ABSTRACT
Background: Women carrying the APOE4 allele are at greater risk of developing Alzheimer's disease (AD) from ages 65-75 years compared to men. To better understand the elevated risk conferred by APOE4 carrier status among midlife women, we investigated the separate and interactive associations of endogenous estrogens, plasma AD biomarkers, and APOE4 carrier status on regional brain volumes in a sample of late midlife postmenopausal women. Methods: Participants were enrolled in MsBrain, a cohort study of postmenopausal women (n = 171, mean age = 59.4 years, mean MoCA score = 26.9; race = 83.2% white, APOE4 carriers = 40). Serum estrone (E1) and estradiol (E2) levels were assessed using liquid chromatography-tandem mass spectrometry. APOE genotype was determined using TaqMan SNP genotyping assays. Plasma AD biomarkers were measured using single molecule array technology. Cortical volume was measured and segmented by FreeSurfer software using individual T1w MPRAGE images. Multiple linear regression models were conducted to determine whether separate and interactive associations between endogenous estrogen levels, plasma AD biomarkers (Aß42/Aß40, Aß42/p-tau181), and APOE4 carrier status predict regional brain volume (21 regions per hemisphere, selected a priori); and, whether significant interactive associations between estrogens and AD biomarkers on brain volume differed by APOE4 carrier status. Results: There was no main effect of APOE4 carrier status on regional brain volumes, endogenous estrogen levels, or plasma AD biomarkers. Estrogens did not associate with regional brain volumes, except for positive associations with left caudal middle frontal gyrus and fusiform volumes. The interactive association of estrogens and APOE4 carrier status on brain volume was not significant for any region. The interactive association of estrogens and plasma AD biomarkers predicted brain volume of several regions. Higher E1 and E2 were more strongly associated with greater regional brain volumes among women with a poorer AD biomarker profile (lower Aß42/40, lower Aß42/p-tau181 ratios). In APOE4-stratified analyses, these interactions were driven by non-APOE4 carriers. Conclusion: We demonstrate that the brain volumes of postmenopausal women with poorer AD biomarker profiles benefit most from higher endogenous estrogen levels. These findings are driven by non-APOE4 carriers, suggesting that APOE4 carriers may be insensitive to the favorable effects of estrogens on brain volume in the postmenopause.
ABSTRACT
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.
ABSTRACT
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.
