New research suggests that hormone replacement therapy may reverse some of the detrimental effects menopause has on the body’s immune system, potentially restoring its ability to fight infections. The findings provide a deeper understanding of why women become more susceptible to illness after menopause and indicate that hormonal changes, not just chronological aging, are a primary driver of this immune decline.
A study led by researchers at Queen Mary University of London provides new evidence that the loss of hormones during menopause significantly alters the immune system. Menopause leads to an increase in inflammatory white blood cells that are less effective at clearing pathogens, a change not seen in men of the same age. The research, published in Aging Cell, found that hormone therapy appears to counteract this shift, restoring key immune functions and bringing them closer to the levels seen in younger women.
The Onset of Immune Senescence
Menopause, which typically occurs between the ages of 45 and 55, marks the cessation of ovarian estrogen and progesterone production, triggering a gradual deterioration of the female immune system in a process known as immune senescence. This is not merely a consequence of growing older; the loss of ovarian sex steroids accelerates the decline. The process is characterized by a general increase in inflammation throughout the body. Post-menopause, the body produces higher levels of pro-inflammatory cytokines—signaling proteins that can cause chronic inflammation—including interleukin-1 (IL-1), IL-6, and tumor necrosis factor-α (TNF-α).
This hormonal shift also changes the cellular makeup of the immune system. The number of circulating B cells, which are responsible for producing antibodies, is significantly reduced after menopause. Additionally, the ratio of CD4 to CD8 T cells, a key indicator of immune health and resistance to infection, decreases with age and is substantially reduced by menopause. These collective changes leave post-menopausal women with a weakened defense system.
A Focus on First Responders
The Queen Mary University study was the first to offer a detailed analysis of how aging and sex differences influence monocytes, a type of white blood cell that acts as the body’s first line of defense against infection. Researchers analyzed blood samples from different groups to isolate the effects of menopause from general aging.
Study Design and Participants
To understand the specific impact of menopause, the research team compared blood samples from younger adults under 40 with those from older adults aged 65 and above. Within the older cohort, they further compared post-menopausal women who were not taking hormone therapy to those who were. This allowed them to distinguish between age-related changes and those directly linked to the hormonal shifts of menopause.
Key Cellular Findings
The analysis revealed that women who had gone through menopause developed more inflammatory types of monocytes compared to both younger women and men of the same age. These monocytes were found to be less effective at their job of engulfing and destroying harmful microbes. The researchers linked this reduced function to lower levels of an immune protein called complement C3, which acts as a tag to help monocytes identify and clear pathogens. Because men did not show these same changes, the findings suggest menopause has a uniquely disruptive effect on female immunity.
Restoring the Body’s Defenses
The most encouraging finding from the study was the apparent effect of hormone replacement therapy (HRT) on these immune deficiencies. Women taking HRT showed healthier immune profiles compared to their age-matched peers who were not on the therapy. Their immune systems more closely resembled those of women decades younger.
Rejuvenating Immune Cells
In women receiving HRT, the researchers observed fewer inflammatory monocytes and a stronger ability to fight infection. Crucially, their blood levels of the complement C3 protein were higher, restoring a key mechanism for clearing bacteria. These results align with previous studies showing HRT can reverse other menopausal changes, such as by increasing the number of circulating B cells and neutralizing the decline in the CD4/CD8 T-cell ratio. While some studies report no effect on certain interleukins, the overall evidence points toward a partial reversal of immune senescence.
Reducing Systemic Inflammation
Estrogen, a key component of HRT, is renowned as an anti-inflammatory agent. It works by suppressing the production of pro-inflammatory cytokines like IL-6 and TNF-α. At the same time, estrogen can stimulate the production of anti-inflammatory cytokines, such as IL-4 and IL-10, which help regulate and calm the immune response. By restoring estrogen levels, HRT appears to mitigate the chronic inflammatory state that develops after menopause.
Implications Beyond Symptom Relief
While HRT is widely prescribed to manage symptoms like hot flashes, fatigue, and brain fog, this research suggests its benefits may be more profound. The therapy could play a vital role in maintaining immune health and reducing the risk of infection as women age. Given that over 4 million women are in the menopausal age bracket in the UK alone, the findings have significant public health implications.
Dr. Emma Chambers, the lead author of the study and a Senior Lecturer in Immunology at Queen Mary, stated that the research highlights a critical turning point for female immunity. “While ageing affects everyone, the loss of female hormones appears to accelerate immune decline in women,” she said. “Encouragingly, hormone therapy seems to restore key aspects of immune health, offering benefits that go beyond easing menopausal symptoms.”