In a recent study published in JAMA Network Open, researchers evaluated the association between hormone treatment (HT) and the difference between the biological (or phenotypic) and chronological ages of postmenopausal women, stratified by socioeconomic status (SES). They also explored the mediating effects of the aging discrepancy on the association.

Study: Hormone Therapy and Biological Aging in Postmenopausal Women. Image Credit: fizkes/Shutterstock.com

Background

Preventing diseases and improving health in the aging population requires efforts to target delaying aging and measuring the rate of aging to capture population heterogeneity. The discrepancy between biological and chronological age is superior to other aging measures in predicting adverse outcomes.

HT supplies estrogen and is a primary focus concerning the health of women, a population that experiences menopause, a condition associated with estrogen loss. Clinicians recommend exogenous systemic estrogen to manage menopausal vasomotor symptoms.

However, there are concerns regarding the health effects of HT. The Women’s Health Initiative Hormone Trials found that HT increased stroke and dementia risks among postmenopausal women.

Observational data from the Nurses’ Health Study suggested HT may protect against major coronary events. Determining HT’s health effects is crucial for current practice.

About the study

The researchers of the present study evaluated associations between hormonal treatment, SES, and differences between biological and chronological ages among postmenopausal women. They also investigated whether the discrepancy mediates the association between hormonal treatment and mortality risk.

The study included 117,763 postmenopausal female United Kingdom Biobank participants aged 40 to 69. Between March 2006 and October 2010, the researchers surveyed the participants about hormonal therapy use and markers of biological aging.

They analyzed the data during December 2023. The study exposures included hormonal therapy usage, the age of initiation, and treatment duration, with related data obtained from digital questionnaires.

The primary study outcome was the discrepancy in biological aging, evaluated using phenotypic age. Researchers calculated the biological age by proportional hazard modeling using the chronological age of the participants and nine biomarkers obtained from participant biological samples. Linear regressions determined the discrepancy between the biological and chronological ages.

Socioeconomic status indicators included education, occupation, income, and the Townsend Deprivation Index. The National Health Service Information Centres of England and Wales and the National Health Service Central Register of Scotland provided mortality data. The International Classification of Diseases, tenth revision (ICD-10) codes ascertained the cause of death.

Cox proportional hazard regressions calculated the hazard ratios (HR), adjusting for education, ethnicity, physical exercise, nicotine and tobacco exposure, hypertension, diabetes, chronic renal disease, bilateral oophorectomy, and hysterectomy.

In sensitivity analyses, the researchers retained current HT users and considered hormonal treatment users a single category. They excluded individuals with bilateral oophorectomy or hysterectomy and those completing the biological aging assessment within a year of the survey.

They used the restricted cubic spline method and performed segmented regression analysis, excluding women experiencing menopause before 44 years.

Results

Of 117,763 postmenopausal females (mean age, 60 years), 47,461 (40%) ever used hormonal therapy. The mean biological age of the participants was 52 years. HT recipients were less educated, and they had lower annual income, higher exposure to nicotine, more prevalent comorbidities, and higher proportions of bilateral oophorectomies and hysterectomies than HT non-recipients.

HT use was linked to 0.2 fewer years of aging difference than non-HT use. This lower discrepancy in aging compared to non-users was especially pronounced among individuals starting hormonal therapy at 55 years of age or older and among those who underwent treatment for four to eight years.

Initiating hormone therapy after age 45 reduced aging discrepancies, while those initiating before age 44 experienced higher aging discrepancies compared to non-users.

The relationship between hormonal treatment and a lower discrepancy in biological aging was more pronounced among females with low socioeconomic status, with significant interactions for education.

Biological age discrepancy significantly influenced the relationship between HT use and mortality risk. The discrepancy mediated 13%, 19%, and 8.3% of the associations of hormonal treatment with mortality from any cause, cardiovascular disease, and cancer, respectively. Sensitivity analyses yielded similar results.

Conclusion

The study findings showed that postmenopausal women who use hormonal therapy are biologically or phenotypically younger than non-users, especially individuals with low socioeconomic status.

Using HT for four to eight years is associated with 0.3 fewer years of discrepancy in biological aging, which mediated 8.3% to 19% of the relationship between hormonal treatment and mortality.

The relationship between hormonal treatment and a lower aging discrepancy was more prominent before age 48 and within 7.4 years, with an inverse association for HT usage longer than 7.4 years. Promoting HT among postmenopausal females could be crucial for healthy aging; however, further research could evaluate the clinical benefits.