Perimenopause significantly impacts women\'s health globally, often managed with hormone replacement therapy (HRT) despite the associated risks. This study explores a novel alternative exosome therapy, aimed at stimulating estrogen production in ovarian tissues, thus offering a potential non-hormonal treatment for perimenopausal symptoms. Employing ex vivo methodologies, ovarian cortex specimens from perimenopausal women were treated with exosomes derived from human umbilical cord mesenchymal stem cells and cultured under specific conditions (patent number: PCT/US2022/073467). The exosomes were produced under cyclic guanosine monophosphate (cGMP) conditions, ensuring high safety standards. Estrogen levels were quantified using enzyme-linked immunosorbent assay (ELISA), and gene expression changes in estrogen and follicle-stimulating hormone (FSH) receptors were assessed via quantitative polymerase chain reaction (PCR). Immunohistochemistry (IHC) was utilized to evaluate cellular proliferation and apoptotic markers. The results indicated a significant increase in estrogen levels and estrogen receptor-alpha (Erα) expression in treated tissues compared to controls. Additionally, a decrease in apoptotic markers and an increase in cellular proliferation markers were observed. These findings suggest that exosome therapy can effectively enhance estrogen production and modulate receptor sensitivity in perimenopausal ovarian tissues. This approach could serve as a safer alternative to HRT, aligning with the body\'s natural regulatory mechanisms and potentially offering a more effective treatment option for managing perimenopausal symptoms.

Levonorgestrel releasing intrauterine system have excellent contraceptive efficacy with simultaneous lowering of menstruation\'s blood loss. It could be used for therapy of endometrial hyperplasia in perimenopause. In position of gestagen part of the hormone replacement therapy it has high control of endometrial proliferation. It is conjoined with the zero increasing of risk of thromboembolic disease in combination with transdermal oestrogen\'s application.

This study aimed to identify hub genes and elucidate the molecular mechanisms underlying low bone mineral density (BMD) in perimenopausal women. R software was used to normalize the dataset and screen the gene set associated with BMD in perimenopausal women from the Gene Expression Omnibus database. Cytoscape software was used to identify 7 critical genes. Gene enrichment analysis and protein interaction was employed to further analyze the core genes, and the CIBERSORT deconvolution algorithm was used to perform immune infiltration analysis of 22 immune genes in the samples. Furthermore, an analysis of the immune correlations of 7 crucial genes was conducted. Subsequently, a receiver operating characteristic curve was constructed to assess the diagnostic efficacy of these essential genes. A total of 171 differentially expressed genes were identified that were primarily implicated in the signaling pathways associated with apoptosis. Seven crucial genes (CAMP, MMP8, HMOX1, CTNNB1, ELANE, AKT1, and CEACAM8) were effectively filtered. The predominant functions of these genes were enriched in specific granules. The pivotal genes displayed robust associations with activated dendritic cells. The developed risk model showed a remarkable level of precision, as evidenced by an area under the curve of 0.8407 and C-index of 0.854. The present study successfully identified 7 crucial genes that are significantly associated with low BMD in perimenopausal women. Consequently, this research offers a solid theoretical foundation for clinical risk prediction, drug sensitivity analysis, and the development of targeted drugs specifically tailored for addressing low BMD in perimenopausal women.

Objective: To explore the menopause status of patients with rheumatoid arthritis (RA) and clinical characteristics of perimenopausal RA patients. Methods: A cross-sectional study. Female RA patients were recruited retrospectively in the Sun Yat-Sen Memorial Hospital from August 2015 to August 2023. Clinical data were collected, including onset age, disease duration, RA disease activity indicators, functional assessment, and radiographic scores. According to menopausal status, the patients were categorized as pre-menopausal, perimenopausal and post-menopausal groups to explore their menopausal and clinical characteristics. Results: A total of 1 151 female patients were enrolled, with a mean age of (50.2±13.0) years. At enrollment, there were 470 (40.8%), 140 (12.2%) and 541 (47.0%) patients in pre-menopause, perimenopause and post-menopause status, respectively. The mean age of menopause was (49.0±4.2) years. Compared with pre-menopausal group, perimenopausal RA patients had higher disease activity indicators [clinical disease activity index (CDAI) 17 (6, 26) vs 10 (3, 19) ], higher levels of inflammation [erythrocyte sedimentation rate (ESR) 35 (21, 65) vs 26 (14, 44) mm/1h, C-reactive protein (CRP) 6.2 (3.2, 16.8) vs 3.3 (3.2, 13.6) mg/L], and a higher proportion of functional limitation [25.0%(35/140) vs 10.4%(49/470)] (all P<0.016 7); while there was no significant differences in disease activity[M(Q1, Q3)] [CDAI 17 (6, 26) vs 14 (6, 25)], levels of inflammation [ESR 35(21, 65) vs 42 (23, 72) mm/1h, CRP 6.2 (3.2, 16.8) vs 6.2 (3.3, 23.9) mg/L] and functional limitation [25.0%(35/140) vs 28.8%(156/541)] when compared with those in post-menopausal group (all P>0.016 7). In RA patients during the perimenopausal period, 49 cases (35.0%) developed RA during this period. Compared with patients with RA onset during reproductive age, patients with RA onset during the perimenopausal period had higher numbers of 28-joint tender joints [7 (2, 10) vs 4 (0, 8)], higher CDAI [20 (12, 29) vs 14 (4, 24)], and higher ESR [45 (25, 72) vs 32 (18, 56) mm/1h] (all P<0.05). Conclusion: Perimenopausal patients with RA have severe disease activity and functional limitation.
目的： 了解女性类风湿关节炎（RA）患者的绝经状态及围绝经期患者临床特征。 方法： 横断面研究。回顾性纳入2015年8月至2023年8月就诊于中山大学孙逸仙纪念医院的女性RA患者，收集其临床资料，包括发病年龄、病程、RA疾病活动、功能及放射学指标和绝经状态等。依绝经状态情况，将患者分为生育期、围绝经期和绝经后期组，分析绝经状态分布及比较3组的临床特征。 结果： 共纳入女性RA患者1 151例，年龄为（50.2±13.0）岁，入组时处于生育期患者470例（40.8%）、围绝经期140例（12.2%）和绝经后期541例（47.0%），绝经年龄为（49.0±4.2）岁。与生育期患者相比，围绝经期女性RA患者的疾病活动指标［临床疾病活动指数（CDAI）［M（Q1，Q3）］：17（6，26）比10（3，19）］、炎症水平［红细胞沉降率（ESR）：35（21，65）比26（14，44）mm/1h、C反应蛋白（CRP）：6.2（3.2，16.8）比3.3（3.2，13.6）mg/L］和功能受限的比例［25.0%（35/140）比10.4%（49/470）］均更高（均P<0.016 7）；而与绝经后期患者相比，RA疾病活动指标［CDAI：17（6，26）比14（6，25）分，ESR：35（21，65）比42（23，72）mm/1h、CRP：6.2（3.2，16.8）比6.2（3.3，23.9）mg/L］及功能受限比例［25.0%（35/140）比28.8%（156/541）］相当（均P>0.016 7）。围绝经期RA患者中，35.0%（49/140）患者RA为围绝经期发病，与生育期发病患者相比，围绝经期发病的RA患者28个压痛关节数［7（2，10）比4（0，8）个］、CDAI［20（12，29）比14（4，24）］及ESR水平［45（25，72）比32（18，56）mm/1h］均较高（均P<0.05）。 结论： 围绝经期女性RA患者的疾病活动和功能受限均较重。.

UNASSIGNED: Healthcare professionals and educators closely monitor the occurrence of climacteric symptoms in women\'s primes. Knowledge and perception of menopause play a crucial role in improving quality of life. This study aimed to assess the knowledge and perceptions of menopause among Saudi women and identify its predictors. This study is the first of its kind in the southern region of Saudi Arabia.
UNASSIGNED: Conducted in accordance with the STROBE guidelines, this cross-sectional study was carried out in the Jazan region from May 2022 to January 2023 and involved 480 Saudi women who provided consent. Data were collected through interviews using a validated questionnaire and random sampling. The questionnaire consisted of four parts: informed consent, demographics, 21 knowledge questions, and ten menopause perception questions. The validity of the content and the internal consistency were evaluated before data collection. Primary healthcare centers were randomly selected from four governorates with a proportional sample size to the population. Descriptive analysis, Pearson correlation, and multivariate logistic regression analyses were performed using IBM-SPSS.
UNASSIGNED: Among the participants, 64 % were under 40 years old, 80 % had experienced menarche between the ages of 10 and 15, 48 % were employed, approximately half held a bachelor\'s degree, and they had a good family income. The mean knowledge score of the participants was 48.87 ± 11.72, with a minimum score of 27 and a maximum score of 78. In terms of knowledge categories, 56.3 % of the participants (N = 270) were classified as having low knowledge, while 43.8 % (N = 210) were classified as having high knowledge. Most of the participants had positive perceptions and agreed that menopause is a natural event in women\'s lives. There was a significant positive correlation between knowledge and perception (R = 0.219, P < 0.01). Variable findings were observed regarding the role of explanatory variables in women\'s knowledge of menopause between univariate and multivariate models. The results of the multivariate model showed that age (46-50 years, OR = 0.42), having children (OR = 1.09), residence (OR = 0.45-5.73) and family income categories (medium: OR = 3.98, good: OR = 3.78, and excellent: OR = 1.95) had a significant impact on knowledge, highlighting the correlation between demographic factors and knowledge.
UNASSIGNED: Based on the study findings, we recommend implementing workplace and community-based activities to increase women\'s awareness of menopause and incorporating it as an integral part of counseling sessions for women in this age group. Therefore, the results of the study will be shared with the relevant authorities responsible for women\'s health, enabling them to effectively support and educate women.

Abnormal uterine bleeding (AUB) is the most common and frequent presenting complaint in Gynaecology in all age group especially in perimenopausal and postmenopausal women. The spectrum of AUB in women of our country includes a wide varieties of organic pathology. The objective of this study was to assess the role of endometrial thickness as a predictor of endometrial malignancy among the women presenting with AUB. This cross-sectional descriptive type of observational study was conducted among 122 women of perimenopausal (40-50 years) and 87 women of postmenopausal (>50 years) age group presenting with AUB in the Obstetrics and Gynaecology department of Mymensingh Medical College Hospital, Bangladesh from February 2020 to August 2021. These patients were subjected to a detailed history and meticulous general, systemic and local examination. The relevant investigations like Transvaginal Sonography (TVS) followed by endometrial biopsy by dilatation and curettage were done in all study participants. Most of the women were in the age group 41-45 years in perimenopause and 51-55 years in postmenopause. Mean±SD was 45.8±4.1 years in perimenopause and 56.3±6.4 years in postmenopause. There was statistical significance in developing endometrial malignancy regarding risk factors of nulliparity, Hypertention (HTN), Diabetes mellitus (DM) and hormone intake between perimenopause and postmenopause. Endometrial thickness was measured in perimenopause and postmenopause. Mean±SD of Endometrial thickness (ET) in perimenopause and postmenopause was 11.3±4.4mm and 7.2±6.3mm with statistical significance (p<0.001). Sensitivity, specificity, Positive predictive value (PPV), Negative predictive value (NPV) and accuracy of TVS were 85.5%, 67.4%, 81.2%, 73.8% and 78.7% in perimenopause and 85.9%, 20%, 89%, 75% & 83.9% in postmenopause. Cut off limit of ET in detection of endometrial malignancy was 18.5mm with sensitivity 74.8% and specificity 63.6% in perimenopause and 12.2mm with sensitivity 81.0% and specificity 65.8% in postmenopausal women. Women with AUB, endometrial malignancy should be suspected when endometrial thickness on TVS >18.5mm and >12.2mm in perimenopause and postmenopausal age group respectively. TVS has high sensitivity in detection of endometrial malignancy both in perimenopausal and postmenopausal women with AUB and TVS is a reliable, noninvasive method.

Risk of cardiovascular disease mortality rises in women after menopause. While increased cardiovascular risk is largely attributed to postmenopausal declines in estrogens, the molecular changes in the heart that contribute to risk are poorly understood. Disruptions in intracellular calcium handling develop in ovariectomized mice and have been implicated in cardiac dysfunction. Using a mouse model of menopause in which ovarian failure occurs over 120 days, we sought to determine if perimenopause impacted calcium removal mechanisms in the heart and identify the molecular mechanisms. Mice were injected with 4-vinylcyclohexene diepoxide (VCD) to induce ovarian failure over 120 days, mimicking perimenopause. Hearts were removed at 60 and 120 days after VCD injections, representing the middle and end of perimenopause. SERCA2a function was significantly diminished at the end of perimenopause. Neither SERCA2a nor phospholamban expression changed at either time point, but phospholamban phosphorylation at S16 and T17 was dynamically altered. Intrinsic SERCA inhibitors sarcolipin and myoregulin increased >4-fold at day 60, as did the native activator DWORF. At the end of perimenopause, sarcolipin and myoregulin returned to baseline levels while DWORF was significantly reduced below controls. Sodium-calcium exchanger expression was significantly increased at the end of perimenopause. These results show that the foundation for increased cardiovascular disease mortality develops in the heart during perimenopause and that regulators of calcium handling exhibit significant fluctuations over time. Understanding the temporal development of cardiovascular risk associated with menopause and the underlying mechanisms is critical to developing interventions that mitigate the rise in cardiovascular mortality that arises after menopause.

BACKGROUND: Perimenopause is a time of transition in a woman\'s life that links her reproductive years to the cessation of ovulation, or menopause. For many women, this time is characterized by a variety of physiological and lifestyle changes, including increasing irregularity in menstrual bleeding, frequency and severity of vasomotor symptoms, etc. Therapies evaluated specifically for the perimenopausal women are very limited. This study aimed to evaluate the effectiveness and safety of Amberen® (a succinate-based non-hormonal supplement) combined with a Smart B® (vitamin B) complex in women with typical (without complications) mild to moderate climacteric syndrome during perimenopause.
METHODS: Women up to 50 years of age, in perimenopause, with vasomotor and psychosomatic symptoms of the climacteric syndrome were enrolled for the study. The trial was randomized, double-blinded, placebo-controlled, comparative, and prospective.
RESULTS: A total of 106 participants were enrolled in the trial and, per protocol, 105 completed the trial. We observed statistically significant improvements in most of the Greene Climacteric Scale symptoms, State-Trait Anxiety Inventory (STAI), Hospital Anxiety and Depression Scale (HADS), and Well-being, Activity, and Mood (WAM) scores. The intervention was well tolerated with few adverse effects reported to be mild and transient.
CONCLUSIONS: The use of this dietary supplement is safe and eliminates or improves vasomotor and psychosomatic symptoms of climacteric symptoms in perimenopausal women: it improves sleep and cognitive abilities, lowers depression and anxiety, improves mood and well-being, and positively affects quality of life.
RESULTS:
UNASSIGNED: NCT03897738.

BACKGROUND: The average age of the menopause in the United Kingdom is 52 but symptoms of the perimenopause (PMP) can start at 40 or earlier. The UK Armed Forces (UKAF) has a young demographic but women serving over the age of 40, potentially with PMP symptoms, has increased. Recent evidence suggested PMP management by Defence GPs was satisfactory but variable. Because of small numbers, Defence GPs have less exposure to the PMP than NHS GPs, a problem exacerbated for Uniformed GPs who have reduced clinical contact time due to military duties.
OBJECTIVE: This study aimed to explore Defence GP knowledge and confidence in managing the PMP, identifying factors contributing to disparities.
METHODS: This study used a sequential mixed-methods approach. A survey with self-rating questions and vignettes was undertaken, followed by semi-structured interviews of selectively sampled respondents.
RESULTS: 164 out of 542 Defence GPs responded to a survey, which identified reasonable knowledge (91.3% managing cases per guidelines) but reduced confidence (54.3%). Regression analysis identified case exposure to the PMP, education, and gender as significant factors affecting confidence in PMP management. Themes identified from interviews which were felt to affect knowledge and confidence included: Characteristics of the GP (such as gender); lifelong learning and reflective practice; professional exposure to, and awareness of, the PMP; the changing demographic of Defence; an integrated PMP service to provide experiential learning. Case exposure and experiential learning emerged as the main drivers for confidence. For Uniformed GPs, this was affected by limited clinical time, but confidence returned once exposed to just a few PMP cases.
CONCLUSIONS: Establishing an integrated PMP service in Defence was seen as crucial for improving care as well as providing educational opportunities through experiential learning for Defence GPs.

OBJECTIVE: Aim: The aim of the study was to determine the level of anxiety and depression in patients with endometrial hyperplastic processes and somatic pathology in the perimenopausal period.
METHODS: Materials and Methods: Overall, 150 women who were split into 2 groups, participated in this study and answered on questionnaires that were conducted according to the Hospital Anxiety and Depression Scale (HADS) to assess the degree of anxiety and depressive symptoms in patients. PHQ-2 and PHQ-9 questionnaires were used to study the level of anxiety and depression.
RESULTS: Results: Analysis of the results obtained using the HADS scale revealed that both anxiety and depressive symptoms in patients of the main group were more pronounced than in women of the control group. Identification of psycho-emotional disorders is the result of adverse effects of somatic diseases and gynecological pathology.
CONCLUSIONS: Conclusions: The results of the study indicate the need to correct psycho-emotional disorders and take them into account when choosing a method of treatment in such patients.