Hormone therapy use may slow biological aging for postmenopausal women
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Key takeaways:
- Current or past menopausal hormone therapy use was tied to a small biological aging discrepancy vs. never use.
- The association was stronger for women of lower socioeconomic status.
Postmenopausal women with a history of hormone therapy use were biologically younger compared with never-using counterparts, regardless of socioeconomic background, according to study results published in JAMA Network Open.
“We found that historical HT [use] was related to a slower biological aging pace, especially in postmenopausal women with disadvantaged socioeconomic status,” Chenglong Li, PhD, a postdoctoral fellow at the National Institute of Health Data Science at Peking University in Beijing, told Healio. “Moreover, we found the slower biological aging pace was more evident in postmenopausal women receiving hormone therapy after age 55 years or historically using HT for 4 to 8 years, supporting the hypothesis of appropriate timing of receiving HT.”
Li and colleagues conducted a population-based, retrospective cohort study using data from 117,763 postmenopausal women (mean age, 60.2 years) registered in the UK Biobank. At baseline, all participants completed a survey providing data on HT use and biological aging biomarkers from March 2006 to October 2010. Researchers assessed socioeconomic status by education, family income, occupation and the Townsend deprivation index.
Primary outcome was biological aging discrepancy assessed using validated phenotype age calculated through chronological age and nine biomarkers from baseline. Secondary outcomes included all-cause and cause-specific mortality.
Overall, 40.3% of postmenopausal women reported ever having used HT. Mean phenotypic age was 52.1 years for all postmenopausal women.
Current or past HT use was associated with 0.17 fewer years of aging discrepancy compared with never use (P < .001). This discrepancy was more apparent for women who initiated HT at age 55 years or older and for women who used HT for 4 to 8 years, with 0.32 and 0.25 fewer years of aging discrepancy, respectively.
Current or prior HT use was associated with a smaller aging discrepancy, regardless of socioeconomic status. However, the association between HT use and a smaller aging discrepancy was more apparent for women with low socioeconomic status. Researchers observed interactions for higher education and other education, with 0.08 and 0.23 fewer years of aging discrepancy, respectively (P = .02).
In addition, 12.7% of associations with all-cause mortality were explained by ties between HT use and phenotypic aging discrepancy. For cause-specific mortality, 19.3% of associations with CVD and 8.3% of associations with cancer mortality were explained by ties between HT use and phenotypic aging discrepancy.
“Due to the nature of observational study, we could not make formal conclusions about the causal relationships between HT and biological aging,” Li told Healio. “Further investigations capable of making causal inference, especially high-quality randomized controlled clinical trials, are needed to confirm our findings.”
For more information:
Chenlong Li, PhD, can be reached at chenglongli@bjmu.edu.cn
Perspective
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Nanette Santoro, MD
If you are looking to see if hormone therapy makes a difference in mortality for women, this is not a preferred study design. It is a retrospective cohort study, which means users and nonusers of HT may differ in meaningful ways that are related to mortality, thereby attributing a benefit to hormones that might not exist.
Table 1 in the study shows that almost all of the characteristics of the two populations differ. This is likely to be true because doctors are less likely to prescribe HT to women who are relatively unhealthy. Nonusers of hormones are handicapped from the start in a study design like this. Not surprisingly, women with hysterectomy and oophorectomy were overrepresented in the hormone user group. This is also important because there may be some differences in health among these groups that alter their risk for disease or response to hormones. Bottom line: The whole point of performing randomized controlled studies is to eliminate these kinds of biases that you really cannot explain or fully mathematically adjust away when conducting your analysis.
All of the beneficial data quoted in the discussion regarding CVD and dementia indicate large improvements and reductions in disease, but these are observational studies. The Danish Osteoporosis Prevention Study, in fact, shows the exact opposite finding for dementia.
Perhaps most egregious in terms of scholarship is the inclusion of a review article by Howard Hodis, MD, to which the authors have lifted a quote indicating that many lives would be “saved” by HT. Again, this is not supported by any randomized trial. A follow-up of the Women’s Health Initiative (WHI) indicated that lives were saved by not taking HT.
Importantly, nowhere in the publication do they tell us the “biomarkers” they selected. They simply quote another publication that claims they are a good idea.
Importantly, a 17-year follow-up of the WHI did not show hormones extended life for women. Only women who took HT in the age group 50 to 59 years demonstrated a reduction in overall mortality, and that was one among a large number of analyses, so its validity remains to be tested in an appropriate randomized controlled trial.
Overall, this is a suboptimal study design to answer the question posed, with an unclear selection of biomarkers and no real discussion of the relative merits of one biomarker over another. The findings suggest a small effect size, although it meets “statistical significance,” along with an overinterpretation of the data to suggest HT will extend women’s lives.
This is a publication for the times. Menopause is having a moment and everyone wants to take a “position” on it. However, when you look at the factual data that are out there, there is not a lot of support for HT being a miraculous life extension therapy. I fear that this publication will make headlines with that tag. The best the authors can attribute to hormones here is a 0.2-year improvement in “aging.” That is a month or two of life in exchange for years — or perhaps decades — of taking hormones. And those women will have to gamble that they escape the known risks for breast cancer, blood clots and dementia to make those 2 months worthwhile.
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