The study was a collaboration between researchers at the Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS), at the University of Oxford and Queen Mary, University of London.
Published in Aging Cell it is the first detailed analysis of how ageing and sex differences influence monocytes - a key group of white blood cells that act as one of the body's first responders to infection. Analysing blood samples from younger adults less than 40 years of age and older adults aged 65 and above, the team found that after menopause, women develop more inflammatory types of monocytes, which are less effective at clearing bacteria.
These changes were linked to lower levels of an immune protein called complement C3 that helps monocytes engulf and destroy harmful microbes. In contrast, men of the same age did not show these changes, suggesting menopause has a uniquely disruptive effect on female immunity.
To test whether hormone therapy could influence this decline, the researchers studied peri-and post-menopausal women taking HRT. They found that these women had healthier immune profiles, with fewer inflammatory monocytes and stronger infection-fighting ability as compared to age-matched controls. Levels of complement C3 in their blood were also higher in those taking HRT, bringing them closer to the immune status of younger women.
Dr Roel De Maeyer, Research Fellow and joint first author of the study said: 'Our findings show that menopause, more so than ageing in general, causes a shift in immune function for women. This could help to explain why post-menopausal women are more susceptible to certain diseases such as urinary tract infections and autoimmunity. Importantly, this provides a biological rationale for viewing hormone replacement therapy (HRT) not only as a means of symptom relief but also as a way to support immune health.'
Menopause typically occurs in women between the ages of 45 and 55 and is often preceded by a decade-long peri-menopausal phase. Symptoms such as hot flushes, joint pain, fatigue and brain fog can have a profound effect on quality of life. In the UK alone, more than four million women are in this age bracket, and women over 50 make up a growing proportion of the workforce. Yet they are also among the most likely to experience work disruption due to menopausal symptoms.
HRT is already prescribed to manage symptoms, but this study suggests it may also help maintain immune health and reduce infection risk in later life. The researchers caution, however, that more work is needed to confirm whether HRT reduces real-world infection rates, and to understand how different formulations or delivery methods affect the immune system.
The authors caution that while the findings are promising, the study does not mean HRT should automatically be prescribed for immune health. More research is needed to confirm whether women taking HRT have lower infection rates in real-world settings, and to investigate how different types and route of HRT administration may affect the immune system.
The study was funded by Barts Charity and Vivensa Foundation.