HRT linked to lower mortality risk, but less so with impaired blood sugar
Hormone replacement therapy is associated with a lower risk of death after menopause. But in women with impaired blood sugar regulation, that benefit appears to diminish as biological aging accelerates.
Hormone replacement therapy (HRT) is widely used around and after the menopause. Researchers wanted to know whether its protective effect depends on how fast someone is biologically aging, and on blood sugar levels. They drew on data from the National Health and Nutrition Examination Survey, using so-called epigenetic aging clocks: tools that estimate how quickly cells are aging biologically, based on chemical tags on the genetic material.
What the clocks revealed
According to the study, HRT was associated with a lower risk of all-cause mortality (hazard ratio: 0.65) and cardiovascular mortality (hazard ratio: 0.52). Higher expression of the estrogen receptor alpha (ESR1) was also associated with slower biological aging on one of the clock measures.
The most striking pattern emerged in women with abnormal blood sugar. In this group, the survival benefit of HRT appeared to diminish as biological aging accelerated. No such pattern was seen in women with normal blood sugar levels. The researchers describe this as a counteracting interaction: HRT and accelerated biological aging work against each other, but only when blood sugar regulation is impaired.
What this does and does not mean
This study tracks patterns in existing data. It identifies associations, not causes. The researchers could not fully account for all the differences between the groups. It also remains unclear whether the biological aging clocks are equally accurate in women using HRT. The authors acknowledge that the clocks and the therapies are currently being tested and refined at the same time.
The study was published in Biology of Sex Differences.
Search terms to explore further: epigenetic aging clock, chemical tags on DNA and the menopause, blood sugar levels and HRT survival