Pub Date : 2026-02-02DOI: 10.1016/j.maturitas.2026.108863
Julie Sang , Imo A. Ebong , Duke Appiah
Introduction
Limited inconsistent evidence suggests a potential association between advanced paternal age (APA) and simple congenital heart defects, which often resolve without surgical interventions, in offspring. There is no reported potential relationship between APA with major cardiac defects like cyanotic congenital heart defects (CCHD). This study evaluated the association between APA (age at birth ≥40 years) and the occurrence of CCHD among livebirths in the USA, accounting for maternal and other potential confounding factors.
Methods
Data were from the National Vital Statistics System, comprising 9.9 million singleton first-time livebirths among mothers and fathers aged ≥15 years from 2016 to 2023. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI).
Results
From 2016 to 2023, the proportion of births to fathers with APA increased from 7.5% to 7.9%. A greater proportion of fathers with APA had offspring with CCHD (62.0 vs. 53.1 per 100,000), used infertility treatment (9.5% vs. 2.3%), and their partners were also older (34.6 vs. 27.0 years). In models adjusted for paternal factors (age, race and ethnicity, and education), APA was associated with a modest elevated odds for CCHD (OR = 1.22, 95% CI 1.11–1.34) which remained significant after further control for maternal pre-pregnancy sociodemographic and health factors (OR = 1.12, 95% CI 1.01–1.25). However, additional adjustments for infertility treatment attenuated the observed association (OR = 1.08, 95% CI 0.98–1.20).
Conclusions
The findings of this large population-based study suggest no association between APA and CCHD after accounting for important confounders, including maternal factors and infertility treatment.
有限的不一致的证据表明，父亲高龄（APA）与后代的单纯性先天性心脏缺陷（通常无需手术干预即可解决）之间存在潜在关联。目前还没有报道APA与主要心脏缺陷如青紫型先天性心脏缺陷（CCHD）之间的潜在关系。本研究评估了美国活产婴儿中APA（出生年龄≥40岁）与CCHD发生之间的关系，考虑了产妇和其他潜在的混杂因素。方法数据来自国家生命统计系统，包括2016年至2023年990万名年龄≥15岁的母亲和父亲的单胎首次分娩。Logistic回归模型用于估计比值比（OR）和95%置信区间（CI）。结果从2016年到2023年，父亲患有APA的新生儿比例从7.5%上升到7.9%。患有APA的父亲有更大比例的后代患有CCHD(62.0比53.1 / 100000)，使用不孕症治疗（9.5%比2.3%），他们的伴侣年龄也更大（34.6比27.0岁）。在调整了父亲因素（年龄、种族、民族和教育）的模型中，APA与CCHD的几率适度升高相关（OR = 1.22, 95% CI 1.11-1.34），在进一步控制了母亲孕前社会人口统计学和健康因素（OR = 1.12, 95% CI 1.01-1.25）后，这一结果仍然显著。然而，对不孕症治疗的额外调整减弱了观察到的相关性（OR = 1.08, 95% CI 0.98-1.20）。结论：这项基于人群的大型研究结果表明，在考虑了重要的混杂因素（包括母体因素和不孕症治疗）后，APA和CCHD之间没有关联。
{"title":"Advanced paternal age at birth and risk of cyanotic congenital heart defects in the United States","authors":"Julie Sang , Imo A. Ebong , Duke Appiah","doi":"10.1016/j.maturitas.2026.108863","DOIUrl":"10.1016/j.maturitas.2026.108863","url":null,"abstract":"<div><h3>Introduction</h3><div>Limited inconsistent evidence suggests a potential association between advanced paternal age (APA) and simple congenital heart defects, which often resolve without surgical interventions, in offspring. There is no reported potential relationship between APA with major cardiac defects like cyanotic congenital heart defects (CCHD). This study evaluated the association between APA (age at birth ≥40 years) and the occurrence of CCHD among livebirths in the USA, accounting for maternal and other potential confounding factors.</div></div><div><h3>Methods</h3><div>Data were from the National Vital Statistics System, comprising 9.9 million singleton first-time livebirths among mothers and fathers aged ≥15 years from 2016 to 2023. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI).</div></div><div><h3>Results</h3><div>From 2016 to 2023, the proportion of births to fathers with APA increased from 7.5% to 7.9%. A greater proportion of fathers with APA had offspring with CCHD (62.0 vs. 53.1 per 100,000), used infertility treatment (9.5% vs. 2.3%), and their partners were also older (34.6 vs. 27.0 years). In models adjusted for paternal factors (age, race and ethnicity, and education), APA was associated with a modest elevated odds for CCHD (OR = 1.22, 95% CI 1.11–1.34) which remained significant after further control for maternal pre-pregnancy sociodemographic and health factors (OR = 1.12, 95% CI 1.01–1.25). However, additional adjustments for infertility treatment attenuated the observed association (OR = 1.08, 95% CI 0.98–1.20).</div></div><div><h3>Conclusions</h3><div>The findings of this large population-based study suggest no association between APA and CCHD after accounting for important confounders, including maternal factors and infertility treatment.</div></div>","PeriodicalId":51120,"journal":{"name":"Maturitas","volume":"207 ","pages":"Article 108863"},"PeriodicalIF":3.6,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146116775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-30DOI: 10.1016/j.maturitas.2026.108861
Tugba Akcaoglu
{"title":"Comment on “Endometriosis and menopausal health: An EMAS clinical guide”","authors":"Tugba Akcaoglu","doi":"10.1016/j.maturitas.2026.108861","DOIUrl":"10.1016/j.maturitas.2026.108861","url":null,"abstract":"","PeriodicalId":51120,"journal":{"name":"Maturitas","volume":"207 ","pages":"Article 108861"},"PeriodicalIF":3.6,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146191463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-30DOI: 10.1016/j.maturitas.2026.108858
Silvia P. González , Laura Nieto-Pascual , Diana López-Freire , Santiago Palacios
Objective
To review the biological basis of the “window of opportunity” hypothesis for the treatment of vulvovaginal atrophy (VVA), focusing on the distribution of oestrogen receptors (ERs) in vulvovaginal tissues, the impact of sustained oestrogen deficiency over time, and the rationale for a preventive or very early sequential therapeutic approach.
Methods
Narrative review of experimental and clinical studies evaluating ER expression in vaginal and vulvar tissues, its modulation by age and menopause, and clinical response to local and systemic hormonal therapy, with emphasis on timing of initiation and management strategies.
Main results
ER distribution and expression vary with age and menopausal status, with ER-α predominating after menopause. Experimental models show that immediate hormonal intervention after oestrogen deprivation restores tissue trophism and ER expression, whereas delayed treatment is associated with attenuated responses and irreversible histological changes. Loss of collagen, reduced angiogenesis, altered innervation, and inflammatory infiltration contribute to VVA progression. Clinical data suggest that early initiation of vaginal oestrogens enhances therapeutic efficacy. No consistent differences have been observed among local formulations, although ER subtype profile and time since menopause may influence outcomes.
Conclusions
Early initiation of ER-directed therapies may optimise tissue responses and prevent irreversible changes. A sequential treatment framework is useful for long-term management—particularly in women who did not start therapy early—yet further studies incorporating time since menopause and evaluating the long-term safety of hormonal therapy for VVA are warranted.
{"title":"The window of opportunity for treating vulvovaginal atrophy in menopause: Insights from oestrogen receptor distribution and age-related changes","authors":"Silvia P. González , Laura Nieto-Pascual , Diana López-Freire , Santiago Palacios","doi":"10.1016/j.maturitas.2026.108858","DOIUrl":"10.1016/j.maturitas.2026.108858","url":null,"abstract":"<div><h3>Objective</h3><div>To review the biological basis of the “window of opportunity” hypothesis for the treatment of vulvovaginal atrophy (VVA), focusing on the distribution of oestrogen receptors (ERs) in vulvovaginal tissues, the impact of sustained oestrogen deficiency over time, and the rationale for a preventive or very early sequential therapeutic approach.</div></div><div><h3>Methods</h3><div>Narrative review of experimental and clinical studies evaluating ER expression in vaginal and vulvar tissues, its modulation by age and menopause, and clinical response to local and systemic hormonal therapy, with emphasis on timing of initiation and management strategies.</div></div><div><h3>Main results</h3><div>ER distribution and expression vary with age and menopausal status, with ER-α predominating after menopause. Experimental models show that immediate hormonal intervention after oestrogen deprivation restores tissue trophism and ER expression, whereas delayed treatment is associated with attenuated responses and irreversible histological changes. Loss of collagen, reduced angiogenesis, altered innervation, and inflammatory infiltration contribute to VVA progression. Clinical data suggest that early initiation of vaginal oestrogens enhances therapeutic efficacy. No consistent differences have been observed among local formulations, although ER subtype profile and time since menopause may influence outcomes.</div></div><div><h3>Conclusions</h3><div>Early initiation of ER-directed therapies may optimise tissue responses and prevent irreversible changes. A sequential treatment framework is useful for long-term management—particularly in women who did not start therapy early—yet further studies incorporating time since menopause and evaluating the long-term safety of hormonal therapy for VVA are warranted.</div></div>","PeriodicalId":51120,"journal":{"name":"Maturitas","volume":"207 ","pages":"Article 108858"},"PeriodicalIF":3.6,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146116773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-30DOI: 10.1016/j.maturitas.2026.108850
Lakshmi Khatri , Jessica Fraker , Sandhya Pruthi
Males account for a small but clinically significant component of overall breast conditions, both benign and malignant. This review summarizes current evidence on epidemiology, male breast anatomy, clinical presentation, diagnosis, management, and identification of risk factors for male breast disease. Benign male breast disease, including gynecomastia, prompts clinical evaluation and requires understanding of hormonal and pharmacological causes to guide diagnostics and management. Although male breast cancer is rare, accounting for less than 1% of all breast cancers, it carries important hereditary and clinical implications. Pathogenic germline variants in BRCA2 are the predominant genetic contributor, conferring a lifetime risk of ~7%, while BRCA1, CHEK2 and PALB2 variants confer lower risk. Males with breast cancer typically present with subareolar masses, nipple changes, or pain, often at older ages and later stages compared with females. Imaging evaluation, including mammography and ultrasound, is central to diagnosis and management. Screening recommendations for high-risk men remain limited due to sparse prospective data, with multigene panel testing and family history assessment guiding individualized risk assessment. Management strategies for male breast cancer generally parallel female protocols, despite unique biological features. By integrating considerations of benign and malignant conditions, this review underscores the importance of tailored evaluation, risk assessment, and individualized care for males, while identifying knowledge gaps to inform future research and improve outcomes in this under-recognized population.
{"title":"Male breast health and breast cancer risk","authors":"Lakshmi Khatri , Jessica Fraker , Sandhya Pruthi","doi":"10.1016/j.maturitas.2026.108850","DOIUrl":"10.1016/j.maturitas.2026.108850","url":null,"abstract":"<div><div>Males account for a small but clinically significant component of overall breast conditions, both benign and malignant. This review summarizes current evidence on epidemiology, male breast anatomy, clinical presentation, diagnosis, management, and identification of risk factors for male breast disease. Benign male breast disease, including gynecomastia, prompts clinical evaluation and requires understanding of hormonal and pharmacological causes to guide diagnostics and management. Although male breast cancer is rare, accounting for less than 1% of all breast cancers, it carries important hereditary and clinical implications. Pathogenic germline variants in <em>BRCA2</em> are the predominant genetic contributor, conferring a lifetime risk of ~7%, while <em>BRCA1</em>, <em>CHEK2</em> and <em>PALB2</em> variants confer lower risk. Males with breast cancer typically present with subareolar masses, nipple changes, or pain, often at older ages and later stages compared with females. Imaging evaluation, including mammography and ultrasound, is central to diagnosis and management. Screening recommendations for high-risk men remain limited due to sparse prospective data, with multigene panel testing and family history assessment guiding individualized risk assessment. Management strategies for male breast cancer generally parallel female protocols, despite unique biological features. By integrating considerations of benign and malignant conditions, this review underscores the importance of tailored evaluation, risk assessment, and individualized care for males, while identifying knowledge gaps to inform future research and improve outcomes in this under-recognized population.</div></div>","PeriodicalId":51120,"journal":{"name":"Maturitas","volume":"206 ","pages":"Article 108850"},"PeriodicalIF":3.6,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-29DOI: 10.1016/j.maturitas.2026.108854
Mingming Liu , Shanshan Wang , Mengmei E. Wang , Yuxiao Li , Qiaoye J. Wang , Lingyao Meng
Background
The prospective association between social frailty and motoric cognitive risk syndrome in China is understudied.
Objective
To investigate the prospective association between social frailty and motoric cognitive risk syndrome among Chinese middle-aged and older adults.
Methods
Data were derived from the China Health and Retirement Longitudinal Study, 2011–2015. The sample comprised 3373 adults aged ≥45 years without motoric cognitive risk syndrome at baseline (2011). Social frailty was constructed from five indicators and categorized into three levels: robust, pre-frail, and frail. Motoric cognitive risk syndrome was defined as concurrent slow gait and subjective cognitive complaint at the 2013 and/or 2015 follow-ups. Associations were estimated using Cox proportional hazards models with sequential adjustment.
Results
After multivariate adjustment, compared with the robust group, pre-frailty (HR 1.63; 95% CI 1.12–2.36) and frailty (HR 2.02; 95% CI 1.38–2.96) were associated with a higher risk of incident motoric cognitive risk syndrome. In sex-stratified analyses, associations were stronger in males, whereas among females only frailty was significantly associated with a higher risk.
Conclusions
Social frailty was associated with subsequent motoric cognitive risk syndrome in Chinese middle-aged and older adults, supporting social-risk screening and interventions.
背景：在中国，社会脆弱与运动认知风险综合征之间的潜在关联尚不清楚。目的探讨中国中老年人群社会衰弱与运动认知危险综合征的相关性。方法数据来源于2011-2015年中国健康与退休纵向研究。样本包括3373名年龄≥45岁的成年人，基线时无运动认知风险综合征（2011年）。社会脆弱性由五个指标构成，分为三个层次：健全、预脆弱和脆弱。在2013年和/或2015年随访中，运动认知风险综合征被定义为同时伴有步态缓慢和主观认知主诉。使用Cox比例风险模型进行序列调整。结果多因素调整后，与稳健组相比，虚弱前（HR 1.63; 95% CI 1.12-2.36）和虚弱（HR 2.02; 95% CI 1.38-2.96）与发生运动认知危险综合征的高风险相关。在性别分层分析中，相关性在男性中更强，而在女性中，只有虚弱与更高的风险显著相关。结论社会脆弱与中国中老年人群随后发生的运动认知风险综合征相关，支持社会风险筛查和干预。
{"title":"Prospective association of social frailty with incident motoric cognitive risk syndrome among middle-aged and older adults","authors":"Mingming Liu , Shanshan Wang , Mengmei E. Wang , Yuxiao Li , Qiaoye J. Wang , Lingyao Meng","doi":"10.1016/j.maturitas.2026.108854","DOIUrl":"10.1016/j.maturitas.2026.108854","url":null,"abstract":"<div><h3>Background</h3><div>The prospective association between social frailty and motoric cognitive risk syndrome in China is understudied.</div></div><div><h3>Objective</h3><div>To investigate the prospective association between social frailty and motoric cognitive risk syndrome among Chinese middle-aged and older adults.</div></div><div><h3>Methods</h3><div>Data were derived from the China Health and Retirement Longitudinal Study, 2011–2015. The sample comprised 3373 adults aged ≥45 years without motoric cognitive risk syndrome at baseline (2011). Social frailty was constructed from five indicators and categorized into three levels: robust, pre-frail, and frail. Motoric cognitive risk syndrome was defined as concurrent slow gait and subjective cognitive complaint at the 2013 and/or 2015 follow-ups. Associations were estimated using Cox proportional hazards models with sequential adjustment.</div></div><div><h3>Results</h3><div>After multivariate adjustment, compared with the robust group, pre-frailty (HR 1.63; 95% CI 1.12–2.36) and frailty (HR 2.02; 95% CI 1.38–2.96) were associated with a higher risk of incident motoric cognitive risk syndrome. In sex-stratified analyses, associations were stronger in males, whereas among females only frailty was significantly associated with a higher risk.</div></div><div><h3>Conclusions</h3><div>Social frailty was associated with subsequent motoric cognitive risk syndrome in Chinese middle-aged and older adults, supporting social-risk screening and interventions.</div></div>","PeriodicalId":51120,"journal":{"name":"Maturitas","volume":"206 ","pages":"Article 108854"},"PeriodicalIF":3.6,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-29DOI: 10.1016/j.maturitas.2026.108859
Louise Polano , Tine Worm Thinggaard , Mette Kildevæld Simonsen , Maarten van Wijhe , Marianne Vámosi
Objective
To examine the association between body mass index and the severity of menopausal symptoms among Danish nurses.
Study design
Cross-sectional analysis of the 2024 wave of the Danish Nurse Cohort.
Main outcome measures
Total score on the Menopause Rating Scale dichotomized as no-to-mild (<9) versus moderate-to-severe (≥9), with domain cut-offs applied for somatic, psychological, and urogenital symptoms. Multiple logistic regression models were applied, adjusted for age, smoking, alcohol, physical activity, diet, cohabitation, and age at last menstrual period.
Results
Of 6078 women (mean age 63.5 (standard deviation 9.3) years), 55.8% reported moderate-to-severe symptoms. Each 5-unit increase in body mass index was associated with higher odds of moderate-to-severe symptoms (odds ratio 1.13, 95% confidence interval 1.06–1.20). Domain analyses showed associations for psychological (odds ratio 1.15, 95% confidence interval 1.08–1.23) and somato-vegetative (odds ratio 1.15, 95% confidence interval 1.08–1.22) domains, but not urogenital (odds ratio 0.96, 95% confidence interval 0.91–1.03). Participants with a body mass index of less than 18.5 kg/m2 had lower associated odds (odds ratio 0.53, 95% confidence interval 0.34–0.83) and participants with a body mass index of 30 kg/m2 or more had higher odds (odds ratio 1.24, 95% confidence interval 1.05–1.46) than women with an eutrophic body mass index.
Conclusions
In a large national representative cohort of Danish nurses, higher body mass index was significantly associated with greater severity of menopausal symptoms, particularly psychological and somato-vegetative. These findings highlight the importance of considering weight-related factors when addressing midlife women's health and menopause care.
{"title":"Associations between BMI and menopausal symptoms among Danish nurses: A cross-sectional study","authors":"Louise Polano , Tine Worm Thinggaard , Mette Kildevæld Simonsen , Maarten van Wijhe , Marianne Vámosi","doi":"10.1016/j.maturitas.2026.108859","DOIUrl":"10.1016/j.maturitas.2026.108859","url":null,"abstract":"<div><h3>Objective</h3><div>To examine the association between body mass index and the severity of menopausal symptoms among Danish nurses.</div></div><div><h3>Study design</h3><div>Cross-sectional analysis of the 2024 wave of the Danish Nurse Cohort.</div></div><div><h3>Main outcome measures</h3><div>Total score on the Menopause Rating Scale dichotomized as no-to-mild (<9) versus moderate-to-severe (≥9), with domain cut-offs applied for somatic, psychological, and urogenital symptoms. Multiple logistic regression models were applied, adjusted for age, smoking, alcohol, physical activity, diet, cohabitation, and age at last menstrual period.</div></div><div><h3>Results</h3><div>Of 6078 women (mean age 63.5 (standard deviation 9.3) years), 55.8% reported moderate-to-severe symptoms. Each 5-unit increase in body mass index was associated with higher odds of moderate-to-severe symptoms (odds ratio 1.13, 95% confidence interval 1.06–1.20). Domain analyses showed associations for psychological (odds ratio 1.15, 95% confidence interval 1.08–1.23) and somato-vegetative (odds ratio 1.15, 95% confidence interval 1.08–1.22) domains, but not urogenital (odds ratio 0.96, 95% confidence interval 0.91–1.03). Participants with a body mass index of less than 18.5 kg/m<sup>2</sup> had lower associated odds (odds ratio 0.53, 95% confidence interval 0.34–0.83) and participants with a body mass index of 30 kg/m<sup>2</sup> or more had higher odds (odds ratio 1.24, 95% confidence interval 1.05–1.46) than women with an eutrophic body mass index.</div></div><div><h3>Conclusions</h3><div>In a large national representative cohort of Danish nurses, higher body mass index was significantly associated with greater severity of menopausal symptoms, particularly psychological and somato-vegetative. These findings highlight the importance of considering weight-related factors when addressing midlife women's health and menopause care.</div></div>","PeriodicalId":51120,"journal":{"name":"Maturitas","volume":"207 ","pages":"Article 108859"},"PeriodicalIF":3.6,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146138262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-25DOI: 10.1016/j.maturitas.2026.108851
Zhenyi Xu , Ce Wang , Jiaofeng Wang , Jie Chen , Xiaojun Wang , Zhijun Bao , Yan Zhang
Objectives
The frailty phenotype has limitations in capturing the biological heterogeneity of the condition. Our study identified subtypes of frailty based on proteomics and examined their associations with several adverse outcomes.
Method
The study included 1513 frail individuals and 29,339 non-frail individuals from the UK Biobank and analyzed 2920 proteins. Unsupervised K-means clustering was applied to identify molecular subtypes of frailty and the Boruta algorithm was applied to identify the key proteins for distinguishing these subtypes.
Results
Four novel subtypes were identified among frail individuals: S1 (n = 403), S2 (n = 209), S3 (n = 587) and S4 (n = 314). In total, 567 key proteins for distinguishing subtypes were identified, in diverse biological pathways. Each subtype exhibited distinct molecular characteristics. S1 was characterized by elevated genomic instability, S2 by altered intercellular communication, S3 by broad upregulation of aging-related features, and S4 by loss of proteostasis and mitochondrial dysfunction. While the prognosis of S3 was similar to S1, S2 and S4 had a worse prognosis than S1. S2, in particular, presented a significantly increased risk of multiple adverse outcomes compared with S1, including all-cause mortality (hazard ratio 2.13; 95% confidence interval 1.60–2.85), cardiovascular disease (hazard ratio 1.78; 95% confidence interval 1.00–3.17), respiratory disease (hazard ratio 1.83; 95% confidence interval 1.24–2.70), kidney disease (hazard ratio 2.76; 95% confidence interval 1.57–4.85), liver disease (hazard ratio 6.19; 95% confidence interval 4.13–9.29), and cancer (hazard ratio 2.06; 95% confidence interval 1.43–2.96).
Conclusion
Our study identified four proteomic subtypes of frailty with distinct molecular signatures and differential prognostic implications, highlighting the biological heterogeneity of frailty and the need for personalized medicine and management strategies.
{"title":"Novel proteomic subtypes of frailty with distinct molecular patterns and prognosis","authors":"Zhenyi Xu , Ce Wang , Jiaofeng Wang , Jie Chen , Xiaojun Wang , Zhijun Bao , Yan Zhang","doi":"10.1016/j.maturitas.2026.108851","DOIUrl":"10.1016/j.maturitas.2026.108851","url":null,"abstract":"<div><h3>Objectives</h3><div>The frailty phenotype has limitations in capturing the biological heterogeneity of the condition. Our study identified subtypes of frailty based on proteomics and examined their associations with several adverse outcomes.</div></div><div><h3>Method</h3><div>The study included 1513 frail individuals and 29,339 non-frail individuals from the UK Biobank and analyzed 2920 proteins. Unsupervised K-means clustering was applied to identify molecular subtypes of frailty and the Boruta algorithm was applied to identify the key proteins for distinguishing these subtypes.</div></div><div><h3>Results</h3><div>Four novel subtypes were identified among frail individuals: S1 (<em>n</em> = 403), S2 (<em>n</em> = 209), S3 (<em>n</em> = 587) and S4 (<em>n</em> = 314). In total, 567 key proteins for distinguishing subtypes were identified, in diverse biological pathways. Each subtype exhibited distinct molecular characteristics. S1 was characterized by elevated genomic instability, S2 by altered intercellular communication, S3 by broad upregulation of aging-related features, and S4 by loss of proteostasis and mitochondrial dysfunction. While the prognosis of S3 was similar to S1, S2 and S4 had a worse prognosis than S1. S2, in particular, presented a significantly increased risk of multiple adverse outcomes compared with S1, including all-cause mortality (hazard ratio 2.13; 95% confidence interval 1.60–2.85), cardiovascular disease (hazard ratio 1.78; 95% confidence interval 1.00–3.17), respiratory disease (hazard ratio 1.83; 95% confidence interval 1.24–2.70), kidney disease (hazard ratio 2.76; 95% confidence interval 1.57–4.85), liver disease (hazard ratio 6.19; 95% confidence interval 4.13–9.29), and cancer (hazard ratio 2.06; 95% confidence interval 1.43–2.96).</div></div><div><h3>Conclusion</h3><div>Our study identified four proteomic subtypes of frailty with distinct molecular signatures and differential prognostic implications, highlighting the biological heterogeneity of frailty and the need for personalized medicine and management strategies.</div></div>","PeriodicalId":51120,"journal":{"name":"Maturitas","volume":"206 ","pages":"Article 108851"},"PeriodicalIF":3.6,"publicationDate":"2026-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lynch syndrome, caused by germline pathogenic variants in mismatch repair genes, markedly increases risks of endometrial, ovarian, and possibly breast cancer in women. We aimed to establish gene-specific risk profiles for these cancers using a unified multivariate model accounting for correlated outcomes.
Methods
Eligible studies reported frequencies of endometrial, ovarian, and breast cancer in female with Lynch syndrome carriers, for at least two mismatch repair genes. We applied a Bayesian multivariate random-effects meta-analysis with a copula model to jointly model prevalence and odds ratios across cancers, accounting for between-study heterogeneity and inter-cancer correlation.
Results
Using a copula-based multivariate meta-analysis to account for outcome interdependence, the estimated prevalence was 20% for endometrial cancer, 5.7% for ovarian cancer, and 11% for breast cancer. Gene-specific analyses showed increased endometrial cancer risk with MSH6 (OR = 1.46, 95% CrI 1.02–2.04) and reduced risk with PMS2, relative to other Lynch genes (OR = 0.36, 95% CrI 0.14–0.95). Ovarian cancer risk did not differ significantly by gene. For breast cancer, PMS2 (OR = 1.52, 95% CI 1.02–2.25) and MSH6 (OR = 2.27, 95% CrI 1.08–2.49) were associated with higher risk, while MLH1 and MSH2 carried significantly lower risk.
Conclusions
This copula-based meta-analysis identifies gene-specific risks of endometrial and ovarian cancer in female Lynch syndrome carriers, supporting personalized gynecologic surveillance. It also notes higher breast cancer risks in MSH6 and PMS2 carriers, but conflicting evidence from large perspective databases prevents definitive conclusions about breast cancer as part of the Lynch syndrome spectrum.
{"title":"Gene-specific cancer risks in female Lynch syndrome carriers: A copula-based meta-analysis","authors":"Raheleh Karimi , Iraj Kazemi , Marjan Mansourian , Hamid Reza Marateb , Miquel Angel Mañanas","doi":"10.1016/j.maturitas.2026.108829","DOIUrl":"10.1016/j.maturitas.2026.108829","url":null,"abstract":"<div><h3>Background</h3><div>Lynch syndrome, caused by germline pathogenic variants in mismatch repair genes, markedly increases risks of endometrial, ovarian, and possibly breast cancer in women. We aimed to establish gene-specific risk profiles for these cancers using a unified multivariate model accounting for correlated outcomes.</div></div><div><h3>Methods</h3><div>Eligible studies reported frequencies of endometrial, ovarian, and breast cancer in female with Lynch syndrome carriers, for at least two mismatch repair genes. We applied a Bayesian multivariate random-effects meta-analysis with a copula model to jointly model prevalence and odds ratios across cancers, accounting for between-study heterogeneity and inter-cancer correlation.</div></div><div><h3>Results</h3><div>Using a copula-based multivariate meta-analysis to account for outcome interdependence, the estimated prevalence was 20% for endometrial cancer, 5.7% for ovarian cancer, and 11% for breast cancer. Gene-specific analyses showed increased endometrial cancer risk with <em>MSH6</em> (OR = 1.46, 95% CrI 1.02–2.04) and reduced risk with <em>PMS2</em>, relative to other Lynch genes (OR = 0.36, 95% CrI 0.14–0.95). Ovarian cancer risk did not differ significantly by gene. For breast cancer, <em>PMS2</em> (OR = 1.52, 95% CI 1.02–2.25) and <em>MSH6</em> (OR = 2.27, 95% CrI 1.08–2.49) were associated with higher risk, while <em>MLH1</em> and <em>MSH2</em> carried significantly lower risk.</div></div><div><h3>Conclusions</h3><div>This copula-based meta-analysis identifies gene-specific risks of endometrial and ovarian cancer in female Lynch syndrome carriers, supporting personalized gynecologic surveillance. It also notes higher breast cancer risks in <em>MSH6</em> and <em>PMS2</em> carriers, but conflicting evidence from large perspective databases prevents definitive conclusions about breast cancer as part of the Lynch syndrome spectrum.</div></div>","PeriodicalId":51120,"journal":{"name":"Maturitas","volume":"206 ","pages":"Article 108829"},"PeriodicalIF":3.6,"publicationDate":"2026-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-25DOI: 10.1016/j.maturitas.2026.108852
Xue Wang , Huaxin Si , Yanyan Li , Jiaqi Yu , Wendie Zhou , Hejing Chen , Cuili Wang
Objective
The association between social frailty and the long-term trajectories of cognitive domains remains understudied in Chinese middle-aged and older adults. This study explores this association using data from a nationwide longitudinal study.
Methods
This study analyzed data obtained from the 2011–2020 waves of the China Health and Retirement Longitudinal Study. Trajectories in the three cognitive domains of global cognition, episodic memory, and executive function were determined through group-based trajectory modeling. Logistic regression models were employed to assess the associations between social frailty (classified as social frailty, pre-social frailty or robust) and the identified trajectories of global cognition, episodic memory, and executive function. In addition, network analysis was conducted to detect central nodes.
Results
A total of 7961 participants were included. The group-based trajectory modeling identified two distinct trajectories for global cognition, episodic memory, and executive function: a persistently low trajectory and a persistently high trajectory. Compared with the robust group, the pre-social frailty and social frailty groups were associated with higher odds of having a persistently low trajectory for global cognition, episodic memory, and executive function (pre-social frailty: odds ratio (OR) = 1.37, 95% confidence interval (CI) 1.22, 1.54, for global cognition; OR = 1.31, 95% CI 1.17, 1.46, for episodic memory; OR = 1.40, 95% CI 1.25, 1.58, for executive function; social frailty: OR = 1.86, 95% CI 1.45, 2.40, for global cognition; OR = 1.74, 95% CI 1.34, 2.27, for episodic memory; OR = 1.89, 95% CI 1.47, 2.44, for executive function). Moreover, network analysis revealed “loneliness” to be the most influential node in the network.
Conclusions
These findings underscore the relevance of social frailty and loneliness to cognitive trajectories and support further research to evaluate whether interventions that enhance social support and reduce loneliness can improve cognitive outcomes in at-risk populations.
目的探讨中国中老年人群社会脆弱性与认知领域长期发展轨迹之间的关系。本研究利用一项全国性的纵向研究的数据来探讨这种联系。方法本研究分析2011-2020年中国健康与退休纵向研究的数据。通过基于群体的轨迹模型确定了整体认知、情景记忆和执行功能三个认知领域的轨迹。采用Logistic回归模型来评估社会脆弱性（分为社会脆弱性、前社会脆弱性或稳健性）与全球认知、情景记忆和执行功能的确定轨迹之间的关系。此外，通过网络分析检测中心节点。结果共纳入受试者7961人。基于群体的轨迹模型确定了整体认知、情景记忆和执行功能的两种不同轨迹：持续低的轨迹和持续高的轨迹。与稳健组相比，前社会脆弱组和社会脆弱组整体认知、情景记忆和执行功能的持续低轨迹的几率更高(前社会脆弱：整体认知的优势比(OR) = 1.37, 95%可信区间（CI） 1.22, 1.54；情景记忆OR = 1.31, 95% CI 1.17, 1.46；执行功能OR = 1.40, 95% CI 1.25, 1.58；社会脆弱性：全球认知OR = 1.86, 95% CI 1.45, 2.40；情景记忆OR = 1.74, 95% CI 1.34, 2.27；OR = 1.89, 95% CI 1.47, 2.44，执行功能)。此外，网络分析显示，“孤独”是网络中最具影响力的节点。这些发现强调了社会脆弱性和孤独感与认知轨迹的相关性，并支持进一步的研究来评估增强社会支持和减少孤独感的干预措施是否可以改善高危人群的认知结果。
{"title":"Association of social frailty and cognitive domain trajectories in middle-aged and older adults in China: A population-based cohort study from a network perspective","authors":"Xue Wang , Huaxin Si , Yanyan Li , Jiaqi Yu , Wendie Zhou , Hejing Chen , Cuili Wang","doi":"10.1016/j.maturitas.2026.108852","DOIUrl":"10.1016/j.maturitas.2026.108852","url":null,"abstract":"<div><h3>Objective</h3><div>The association between social frailty and the long-term trajectories of cognitive domains remains understudied in Chinese middle-aged and older adults. This study explores this association using data from a nationwide longitudinal study.</div></div><div><h3>Methods</h3><div>This study analyzed data obtained from the 2011–2020 waves of the China Health and Retirement Longitudinal Study. Trajectories in the three cognitive domains of global cognition, episodic memory, and executive function were determined through group-based trajectory modeling. Logistic regression models were employed to assess the associations between social frailty (classified as social frailty, pre-social frailty or robust) and the identified trajectories of global cognition, episodic memory, and executive function. In addition, network analysis was conducted to detect central nodes.</div></div><div><h3>Results</h3><div>A total of 7961 participants were included. The group-based trajectory modeling identified two distinct trajectories for global cognition, episodic memory, and executive function: a persistently low trajectory and a persistently high trajectory. Compared with the robust group, the pre-social frailty and social frailty groups were associated with higher odds of having a persistently low trajectory for global cognition, episodic memory, and executive function (pre-social frailty: odds ratio (OR) = 1.37, 95% confidence interval (CI) 1.22, 1.54, for global cognition; OR = 1.31, 95% CI 1.17, 1.46, for episodic memory; OR = 1.40, 95% CI 1.25, 1.58, for executive function; social frailty: OR = 1.86, 95% CI 1.45, 2.40, for global cognition; OR = 1.74, 95% CI 1.34, 2.27, for episodic memory; OR = 1.89, 95% CI 1.47, 2.44, for executive function). Moreover, network analysis revealed “loneliness” to be the most influential node in the network.</div></div><div><h3>Conclusions</h3><div>These findings underscore the relevance of social frailty and loneliness to cognitive trajectories and support further research to evaluate whether interventions that enhance social support and reduce loneliness can improve cognitive outcomes in at-risk populations.</div></div>","PeriodicalId":51120,"journal":{"name":"Maturitas","volume":"206 ","pages":"Article 108852"},"PeriodicalIF":3.6,"publicationDate":"2026-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146079304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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