the 12 E1G measurements) with weekly mood and cardiovascular, salivary cortisol, and subjective emotional responses to the Trier Social Stress Test (TSST) at weeks 4, 8, and 12. Protocol acceptability and adherence was high; furthermore, E1G fluctuation was positively associated with anhedonic depressive symptoms and weekly negative affect. E1G fluctuation was also associated with increased heart rate throughout the TSST as well as higher levels of rejection, anger, and sadness. E1G fluctuation was not significantly associated with TSST blood pressure or cortisol levels. This study suggests a feasible method of assessing estradiol fluctuation in the menopause transition and provides support for the hypothesis that perimenopausal estradiol fluctuation increases sensitivity to psychosocial stress and vulnerability to depressed mood.

What's in a line? Verbal, facial, and emotional influences on the line bisection task.

In Bryden and MacRae's [(1988). Dichotic laterality effects obtained with emotional words. Neuropsychiatry, Neuropsychology, and Behavioral Neurology, 1(3), 171-176] dichotic listening task, attending to verbal (left hemisphere) or emotional (right hemisphere) auditory stimuli can result in opposite patterns of behaviour. We examined whether performance on the line bisection task might also be influenced in opposite ways by left- and right-lateralized functions. The line bisection task is a simple and effective measure of visuospatial bias. Pseudoneglect, a leftward bias, is typically found on this task, and appears to result from right hemisphere dominance for spatial processing. We investigated how emotion, verbal, and facial processing impacted line bisection performance, while also examining the influence of hand-use. Line type (face, word, and solid), valence (positive, negative, and neutral), and hand-use (left, right, and both) were manipulated. Results indicated that face and word lines decreased and increased the extent of pseudoneglect, respectively, and that valence accentuated these results. These results were in the opposite direction from our predictions. Hand-use had little influence. We discuss the impact that visual scanning, and local and global processing, may have had on line bisection performance. Until future research clarifies how lateralized functions affect line bisections, we suggest caution in adapting the line bisection task as a general measure of relative hemispheric activation.

The relationship between line bisection performance and emotion processing: Where do you draw the line?

A recent study demonstrated that higher accuracy on a line bisection task related to greater ratings of evocative impact from paintings. The authors suggested that line bisection accuracy may act as a "barometer" for both visuospatial and emotion processing, likely as a function of overlapping neural correlates in the right temporoparietal region. We suggest and test an alternative explanation: that visuospatial bias interacted with asymmetries in the paintings and the rating scales to produce the apparent relationship between emotion and visuospatial functions. In the present study, using both visual-analogue and numeric rating scales, the relationship between line bisection performance and ratings of paintings (evocative impact, aesthetics, novelty, technique, and closure) was examined in a young adult sample. We demonstrate that left-hand line bisection bias direction, not line bisection accuracy, is related to most ratings, and that line bisection bias interacts with stimulus orientation (non-mirrored/mirrored) and rating scale direction (ascending/descending) in such a way that can explain the results of the previous study. We conclude that the line bisection task appears to be a sensitive measure of visuospatial attentional biases, which can influence ratings of asymmetrical paintings, and may affect how individuals perceive stimuli in their environment.

The relationship between collisions and pseudoneglect: is it right?

When walking through narrow doorways people collide more frequently on the right side than on the left. This rightward collision bias has been attributed to pseudoneglect. Originally pseudoneglect was defined as leftward errors on a line bisection task; however, the term is used more broadly now to refer to the slight tendency to neglect the right side of space and attend more towards the left. Thus, rightward collisions are said to occur because the right side is neglected. In the present experiments, we examined this pseudoneglect hypothesis by assessing the influence of three factors (age, cuing, and motor activity) known to affect performance on traditional measures of pseudoneglect, such as line bisection tasks. Navigation and line bisection tasks were completed by younger and older adults performing a concurrent motor task (Experiment 1) and by younger adults performing no concurrent motor task (Experiment 2). In both experiments, attention was cued to the left, right, or both sides of space, or was uncued. In contrast to previous reports, in both experiments we found a leftward collision bias on the navigation task; this bias was relatively unaffected by age or cuing manipulations, and was attenuated by concurrent motor activity. In addition, we found no relation between performance on the navigation and line-bisection tasks, indicating that the leftward bias on the navigation task cannot be attributed to pseudoneglect. We provide alternative hypotheses that may explain differences between our results and those observed in others' studies.

Men are more accurate than women in aiming at targets in both near space and extrapersonal space.

Men excel at motor tasks requiring aiming accuracy whereas women excel at different tasks requiring fine motor skill. However, these tasks are confounded with proximity to the body, as fine motor tasks are performed proximally and aiming tasks are directed at distal targets. As such, it is not known whether the male advantage on tasks requiring aiming accuracy is because men have better aim or is better in the proximal domain in which the task is usually presented. 18 men (M age = 20.6 yr., SD = 3.0) and 20 women (M age = 18.7 yr., SD = 0.9) performed 2 tasks of extrapersonal aiming accuracy (>2 m away), 2 tasks of aiming accuracy performed in near space (< 1 m from them), and a task of fine motor skill. Men outperformed women on both the extrapersonal aiming tasks, and women outperformed men on the task of fine motor skill. However, a male advantage was observed for one of the aiming tasks performed in near space, suggesting that the male advantage for aiming accuracy does not result from proximity.