Hormone Therapy May Slow Biological Aging in Women, Study Suggests

Postmenopausal women who have used hormone therapy may be biologically younger than those who have not, a retrospective study of women in the U.K. Biobank suggested.

Examining nine biomarkers linked with mortality risk, adjusted analyses showed historical use of hormone therapy to be associated with a smaller discrepancy between phenotypic and chronological age (-0.17 years vs never use, 95% CI -0.23 to -0.10), an association that was more evident in women of lower socioeconomic status.

Furthermore, analyses showed that this phenotypic age discrepancy mediated the association between hormone therapy use and decreased mortality risk, reported Chenglong Li, PhD, of the National Institute of Health Data Science at Peking University, and Yufan Liu, of Capital Medical University, both in Beijing.

“These findings support HT [hormone therapy] use in postmenopausal women to promote healthy aging and address related health inequalities,” they wrote in JAMA Network Open.

While any duration of hormone therapy use was linked with a smaller biological age discrepancy, the largest magnitude of effect was seen with 4 to 8 years of use (-0.25 years, 95% CI -0.35 to -0.15), which could translate to about a “2.25% decreased risk of all-cause mortality and 5% decreased risk of cause-specific mortality,” wrote Li and Liu. “Therefore, the observed magnitude of associations in our study could be relevant for current clinical practice.”

But “further investigations capable of making causal inferences are warranted to confirm our findings,” Li told MedPage Today, as hormone therapy doesn’t come without its concerns.

“There have been debates regarding the risk and benefit of hormone therapy in postmenopausal women,” he said. “For instance, the Women’s Health Initiative Hormone Trials revealed that hormone therapy increased the risks of stroke and probable dementia. However, reports from the Nurses’ Health Study showed potentially protective roles of hormone therapy against major coronary events. These inconsistent findings raise concerns about the appropriateness of initiating hormone therapy.”

The Menopause Society states the benefit-risk ratio of hormone therapy is favorable to treat vasomotor symptoms and prevent bone loss for women 60 and younger or those who are within 10 years of menopause onset and have no contraindications. But the benefit-risk ratio may be less favorable for women over 60 or those who start hormone therapy more than 10 years from menopause onset due to risks of coronary heart disease, stroke, venous thromboembolism, and dementia.

For their population-based cohort study, Li and Liu looked at 117,763 postmenopausal women (96% white, mean 60.2 years) registered in the U.K. Biobank. Baseline surveys from 2006 to 2010 captured use of hormone therapy and the biomarkers of biological aging.

Of those women, 40.3% had ever used hormone therapy. The average chronological age in the cohort was 61.6 years for ever users and 59.3 years for never-users, while the average phenotypic age was 53.5 and 51.2 years, respectively.

Phenotypic age was calculated using chronological age plus nine biomarkers associated with mortality risk: albumin, creatinine, glucose, C-reactive protein, lymphocyte percent, mean cell volume, red blood cell distribution width, alkaline phosphatase, and white blood cell count.

Analyses adjusted for sociodemographic and lifestyle characteristics, major chronic diseases, and a history of bilateral oophorectomy and hysterectomy.

Women who started hormone therapy at age 44 or younger were found to be 0.33 years older in phenotypic age than never users, while those who started at age 45 were biologically younger: by 0.20 years for those starting at ages 45 to 49 and by 0.32 years for those starting at age 50 or older.

Together with these findings, Li said that “the optimal hormone therapy duration for significantly decreasing aging discrepancy can also inform flexible hormone therapy treatment plans in clinical settings.”

The link between hormone therapy and a smaller aging discrepancy was more strongly evident in women with disadvantaged socioeconomic status (annual household income under £31,000 [~$40,000], lack of higher education, not employed, Townsend Deprivation Index). It was also stronger in women with lower levels of physical activity and those who had hypertension, cardiovascular disease, diabetes, and chronic kidney disease.

Phenotypic aging discrepancy mediated 12.7% of the lower all-cause mortality risk with historical hormone therapy use. The association also explained 19.3% of the non-significant link with cardiovascular mortality and 8.3% of the association with cancer-related mortality:

• All-cause mortality: adjusted HR 0.92 (95% CI 0.88-0.96)
• Cardiovascular mortality: adjusted HR 0.93 (95% CI 0.84-1.03)
• Cancer-related mortality: adjusted HR 0.92 (95% CI 0.87-0.98)

Limitations to the study included the reliance on self-reported data regarding hormone therapy. Also, biological age measurements only reflected a single point in time rather than a long-term biological aging trajectory.

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