Menopause Status and Within-Group Differences in Chronological Age Affect the Functional Neural Correlates of Spatial Context Memory in Middle-Aged Females.

Reductions in the ability to encode and retrieve past experiences in rich spatial contextual detail (episodic memory) are apparent by midlife-a time when most females experience spontaneous menopause. Yet, little is known about how menopause status affects episodic memory-related brain activity at encoding and retrieval in middle-aged premenopausal and postmenopausal females, and whether any observed group differences in brain activity and memory performance correlate with chronological age within group. We conducted an event-related task fMRI study of episodic memory for spatial context to address this knowledge gap. Multivariate behavioral partial least squares was used to investigate how chronological age and retrieval accuracy correlated with brain activity in 31 premenopausal females (age range, 39.55-53.30 years; mean age, 44.28 years; SD age, 3.12 years) and 41 postmenopausal females (age range, 46.70-65.14 years; mean age, 57.56 years; SD age, 3.93 years). We found that postmenopausal status, and advanced age within postmenopause, was associated with lower spatial context memory. The fMRI analysis showed that only in postmenopausal females, advanced age was correlated with decreased activity in occipitotemporal, parahippocampal, and inferior parietal cortices during encoding and retrieval, and poorer spatial context memory performance. In contrast, only premenopausal females exhibited an overlap in encoding and retrieval activity in angular gyrus, midline cortical regions, and prefrontal cortex, which correlated with better spatial context retrieval accuracy. These results highlight how menopause status and chronological age, nested within menopause group, affect episodic memory and its neural correlates at midlife.SIGNIFICANCE STATEMENT This is the first fMRI study to examine how premenopause and postmenopause status affect the neural correlates of episodic memory encoding and retrieval, and how chronological age contributes to any observed group similarities and differences. We found that both menopause status (endocrine age) and chronological age affect spatial context memory and its neural correlates. Menopause status directly affected the direction of age-related and performance-related correlations with brain activity in inferior parietal, parahippocampal, and occipitotemporal cortices across encoding and retrieval. Moreover, we found that only premenopausal females exhibited cortical reinstatement of encoding-related activity in midline cortical, prefrontal, and angular gyrus, at retrieval. This suggests that spatial context memory abilities may rely on distinct brain systems at premenopause compared with postmenopause.

Hormonal contraception and cognition: Considering the influence of endogenous ovarian hormones and genes for clinical translation.

Despite the well-known influence of ovarian hormones on the brain and widespread use of hormonal contraception (HC) since the 1960s, our knowledge of HC's cognitive effects remains limited. To date, the cognitive findings have been inconsistent. In order to establish what might make HC studies more consistent, we surveyed the literature on HCs and cognition to determine whether studies considered HC formulation, phase, pharmacokinetics, duration, and gene interactions, and assessed whether oversight of these factors might contribute to variable findings. We found that synthetic HC hormones exert dose-dependent effects, the day of oral contraceptive (Pill) ingestion is critical for understanding cognitive changes, and gene-cognition relationships differ in women taking the Pill likely due to suppressed endogenous hormones. When these factors were overlooked, results were not consistent. We close with recommendations for research more likely to yield consistent findings and be therefore, translatable.

Review of the effects of polycystic ovary syndrome on Cognition: Looking beyond the androgen hypothesis.

Polycystic-ovary syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive age, and many features associated with PCOS - such as elevated androgens, insulin resistance and inflammation - are known to affect cognition. However, effects of PCOS on cognition are not well-understood. Here we review the current literature on PCOS and cognition, note the extent of PCOS symptomatology studied in relation to cognitive outcomes, and identify key research gaps and common methodological concerns. Findings indicate a pattern of worse performance across cognitive domains and brain measures in women with PCOS relative to non-PCOS controls, as well as a lack of evidence for the common assumption that women with PCOS will have higher performance on tasks with a demonstrated male-advantage due to high testosterone levels. We suggest strategies for moving beyond the focus on elevated androgens, in favor of research practices that account for the nuances and heterogeneity of PCOS symptoms.

How Canadian Law Shapes the Health Care Experiences of Women with Female Genital Mutilation/Cutting/Circumcision and Their Providers: A Disjuncture Between Expectation and Actuality.

This study explored how the reproductive health care experiences of women with female genital mutilation/cutting/circumcision (FGC) were shaped. We used Institutional Ethnography, a sociological approach which allows for the study of social relations and the coordination of health care. From qualitatively interviewing eight women with FGC, we learned that they felt excluded within the Canadian health care system because they were unable to access reconstructive surgery, which was not covered by Ontario's universal health coverage (Ontario Health Insurance Plan). We then talked with seven obstetricians/gynecologists (OB/GYNs) and learned that while it was legal to perform certain genital (e.g., female genital cosmetic surgery) and reproductive (e.g., elective caesarean section) surgeries commonly requested by Western-born women, it was not legal for them to perform other genital surgeries often requested by immigrant populations (e.g., reinfibulation), nor were these covered by OHIP (e.g., clitoral reconstructive surgery). From participants' comparison of clitoral reconstructive surgery and reinfibulation to female genital cosmetic and gender confirming surgeries, it became clear that the law and policies within the health care system favored surgeries elected by Western adults over those wished for by women with FGC. We found that the law had an impact on the choices that OB/GYNs and the women they treated could make, shaping their respective experiences. This created ethical dilemmas for OB/GYNs and a sense of exclusion from the health care system for women with FGC.

Sex and gender differences in cognitive and brain reserve: Implications for Alzheimer's disease in women.

Women represent ⅔ of the cases of Alzheimer's disease (AD). Current research has focused on differential risks to explain higher rates of AD in women. However, factors that reduce risk for AD, like cognitive/brain reserve, are less well explored. We asked: what is known about sex and gender differences in how reserve mitigates risk for AD? We conducted a narrative review of the literature, with keywords: "sex/gender differences", "cognitive/brain reserve", "Alzheimer's Disease", and the following cognitive reserve contributors: "education", "IQ", "occupation", "cognitive stimulation", "bilingualism", "socioeconomic status", "physical activity", "social support". Sixteen papers disaggregated their data by sex. Those papers observed sex and gender differences in reserve contributors. There is also evidence that greater reserve may be more beneficial in lowering AD risk in women, although more research is needed. We discuss how traditional reserve contributors are gendered and may not capture factors that support cognition in aging women.

Intersectional inequalities in younger women's experiences of physical intimate partner violence across communities in Bangladesh.

BACKGROUND: Physical intimate partner violence (IPV) risk looms large for younger women in Bangladesh. We are, however, yet to know the association between their intersectional social locations and IPV across communities. Drawing on intersectionality theory's tenet that interacting systems of power, oppressions, and privileges work together, we hypothesized that (1) younger, lower educated or poor women's physical IPV experiences will be exacerbated in disadvantaged communities; and conversely, (2) younger, higher educated or nonpoor women's physical IPV experiences will be ameliorated in advantaged communities. METHODS: We applied intercategorical intersectionality analyses using multilevel logistic regression models in 15,421 currently married women across 911 communities from a national, cross-sectional survey in 2015. To test the hypotheses, women's probabilities of currently experiencing physical IPV among intersectional social groups were compared. These comparisons were made, at first, within each type of disadvantaged (e.g., younger or poor) and advantaged (e.g., older or nonpoor) communities; and then, between different types of communities. RESULTS: While our specific hypotheses were not supported, we found significant within community differences, suggesting that younger, lower educated or poor women were bearing the brunt of IPV in almost every community (probabilities ranged from 34.0-37.1%). Younger, poor compared to older, nonpoor women had significantly higher IPV probabilities (the minimum difference = 12.7, 95% CI, 2.8, 22.6) in all communities. Similar trend was observed between younger, lower educated compared to older, higher educated women in all except communities that were poor. Interestingly, younger women's advantage of higher education and material resources compared to their lower educated or poor counterparts was observed only in advantaged communities. However, these within community differences did not vary between disadvantaged and advantaged communities (difference-in-differences ranged from - 0.9%, (95% CI, - 8.5, 6.7) to - 8.6%, (95% CI, - 17.6, 0.5). CONCLUSIONS: Using intersectionality theory made visible the IPV precarity of younger, lower educated or poor women across communities. Future research might examine the structures and processes that put them at these precarious locations to ameliorate their socio-economic-educational inequalities and reduce IPV in all communities. For testing hypotheses using intersectionality theory, this study might advance scholarship on physical IPV in Bangladesh and quantitative intersectionality globally.

Explicit and Implicit Gender-Related Stereotyping in Transgender, Gender Expansive, and Cisgender Adults.

Little is known about gender-related stereotyping among transgender and gender expansive adults. Using the Ambivalent Sexism Inventory (AIS; Glick & Fiske, 1996), we examined explicit gender attitudes in 3298 cisgender, transgender, and gender expansive respondents designated female at birth (FAB; n = 1976 cisgender, n = 108 transgender, n = 188 gender expansive) and male at birth (MAB; n = 922 cisgender, n = 52 transgender, n = 52 gender expansive). In order to learn more about implicit gender-related stereotyping, a subset of 822 participants (FAB; n = 445 cisgender, n = 32 transgender, n = 51 gender expansive. MAB; n = 254 cisgender, n = 21 transgender, n = 19 gender expansive) completed the gender-leadership Implicit Association Test (IAT; Dasgupta & Asgari, 2004). Cisgender men scored significantly higher than all other groups on hostile sexism, but patterns of endorsement for benevolent sexism and implicit attitudes were more nuanced, with cisgender women and gender expansive FAB often scoring significantly below other groups. We observed that transgender men and transgender women, along with cisgender men and gender expansive MAB, moderately endorsed essentialist views regarding differences between men and women (i.e., complementary gender differentiation). These data reveal novel patterns of gender-related stereotyping, with some corresponding to sex designated at birth and others corresponding to current gender identification. Together, these findings suggest that one's experienced gender, designated sex at birth, and the intersection between them may relate to gender stereotyping, underscoring the importance of including transgender and gender expansive individuals in this research.

Perceived organizational support and emotional labour among police communicators: what can organizational context tell us about posttraumatic stress?

OBJECTIVE: As central members of the emergency response system, communicators are regularly exposed to potentially traumatic events and experience some of the highest rates of posttraumatic stress. Given elevated rates of distress, they are regularly called upon to manage emotions-their own and others'-during high-risk and high-stress situations, within a highly controlled organizational context. Emotional labour (EL) theory suggests that many individuals faced with this challenge utilize a strategy in which emotions are suppressed or faked (surface acting-SA) in keeping with organizational expectations. METHODS: This study was designed to examine the relationships among reported EL, perceived organizational support, job stress, and severity of posttraumatic stress among a population of communicators. RESULTS: Job pressure and perceived lack of organizational support were positively associated with posttraumatic stress. Although the highest reported levels of SA occurred when interacting with members of the public, this SA was not associated with posttraumatic stress, unlike SA with co-workers and supervisors. SA with co-workers and supervisors was further related to perceptions of lack of organizational support. CONCLUSION: Thus, an organization perceived as unsupportive may create a culture in which individuals are dissuaded from expressing true emotions with colleagues and supervisors, potentially magnifying the traumatic effects of exposure to critical incidents.

Emotional Health Work of Women With Female Genital Cutting Prior to Reproductive Health Care Encounters.

We used institutional ethnography to explore the social relations that shaped the reproductive health care experiences of women with female genital cutting. Interviews with eight women revealed that they engaged in discourse that opposed the practices of cutting female genitals as a human-rights violation. This discourse worked to protect those affected by the practices, but also stigmatized female genital cutting, making participants anticipate experiencing stigmatization during health care. Women's engagement in this discourse shaped their emotional health work to prepare for such encounters. This work included navigating feelings of worry, shame, and courage to understand what to expect during their own appointment; learning from family/friends' experiences; and seeking a clinic with the reputation of best care for women with female genital cutting. It is important to strive for more inclusive health care in which women do not have to engage in emotional health work to prepare for their clinical encounters.

Menopause, anti-Müllerian hormone and cognition in a cohort of women with persistent symptoms following TBI: a case for future research.

Objectives: Primary: To explore anti-Müllerian Hormone (AMH) levels in community dwelling women following TBI. Secondary: To explore the relation of AMH to menstrual cycle, cognition, distress and symptoms of menopause.Setting: Large adult TBI outpatient clinic in Toronto Canada.Research design: Prospective study of 10 women with persistent symptoms who were one or more years post TBI.Methods: Consenting participants provided a serum sample for AMH levels, and completed the Menopause Rating Scale (MRS), Symptom Checklist-90 r (SCL-90 r), Repeatable Battery for the Assessment of Neurological Status (RBANS) and a health questionnaire.Main outcomes and results: This study found lower than expected levels of AMH in 50% of participants relative to age matched norms and 50% of participants experienced new onset of menstrual changes. Also notable were findings of lower-than-expected cognitive scores in women over 35 and reports of menopause-related symptoms across all ages groups.Conclusions: As our understanding of the role of AMH grows, examining changes in this novel biomarker in the long-term post-TBI is warranted. Future research should be sufficiently powered to expand on and validate the study's findings.

Where boys don't dance, but women still thrive: using a development approach as a means of reconciling the right to health with the legitimization of cultural practices.

Human rights language has become a common method of internationally denouncing violent, discriminatory or otherwise harmful practices, notably by framing them as reprehensible violations of those fundamental rights we obtain by virtue of being human. While often effective, such women's rights discourse becomes delicate when used to challenge practices, which are of important cultural significance to the communities in which they are practiced. This paper analyses human rights language to challenge the gender disparity in access to health care and in overall health outcomes in certain countries where such disparities are influenced by important cultural values and practices. This paper will provide selected examples of machismo and marianismo discourses in certain Latin American countries on the one hand and of female genital cutting/excision (FGC/E) in practicing countries, both of which exposed to women's rights language, notably for causing violations of women's right to health. In essence, a reflective exercise is provided here with the argument that framing such discourses and practices as women's rights violations. Calling for their abandonment have shown that it may not only be ineffective nor at times appropriate, it also risks delegitimizing associated discourses, norms and practices thereby enhancing criticisms of the women's rights movement rather than adopting its principles. A sensitive community-based collaborative approach aimed at understanding and building cultural discourses to one, which promotes women's capabilities and health, is proposed as a more effective means at bridging cultural and gender gaps.

Considering sex as a biological variable in preclinical research.

In June 2015, the National Institutes of Health (NIH) released a Guide notice (NOT-OD-15-102) that highlighted the expectation of the NIH that the possible role of sex as a biologic variable be factored into research design, analyses, and reporting of vertebrate animal and human studies. Anticipating these guidelines, the NIH Office of Research on Women's Health, in October 2014, convened key stakeholders to discuss methods and techniques for integrating sex as a biologic variable in preclinical research. The workshop focused on practical methods, experimental design, and approaches to statistical analyses in the use of both male and female animals, cells, and tissues in preclinical research. Workshop participants also considered gender as a modifier of biology. This article builds on the workshop and is meant as a guide to preclinical investigators as they consider methods and techniques for inclusion of both sexes in preclinical research and is not intended to prescribe exhaustive/specific approaches for compliance with the new NIH policy.-Miller, L. R., Marks, C., Becker, J. B., Hurn, P. D., Chen, W.-J., Woodruff, T., McCarthy, M. M., Sohrabji, F., Schiebinger, L., Wetherington, C. L., Makris, S., Arnold, A. P., Einstein, G., Miller, V. M., Sandberg, K., Maier, S., Cornelison, T. L., Clayton, J. A. Considering sex as a biological variable in preclinical research.

Estrogens, inflammation and cognition.

The effects of estrogens are pleiotropic, affecting multiple bodily systems. Changes from the body's natural fluctuating levels of estrogens, through surgical removal of the ovaries, natural menopause, or the administration of exogenous estrogens to menopausal women have been independently linked to an altered immune profile, and changes to cognitive processes. Here, we propose that inflammation may mediate the relationship between low levels of estrogens and cognitive decline. In order to determine what is known about this connection, we review the literature on the cognitive effects of decreased estrogens due to oophorectomy or natural menopause, decreased estrogens' role on inflammation--both peripherally and in the brain--and the relationship between inflammation and cognition. While this review demonstrates that much is unknown about the intersection between estrogens, cognition, inflammation, we propose that there is an important interaction between these literatures.

Is immune system-related hypertension associated with ovarian hormone deficiency?

NEW FINDINGS: What is the topic of this review? This review summarizes recent data on the role of ovarian hormones and sex in inflammation-related hypertension. What advances does it highlight? The adaptive immune system has recently been implicated in the development of hypertension in males but not in females. The role of the immune system in the development of hypertension in women and its relationship to ovarian hormone production are highlighted. The immune system is known to contribute to the development of high blood pressure in males. However, the role of the immune system in the development of high blood pressure in females and the role of ovarian hormones has only recently begun to be studied. In animal studies, both the sex of the host and the T cell are critical biological determinants of susceptibility and resistance to hypertension induced by angiotensin II. In women, natural menopause is known to result in significant changes in the expression of genes regulating the immune system. Likewise, in animal models, ovariectomy results in hypertension and an upregulation in T-cell tumour necrosis factor-α-related genes. Oestrogen replacement results in decreases in inflammatory genes in the brain regions involved in blood pressure regulation. Together, these studies suggest that the response of the adaptive immune system to ovarian hormone deficiency is a significant contributor to hypertension in women.

The hermunculus: what is known about the representation of the female body in the brain?

The representation of the body in the brain, the homunculus, was posited by Wilder Penfield based on his studies of patients with intractable epilepsy. While he mapped both male and female patients, Penfield reports little about the females. The now iconic illustration of the map is clearly male with testicles, penis, and no breasts. In order to bring attention to this omission and to stimulate studies of female somatosensory cortex (SS), we discuss what is known about the map of the female body in the brain, including Penfield's findings in his female patients and subsequent work by others exploring the human female SS. We reveal that there is much we do not know about how the entire female body is represented in the brain or how it might change with different reproductive life stages, hormones, and experiences. Understanding what is and is not currently known about the female SS is a first step toward fully understanding neurological and physiological sex differences, as well as producing better-informed treatments for pain conditions related to mastectomy, hysterectomy, vulvodynia, and fibromyalgia. We suggest that the time is ripe for a full mapping of the female brain with the production of a hermunculus.

The double-edged sword of PCOS and gender: exploring gender-diverse experiences of polycystic ovary syndrome.

Background: Past research on polycystic ovary syndrome (PCOS), a chronic endocrine condition, has focused on the experiences of cisgender women. Aims: The purpose of the present study was to address the knowledge gap about gender-diverse individuals by exploring their lived experiences with PCOS and to better understand if and how their gender identity affected their experience of PCOS. Methods: To explore this, we recruited nine non-binary people and one transgender man with a PCOS diagnosis for qualitative interviews. Results: Three overarching themes emerged: PCOS as a burden, PCOS as an occasion, and PCOS as a benefit. While some aspects of PCOS created an additional burden for our participants, other symptoms such as excess body and facial hair could be empowering and affirming, revealing a positive aspect of this chronic condition. Conclusion: This study is the first to describe the lived experiences of gender-diverse individuals with PCOS, uncovering burdens as well as some benefits. Future research in this population may reveal not only the particulars of what PCOS is like for them but also more generalizable insights into the highly gendered perception and treatment of PCOS.

Gray matter volume in women with the BRCA mutation with and without ovarian removal: evidence for increased risk of late-life Alzheimer's disease or dementia.

OBJECTIVE: Ovarian removal prior to spontaneous/natural menopause (SM) is associated with increased risk of late life dementias including Alzheimer's disease. This increased risk may be related to the sudden and early loss of endogenous estradiol. Women with breast cancer gene mutations (BRCAm) are counseled to undergo oophorectomy prior to SM to significantly reduce their risk of developing breast, ovarian, and cervical cancers. There is limited evidence of the neurological effects of ovarian removal prior to the age of SM showing women without the BRCAm had cortical thinning in medial temporal lobe structures. A second study in women with BRCAm and bilateral salpingo-oophorectomy (BSO) noted changes in cognition. METHODS: The present, cross-sectional study examined whole-brain differences in gray matter (GM) volume using high-resolution, quantitative magnetic resonance imaging in women with BRCAm and intact ovaries (BRCA-preBSO [study cohort with BRCA mutation prior to oophorectomy]; n = 9) and after surgery with (BSO + estradiol-based therapy [ERT]; n = 10) and without (BSO; n = 10) postsurgical estradiol hormone therapy compared with age-matched women (age-matched controls; n = 10) with their ovaries. RESULTS: The BRCA-preBSO and BSO groups showed significantly lower GM volume in the left medial temporal and frontal lobe structures. BSO + ERT exhibited few areas of lower GM volume compared with age-matched controls. Novel to this study, we also observed that all three BRCAm groups exhibited significantly higher GM volume compared with age-matched controls, suggesting continued plasticity. CONCLUSIONS: The present study provides evidence, through lower GM volume, to support both the possibility that the BRCAm, alone, and early life BSO may play a role in increasing the risk for late-life dementia. At least for BRCAm with BSO, postsurgical ERT seems to ameliorate GM losses.

Associations Between Age at Menopause, Vascular Risk, and 3-Year Cognitive Change in the Canadian Longitudinal Study on Aging.

BACKGROUND AND OBJECTIVES: Mounting evidence supports sex differences in Alzheimer disease (AD) risk. Vascular and hormonal factors may together contribute to AD risk in female adults. We investigated whether age at menopause, vascular risk, and history of hormone therapy (HT) containing estrogens together influence cognition over a 3-year follow-up period. We hypothesized that earlier menopause and elevated vascular risk would have a synergistic association with lower cognitive scores at follow-up and that HT containing estrogens would attenuate this synergistic association to preserve cognition. METHODS: We used data from postmenopausal female participants and age-matched male participants in the Canadian Longitudinal Study on Aging. Vascular risk was calculated using a summary score of elevated blood pressure, antihypertensive medications, elevated low-density lipoprotein cholesterol, diabetes, smoking, and obesity. Cognition was measured with a global cognitive composite at baseline and 3-year follow-up. Linear models tested independent and interactive associations of age at menopause, vascular risk, and HT history with cognition at 3-year follow-up, adjusting for baseline cognition, baseline age, years of education, and test language (English/French). RESULTS: We included 8,360 postmenopausal female participants (mean age at baseline = 65.0 ± 8.53 years, mean age at menopause = 50.1 ± 4.62 years) and 8,360 age-matched male participants for comparison. There was an interaction between age at menopause and vascular risk, such that earlier menopause and higher vascular risk were synergistically associated with lower cognitive scores at follow-up (ß = 0.013, 95% CI 0.001-0.025, p = 0.03). In stratified analyses, vascular risk was associated with lower cognitive scores in female participants with earlier menopause (menopausal ages 35-48 years; ß = -0.044, 95% CI -0.066 to -0.022, p < 0.001), but not average (ages 49-52 years; ß = -0.007, 95% CI -0.027 to 0.012, p = 0.46) or later menopause (ages 53-65 years; ß = 0.003, 95% CI -0.020 to 0.025, p = 0.82). The negative association of vascular risk with cognition in female participants with earlier menopause was stronger than the equivalent association in age-matched male participants. HT history did not further modify the synergistic association of age at menopause and vascular risk with follow-up cognition (ß = -0.005, 95% CI -0.032 to 0.021, p = 0.69). DISCUSSION: Endocrine and vascular processes may synergistically contribute to increased risk of cognitive decline in female adults. These findings have implications for the development of sex-specific dementia prevention strategies.