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HRT does not affect cognition if given early during menopausal transition

Pearl Toh
31 Jul 2018

There is no evidence that hormone replacement therapy (HRT) may affect cognitive ability, especially when it is initiated early on during menopausal transition, according to studies presented at AAIC 2018, suggesting a need to rethink the long-held belief that HRT may negatively affect cognition.

“These findings add to our understanding of the complex effects of hormones on the brain,” said lead author Dr Carey Gleason of University of Wisconsin School of Medicine and Public Health in Madison, Wisconsin, US, who noted that Alzheimer’s disease (AD) or other dementias are more prevalent in women than men. The reasons behind this disparity between genders are not yet clear, although several biological and social reasons have been proposed, such as the longer average lifespan of women vs men, whereby old age is a known risk factor for AD.

Previously, a series of studies from the WHIMS* cohort showed that oestrogen plus progestin therapy may increase the risk of probable dementia in postmenopausal women aged 65 years. [JAMA 2003;289:2651-2662; JAMA 2003;289:2663-2672] However, the WHIMSY** study indicated that CEE-based hormone therapy initiated near the time of menopause conferred no cognitive benefit nor detriment in the study population, except in older women . [J Gerontol A Biol Sci Med Sci 2017;72:838-845]

To address the controversies, two new studies — KEEPS-Cog*** and ELITE-Cog# — were conducted and the data presented in the recent AAIC 2018. [AAIC 2018, abstract 22970]

In KEEPS-Cog, 662 women who were within 3 years of the last menstrual period were randomized to HRT or placebo for 4 years. Women who took HRT showed comparable performance as those on placebo across multiple cognitive domains tested. Furthermore, a form of HRT known as oral conjugated equine oestrogen (CEE) was associated with additional benefits of improvement in mood and reductions in depressive and anxiety symptoms.

Another trial, ELITE-Cog, enrolled women who were within 6 years of menopause or more than 10 years past menopause. All participants received oral oestradiol for 5 years. The researchers found no benefit or harm of HRT on the cognition of either group of women. 

The investigators went on to re-examine the data from the WHIMS study in order to compare the cognitive effects of HRT in women subgroups of different age. In the WHIMS-Young study which enrolled women aged 50–54 years who were randomized to HRT or placebo, there was no significant difference in cognitive scores between the two groups. In contrast, women who received HRT in WHIMS (which enrolled women aged 65–79 years) showed persistently worsening working memory, global cognition, and executive functioning compared with the placebo group.   

Moreover, the WHIMS study also showed that women with type 2 diabetes who took the HRT CEE had increased risk of both cognitive impairment and probable dementia, when compared with age-matched counterparts free of diabetes as well as those with diabetes but were receiving placebo.    

“Altogether, data suggest that HRT is not associated with cognitive harm when therapy is initiated proximal to the menopausal transition, and/or when women are healthy, eg, nondiabetic,” said Gleason, who noted that nonetheless, the long-term effects of menopausal HRT remain unclear.

“These data are sorely needed to guide women’s health care during and after the menopausal transition and to help women make personalized and informed decisions regarding management of their menopausal symptoms and the prevention of future adverse health outcomes,” she added.

 

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