Hormone therapy linked to reduced biological aging

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Hormone therapy (HT) use is associated with a reduced biological age among postmenopausal women, according to a recent study published in JAMA Network Open.¹

As the overall worldwide population ages, more attention has been drawn to the aging process and contributing factors. Biological aging is often used to evaluate the aging process, with data indicating a discrepancy between chronological age and phenotypic age based on factors such as lifestyle and childhood adversity.

HT is a major factor of women’s health, as estrogen production in the ovaries halts during menopause.² While exogenous systemic estrogen is recommended in menopausal women experiencing hot flashes, the health effects of HT are unclear.¹

Investigators conducted a study to evaluate the association between HT and biological aging. Data was obtained from the UK biobank, a large-scale cohort with over 500,000 individuals aged 40 to 69 years.

UK Biobank participants were asked “Have you ever used hormone therapy (HT)?” in a touchscreen questionnaire, with answers including yes, no, do not know, and prefer not to answer. Those who replied yes were asked their age when first using HT and when last using HT.

Relevant data included HT use, age of starting HT, and duration of HT use. Socioeconomic status (SES) was used as an indicator of total household income. Categories included under £18,000, £18,000 to £30,999, £31,000 to £51,999, £52,000 to £100,000, and over £100,000.

Phenotypic age was calculated using a Cox proportional hazard elastic net model. Biomarkers associated with mortality were selected and obtained from participants’ biological samples at baseline. These biomarkers were used alongside chronological age when calculating phenotypic age.

Death certificates from the National Health Service Information Centre and National Health Service Central Register Scotland were assessed to identify the death date and cause of death. Causes of death were determined based on International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes.

Covariates included sociodemographic characteristics, lifestyles, and major chronic diseases. Histories of bilateral oophorectomy and hysterectomy were also considered in the analysis.

There were 117,763 postmenopausal women aged a mean 60.2 years included in the analysis, 40.3% of whom reported a history of HT use. Older chronological and phenotypical age, lower education, lower income, higher nicotine exposure, more prevalent chronic diseases, and higher proportions of bilateral oophorectomy and hysterectomy were reported in HT users vs nonusers.

A history of HT use was linked with 0.17 fewer years of aging discrepancy in the adjusted analysis. The aging discrepancy was reduced in patients starting HT when aged over 45 years, as well as in those with HT use for 4 to 8 years.

A reduced aging discrepancy in HT users vs nonusers was observed regardless of SES. Additionally, an increased aging discrepancy was observed in individuals with a low SES regardless of HT use.

HT use also had significant interactions with education. Aging discrepancies of 5.03 and 4.95 were seen among participants with a higher education who were nonusers and users, respectively. For those with other education, aging discrepancies were 5.71 and 5.48, respectively.

Significant mediation was reported for the association between HT use and mortality risk. The association between HT and phenotype age discrepancy was linked to 12.7% of all-cause mortalities.

These results indicated a reduced biological age among postmenopausal women with HT use vs those without HT use. Investigators recommended further research about the clinical benefits of HT.

References

1. Liu Y, Li C. Hormone therapy and biological aging in postmenopausal women. JAMA Netw Open. 2024;7(8):e2430839. doi:10.1001/jamanetworkopen.2024.30839
2. MiquelJ, Ramírez-BoscáA, Ramírez-BoscaJV, AlperiJD.Menopause: a review on the role of oxygen stress and favorable effects of dietary antioxidants. Arch Gerontol Geriatr. 2006;42(3):289-306. doi:10.1016/j.archger.2005.08.005