There’s a lot in the news these days about menopausal symptoms and HRT. Concerns about it increasing risk of certain cancers appear minimal and there is increasing evidence of benefits which are not limited to menopausal symptoms. In addition to typical menopausal and peri-menopausal symptoms such as hot flushes, brain fog, joint pains, mood swings and vaginal dryness, there is also evidence of it increasing longevity and reducing age-related loss of bone density and cardiovascular changes.
Considering the underlying mechanisms for how oestrogen is protective, it appears that the beneficial effects of oestrogen are medicated through its ability to reduce inflammatory species. Evidence suggests that menopause is closely associated with an increased release of pro-inflammatory cytokines, such as interleukin (IL)-6, IL-1, and tumor necrosis factor-α (TNF-α) (Cioffi et al., 2002). Oestrogen has been shown to inhibit such chemicals (Lambert et al. 2004).
Evidence suggests that HRT is protective against the development of cardiovascular disease and atherosclerosis and all cause mortality if started before the age of 60 or within 10 years of menopause (Hodis et al., 2022; Vigneswaran & Hamoda, 2022).
Following evidence of significant benefit, NICE guidelines recommend HRT to help preserve bone density and prevent osteoporosis and fractures in women under 60 (Vigneswaran & Hamoda, 2022; NIfHaC, 2015).
It has been suggested that HRT may help to reduce age-related muscle loss, specifically via antiinflammatory effects which may also support muscle satellite cell function involved in muscle repair (La Colla et al., 2015; Perandini et al., 2018). However evidence from reviews of many studies is conflicting (Burton & Sumukadas, 2010) and suggests it is either minimally protective (Taaffe et al., 2005; Greising et al. 2009), or not at all (Kenny et al., 2003; Javed et al., 2019).
However, questions about HRT benefit in dementia remain. Although observational data suggests a that HRT is beneficial, more robust exprimental data suggests that is may be associated with an increase in risk of dementia. Recent evidence from a study of over 100,000 women concluded that HRT is associated with an increased risk (Sung et al., 2022).
HRT may therefore be viewed as protective in many ways through its antiiinflammatory effects and it appears to be of benefit not only for relieving immediate menopausal symptoms but also for longer term protection from the effects of aging, although findings concerning dementia risk are concerning. Hormonal changes at the menopause (and pre-menstrually) are an additional stress on the body, which increases inflammation further. However there are many other ways in which inflammation may be addressed to reduce unwelcome development of a wide range of inflammatory health problems. The significant benefits of HRT in studies above may also be related to the populations to which they apply. In the UK 34% of 46-48 year olds were found to have two or more chronic inflammatory health problems in The British Cohort Study (2015). This suggests that anything (such as HRT) that reduces inflammatory load will be particularly beneficial and also shows that other ways of reducing inflammation will also be of benefit, including for those who cannot take HRT or choose not to. For those women who cannot or prefer not to take HRT it is therefore of great importance that they focus on an anti-inflammatory lifestyle.
It is also worth noting that declining oestrogen from the ovaries may be compensated for by other tissues in the body such as the adrenals, fat, bones and brain. Crucially, oestrogens are produced to act locally – for example cardiovascular problems have been observed to increase post-menopausally but the cells of a healthy blood vessel lining actually produce oestrogen locally (Simpson 2003) which acts directly to reduce inflammation in those cells. The action of oestrogen does not therefore depend on circulating levels in the wider system and it is therefore important to keep damaging inflammation down in these tissues in order to support oestrogen production.
Recommendations for good menopausal health
An anti-inflammatory diet based on good fats, protein, veg, berries and limited carbohydrate is crucial for reducing inflammatory insulin and middle weight gain that is increased with high carbohydrate intake and fluctuating blood glucose.
Practices that offer short-term stress to the body also modulate the inflammatory response e.g. in the form of intermittent fasting, high intensity interval training, cold shower/wild swimming.
Strength training is also important for building muscle which is more metabolically active and reduces inflammatory insulin, as well as for bone health.
A good quality multi supplement plus separate magnesium supplement may be needed for guaranteeing good levels of antioxidant and anti-inflammatory, bone building, glucose balancing, stress reducing, energy supporting nutrients.
Foods and herbs contain multiple phytonutrients that help to reduce inflammation directly and indirectly.
Many herbs are of particular benefit in menopause both generally for reducing inflammation and additionally for individual symptoms:
• Direct anti-inflammatories and antioxidants include turmeric, marigold, red clover, rosemary, rosehip, hawthorn, ginger, green tea, ginkgo…..
• Herbs also help to reduce inflammation by supporting optimal elimination via the lymphatic system (e.g. red clover, Echinacea) and liver (e.g. dandelion root, artichoke leaf).
• Supporting good digestive function also reduces the absorption of inflammatory substances from the gut (e.g. chamomile, fennel, dandelion, ginger).
• Nourishing dry tissue with good fats, good digestion and herbs such as Shatavari and red clover help to keep fluids moving and reduce inflammatory congestion.
• Strengthening ‘adaptogens’ (e.g. Shatavari, Astragalus, Ashwaganda) help to make the body more resilient to stress and therefore reduce inflammation, particularly given the additional stress on the system of hormonal changes in menopause.
• Mood issues can be helped with herbs that help to balance and strengthen a stressed nervous system (e.g Ashwaganda, St John’s Wort, rosemary).
• Cognitive issues / brain fog may be helped by supporting good cerebral circulation (e.g. rosemary, ginkgo, Astragalus).
• Cardiovascular protection from hawthorn berry and Astragalus that also protects the endothelial lining of blood vessels and therefore supports local protective oestrogen production.
• Bone health is also supported by herbs such as horsetail and black cohosh.
• Finally, herbs can offer hormone support and boost the effect of remaining oestrogens that continue to be produced in smaller amounts in the body (e.g. red clover, soy, wild yam, shatavari).
References
Burton LA, Sumukadas D. Optimal management of sarcopenia. Clin Interv Aging. 2010 Sep 7;5:217-28. doi: 10.2147/cia.s11473. PMID: 20852669; PMCID: PMC2938029.
Cioffi, M., Esposito, K., Vietri, M. T., Gazzerro, P., D’Auria, A., Ardovino, I., Puca, G. A., & Molinari, A. M. (2002). Cytokine pattern in postmenopause. Maturitas, 41(3), 187–192. https://doi.org/10.1016/s0378-5122(01)00286-9
Geraci A, Calvani R, Ferri E, Marzetti E, Arosio B, Cesari M. Sarcopenia and Menopause: The Role of Estradiol. Front Endocrinol (Lausanne). 2021 May 19;12:682012. doi: 10.3389/fendo.2021.682012. PMID: 34093446; PMCID: PMC8170301.
Greising, S. M., Baltgalvis, K. A., Lowe, D. A., & Warren, G. L. (2009). Hormone therapy and skeletal muscle strength: a meta-analysis. The journals of gerontology. Series A, Biological sciences and medical sciences, 64(10), 1071–1081. https://doi.org/10.1093/gerona/glp082
Hodis, H. N., & Mack, W. J. (2022). Menopausal Hormone Replacement Therapy and Reduction of All-Cause Mortality and Cardiovascular Disease: It Is About Time and Timing. Cancer journal (Sudbury, Mass.), 28(3), 208–223. https://doi.org/10.1097/PPO.0000000000000591
Javed, A. A., Mayhew, A. J., Shea, A. K., & Raina, P. (2019). Association Between Hormone Therapy and Muscle Mass in Postmenopausal Women: A Systematic Review and Meta-analysis. JAMA network open, 2(8), e1910154. https://doi.org/10.1001/jamanetworkopen.2019.10154
Kenny, A. M., Dawson, L., Kleppinger, A., Iannuzzi-Sucich, M., & Judge, J. O. (2003). Prevalence of sarcopenia and predictors of skeletal muscle mass in nonobese women who are long-term users of estrogen-replacement therapy. The journals of gerontology. Series A, Biological sciences and medical sciences, 58(5), M436–M440. https://doi.org/10.1093/gerona/58.5.m436
La Colla, A., Pronsato, L., Milanesi, L., & Vasconsuelo, A. (2015). 17β-Estradiol and testosterone in sarcopenia: Role of satellite cells. Ageing research reviews, 24(Pt B), 166–177. https://doi.org/10.1016/j.arr.2015.07.011
Lambert, K. C., Curran, E. M., Judy, B. M., Lubahn, D. B., & Estes, D. M. (2004). Estrogen receptor-alpha deficiency promotes increased TNF-alpha secretion and bacterial killing by murine macrophages in response to microbial stimuli in vitro. Journal of leukocyte biology, 75(6), 1166–1172. https://doi.org/10.1189/jlb.1103589
NIfHaC, E. (2015). Menopause: diagnosis and management of menopause. NICE guideline.
Perandini, L. A., Chimin, P., Lutkemeyer, D., & Câmara, N. (2018). Chronic inflammation in skeletal muscle impairs satellite cells function during regeneration: can physical exercise restore the satellite cell niche?. The FEBS journal, 285(11), 1973–1984. https://doi.org/10.1111/febs.14417
Simpson E. R. (2003). Sources of estrogen and their importance. The Journal of steroid biochemistry and molecular biology, 86(3-5), 225–230. https://doi.org/10.1016/s0960-0760(03)00360-1
Sipilä, S., Taaffe, D. R., Cheng, S., Puolakka, J., Toivanen, J., & Suominen, H. (2001). Effects of hormone replacement therapy and high-impact physical exercise on skeletal muscle in post-menopausal women: a randomized placebo-controlled study. Clinical science (London, England : 1979), 101(2), 147–157.
Sung, Y. F., Tsai, C. T., Kuo, C. Y., Lee, J. T., Chou, C. H., Chen, Y. C., Chou, Y. C., & Sun, C. A. (2022). Use of Hormone Replacement Therapy and Risk of Dementia: A Nationwide Cohort Study. Neurology, 10.1212/WNL.0000000000200960. Advance online publication. https://doi.org/10.1212/WNL.0000000000200960
Taaffe, D. R., Newman, A. B., Haggerty, C. L., Colbert, L. H., de Rekeneire, N., Visser, M., Goodpaster, B. H., Nevitt, M. C., Tylavsky, F. A., & Harris, T. B. (2005). Estrogen replacement, muscle composition, and physical function: The Health ABC Study. Medicine and science in sports and exercise, 37(10), 1741–1747. https://doi.org/10.1249/01.mss.0000181678.28092.31
The 1970 British Cohort Study (2022) https://cls.ucl.ac.uk/cls-studies/1970-british-cohort-study/
Vigneswaran, K., & Hamoda, H. (2022). Hormone replacement therapy – Current recommendations. Best practice & research. Clinical obstetrics & gynaecology, 81, 8–21. https://doi.org/10.1016/j.bpobgyn.2021.12.001
