Hormone Therapy May Slow Biological Aging in Postmenopausal Women

Hormone therapy (HT) may slow down biological aging in postmenopausal women, according to research from Peking University. The study, published in JAMA Network Open, could play an important role in promoting healthy aging.

Menopause, HT and senescence

As the global population ages, there is a growing need for more research into understanding the aging process. Senescence, also called biological aging, refers to the gradual accumulation of cell and tissue damage that occurs as an individual ages. While biological age is influenced by a person’s chronological age, these two numbers can differ. Factors such as genetics, lifestyle, nutrition and diseases also impact senescence. One method to assess biological age is by calculating phenotypic age, which uses a machine learning approach to estimate morbidity and mortality risks independently of chronological age.

Menopause has been linked to accelerated biological aging. This transition typically occurs at midlife and is characterized by a decline in estrogen levels. Although menopause is a natural stage of aging, women who experience early menopause have been found to show increased epigenetic age acceleration in the blood.

Many women are recommended HT to help manage menopausal symptoms, however, there are concerns surrounding its potential health risks. Recent studies have indicated that HT use may be associated with an increased risk of dementia, with the age at which HT is started possibly influencing this risk. Understanding the full effects of HT on the body and its impact on biological age is vital for progressing women’s health.

Earlier HT use is associated with increased biological age

A total of 117,763 participants were selected from the UK Biobank with baseline surveys used to record their use of HT. Phenotypic age was calculated for each participant based on nine biomarkers that were selected based on their association with mortality risk. Multivariable linear regression models were then used to assess associations of HT use, including whether HT was used, the age of starting and the duration of HT use, with phenotypic age discrepancy.

“We found a slower biological aging pace was observed in women initiating HT post midlife, while initiating HT in early menopause was related with a faster aging pace,” said corresponding author Dr. Chenglong Li, postdoctoral fellow of health data science at Peking University.

Women who started HT before age 45 were found to be 0.33 years older, in phenotypic age, compared to participants who had never taken HT. Whereas those that started HT post 45 years, were between 0.20–0.32 years biologically younger.

Duration of HT was also associated with a decrease in biological age. Women who used HT for 4–8 years experienced a delay in aging of 0.25 years, equivalent to a 2.25% decreased risk of all-cause mortality and a 5% decreased risk of cause-specific mortality.

Socioeconomic status impacts biological aging in postmenopausal women

Li also investigated the role of socioeconomic status (SES) on the association of biological age and HT. The participant’s total household income, education qualifications and occupation were recorded at baseline.

HT users had a smaller discrepancy between their phenotypic and chronological ages, compared to those who had never used HT, regardless of their SES. However, individuals with lower SES had a larger discrepancy regardless of HT use.

Balancing the risks and benefits of HT

“Our study indicates the crucial significance of accounting for HT initiating timing when determining the harms/benefits. Moreover, we found the potential effects of HT on aging were more evident in women with disadvantaged socioeconomic status, showing that this subgroup of women might benefit from an appropriate HT regime,” said Li.

Further research is needed to fully understand the role of HT and how its timing, and duration, impact biological aging.

“Despite the many other possible explanations, we think the abnormal menopause process could be the possible pathway linking HT usage and the biological aging pace. Previous reports showed that women with premature menopause had elevated odds of developing multimorbidity, with the autoimmune processes viewed as a hidden mechanism. This potential mechanism is supported by our findings, showing that women initiating HT before age 44 years (an indication of experiencing early menopause) had a faster biological aging pace, unlike women experiencing a “natural” menopause process,” said Li.

“The decision of initiating HT should be made cautiously, with appropriate clinical evaluations and personalized assessments warranted. Public policies may have to avoid over-exaggeration of the health benefits of HT and improve regulations to foster a healthy, sustainable system,” Li concluded.

Reference: 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

About the interviewee:

Dr. Chenglong Li is a postdoctoral fellow at the National Institute of Health Data Science at Peking University, where he focuses on life-course epidemiology, chronic disease epidemiology and cognitive aging. Li holds a Bachelor of Medicine from the School of Public Health at Shanxi Medical University, and a Doctor of Medicine in Sciences in Clinical Research at Peking University Clinical Research Institute.