What was this study asking?

This study examined whether hormonal factors (such as menopause status, hormone-replacement therapy (HRT), and testosterone levels) change how vascular risk factors affect the brain.

Specifically, the researchers looked at whether hormone status modifies the relationship between common cardiovascular risks (high blood pressure, obesity, diabetes, cholesterol, smoking, arterial stiffness) and white matter hyperintensities (WMH) - small lesions in the brain linked to vascular damage, cognitive decline, and increased dementia risk.

Rather than asking “Do hormones directly increase or decrease brain damage?”, the study asked:
Do hormones change how vulnerable the brain is to vascular stress?

How was the study done?

• Data came from the UK Biobank, a large population database.
• Brain MRI scans from 18,294 adults aged approximately 45–80 were analyzed.
• The amount of white matter hyperintensities (WMH) in the brain was measured and separated into:
  • Periventricular WMH (near the brain’s ventricles)
  • Deep WMH (within deeper white matter regions)
• Vascular risk factors evaluated included:
  • Body mass index (BMI)
  • Hypertension
  • Diabetes
  • Cholesterol status
  • Smoking
  • Arterial stiffness (pulse-wave velocity)
• Hormonal factors included:
  • Testosterone levels (in men)
  • Menopausal status, hormone-replacement therapy (HRT) use and duration, and contraceptive history (in women)
• Statistical models were run separately for men and women, adjusting for age and other relevant variables.
• The key analysis tested interaction effects — whether hormone status changed the strength of the relationship between vascular risk and WMH.

Key findings

Overall patterns

• Women had more white matter lesions than men, even after adjusting for age.
• Vascular risk factors were linked to higher WMH in both sexes.
• However, hormonal status changed how strongly vascular risks impacted the brain.

Findings in women (menopause & HRT)

• Menopause or HRT use alone did not directly predict total white matter damage.
• But HRT duration and menopausal timing clearly mattered in how vascular risks affected the brain.

Key observations:

• In women with no or short HRT use, high blood pressure and arterial stiffness were associated with significantly more white matter damage.
• In women with longer HRT duration, the harmful effects of these vascular risks were weaker.
• Women in early post-menopause showed stronger associations between vascular risk factors and white matter damage than those further from menopause.

Interpretation: After menopause, the brain may be more vulnerable to vascular injury — particularly when estrogen exposure is low or short-lived.

Why this matters for menopause and brain health

White matter hyperintensities are associated with:

• Cognitive decline
• Stroke risk
• Dementia
• Accelerated brain aging

This study suggests that:

• Hormonal status does not simply cause or prevent brain changes.
• Instead, hormones modify the brain’s resilience or vulnerability to vascular stressors.
• In post-menopausal women, short or absent estrogen exposure may increase sensitivity to vascular damage, especially from high blood pressure and arterial stiffness.

In other words:
Menopause may not cause brain damage directly — but it may increase susceptibility to damage from cardiovascular risk factors.

Study limitations:

• The study is cross-sectional, meaning it captures one point in time and cannot prove cause-and-effect.
• Hormone information was relatively broad (e.g., HRT duration, not specific hormone formulations).
• Lifestyle factors and lifetime hormone exposure patterns may not be fully captured.

Conclusions:

This 2022 study adds important nuance to menopause research:

• Sex hormones do not act in isolation.
• Hormones influence how strongly vascular risk factors affect the aging brain.
• In women, menopause and limited estrogen exposure appear to increase vulnerability to vascular-related white matter damage.
• These findings support a more personalized approach to brain and cardiovascular risk management in midlife and beyond.

The study: Hormonal Factors Moderate the Associations Between Vascular Risk Factors and White Matter Hyperintensities
Alqarni A., Wen W., Lam B.C.P., Crawford J.D., Sachdev P.S., Jiang J., et al. (2022)