Is hormone therapy keeping postmenopausal women ‘younger’?

Hormone therapy (HT) may help postmenopausal women stay biologically younger, meaning their phenotypic age less than their chronological age. It also impacts all-cause mortality, especially among those who have lower socioeconomic status (SES).While numerous studies have investigated the effects of HT and risks on cardiovascular disease (CVD), dementia and other health issues, there have been no studies investigating HT and biological aging, according to a study in JAMA Network Open.“Our study may offer a new perspective regarding the potential health benefits of HT use because of the continually increasing demand for therapy for postmenopausal women,” the authors wrote.The goal was to investigate the associations between HT use in postmenopausal women, the timing of starting treatment; phenotypic age discrepancy; and the potential impact of socioeconomic status (SES). Phenotypic age was compared to chronologic age in women who took HT and compared to those who did not use the therapy. All-cause, and cause-specific, mortality were also assessed.Phenotypic age is a biological aging measure which is calculated using nine biomarkers known to be associated with mortality risk, and chronological age. The biomarkers included albumin, creatinine, glucose, C-reactive protein, lymphocyte percent, mean cell volume, red blood cell distribution width, alkaline phosphatase, and white blood cell count.“The ‘phenotypic age discrepancy’ is calculated as the difference between phenotypic age and chronological age. In that case, a negative phenotypic age discrepancy actually means the individual is younger than their chronological age,” study coauthor Chenglong Li, PhD told the Medical Post. She is from the National Institute of Health Data Science at Peking University.The population-based, retrospective cohort study included 117,763 postmenopausal women who were registered in the UK Biobank. There were details of HT use from baseline questionnaires that were conducted from March 2006 to October 2010, as well as data that could be used for calculating phenotypic age. Education, occupation, household incomes and other SES details were also known.Overall, participants had a mean age of 60.2 years, and 47,461 (40.3%) had ever used HT. The mean phenotypic age of the overall population was 52.1 years.A total of 70,302 participants had never used HT. They had a mean chronologic age of 59.3 years and phenotypic age of 51.2 years. The remaining 47,461 had ever used HT and had a mean chronologic age of 61.6 years and phenotypic age of 53.5 years.After controlling for various factors, the analyses showed that having ever used HT was associated with 0.17 fewer years of aging discrepancy.This “means postmenopausal women historically receiving HT were 0.17 years biologically younger than their counterparts,” Dr. Li told said. The researchers cited a study from 2018 which used data from NHANES which showed that middle-aged adults who had one major chronic disease were an average of 0.2 years older in phenotypic age than disease-free counterparts. Moreover, each one-year increment in phenotypic age, which was adjusted for chronological age, was associated with up to 9% higher all-cause, and a 20% higher cause specific, mortality risk. Dr. Li and her team stated “the 0.25 years of delayed aging observed in our study could translate to approximately 2.25% decreased risk of all-cause mortality and 5% decreased risk of cause-specific mortality. Therefore, the observed magnitude of associations in our study could be relevant for current clinical practice.”In other words, that 0.25 years is almost three months of biological aging discrepancy. And this was for those who used HT for four to eight years, she said.When HT was started made a difference. Starting HT after age 45 years was associated with a smaller aging discrepancy, while a larger aging discrepancy was observed in those who started HT before age 44 years compared to individuals who never used HT.This smaller aging discrepancy was more evident in those who started HT at age 55 years or older and in those who used HT for four to eight years, said Dr. Li.One of the biggest anti-aging effects from HT use was seen in women with lower SES.Analyses also showed that use of HT was associated with a decreased mortality risk, especially from cardiovascular disease, something that is echoed in other studies.The study did not speculate on possible mechanisms on how HT might affect phenotypic among women or why SES or other factors might make a difference. But they did add that further investigations are warranted.Other studies in the medical literature concur that HT offers protective effects against CVD. In one overview of menopausal hormone replacement therapy (HRT) in a 2022 issue of the Cancer Journal stated that much of the benefit is about timing.When HRT is initiated in women under 60 years of age, or less than 10 years since menopause, HRT can significantly reduce all-cause mortality and CVD, even moreso than therapies such as lipid-lowering, according to the University of Southern California authors.Studies suggest it does this by helping maintain healthy epithelium. But HRT is more effective at doing this if it is started before endothelium health declines and plaque starts building up, hence the importance of timing.CVD is important in looking at mortality overall because it is the number one killer of women causing 1 in 3.2 deaths in women each year in the U.S.

Is hormone therapy keeping postmenopausal women ‘younger’?

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