Summary: Menopausal testosterone therapy ( MHT) has nuanced effects on mental health, influenced by factors like age, cure period, and past medical history. The research found that while prior MHT people did not show any significant differences from non-users, present MHT users had longer mental age gaps and smaller cortical volumes.
Also, women who stopped MHT later in life or used it long had larger mental age gaps. These findings emphasize the need for individual approaches to MHT employ given its varied effects on mental health.
Important Facts:
- MHT’s effect on brain wellbeing depends on era, duration, and medical history.
- Recent MHT users had older mind era gaps and smaller cortical volumes.
- Due to the complex brain consequences, personalized MHT strategies are required.
Origin: covering
A research suggests that menopausal estrogen therapy ( MHT) may have moderate effects on mental health, but this depends on past medical history, the length of care, and a person’s age at last use.
Editors praised the study’s use of a robust type of mental age to explore the connections between MHT and mental wellbeing in a sizable population of English women. It was published on October 8 as a Reviewed Preprint in eLife.
The authors point out that a topic of great importance needs to be understood in order to provide effective and individual medical care to women going through menopause.
Ovarian hormones like oestrogens and progesterone fluctuate throughout a woman’s life, particularly during the years leading up to menopause, when ovarian function begins to decline.
The evidence to support this theory is contradictory, but MHT is frequently prescribed to lessen these symptoms during the menopause. It is frequently believed to protect the brain and lessen the risk of Alzheimer’s disease.  ,
According to lead author Claudia Barth, a researcher in the Diakonhjemmet Hospital, Oslo, Norway,” Mixed findings from previous studies of MHT and brain health raise the question whether a combination of timing, formulation, and route of administration might play a crucial role in the effectiveness of MHT.”  ,
” In this study, we investigated links between MHT variables, different MHT regimes, genetic factors, and brain measures in middle-to older aged women” . ,
The researchers used data from the UK Biobank, which contains de-identified genetic, lifestyle and health information and biological samples. Nearly 20, 000 women who had MRI brain scans, who were either current or former MHT users or who had never used MHT before, most of whom said they had menopaused.
They examined brain MRI images to find out the “brain age gap,” or the difference between chronological and chronological age, as well as other proxies of brain health.  ,
The team says the results were puzzling. Women who had previously used MHT did not notice a difference in brain age between never-users and women. However, women who are currently using MHT had on average higher grey and white matter brain age gaps than women who have never taken MHT, which indicates that their brain age was older than their actual chronological age. Additionally, the brains of their left and right hippocampuses were smaller.  ,
Moreover, amongst past users, the age the women were when they last took MHT made a difference. People who were older at the time of their last menopause use had a larger brain age gap and smaller hippocampal volumes. Women who took MHT for a longer period of time found similar results.  ,
Women on MHT  had a lower brain age gap than women on MHT , but they had less surgical history and had less womb and/or both ovaries removed. And unexpectedly, there was no difference in MHT-related variables such as dose or active ingredients, whether it was synthetic or bioidentical, or taken as a pill or a patch.  ,
No connection was established between the findings and the study’s investigation into whether APOE 4, a known risk gene for Alzheimer’s disease, had an impact on MHT’s ability to affect proxies of brain health.  ,
The authors note that while some minor adverse brain health characteristics were related to current MHT use and women being older at the time of use, the findings do not support a general neuroprotective effect of MHT nor significant adverse effects on the female brain.  ,
The findings “underline the importance of a personalised approach to MHT use,” according to Barth, “highlighting the subtle yet complex relationships between MHT use and brain health.”
” Importantly, our analyses provide a broad view of population-based associations and are not designed to guide individual-level decisions regarding the benefits versus risks of MHT use”.
The authors suggest that a higher proportion of these women may have been in perimenopause, which is frequently associated with neurological symptoms like cognitive decline and mood changes, and that current MHT users were significantly younger than previous and never-users ( 67 % ) versus 80 % ).
They speculate that the need for MHT may be a sign of neurological changes that will stabilize after this transition, which they suggest will continue.  ,
” Our results indicate that the effect of MHT on female brain health might vary depending on factors including timing, duration of use and past surgical history”, concludes senior author Ann Marie de Lange, Senior Research Fellow in the Department of Clinical Neurosciences, Lausanne University Hospital, Switzerland.
” However, our study is cross-sectional and we cannot establish causality. It is crucial to understand individual risk profiles and benefits as well as future studies mapping the long-term effects of MHTs on brain health.
Women are faced with difficult choices about whether to use MHT, but the lack of thorough research right now renders them without the necessary evidence to make informed choices.
About HRT and brain health research news
Author: Emily Packer
Source: eLife
Contact: Emily Packer – eLife
Image: The image is credited to Neuroscience News
Original Research: Open access.
By Claudia Barth et al.,” Menopausal hormone therapy and the female brain: utilizing neuroimaging and prescription registry data from the UK Biobank cohort.” eLife
Abstract
Using neuroimaging and prescription registry data from the UK Biobank cohort to explore menopausal hormone therapy and the female brain
Menopausal hormone therapy ( MHT) is generally thought to be neuroprotective, yet results have been inconsistent. Here, we present a comprehensive study of MHT use and brain characteristics in middle-to older aged females from the UK Biobank, assessing detailed MHT data, APOE ε4 genotype, and tissue-specific gray ( GM ) and white matter ( WM ) brain age gap ( BAG ), as well as hippocampal and white matter hyperintensity ( WMH) volumes.
A total of 19, 846 females with magnetic resonance imaging data were included ( current-users = 1, 153, 60.1± 6.8 years, past-users = 6, 681, 67.5 ± 6.2 years, never-users = 12, 012, mean age 61.6 ± 7.1 years ). For a sub-sample ( n = 538 ), MHT prescription data was extracted from primary care records. Brain measures were derived from T1-, T2- and diffusion-weighted images.
We fitted regression models to test for associations between the brain measures and MHT variables including user status, age at initiation, dosage and duration, formulation, route of administration, and type ( i. e., bioidentical vs synthetic ), as well as active ingredient ( e. g., estradiol hemihydrate ). We further examined associations by APOE4 status and assessed differences in brain tests between MHT users who have and do n’t have a history of hysterectomy, bilateral oophorectomy, and other brain measurements.
We found that current MHT users, not past users, and never-users, had significantly higher GM and WM BAG ( i .e., older brain age relative to chronological age ), as well as smaller left and right hippocampus volumes. Effects were modest, with the largest effect size indicating a group difference of 0.77 years ( ∼9 months ) for GM BAG. We found no statistically significant connections between age at MHT initiation and brain measurements among MHT users.
Higher GM and WM BAG, larger WMH volume, and smaller left and right hippocampal volumes were related to longer duration of use and older age at last use post menopause. MHT users with a history of hysterectomy ± bilateral oophorectomy showed , lower , GM BAG relative to MHT users without such history. We found no interactions with MHT variables, despite the fact that carriers of two APOE ( 4 ) alleles had smaller hippocampus volumes than non-carriers.
After adjusting for multiple comparisons, we found no statistical associations between detailed MHT variables and brain measurements in the sub-sample with prescription data.
Our findings point to the possibility that population-level associations between MHT use and female brain health could be affected by use history and past surgical history. Future research is crucial to establish causality, examine the connections between menopause-related neurological changes and MHT use, and look at individual-level implications for the development of precision medicine in female health care.
