Without a healthy immune system, the human body cannot survive. Your immune system can become weakened for a variety of reasons.

How good is your immune system? If a woman is menopausal, or postmenopausal, you may not be aware that both aging, and lack of estrogen, affect your immune response. In the face of the COVID-19 pandemic – this is especially topical.

Read on and find out more.

What does the immune system do?

The immune system is a complex network of specialized cells and cell signaling mechanisms. The function of the immune system is to protect your body from a harmful attack. This could be from a single bacterium, a virus, or one for your own cells which is damaged, or dead and requires clearance.

Without a healthy immune system, the human body cannot survive. Your immune system can become weakened for a variety of reasons.

What causes a weak immune system?

The strength of your immune response naturally deteriorates as you get older – often referred to as ‘immune senescence’. This is why older people seem to have more infections and are more at risk of dying from them, than younger people.

Other medical conditions can cause your immune system to become weak. For example, obesity, drinking excess alcohol, or suffering from malnutrition. HIV (the human immunodeficiency virus) also damages the immune system.

Medical conditions such as Type-1 diabetes, Rheumatoid Arthritis, and coeliac disease, are autoimmune conditions, in which your body’s immune system, is mistakenly attacking itself.

There is also a difference between the male and female immune systems. The female immune system seems generally stronger and reacts more vigorously to infection – that is – until menopause.

What happens to the immune system at and after menopause?

Estrogen levels start to decline many years before your final menstrual period. This is because your ovaries are gradually becoming less responsive, and eventually, they completely fail.

After menopause, your estrogen levels fall dramatically. They remain around 90% lower than they were in the premenopausal period. Low estrogen levels seem to be associated with a weak immune system. For example, in postmenopausal women, the following observations have been reported in medical studies:

  • The CD4/CD8 cell ratio is reduced. CD4 cells are a specific type of lymphocyte – white blood cells – which summon other cells such as macrophages, CD8 lymphocytes, and B lymphocytes to fight off an infection.
  • There are higher circulating levels of inflammatory cytokines, such as Interleukin- 6 (IL-6), and Tumour Necrosis Factor-alpha (TNF-alpha). These are signs of chronic inflammation (see below). IL-6 has numerous complex functions in the inflammatory response. TNF-alpha is a cytokine with a key role in cell destruction and clearance of dead cells.
    The immune response to infection is slower or impaired. For example, CD4 T and B lymphocytes, and natural killer(NK) cell functions are all reduced.
    NK cells are white cells that have a specific role in destroying early cancer cells and virally infected cells.

The importance of chronic inflammation, in aging and age-related disease.

Chronic inflammation occurs when acute inflammation has taken place – but failed to switch off.

Acute inflammation occurs when the body recognizes a foreign substance or a damaged cell. The cell signaling process leads to a rise in the level of chemical messengers called cytokines. These put out a call for help, summoning much-needed immune cells to kill the organism, and clear away the dead cell.

However, with aging, this acute process becomes chronic. Persistent high levels of inflammatory cytokines, instead of being protective – now cause long-term cell damage. This is all part of the aging process.

Chronic inflammation is a major underlying cause of medical conditions such as atherosclerosis, obesity, diabetes, and Alzheimer’s Disease.

Does estrogen in hormone replacement therapy increase the immune response?

Some medical evidence is now available that this seems to be the case. Below are 2 examples from the literature – HRT reverses the changes to the immune system in women after hysterectomy.

In a 2004 study in the Journal of Reproductive Immunology, the authors studied a group of 17 women undergoing a hysterectomy and removal of both ovaries. They took blood samples before surgery, after 30 days, then 30 days after starting estrogen-only hormone replacement – using HRT patches.

The results showed that immediately after surgery, there was a significant decrease in the ratio of CD to CD8 cells, and the levels of cytokines, serum IL-4 and INF-gamma.

After completing 30 days of estrogen replacement, the CD4 to CD8 ratio and levels of INF-alpha had significantly increased. The IL- 4 levels, however, remained unchanged.

The authors concluded that estrogen has an important role in the female immune response.

A comprehensive medical review concluded that HRT can alter the immune response.

In a 2016 review in the journal Climacteric, the authors reviewed all the research studies on this topic, published from 1995-2015. There were 209 studies that met the study criteria for inclusion.

The authors concluded that HRT, taken by women at menopause, can alter the immune response as a result of specific changes to various chemical mediators.

Below are some specific findings:

  • Postmenopausal women have higher levels of Tumour Necrosis Factor-alpha (TNFα), Interferon-gamma (IFNγ), and Interleukin-6 (ILN-6) than premenopausal women.
    HRT has been shown to reduce the levels of these three cytokines.
  • After surgical menopause, women have been found to have a reduced CD4 to CD8 ratio, an increase in the numbers of circulating Natural Killer (NK) cells, and a reduced number of B lymphocytes.

HRT has been shown to reverse these changes.

Ask anything else you might be interested in concerning hormone replacement therapy.