Researchers from Queen Mary University of London have identified a reversible effect of hormone replacement therapy (HRT) against changes in the immune system linked to menopause, publishing their findings in Aging Cell.1
This was the first detailed analysis about the effects of aging and sex differences toward monocytes, which are the body’s first defense against infection. In adults aged under 40 years or at least 65 years, more inflammatory white blood cells develop after menopause, reducing the immune system’s efficacy toward clearing bacteria.1
Key takeaways:
- HRT may reverse menopause-related immune decline, restoring aspects of immune health in women.
- Menopause accelerates immune aging, leading to more inflammatory white blood cells and reduced infection defense.
- Older adults showed higher inflammatory markers, including IL-6, IL-1β, and TNF, indicating increased “inflammageing.”
- Monocyte differentiation changes with age, with more intermediate and non-classical monocytes seen in older adults.
- Recent evidence supports the safety of HRT, even for some patients after breast cancer, when guided by individualized care.
“Our findings highlight menopause as a critical turning point for women’s immunity,” said Emma Chambers, PhD, lead author and senior lecturer in immunology at Queen Mary. “While ageing affects everyone, the loss of female hormones appears to accelerate immune decline in women.”1
Cellular analysis
The study was conducted to evaluate the impact of increasing age and biological sex on monocyte phenotype and function.2 Participants aged at least 18 years provided 80 ml of peripheral blood collected in sodium heparin tubes for analysis. Those with recent neoplasia, anemia, inflammatory disorders, or current pregnancy were excluded.
Surface antibodies used to label whole blood included CD14 (HCD14), CD16 (3G8), CD19 (HIB19), CD20 (2H7), CD56 (HCD56), CCR2, CX3CR1, HLA-DR (L243) and Zombie Green Fixable Viability Kit (Biolegend). Investigators used Ficoll-Paque (Amersham Biosciences) to isolate peripheral blood mononuclear cells by density centrifugation.2
The BD FACSAria III Cell Sorter (BD Biosciences) was used to sort negatively isolated nonocytes, which were then cultured in RPMI (Merck), 2 mM glutamine, and 100 U/mL penicillin/streptomycin (Thermo Fisher Scientific).2
Monocyte clusters and inflammageing
A significant increase in intermediate and non-classical monocytes was reported among patients aged a mean 73.1 years vs those aged a mean 29.2 years. Additionally, non-classical monocytes such as CCR2-CX3CR1+ were significantly more common in older adults. A correlation was reported for CCR2 and CX3CR1 expression with CD14 and CD16.2
The FlowSOM algorithm identified 4 unique clusters: CLA + CD14+, CLA-CD14+, CD14 + CD16+, and CD16+. The surface expression of assessed proteins did not differ between these clusters, indicating increased monocyte differentiation drives the age-related shift in monocyte subset quantification.2
Increased C Reactive Protein (CRP), an indicator of inflammageing, was observed in aging. Older adults presented with significantly greater serum CRP vs younger adults, with a positive correlation to CD16+ non-classical monocyte frequency. Investigators also highlighted a negative correlation between serum CRP and CD14+ monocyte frequency.2
Inflammatory markers and cytokine levels
Inflammageing was also linked to increased levels of:
Significantly more IL-6, IL-8, and TNF were also observed in monocytes from older vs younger patients, but not IL-10. Overall, a link was identified between inflammageing and an increased frequency of intermediate and non-classical monocytes more often seen in older individuals.2
This data highlighted significant impacts of older age and female sex toward monocyte phenotype and function. Investigators concluded these characteristics contribute to inflammaging and related declines in health-span.2
“Encouragingly, hormone therapy seems to restore key aspects of immune health, offering benefits that go beyond easing menopausal symptoms,” said Chambers.1
Safety and clinical context of HRT
Alongside this positive efficacy data, increased safety data for HRT have been reported, including safe use in patients after breast cancer.3 This evidence was recently discussed by Jayant S. Vaidya, MD, FRCS, PhD, professor of surgery and oncology at the University College London, and Sarah Glynne, MBBS, BSc, GP menopause specialist at The Portland Hospital.
According to Vaidya, prior trials indicating increased recurrence risk from HRT mainly involved treatable local or contralateral breast recurrences, with life-threatening distant metastases accounting for only 0.4%. As breast cancer is not a uniform condition, Glynne highlighted that recommendations should be individualized based on estrogen receptor-negative vs positive status.3
“Ultimately, the decision should be of… the patient and the doctor together as a join, informed decision,” said Vaidya.3
References
- Hormone replacement therapy may help restore immunity in menopausal women. October 9, 2025. Accessed October 14, 2025. https://www.eurekalert.org/news-releases/1101007.
- De Maeyer RPH, Sikora J, Bracken OV, et al. Age-associated inflammatory monocytes are increased in menopausal females and reversed by hormone replacement therapy.
- Vaidya JS, Glynne S. Reassessing hormone therapy after breast cancer. Contemporary OB/GYN. October 7, 2025. Accessed October 14, 2025. https://www.contemporaryobgyn.net/view/reassessing-hormone-therapy-after-breast-cancer.
