In a recent study published in JAMA Network Open, researchers assessed the association between hormone therapy and the difference between biological (or phenotypic) and chronological age in postmenopausal women, stratified by socioeconomic status (SES). They also explored the mediating effects of the aging gap on the association.
Study: Hormone therapy and biological aging in postmenopausal womenPhoto credit: fizkes/Shutterstock.com
Background
Disease prevention and health improvement in the aging population require efforts to delay aging and measure the rate of aging to capture population heterogeneity. The gap between biological and chronological age is superior to other measures of aging in predicting adverse outcomes.
Hormone replacement therapy provides estrogen and is a priority for women’s health, a population experiencing menopause, a condition associated with estrogen loss. Clinicians recommend the administration of exogenous systemic estrogen to manage the vasomotor symptoms of menopause.
However, concerns remain about the health effects of hormone therapy. The Women’s Health Initiative hormone trials found that hormone therapy increased the risk of stroke and dementia in postmenopausal women.
Observational data from the Nurses’ Health Study suggest that heat treatment may protect against major coronary events. Determining the health effects of heat treatment is crucial for current practice.
About the study
The researchers in the current study assessed associations between hormone therapy, socioeconomic status, and differences in biological and chronological ages among postmenopausal women. They also investigated whether this disparity modified the association between hormone therapy and mortality risk.
The study involved 117,763 postmenopausal women from the United Kingdom Biobank, aged 40 to 69. Between March 2006 and October 2010, researchers asked participants about hormone therapy use and markers of biological aging.
They analyzed data through December 2023. Study exposures included hormone therapy use, age of initiation, and duration of treatment, with related data obtained from digital questionnaires.
The primary outcome of the study was the difference in biological aging, assessed using phenotypic age. The researchers calculated biological age by proportional hazards modeling using participants’ chronological age and nine biomarkers obtained from participants’ biological samples. Linear regressions determined the difference between biological and chronological ages.
Socioeconomic status indicators included education, occupation, income, and the Townsend Deprivation Index. The National Health Service Information Centres in England and Wales and the National Health Service Central Register in Scotland provided mortality data. International Classification of Diseases, Tenth Revision (ICD-10) codes were used to determine cause of death.
Cox proportional hazards regressions calculated hazard ratios (HRs), controlling for education, race, exercise, nicotine and tobacco exposure, hypertension, diabetes, chronic kidney disease, bilateral oophorectomy, and hysterectomy.
In sensitivity analyses, the researchers retained current HRT users and considered hormone therapy users as a single category. They excluded people who had undergone bilateral oophorectomy or hysterectomy and those who had completed the biological aging assessment within one year of the survey.
They used the restricted cubic spline method and performed a segmented regression analysis, excluding women who had reached menopause before age 44.
Results
Of 117,763 postmenopausal women (mean age, 60 years), 47,461 (40%) had ever used hormone therapy. The mean biological age of participants was 52 years. Hormone therapy recipients were less educated, had lower annual income, higher nicotine exposure, more frequent comorbidities, and higher proportions of bilateral oophorectomy and hysterectomy than non-hormone therapy recipients.
HRT use was associated with a difference in aging of 0.2 years less than not using HRT. This smaller difference in aging compared with non-users was particularly pronounced among those who started hormone therapy at age 55 or older and among those who had been on treatment for four to eight years.
Initiating hormone therapy after age 45 reduced aging gaps, while those who started before age 44 experienced greater aging gaps compared to non-users.
The relationship between hormone treatment and a smaller difference in biological aging was more pronounced among women with low socioeconomic status, with significant interactions for education.
Biological age difference significantly influenced the relationship between HRT use and mortality risk. Biological age difference accounted for 13%, 19%, and 8.3% of the associations between hormone therapy and all-cause mortality, cardiovascular disease, and cancer, respectively. Sensitivity analyses yielded similar results.
Conclusion
The study results showed that postmenopausal women who use hormone therapy are biologically or phenotypically younger than non-users, particularly those with low socioeconomic status.
Use of HT for four to eight years is associated with a difference in biological aging of 0.3 fewer years, which explains 8.3% to 19% of the relationship between hormone treatment and mortality.
The relationship between hormone therapy and less difference in aging was most pronounced before age 48 and within 7.4 years, with an inverse association for HRT use beyond 7.4 years. Promoting HRT in postmenopausal women may be crucial for healthy aging; however, further research could assess clinical benefits.
