New Large-Scale Study Challenges Previous Research on Menopause and Brain Structure

New research from the Human Connectome Project in Aging suggests that while brain volume does decline in midlife, menopause stage isn't the driver—normal aging is. This distinction has important implications for evidence-based counseling and treatment decisions in primary care.

Patient Care® spoke with coauthor Katrina Wugalter, MA, a PhD candidate in the Department of Psychology at the University of Illinois Chicago, during The Menopause Society's 2025 Annual Meeting held October 21-25 in Orlando, Florida.

In this segment, Wugalter covers:

• Why previous studies on menopause and brain volumes were flawed
• How her team's larger study from the Human Connectome Project addressed these limitations
• Key findings showing age, not menopause stage, drives brain volume decline
• What these results mean for counseling midlife women

The following transcript has been lightly edited for style and clarity.

Patient Care: What prompted you and your colleagues to investigate whether menopause stage, rather than age, affects brain volumes in midlife women?

Katrina Wugalter, PhD: There is increasing interest in the effects of menopause on cognition and brain health, and there are a couple studies that have looked at whether menopause influences brain volumes. And while those studies are all very interesting and hypothesis generating, many of them have study designs that are not optimal for actually addressing that research question.

So for example, they have very small sample sizes, like 12 to 40 women per menopause stage. They don't use the gold standard menopause staging criteria, which is the STRAW+10 criteria. Some of these studies include menopausal hormone therapy users and non-users without controlling, covarying, or stratifying for that. So there are kind of nuances in the sample characteristics that make it difficult to actually interpret those findings from previous studies.

So we knew that we had access to a much larger dataset, a dataset of women that were staged using the gold standard menopause criteria, women who are not taking hormone therapy, and women who have returned multiple times for multiple neuroimaging visits. So that is why we decided to take our kind of turn at addressing this question.

Patient Care: Can you briefly describe the study and how you addressed those limitations?

Katrina Wugalter, PhD: Yeah, so we are using a cohort of women from Human Connectome Project in Aging, which is a multi-site cohort study that is attempting to evaluate typical aging in US adults. So there are multiple sites across America, and this is a very large study.

When we include only women between the ages of 40 and 60 who are not taking hormone therapy, we have 242 women. And so that means that we have twice as many women in each menopause stage as some of the biggest studies that have evaluated this question. All of the women are also cognitively normal. So that means we're looking at normative aging processes, and we're not looking at a group of women that possibly already has mild dementia or anything like that. So all the women are aging normatively. And then we also have, as I mentioned, multiple visits of data. So some of these women returned for follow-up visits, so we're actually including them multiple times in our analyses.

Patient Care: What were the results that you found?

Katrina Wugalter, PhD: So we did not see that there were any differences in cortical volumes or hippocampal volumes by menopause stage. So in other words, in our sample, which is much larger, which uses gold standard menopause staging, we didn't see that menopause is affecting brain structure.

We did see that women's brains are getting smaller in certain regions just because they're getting older. So this is expected. Well-established feature of brain aging is that some areas of the brain will get smaller over time. So we did see those expected age-related declines in brain volumes. We did not see that those age-related declines are accelerated or exacerbated by the menopause transition.