New evidence links menopause to shifts in immune health
In a groundbreaking study led by Queen Mary University of London, researchers report that hormone replacement therapy (HRT) may help reverse immune changes linked to menopause. The study, published in Aging Cell, suggests that the loss of female hormones not only triggers hot flashes and fatigue but also reshapes the immune system, potentially increasing susceptibility to infections in later life.
The research offers a detailed look at monocytes, a crucial group of white blood cells that act as first responders to invading pathogens. By analyzing blood samples from two age groups—younger adults under 40 and older adults aged 65 and above—the team found that postmenopausal women tend to accumulate more inflammatory monocytes. These cells are less efficient at clearing bacteria, which could leave older women more vulnerable to infections than their male counterparts of the same age.
“The menopause period appears to be a turning point for women’s immunity,” says Dr. Emma Chambers, Senior Lecturer in Immunology at Queen Mary University and the study’s senior author. “We see a shift toward inflammatory monocytes and a reduction in the complement system’s C3 protein, which helps monocytes engulf and destroy microbes.”
The immune mechanism: monocytes and complement C3
Monocytes are a frontline defense against pathogens, but their inflammatory subtypes can contribute to tissue damage and impaired infection control if not properly regulated. The study linked menopause-associated changes to lower levels of complement C3, a protein that plays a pivotal role in tagging and destroying invading microbes. In postmenopausal women, C3 levels were reduced compared with younger women, and the inflammatory monocyte profile was more pronounced. This combination may help explain the observed increase in infection risk after menopause.
Differences between sexes
Interestingly, the researchers found that men of the same age did not show the same immune profile changes. The data underscore a sex-specific impact of menopause on the immune system and point to female hormones as a key driver of these differences. The findings align with a growing body of evidence that aging interacts with sex to shape immune function in distinct ways.
HRT shows promise for immune health, with caveats
To assess whether hormone therapy could mitigate this decline, the team studied peri- and postmenopausal women undergoing HRT. Across this group, inflammatory monocytes were fewer, and the capacity to fight infections was noticeably stronger than in age-matched controls not receiving HRT. Blood levels of complement C3 were higher in women on HRT, bringing their immune profile closer to that of younger women.
Professor Fiona Miller Smith, Chief Executive of Barts Charity, notes the broader implications: “This is a brilliant example of how funding innovative ideas in health can lead to advances in our understanding—this time around menopause and women’s immune systems.”
Implications for public health and future research
While the findings are promising, the researchers caution that more work is needed to confirm whether HRT reduces real-world infection rates. They also stress the importance of exploring how different HRT formulations and delivery methods affect immunity, and whether benefits persist over time.
Frameworks for clinical guidance must balance symptom relief with potential immune benefits and risks. The study was funded by Barts Charity and the Vivensa Foundation, highlighting the value of targeted research into women’s health across the life course.
As the UK and beyond grapple with aging populations, these insights could influence how clinicians discuss menopause, infection risk, and preventive strategies with patients. For now, HRT appears to offer a potential twofold benefit: easing menopausal symptoms and supporting immune health—though not a universal prescription, and not a guarantee of lower infection rates without further evidence.
