Phenotypic age is a popular measure of biological age, in part because it is easily calculated using a few commonly available assays conducted on a blood sample. One of the interesting items in this study is the fact that average phenotypic age is somewhat lower than chronological age in a large population of older women. The other is that hormone replacement therapy has only a small effect on phenotypic age. As is the case for all current assessments of biological age, the actual utility of phenotypic age for an individual remains to be determined. Is it actionable, will it accurately reflect the effects of a particular intervention on future life expectancy? These questions do not have satisfactory answers at present.
Among the 117,763 postmenopausal women in the UK Biobank (mean [SD] age, 60.2 [5.4] years), 47,461 (40.3%) had ever used hormone therapy (HT). The mean (SD) phenotypic age of the whole population was 52.1 (7.9) years. Individuals who had ever used HT were older in chronological and phenotypic age and less educated, and they had a lower income, higher exposure to nicotine, more prevalent chronic diseases, and higher proportions of bilateral oophorectomy and hysterectomy than those who never used HT.
In our study, using HT for 4 to 8 years was associated with 0.25 fewer years of biological aging discrepancy. In a previous study, middle-aged adults with 1 major chronic disease were an average of 0.2 years older in phenotypic age than disease-free counterparts. Moreover, each 1-year increment in phenotypic age (adjusted for chronological age) was associated with as much as a 9% higher all-cause and a 20% higher cause-specific mortality risk. Accordingly, the 0.25 years of delayed aging observed in our study could translate to approximately 2.25% decreased risk of all-cause mortality and 5% decreased risk of cause-specific mortality. Therefore, the observed magnitude of associations in our study could be relevant for current clinical practice.
In conclusion, postmenopausal women with historical HT use were biologically younger than those not receiving HT, with a more evident association observed in those with low SES. The biological aging discrepancy mediated the association between HT and decreased mortality. Promoting HT in postmenopausal women could be important for healthy aging.
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