Is perimenopause a critical window for brain health?

A new study in Berlin is exploring how hormonal changes during perimenopause shape the brain, mood, memory, and long-term health—and is now enrolling participants.

Perimenopause is often talked about in terms of irregular periods and hot flashes. But some of the biggest changes during this transition may actually be happening in the brain (1).

Perimenopause is the years-long transition leading up to the final menstrual period. During this time, ovarian hormone levels fluctuate and eventually decline, affecting almost every system in the body. Growing evidence suggests the brain may be particularly sensitive to these hormonal shifts (2).

Many people notice this firsthand. Sleep suddenly becomes disrupted. Concentrating feels harder. Mood and stress tolerance shift. Some experience anxiety, memory problems, or the “brain fog” commonly reported during perimenopause (1,2). Others move through the transition with few noticeable changes.

Importantly, reproductive hormones shape far more than the menstrual cycle. Estrogens influence brain regions involved in memory, mood, and stress regulation, and help protect brain cells across the lifespan (2). During perimenopause, estrogen levels can swing dramatically, with patterns that can look very different from person to person and even from one cycle to the next for the same person.

For most people, the brain is able to adapt to these changes. However, women face roughly twice the lifetime risk of depression and Alzheimer’s disease compared to men. And midlife may be a key window for when that risk begins to take shape (2). This has led to growing interest in whether the hormonal shifts of perimenopause may have longer-term effects for some.

Despite this, we still know surprisingly little about what is happening in the brain during this transition.

Why is the perimenopausal brain so understudied?

One reason for our limited knowledge is that perimenopause is difficult to study. Hormones fluctuate dramatically, symptoms constantly evolve, and cycles become increasingly irregular. 

The transition can also last an unpredictable amount of time, from a few years to more than a decade. Capturing these dynamic changes, therefore, requires repeated data collection over long periods of time and across a large, diverse population—no small challenge.

At the same time, women’s health research has historically received limited attention and funding, and hormonal fluctuations were often treated as something to control for or exclude, rather than something meaningful to study themselves. As a result, many aspects of how perimenopause affects the brain, cognition, mood, and long-term health remain poorly understood.

Mapping the perimenopausal brain

To better understand these changes, our research team at  Charité–Universitätsmedizin Berlin recently launched MappingPerimenopause, a new longitudinal study funded by the European Research Council. 

Over 3 years, the study will follow 300 participants across the perimenopausal transition to better understand how hormonal changes relate to the brain, mental health, cognition, and general wellbeing over time.

The study combines multiple forms of clinical and real-world data, including:

• Brain imaging (MRI)

• Hormone measurements

• Cognitive testing

• Stress measurements

• Gut microbiome analysis

• Questionnaires and clinical assessments

• Menstrual cycle and symptom tracking

Using Clue, participants can track how their experiences—including sleep, mood, and energy—change day to day across the transition, helping connect lived experiences with changes in hormones and brain health over time.

Why new research matters

Perimenopause is often treated as a temporary life stage to simply “get through.” But growing evidence suggests it may also represent one of the most important and understudied windows in women’s brain health.

This is why larger, more detailed longitudinal studies are critical. They can help untangle which symptoms are most closely linked to hormonal changes, which are shaped by factors like stress or sleep disruption, and why experiences differ so dramatically from person to person.

With a clearer picture of what is happening in the brain during perimenopause, future care could become more personalized—helping people recognize changes earlier, reduce trial and error in treatment, and identify which types of support are most likely to help.

Interested in participating?

By combining brain imaging, biological measurements, and real-world symptom tracking over time, MappingPerimenopause could help reshape how we understand—and eventually care for—the perimenopausal brain.

If you live in or around Berlin, are in midlife, and have noticed changes in your cycle, sleep, mood, memory, or overall wellbeing, you may be eligible to participate. 

You can find full eligibility details and sign up for screening here or reach out via Mapping-Perimenopause(at)charite.de.

Are you a researcher interested in collaborating with Clue Research? To learn more about how Clue can support your work, you can visit our research page or reach out at research@helloclue.com.