Abstract
Introduction: Menopausal hormone replacement therapy (HRT) is first-line treatment for distressing vasomotor symptoms, and increasingly popular. However data on the association of HRT with ageing-related conditions including frailty is lacking.
Method: We analysed women in the Danish population registry (n=471206) , Danish Twin Registry and TwinsUK cohort (n=1547). In Denmark, we assessed frailty age 65, 70 and 75, using a modified Hospital Frailty Risk Score. This linked to national prescribing data, to ascertain HRT use by age 55, adjusting for birth year, education and income. In TwinsUK, we assessed frailty after age 65 using a frailty index (TwinFI). HRT use, and covariates (BMI, smoking, alcohol use, education and deprivation) were ascertained from retrospective questionnaires. Analysis used conditional/fixed-effects generalised estimating equations, examining within twin-pair frailty associations.
Results: HRT associated with higher frailty scores amongst both Danish women (beta=0.21, P<0.001) and TwinsUK (beta=0.035, p=0.01) equivalent to ageing 5 years. However, in TwinsUK, HRT only associated with higher frailty for the within-pair analyses in dizygotic twins (Dizygotic: beta=0.061, p=0.01, Monozygotic: beta=0.013, p=0.36). This was robust to multiple sensitivity analyses, including HRT subtypes, duration and imputation.
Conclusions: We found an unexpected relationship between HRT use and higher frailty across both Denmark and the UK. However, twin analysis suggests this relationship is not causal, but confounded by factors shared within monozygotic twins, including genetics. Further investigation is needed to determine whether individuals prescribed HRT are already on the path to frailty, and whether this would be an apt opportunity to intervene.
Comments
Really interesting project!…
Really interesting project! A great use of large data sets and an interesting comparison of frailty assessment in the UK and abroad.
Thank you for taking the…
Thank you for taking the time to read the poster and for your comments. It is much appreciated :)
Given these findings, how do…
Given these findings, how do you think clinicians should interpret frailty risk when counselling patients about starting HRT, should frailty screening or baseline risk assessment become part of the conversation?
Thank you for taking the…
Thank you for taking the time to read the poster. The British Menopause Society currently see menopause consultations as an opportunity to implement preventative health measures for women around issues such as cardiovascular disease and osteoporosis. I think in future, the incorporation of frailty could definitely be considered, although we need more work to see what methods might be best for these women. Many may be similar - for example strength training which is beneficial for bone and muscle health as well as frailty.
Interesting study. However…
Interesting study. However there are quite a lot of evidence to suggest that Hormone replacement therapy has protective effects against Frailty for instance preventing osteoporosis and sarcopenia.
Would you consider doing a systemic review or metaanalysis in the future to further enhance the results?
Thank you for your comments…
Thank you for your comments.
Whilst there is evidence that HRT is beneficial for osteoporosis, though perhaps not forever, the evidence for sarcopenia is actually much less solid. The earlier part of my PhD looked at this, reviewing literature on HRT and sarcopenia, both from trials and observational data. We published earlier this year in Maturitas, 10.1016/j.maturitas.2025.108609 - showing that the quality of evidence was quite poor, though there might be a weak protective effect, particularly around the time of the menopause, whilst HRT is still being taken.
At the moment, there are no other studies that we are aware of looking at the frailty syndrome itself and HRT, either measured by frailty indices or a physical phenotype. That genetic confounding plays a significant role will make studies in other types of cohort difficult, though by not impossible.
Ref