{"title":"Divergent impacts of estradiol/testosterone reduction on biological aging: optimal HRT window in females recommended.","authors":"Yicheng Ma, Junming Han, Qihang Li, Xiao Jiang, Yuan Li, Keke Zhang, Ling Gao","doi":"10.1186/s13293-026-00873-1","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The age-specific magnitude of the impact of hormones on aging and the role of hormone replacement therapy (HRT) remain unclear.</p><p><strong>Methods: </strong>We used data from UK Biobank participants for our analysis. Linear and logistic regression models were employed to investigate the associations and its differences between estradiol/testosterone and biological age acceleration (BAA) across different age group. Then, females were divided into HRT and non-HRT groups, and restricted cubic splines were used to evaluate HRT initiation age and duration.</p><p><strong>Results: </strong>A total of 54,912 participants (71.99% females, 28.01% males) were enrolled, with 39,303 females assessed for the impact of HRT on aging. Estradiol decline in females was linked to a 0.18-0.29-year BAA increase, while testosterone decline in males was linked to a 0.07-0.71-year BAA increase. It showed estradiol protected against aging in females (most prominent at 41-55 years) while elevated testosterone accelerated aging. In males, testosterone was protective (most significant at 56-70 years) and estradiol had no notable effect. Quartile and age-stratified analyses confirmed these findings. In contrast, the decrease of estradiol was associated with biological age younger. Hormone replacement therapy (HRT) in females resulted in sustained BAA reduction (-4.5 to -6.0, 41-70 years) superior to non-HRT (-4.0 to -5.5). HRT initiated at 56-60 years showed optimal efficacy, with longer duration associated with more pronounced aging deceleration.</p><p><strong>Conclusions: </strong>The impact of per standard deviation (SD) decrease in sex hormone levels on aging (BAA) varies by age, with significant effects observed in females aged 50-55 years and males aged 65-70 years. These findings may facilitate the optimization of HRT timing to maximize anti-aging benefits and enable personalized treatment strategies.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":" ","pages":""},"PeriodicalIF":5.3000,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13097923/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biology of Sex Differences","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13293-026-00873-1","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0
Abstract
Background: The age-specific magnitude of the impact of hormones on aging and the role of hormone replacement therapy (HRT) remain unclear.
Methods: We used data from UK Biobank participants for our analysis. Linear and logistic regression models were employed to investigate the associations and its differences between estradiol/testosterone and biological age acceleration (BAA) across different age group. Then, females were divided into HRT and non-HRT groups, and restricted cubic splines were used to evaluate HRT initiation age and duration.
Results: A total of 54,912 participants (71.99% females, 28.01% males) were enrolled, with 39,303 females assessed for the impact of HRT on aging. Estradiol decline in females was linked to a 0.18-0.29-year BAA increase, while testosterone decline in males was linked to a 0.07-0.71-year BAA increase. It showed estradiol protected against aging in females (most prominent at 41-55 years) while elevated testosterone accelerated aging. In males, testosterone was protective (most significant at 56-70 years) and estradiol had no notable effect. Quartile and age-stratified analyses confirmed these findings. In contrast, the decrease of estradiol was associated with biological age younger. Hormone replacement therapy (HRT) in females resulted in sustained BAA reduction (-4.5 to -6.0, 41-70 years) superior to non-HRT (-4.0 to -5.5). HRT initiated at 56-60 years showed optimal efficacy, with longer duration associated with more pronounced aging deceleration.
Conclusions: The impact of per standard deviation (SD) decrease in sex hormone levels on aging (BAA) varies by age, with significant effects observed in females aged 50-55 years and males aged 65-70 years. These findings may facilitate the optimization of HRT timing to maximize anti-aging benefits and enable personalized treatment strategies.
期刊介绍：
Biology of Sex Differences is a unique scientific journal focusing on sex differences in physiology, behavior, and disease from molecular to phenotypic levels, incorporating both basic and clinical research. The journal aims to enhance understanding of basic principles and facilitate the development of therapeutic and diagnostic tools specific to sex differences. As an open-access journal, it is the official publication of the Organization for the Study of Sex Differences and co-published by the Society for Women's Health Research.
Topical areas include, but are not limited to sex differences in: genomics; the microbiome; epigenetics; molecular and cell biology; tissue biology; physiology; interaction of tissue systems, in any system including adipose, behavioral, cardiovascular, immune, muscular, neural, renal, and skeletal; clinical studies bearing on sex differences in disease or response to therapy.
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