Does Oestradiol Preserve Brain Youth?

A new study links the length of a woman’s reproductive years to slower brain aging – and it could reshape how we think about hormones and women’s health.

It’s no secret that aging affects women’s bodies and brains in different ways than it does men’s. But what if one of the most powerful protectors of the female brain isn’t a drug or supplement, but a naturally occurring hormone most women already produce?

A new study published in GigaScience offers compelling evidence that longer reproductive spans (the number of years between a woman’s first period and menopause) are associated with younger-looking brains. The likely reason? Longer exposure to oestradiol, the body’s most active form of oestrogen, appears to help protect the brain, especially after menopause.

Led by researchers from China and the UK, the study used advanced brain imaging and machine learning to assess brain aging in over 9,000 women.

Their findings suggest that oestradiol may be far more important to brain health than previously understood.

Understanding Oestradiol and Brain Health

Oestradiol is a type of oestrogen – a hormone central to female reproductive health. Produced mainly by the ovaries, it regulates menstrual cycles, supports fertility, and drives the physical changes of puberty.

But its role goes beyond reproduction. Oestradiol also affects how the brain develops, functions and adapts over time – through synaptic plasticity (how brain cells communicate), reduced inflammation and repairing damaged neurons.

During reproductive years, oestradiol levels fluctuate monthly, but after menopause, these levels drop sharply. This decline has been linked to an increased risk of cognitive decline, mood disorders, and neurodegenerative diseases such as Alzheimer’s.

Until now, it’s been unclear just how much lifetime oestradiol exposure matters for brain health.

Longer Reproductive Span, Younger Brain

The research team drew on data from the UK Biobank, a large medical database containing brain scans, health records, and genetic information. They looked at 9,408 postmenopausal women and calculated each woman’s reproductive span based on when she started her periods and when she reached menopause.

They then used AI to estimate a ‘brain age’ for each woman – essentially, how old the brain looks on scans compared to the person’s actual age.

Here’s what they found:

• A longer reproductive span was linked to a younger brain. For every additional year between menarche and menopause, brain age decreased by about 0.024 years.

  
  

• Natural hormone exposure mattered more than pregnancy. The key factor was how long a woman was exposed to her own oestradiol, not how many children she had.

  
  

• The differences were most visible in brain regions critical for memory, decision-making, and emotion, including the frontal cortex, hippocampus, and temporal lobe. It’s not just having hormones that matters, but how long the brain gets to benefit from them.

Bridging the Brain Aging Gap Between Women and Men

Women are more likely than men to develop Alzheimer’s, with around two-thirds of cases occurring in women. For years, this was attributed to women living longer, but that alone doesn’t explain the difference.

The “oestradiol hypothesis” offers another angle: could differences in hormone exposure across the lifespan help explain why some women are more vulnerable to brain aging?

We’ve seen hints before. Women who go through menopause earlier, naturally or due to surgery, have a higher risk of dementia. Hormone replacement therapy (HRT) around the time of menopause has shown potential to support brain function, though results vary depending on the type, dose and timing of treatment.

This new study strengthens the idea that timing matters and that brain health is influenced not just by hormones in midlife, but by a woman’s entire hormonal history.

 

Rethinking Hormones Beyond Fertility

In medicine, hormones are still mostly seen through the lens of reproduction – managing periods, assisting fertility, or easing menopause symptoms. But oestradiol is more than a reproductive hormone. It’s also a brain hormone, a heart hormone, and a metabolic hormone.

This study adds to a growing body of research urging us to expand how we think about female hormones. Menopause isn’t just an end point - it may be a crucial turning point for long-term health. And that shift in thinking demands more than curiosity. It demands research funding, public health focus, and better policies that reflect the full arc of hormonal life.

Oestradiol may not be a miracle cure, but it could be one of the most powerful tools we have for protecting women’s brains across the lifespan.

Reference

Ma, Y., Yu, Z., Fu, X. et al. (2024). Reproductive span is associated with brain age in postmenopausal women. GigaScience, giaf060.