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Background <p>The age-specific magnitude of the impact of hormones on aging and the role of hormone replacement therapy (HRT) remain unclear.</p> Methods <p>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&#xa0;(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> Results <p>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&#xa0;years) while elevated testosterone accelerated aging. In males, testosterone was protective (most significant at 56–70&#xa0;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&#xa0;years) superior to non-HRT (-4.0 to -5.5). HRT initiated at 56–60&#xa0;years showed optimal efficacy, with longer duration associated with more pronounced aging deceleration.</p> Conclusions <p>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&#xa0;years and males aged 65–70&#xa0;years. These findings may facilitate the optimization of HRT timing to maximize anti-aging benefits and enable personalized treatment strategies.</p>

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Divergent impacts of estradiol/testosterone reduction on biological aging: optimal HRT window in females recommended

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月13日

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  • Yicheng Ma,
  • Junming Han,
  • Qihang Li,
  • Xiao Jiang,
  • Yuan Li,
  • Keke Zhang,
  • Ling Gao

摘要

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.