Menopause linked to loss of grey matter in the brain, poorer mental health and sleep disturbance with and without hormone replacement therapy

Bad news! Or what is the influence of pre-existing conditions?

"The study ... found that hormone replacement therapy (HRT) does not appear to mitigate these effects, though it can slow the decline in reaction times. ...

The average age of onset of menopause among the participants was around 49.5 years, while the average age that women prescribed HRT began their treatment was around 49 years.

Post-menopausal women were more likely than those pre-menopause to have sought help from their GP or a psychiatrist for anxiety, nerves or depression, and to score more highly on questionnaires for symptoms of depression. Similarly, they were more likely to have been prescribed antidepressants. ...

further analysis showed that these differences in symptoms were already present before menopause. ...

Women post-menopause were more likely to report insomnia, get less sleep, and feel tired. Those on HRT reported feeling the most tired of all three groups ..."

From the abstract:

"Abstract

Background

Menopause is a natural physiological process, but its effects on the brain remain poorly understood. In England, approximately 15% of women use hormone-replacement therapy (HRT) to manage menopausal symptoms. However, the psychological benefits of HRT are not well established. This study aims to investigate the impact of menopause and HRT on mental health, cognitive function, and brain structure.

Methods

We analyzed data from nearly 125,000 participants in the UK Biobank to assess associations between menopause, HRT use, and outcomes related to mental health, cognition, and brain morphology. Specifically, we focused on gray matter volumes in the medial temporal lobe (MTL) and anterior cingulate cortex (ACC).

Results

Menopause was associated with increased levels of anxiety, depression, and sleep difficulties. Women using HRT reported greater mental health challenges than post-menopausal women not using HRT. Post-hoc analyses revealed that women prescribed HRT had higher levels of pre-existing mental health symptoms. In terms of brain structure, MTL and ACC volumes were smaller in post-menopausal women compared to pre-menopausal women, with the lowest volumes observed in the HRT group.

Conclusions

Our findings suggest that menopause is linked to adverse mental health outcomes and reductions in gray matter volume in key brain regions. The use of HRT does not appear to mitigate these effects and may be associated with more pronounced mental health challenges, potentially due to underlying baseline differences. These results have important implications for understanding the neurobiological effects of HRT and highlighting the unmet need for addressing mental health problems during menopause."

Menopause linked to loss of grey matter in the brain, poorer mental health and sleep disturbance | University of Cambridge "Menopause is linked to reductions in grey matter volume in key brain regions as well as increased levels of anxiety and depression and difficulties with sleep, according to new research from the University of Cambridge."

Emotional and cognitive effects of menopause and hormone replacement therapy (open access)

Can we delay the menopause?

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Evidence of menopause in wild chimps upends ideas around human evolution

Amazing stuff!

"Other than a few species of whale, humans are the only mammals that consistently demonstrate the unusual phenomenon of menopause. Most animals maintain their reproductive ability for the vast majority of their lifespan. Humans are big outliers, with females often spending up to 50% of their life in a postreproductive state. ...
The findings reveal a community of female chimpanzees in Uganda display both hormonal and demographic signs of menopause, living for up to 20 years in a postreproductive state. ...

However, female chimpanzees are known to live apart from their offspring, dispersing to new groups as they get older. So the grandmother hypothesis offers no clues as to why the trait of menopause has evolved in this chimpanzee community. ..."

From the abstract:

"Structured Abstract

INTRODUCTION

It is not obvious why selection should favor menopause or the continued survival of individuals that can no longer reproduce. Among mammals, substantial numbers of post-reproductive females living under natural conditions in the wild have only been observed in humans and a few whale species. The rarity of this trait makes it both interesting and difficult to study. Data from our close primate relatives are especially valuable for the reconstruction and causal modeling of human life history evolution. In this study, we combined demographic and hormonal data to investigate post-reproductive life spans and their underlying physiological mechanisms in chimpanzees (Pan troglodytes schweinfurthii), who, along with bonobos, are humans’ closest living relatives.

RATIONALE

We examined the mortality and fertility rates of 185 female chimpanzees in the Ngogo community of wild chimpanzees in Kibale National Park, Uganda, from 21 years of observation (1995–2016). We calculated the demographic measure PrR (post-reproductive representation), representing the fraction of adult life spent in a post-reproductive state. Human menopause, the nonpathological and permanent cessation of ovarian function resulting from the depletion of ovarian follicles, is reflected in increasing levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and decreasing levels of ovarian steroid hormones (estrogens and progestins). To assess whether Ngogo females undergo humanlike menopause, we analyzed age-associated trends in five hormones measured in 560 urine samples from 66 females of varying reproductive status and age (range: 14 to 67 years).

RESULTS

As in other chimpanzee populations and humans, fertility declined after age 30, and no births were observed after age 50. Unlike other chimpanzee populations, but as in humans, it was not unusual for Ngogo females to live past the age of 50 (N = 16 females). The observed PrR value was 0.195, indicating that a female who reached adulthood (age 14) was post-reproductive for about one-fifth of her adult life, around half as long as human hunter-gatherers. Hormonal measures show that Ngogo females experience a reproductive transition similar to that of humans, characterized by increasing levels of FSH and LH and declining levels of estrogens and progestins as they undergo menopause.

CONCLUSION

Menopause ends reproduction around the age of 50 in both humans and wild chimpanzees. Substantial PrR has not been previously observed in any wild primate population, chimpanzees included. One explanation for this discrepancy is that substantial PrR could be a temporary response to unusually favorable ecological conditions at Ngogo, including low levels of predation, high food availability, and successful between-group competition. A second possibility is that substantial PrR is an evolved, species-typical trait in chimpanzees, which has not been observed elsewhere owing to recent negative human impacts, especially disease epidemics. The grandmother hypothesis suggests that older females could evolve to live past their reproductive years to help increase their daughters’ fertility or their grandoffsprings’ survival. This is unlikely to apply to chimpanzees, whose aged females generally live apart from their daughters, as daughters leave their natal groups at adulthood. In the context of female-biased dispersal, a more relevant theory may be the reproductive conflict hypothesis, which highlights the fact that after migrating into a new group, females become increasingly related to other group members as they age and face competition with younger females for limited breeding opportunities. The oldest females might stop reproducing in order to limit the inclusive fitness costs of that competition. The grandmother and reproductive conflict hypotheses are not mutually exclusive alternatives, and both may be required to explain why all human societies have higher PrR than documented here for chimpanzees."

Evidence of menopause in wild chimps upends ideas around human evolution

Menopause in chimpanzees Signs of menopause in wild chimpanzees provide insights into human evolution

Demographic and hormonal evidence for menopause in wild chimpanzees (open access)

Female chimpanzees (Pan troglodytes) from the Ngogo community in Uganda can live for decades after losing the ability to reproduce.