The role of estrogen receptor gene polymorphisms in menopausal symptoms and estradiol levels in perimenopausal women - Findings from the Swiss Perimenopause Study.

OBJECTIVES: Fluctuating estradiol (E2) levels seem to be associated with menopausal symptoms, though not all women suffer from these symptoms to the same extent despite experiencing these hormonal changes. This suggests underlying, interindividual mechanisms, such as single-nucleotide polymorphisms (SNPs) influencing estrogen receptors α and ß, and the g-protein-coupled estrogen receptor (GPER). As research is scarce, we aimed to address this research gap by assessing genetic traits, E2 levels, and menopausal symptoms longitudinally. STUDY DESIGN: 129 perimenopausal women (aged 40-56 years) participated in the 13-month longitudinal Swiss Perimenopause Study. MAIN OUTCOME MEASURES: Menopausal symptoms were assessed fortnightly using the Menopause Rating Scale (MRS II). Salivary E2 levels were assessed 14 times over two non-consecutive months. Blood samples were collected using the dried blood spot (DBS) technique to analyze ESR1 rs2234693, ESR1 rs9340799, ESR2 rs1256049, ESR2 rs4906938, and GPER rs3808350. Group-based trajectory modeling was performed to identify interindividual trajectories of menopausal symptoms. Multinomial logistic regression models were employed to identify factors associated with these trajectories. RESULTS: Four distinct trajectory groups of menopausal symptoms were identified (increase, moderate, rebound, decrease). ER gene polymorphisms and E2 fluctuation were significantly associated with group membership. Furthermore, ER gene polymorphisms modulated the effect of E2 fluctuations on menopausal symptom trajectory. CONCLUSIONS: This study illuminates the multifaceted factors contributing to the individuality of the perimenopausal experience. ER gene polymorphisms emerged as integral factors by modulating the effect of E2 fluctuations on menopausal symptom trajectory. This underscores the intricate interplay of genetic factors, E2 fluctuations, and menopausal symptoms during perimenopause.

Estradiol and progesterone as resilience markers? - Findings from the Swiss Perimenopause Study.

While resilience seems to be associated with a variety of biological markers, studies assessing such correlates in women during the perimenopause are lacking. The perimenopause constitutes a phase of major biopsychosocial changes, during which the sex hormones estradiol (E2) and progesterone (P4) eventually decrease significantly. The aim of this study was to examine the extent to which the declining levels of E2 and P4 serve as resilience markers in perimenopausal women. In 129 healthy perimenopausal women aged 40-56 years, saliva samples were collected on every fourth day over a period of four weeks in order to investigate E2 and P4 levels. All participants completed psychosocial questionnaires including variables related to resilience, well-being, and mental health. Perimenopausal status was determined using the Stages of Reproductive Aging Workshop (STRAW) criteria. The results indicate that P4 is linked to psychosocial resilience. More precisely, women with higher P4 levels seem to be more resilient than women with lower P4 levels, irrespective of the perimenopausal status. No such relation was found for E2 levels. Further analyses revealed that women with higher P4 levels experience significantly higher life satisfaction, lower perceived stress, and lower depressive symptoms than women with lower P4 levels. Accordingly, P4 can be considered as a biological marker of resilience in perimenopause.

Biopsychosocial predictors of depressive symptoms in the perimenopause-findings from the Swiss Perimenopause Study.

OBJECTIVE: The perimenopause is associated with increased hormone fluctuations and an elevated risk of depression. A number of predictors of depressive symptoms in the menopausal transition have previously been suggested. The purpose of this study was to investigate a set of biopsychosocial predictors of depressive symptoms in perimenopausal women. METHODS: This cross-sectional study, investigating 114 perimenopausal women (according to the STRAW criteria) aged 40-56 years, was conducted within the scope of the Swiss Perimenopause Study. Multiple regression analyses were performed to identify the most accurate model predicting perimenopausal depressive symptoms. Depressive symptoms were assessed with the German version of the Center of Epidemiologic Studies Depression Scale (CES-D). Validated questionnaires were used to examine psychophysiological complaints, stress, self-esteem, self-compassion, body image, and social support. Estradiol (E2) and progesterone (P4) were assessed through saliva samples, and follicle-stimulating hormone and luteinizing hormone were determined through dried blood spot samples. Seven saliva samples per participant were used to investigate absolute levels and fluctuations of sex steroids. All other variables were measured once. RESULTS: Multiple regression analyses revealed that E2 fluctuations (ß=0.15, P = 0.015), history of depression (ß=0.14, P = 0.033), menopausal symptoms (ß=0.47, P < 0.0001), perceived stress (ß=0.17, P = 0.014), body image (ß= -0.25, P = 0.014) and self-esteem (ß=-0.35, P < 0.0001) were predictive of perimenopausal depressive symptoms (R2 = 0.60). P4 fluctuations and absolute levels of hypothalamic-pituitary-gonadal hormone were not statistically significant. CONCLUSIONS: E2 fluctuations were shown to be predictive of depressive symptoms in the perimenopause. Moreover, the presence of burdensome complaints and chronic stress as well as a poor self-evaluation seem to promote depressive symptoms in perimenopausal women.

Differential ESR1 Promoter Methylation in the Peripheral Blood-Findings from the Women 40+ Healthy Aging Study.

Background Estrogen receptor α (ERα) contributes to maintaining biological processes preserving health during aging. DNA methylation changes of ERα gene (ESR1) were established as playing a direct role in the regulation of ERα levels. In this study, we hypothesized decreased DNA methylation of ESR1 associated with postmenopause, lower estradiol (E2) levels, and increased age among healthy middle-aged and older women. Methods We assessed DNA methylation of ESR1 promoter region from dried blood spots (DBSs) and E2 from saliva samples in 130 healthy women aged 40-73 years. Results We found that postmenopause and lower E2 levels were associated with lower DNA methylation of a distal regulatory region, but not with DNA methylation of proximal promoters. Conclusion Our results indicate that decreased methylation of ESR1 cytosine-phosphate-guanine island (CpGI) shore may be associated with conditions of lower E2 in older healthy women.

Assessment of perimenopausal depression: A review.

BACKGROUND: Within the female life cycle, the perimenopause is considered as a critical period for the development of depression. Prevalence rates are particularly high during this phase. Perimenopausal depression is characterized by affective symptoms as well as menopause-specific somatic complaints. Currently, a variety of questionnaires are used to assess mood during the perimenopause. The aim of this review is to determine the instruments employed to assess perimenopausal depression. METHODS: We searched the databases PubMed, Cochrane Library and PsycINFO for human studies investigating perimenopausal depression, and subsequently screened for the assessment instruments used to measure mood and menopause. A total of 37 articles were included. RESULTS: Altogether, 14 different instruments were applied to assess mood during menopause. The CES-D was by far the most frequently used depression scale, appearing in 16 out of the 37 studies. The methods used to identify perimenopausal status and symptoms were inconsistent. LIMITATIONS: Due to lacking information about data and methodology, a selection bias is conceivable. Additionally, a publication bias is possible. Finally, there is inevitable subjectivity in the screening process of a systematic search. CONCLUSIONS: The assessment of depression in the menopausal transition is highly heterogeneous, reducing the overall comparability of study results. Furthermore, menopausal complaints are not sufficiently taken into account. Accordingly, the use of a menopause-specific depression scale is highly recommended in order to account for physical and mood-related symptoms in the menopausal transition.