Quick-term and cyclical use of estrogen and progestin remedy for menopausal signs is linked to an elevated threat of dementia, outcomes of a big, observational examine present.
Investigators discovered that girls of their 50s who took hormone alternative remedy (HRT) for menopausal signs had a 24% elevated threat of growing dementia and Alzheimer’s illness (AD) 20 years later in contrast with those that did not use HRT. The danger was current even in ladies who used HRT for transient intervals at menopause onset.
Nonetheless, each the investigators and specialists not concerned within the analysis warning that additional research are wanted to discover whether or not the elevated threat of dementia stems from HRT use or whether or not ladies in want of HRT produce other underlying dementia threat elements.
“We can not assure that our findings illustrate a causal relationship, or in the event that they signify underlying disposition to dementia in ladies in want of HRT,” lead investigator Nelsan Pourhadi, MD, from the Danish Dementia Analysis Centre at Copenhagen College Hospital Rigshospitalet, advised Medscape Medical Information.
Nonetheless, he added, the findings supported proof from the Girls’s Well being Initiative Reminiscence Research (WHIMS), the biggest randomized trial on menopausal hormone remedy and dementia.
The findings have been printed on-line June 28 in BMJ.
Earlier than WHIMS was printed in 2003, HRT was broadly prescribed to alleviate menopausal signs. Nonetheless, WHIMS, which included greater than 4000 ladies aged 65 years or older, revealed that HRT was related to a twofold elevated threat of dementia.
Research printed since then have yielded blended outcomes, including to the controversy surrounding the protection of HRT.
To find whether or not age of initiation or size of period of HRT impacts well being outcomes, Pourhadi and his workforce undertook the observational examine.
Between 2000 and 2018, the researchers tracked greater than 60,000 Danish ladies aged 50 to 60 years utilizing prognosis and prescription info from Denmark’s Nationwide Registry of Sufferers.
The registry information confirmed that just about 5600 ladies developed dementia and 56,000 didn’t develop dementia. Of the 5600 ladies with dementia, 1460 had a prognosis of AD.
Almost 18,000 individuals within the examine pattern obtained HRT — 1790 (29%) within the dementia group and 16,150 (32%) within the management group. Half began remedy earlier than age 53 years and half stopped inside 4 years. Roughly 90% used oral medicines, which included a mix of estrogen and progestin.
The median age at which individuals began HRT was 53 years for each instances and controls, and the median period of use was 4 years.
Longer Use Equals Larger Danger
In contrast with those that didn’t use HRT, those that used estrogen-progestin remedy had a 24% elevated threat of growing all-cause dementia (hazard ratio [HR], 1.24; 95% CI, 1.17 – 1.44).
The elevated dementia threat was comparable between steady (estrogen and progestin taken each day) and cyclic (each day estrogen with progestin taken 10 to 14 days a month) remedy regimens.
Longer durations of HRT use have been related to elevated threat, starting from a 21% elevated threat (HR, 1.21; 95% CI, 1.09 – 1.35) for individuals who used it for 1 yr or much less to a 74% elevated threat (HR, 1.74; 95% CI, 1.45 – 2.10) to be used lasting 12 years or extra.
Girls who began HRT between the age of 45 and 50 had a 26% elevated threat of growing all-cause dementia (HR, 1.26; 95% CI, 1.13 – 1.41) whereas ladies who initiated HRT between age 51 and 60 had a 21% better threat (HR, 1.21; 95% CI, 1.12 – 1.29).
Progestin-only or vaginal-estrogen-only remedy was not related to the event of dementia.
The investigators famous that as a result of that is an observational examine, “additional research are warranted to discover if the noticed affiliation on this examine between menopausal hormone remedy use and elevated threat of dementia illustrates a causal impact.”
No Causal Relationship
In an accompanying editorial, Kejal Kantarci, MD, a professor of radiology on the Mayo Clinic in Rochester, Minnesota, famous that three medical trials, together with the WHIMS of Youthful Girls (WHIMS-Y) in 2013, didn’t present a hyperlink between cognitive perform and HRT.
“Though Pourhadi and colleagues’ examine was completed fastidiously utilizing nationwide registries, the noticed associations may very well be artefactual and shouldn’t be used to deduce a causal relationship between hormone remedy and dementia threat. These findings can not inform shared resolution making about use of hormone remedy for menopausal signs,” she states within the editorial.
Additionally commenting on the findings, Amanda Heslegrave, PhD, a senior analysis fellow on the UK Dementia Analysis Institute in London, England, mentioned in a launch from the UK’s Science Media Centre that whereas the examine “might trigger alarm for ladies taking HRT, it highlights simply how a lot we nonetheless do not know in regards to the results of hormones on ladies’s mind well being, and with promising therapies on the horizon it needs to be a name to motion to make this a precedence space of analysis.”
There was no particular funding for the examine. Kantarci reported engaged on an unpaid academic exercise on Alzheimer’s illness for Biogen Inc. and is the PI on a examine of a PET imaging ligand for Alzheimer’s illness, to which Eli Lilly and Avid Radiopharmaceuticals donated provides.
BMJ. 2023;381:e072770, p1404. Full textual content, Editorial
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