BACKGROUND: Subgingival dental plaque is an ecosystem playing a key role in supporting both oral health and systemic health. Menopause-related changes have the potential to disrupt its balance, which is crucial to postmenopausal well-being. Our study explored how circulating estradiol levels correlate with subgingival microbial composition using checkerboard DNA-DNA hybridization in premenopausal and postmenopausal women. We also demonstrated that combining this method with 16S ribosomal RNA (rRNA) sequencing insights remains valuable for examining subgingival ecology.
METHODS: We assessed 40 bacterial species in 77 premenopausal and 81 postmenopausal women using checkerboard DNA-DNA hybridization and measured serum estradiol with enzyme-linked immunosorbent assay (ELISA). Women were categorized by subgingival dysbiosis severity using a modified Subgingival Microbial Dysbiosis Index (mSMDI). Six women from each normobiotic and dysbiotic subgroup across premenopausal and postmenopausal women underwent 16S rRNA sequencing analysis.
RESULTS: DNA checkerboard analysis revealed that most observed variability in individual bacterial proportions is associated with periodontitis. Two species, Leptotrichia buccalis and Streptococcus constellatus, exhibited differences related to estradiol levels within the premenopausal group (p = 0.055 and p = 0.009, respectively). 16S rRNA sequencing confirmed the mSMDI\'s validity in categorizing normobiotic and dysbiotic states. Menopausal status was not associated with a dysbiotic shift in the subgingival microbiome despite significantly more attachment loss in postmenopausal compared to premenopausal women.
CONCLUSIONS: Our results indicate that decreased estradiol levels or increased attachment loss during menopause are not associated with changes in species abundance or dysbiotic shifts in women. The mSMDI may be a useful tool for classifying subgingival ecology based on its normobiotic or dysbiotic inclination.

BACKGROUND: Women experiencing problematic menopausal symptoms report lower health-related quality of life and greater healthcare use than women without symptoms. Not all women want to or are able to take hormone replacement therapy. Strengthening the evidence for menopause symptom-management options, including physical activity, improves agency for women.
OBJECTIVE: This overview assesses effectiveness of physical activity and exercise interventions targeting women experiencing menopause symptoms.
METHODS: Medline, Embase, CINAHL, Scopus, The Cochrane Database of Systematic Reviews and Social Science Citation Index were searched (June 2023) for systematic reviews of physical activity and exercise interventions targeting women experiencing menopause. Reviews were assessed using AMSTAR-2 and a best-evidence approach to synthesis without meta-analysis (SWIM) was adopted. The protocol was registered on PROSPERO (CRD42022298908).
RESULTS: Seventeen reviews included 80 unique relevant primary studies with 8983 participants. There is evidence showing improvement of physical, urogenital, and total symptoms following yoga interventions. Evidence for vasomotor and psychological symptoms was inconclusive. Findings for aerobic exercise were inconclusive although there were some examples of beneficial effects on total and vasomotor symptoms. Evidence was very limited for other types of physical activity and impact on physical, sexual and urogenital symptoms.
CONCLUSIONS: There is some evidence that yoga, and to lesser extent, aerobic exercise may be beneficial for some menopause symptoms, but there is insufficient evidence to recommend a particular form of exercise. Current reviews categorise women on menopause status; broadening this to include ethnicity, income status, employment and other factors will allow better understanding of context for successful interventions.

OBJECTIVE: Breast cancer patients experience symptoms and side effects from multimodal treatments, which often include menopausal symptoms resulting from cytotoxic chemotherapy or estrogen suppression therapy. This study aimed to explore the symptom network and clusters and its relationship to quality of life (QoL) in breast cancer patients who receive multimodal cancer treatment and experience treatment-related menopausal symptoms.
METHODS: A correlational study was conducted. Breast cancer patients receiving multimodal cancer treatment and experiencing treatment-related menopausal symptoms were included while they were receiving radiation therapy (N = 250). Symptoms, functions and QoL were assessed using the EORTC QLQ-C30 and BR45. Network analysis, principal component analysis, exploratory factor analysis, and multiple linear regression analysis were conducted.
RESULTS: Fatigue was the most central symptom in the symptom-only network as well as in the network consisting of symptoms and QoL. Fatigue, systemic therapy side effects, appetite loss, and cognitive symptoms demonstrated significant associations with QoL. The cancer and treatment related symptom cluster consisted of fatigue, cognitive symptoms, emotional symptoms and systemic therapy side effects. Breast cancer therapy-specific symptoms, such as arm symptoms, skin mucosis symptoms, and breast symptoms, formed a cluster with pain.
CONCLUSIONS: Fatigue was the most central symptom in breast cancer patients receiving multimodal cancer treatment and experiencing menopausal symptoms. Evaluation of fatigue and providing interventions to manage fatigue would contribute to improvement of QoL of breast cancer patients receiving multimodal cancer treatments. Future network analysis and symptom cluster studies should specify the population of interest and the treatment phase using comprehensive symptom evaluation tools.

Postmenopausal osteoporosis, characterized by an imbalance between osteoclast-mediated bone resorption and osteoblast-driven bone formation, presents substantial health implications. In this study, we investigated the role of black goat extract (BGE), derived from a domesticated native Korean goat, estrogen-like activity, and osteoprotective effects in vitro. BGE\'s mineral and fatty acid compositions were analyzed via the ICP-AES method and gas chromatography-mass spectrometry, respectively. In vitro experiments were conducted using MCF-7 breast cancer cells, MC3T3-E1 osteoblasts, and RAW264.7 osteoclasts. BGE exhibits a favorable amount of mineral and fatty acid content. It displayed antimenopausal activity by stimulating MCF-7 cell proliferation and augmenting estrogen-related gene expression (ERα, ERβ, and pS2). Moreover, BGE positively impacted osteogenesis and mineralization in MC3T3-E1 cells through Wnt/β-catenin pathway modulation, leading to heightened expression of Runt-related transcription factor 2, osteoprotegerin, and collagen type 1. Significantly, BGE effectively suppressed osteoclastogenesis by curtailing osteoclast formation and activity in RAW264.7 cells, concurrently downregulating pivotal signaling molecules, including receptor activator of nuclear factor κ B and tumor necrosis factor receptor-associated factor 6. This study offers a shred of preliminary evidence for the prospective use of BGE as an effective postmenopausal osteoporosis treatment.

Existing hormone replacement therapy for menopause has drawbacks, necessitating new treatment agents. Silkworms have demonstrated estrogenic properties, offering promising alternatives. We assessed the therapeutic effects of freeze-dried silkworm powder (SWP) on menopausal symptoms using an ovariectomized (OVX) mouse model. The experimental design comprised a sham surgery group (Sham), an OVX control group, a low-dose SWP group post-OVX (80 mg/kg, OVX-SWP-L), a high-dose SWP group post-OVX (160 mg/kg, OVX-SWP-H), and an estradiol treatment group post-OVX (OVX-E2). Treatments were administered orally thrice weekly over eight weeks; body weight was monitored weekly. The SWP-treated groups (SWP-L and SWP-H) exhibited less weight gain and increased uterine thickness than the OVX control. Molecular analyses demonstrated that SWP significantly enhanced the phosphorylation of estrogen receptor alpha (ERα), ERK, and AKT. Furthermore, biochemical assays revealed reduced serum neutral lipids across all SWP treatment groups. Notably, HDL-cholesterol levels were significantly increased in the SWP-L group compared to the OVX group. Serum estradiol concentrations were elevated in all the SWP groups, with significant increases in the high-dose group. These findings indicate that SWP may promote the activation of estrogen receptor signaling and improve symptoms associated with estrogen deficiency during menopause.

Urinary tract infections (UTIs) are the most common bacterial infections in postmenopausal women, and women with diabetes are possibly at a higher risk. The aim of this study is to evaluate the potential benefit on the prevention of UTI episodes, assessed by urinalysis and urine culture (primary outcome) after two, four and six months, of daily oral dietary supplement (120 mg highly standardized cranberry extract phytosome), compared to placebo, in diabetic postmenopausal women taking SGLT-2 inhibitors. Forty-six subjects (mean age 72.45 ± 1.76) completed the study (23 placebo/23 supplement). Considering UTI episodes, during the six-month supplementation period, an increase of 1.321 (95% CI: -0.322; 2.9650) was observed in the placebo group, while it remained at a steady value of 0.393 (95% CI: -4.230; 5.016) in the supplemented group. Regarding UTI episodes, in both groups, interaction between times for supplementation was statistically significant (p = 0.001). In particular, at follow-up 4, 9% of the placebo group showed infection versus only 3% with cranberry supplementation. Glycaemia and glycated hemoglobin values (secondary outcomes) were not modified at the end of six months with respect to the basal values in both groups, as expected. While in terms of quality of life per the SF-12 health questionnaire, there were no differences between the two groups, an improvement in SF-12 quality of life was observed in both groups (six months vs. basal). In conclusion, highly standardized cranberry extract phytosome supplementation reduced UTI recurrence.

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BACKGROUND: DNA damage/repair gene variants are associated with both primary ovarian insufficiency (POI) and cancer risk.
OBJECTIVE: We hypothesized that a subset of women with POI and family members would have increased risk for cancer.
METHODS: Case-control population-based study using records from 1995-2022.
METHODS: Two major Utah academic healthcare systems serving 85% of the state.
METHODS: Women with POI (n=613) were identified using ICD codes and reviewed for accuracy. Relatives were linked using the Utah Population Database.
METHODS: Cancer diagnoses were identified using the Utah Cancer Registry.
METHODS: The relative risk of cancer in women with POI and relatives was estimated by comparison to population rates. Whole genome sequencing was performed on a subset of women.
RESULTS: Breast cancer was increased in women with POI (OR [95%CI] 2.20 [1.30, 3.47]; p=0.0023) and there was a nominally significant increase in ovarian cancer. Probands with POI were 36.5±4.3 years and 59.5±12.7 years when diagnosed with POI and cancer, respectively. Causal and candidate gene variants for cancer and POI were identified.Among second-degree relatives of these women, there was an increased risk of breast (1.28 [1.08, 1.52]; p=0.0078) and colon cancer (1.50 [1.14, 1.94]; p=0.0036). Prostate cancer was increased in first- (1.64 [1.18, 2.23]; p=0.0026), second- (1.54 [1.32, 1.79]; p<0.001), and third-degree relatives (1.33 [1.20, 1.48]; p<0.001).
CONCLUSIONS: Data suggest common genetic risk for POI and reproductive cancers. Tools are needed to predict cancer risk in women with POI and potentially to counsel about risks of hormone replacement therapy.

OBJECTIVE: To examine the prevalence of overactive bladder (OAB) according to menopausal stages in middle-aged women.
METHODS: Cross-sectional study.
METHODS: Total Healthcare Center in South Korea.
METHODS: Middle-aged Korean women (n=3469, mean age, 49.5 ± 2.9 years).
METHODS: Menopausal stages were defined according to the Stages of Reproductive Aging Workshop +10 criteria, and menopausal symptoms were assessed using the Korean version of Menopause-Specific Quality of Life (MENQOL). Logistic regression models were used to estimate prevalence ratios with 95% confidence intervals for OAB according to menopausal stage and to assess the associations with menopausal symptoms.
METHODS: OAB symptoms were evaluated using the Overactive Bladder Symptom Score (OABSS).
RESULTS: The prevalence of OAB increased with menopausal stage; however, the multivariable-adjusted prevalence ratios for women in menopausal transition and postmenopausal stage were insignificant (ptrend = 0.160) compared to those for premenopausal women. Among individual OAB symptoms, the multivariable-adjusted prevalence ratios for nocturia increased with menopausal stage in a dose-response manner (ptrend = 0.005 for 1 time/day; ptrend < 0.001 for ≥2 times/day). The association between menopausal stages and nocturia occurring ≥2 times/day was evident in women without OAB and with relatively high MENQOL scores, vasomotor symptoms and difficulty sleeping.
CONCLUSIONS: The prevalence of OAB, particularly nocturia, increased with menopausal stage, and the association was obvious in women with other menopausal symptoms. This finding underscores the importance of addressing nocturia as a potential menopausal symptom in middle-aged women. Further studies are required to understand the mechanisms linking OAB with menopausal symptoms in middle-aged women.

UNASSIGNED: This study aimed to investigate the association of hormone replacement therapy (HRT) use, type, duration and age of commencement with myocardial infarction (MI) and stroke in postmenopausal Korean women.
UNASSIGNED: This nested case-control study used data from the National Health Insurance Service database to analyze 2017 data from women aged ≥50 years and diagnosed with natural menopause between 2004 and 2007. Among 356,160 eligible women, 36,446 used HRT for ≥1 year and 319,714 did not (controls). These two groups were matched 1:1 for statistical analysis. Type and duration were categorized into three categories.
UNASSIGNED: Women who started estrogen-progestogen therapy (EPT) or estrogen therapy (ET) in their 50s, or EPT or tibolone in their ≥60s exhibited a lower stroke risk than controls. MI risk was lower among women who used tibolone - regardless of duration - or EPT or ET for 1-3 years than among controls. Stroke risk was lower with tibolone use for ≥5 years or with EPT or ET use for 1-3 years or ≥5 years than non-users.
UNASSIGNED: Our study may support the beneficial effect of HRT by showing that Korean postmenopausal women who used HRT at a relatively younger and healthier age had a relative benefit for MI and stroke.