From a recent study published in JAMA network openedresearchers 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 examined the mediating effects of the aging differences on the association.
Study: Hormone therapy and biological aging in postmenopausal women. Image credits: fizkes/Shutterstock.com
Background
Preventing diseases and improving the health of the aging population requires efforts to slow aging and measure 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 of primary importance to the health of women, a population experiencing menopause, a condition associated with estrogen loss. Doctors recommend exogenous systemic estrogen to manage vasomotor symptoms of menopause.
However, there are concerns about the health effects of HT. The Women’s Health Initiative Hormone Trials found that HT increased the risks of stroke and dementia in postmenopausal women.
Observational data from the Nurses’ Health Study suggested that HT may protect against major coronary events. Determining the health effects of HT is crucial for current practice.
About the study
The researchers of the current study evaluated the associations between hormonal treatment, SES, and differences between biological and chronological ages in postmenopausal women. They also examined whether the discrepancy mediates the association between hormonal treatment and mortality risk.
The study included 117,763 postmenopausal female participants from the United Kingdom Biobank, aged 40 to 69 years. Between March 2006 and October 2010, the researchers surveyed participants about the use of hormonal therapy and markers of biological aging.
They analyzed the data in December 2023. The study exposures included use of hormonal therapy, age of initiation and duration of treatment, with related data obtained from digital questionnaires.
The primary study outcome was the discrepancy in biological aging evaluated by phenotypic age. Researchers calculated biological age through proportional hazard modeling using participants’ chronological age and nine biomarkers obtained from participants’ biological samples. Linear regressions determined the discrepancy between the biological and chronological ages.
Indicators of socio-economic status included education, occupation, income and the Townsend Deprivation Index. The National Health Service Information Centers 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 determined the cause of death.
Cox proportional hazards regressions calculated hazard ratios (HR) adjusted for education, ethnicity, physical activity, nicotine and tobacco exposure, hypertension, diabetes, chronic kidney disease, bilateral oophorectomy, and hysterectomy.
In sensitivity analyses, researchers retained current HT users and considered hormonal treatment users as one category. They excluded individuals with bilateral oophorectomy or hysterectomy and those who completed the biological aging assessment within one year of the survey.
They used the restricted cubic spline method and performed segmented regression analyses, excluding women who entered menopause before age 44.
Results
Of the 117,763 postmenopausal women (average age 60 years), 47,461 (40%) have ever used hormonal therapy. The average biological age of the participants was 52 years. HT recipients were less educated and had lower annual income, higher nicotine exposure, more frequent comorbidities, and a higher rate of bilateral oophorectomies and hysterectomies than HT nonrecipients.
HT use was associated with 0.2 years less aging difference than non-HT use. This lower discrepancy in aging compared to non-users was especially pronounced among individuals who started hormonal therapy at age 55 or older and among those who received treatment for four to eight years.
Starting hormone therapy after age 45 reduced aging differences, while those who started before age 44 experienced higher aging differences compared to non-users.
The relationship between hormonal treatment and lower biological aging discrepancy was more pronounced in women of low socioeconomic status, with significant interactions for education.
Biological age differences significantly influenced the relationship between HT use and mortality risk. The discrepancy mediated 13%, 19%, and 8.3% of the associations between hormonal treatment and mortality from any cause, cardiovascular disease, and cancer, respectively. Sensitivity analyzes 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 of low socioeconomic status.
Use of HT for four to eight years is associated with 0.3 years less discrepancy in biological aging, which mediated 8.3% to 19% of the relationship between hormonal treatment and mortality.
The relationship between hormonal treatment and lower aging discrepancy was more prominent before age 48 years and within 7.4 years, with an inverse relationship for HT use longer than 7.4 years. Promoting HT among postmenopausal women could be crucial for healthy aging; however, further research could evaluate the clinical benefits.