Plain language summary
One characteristic of menopause is immune senescence, the gradual decline of the immune system associated with age and hormone changes. This leads to a reduced immune response and increased inflammatory state. Current options to support the immune system during menopause include hormone replacement therapy (HRT) and flavonoid-rich supplementation. While evidence shows these options may influence immune senescence during menopause, specific inflammatory markers and molecular pathways need to be clarified. The aim of this review is to present the latest findings on these therapies and suggest possible directions for future research and treatment. The current literature suggests HRT can modulate the overall inflammatory state. There is not sufficient evidence to show flavonoids enhance the immune response in menopausal women. Based on the discrepancies in the available studies, the authors conclude future studies are needed to better understand the pathways and mediators connecting HRT and the immune system. This understanding will lead to more targeted therapies for menopausal women and the authors point to flavonoid-rich products as a basis for developing future treatment directions.
Abstract
Menopause, probably the most important natural change in a woman's life and a major component of female senescence, is characterized, inter alia, by cessation of ovarian estrogen and progesterone production, resulting in a gradual deterioration of the female immune system. Hormone replacement therapy (HRT) is used in postmenopausal women to relieve some of the peri- and postmenopausal symptoms, while there is also evidence that the therapy may additionally partially reverse menopausal immune senescence. Flavonoids, and especially isoflavones, are widely used for the treatment of menopausal symptoms, although it is not at present clear whether they can reverse or alleviate other menopausal changes. HRT reverses the menopausal CD4/CD8 ratio and also limits the general peri- and postmenopausal inflammatory state. Moreover, the increased levels of interleukins (IL)-1β, IL-6, and IL-8, as well as of tumor necrosis factor-α (TNF-α) are decreased after the initiation of HRT. However, some reports show no effect of HRT on IL-4, IL-10, and IL-12. It is thus evident that the molecular pathways connecting HRT and female immune senescence need to be clarified. Interestingly, recent studies have suggested that the anti-inflammatory properties of isoflavones possibly interact with inflammatory cytokines when applied in menopause treatments, thereby potentially reversing immune senescence. This narrative review presents the latest data on the effect of menopausal therapies, including administration of flavonoid-rich products, on age-associated immune senescence reversal with the aim of revealing possible directions for future research and treatment development.
Methodological quality
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