We might have all sadly experienced gender bias in our day-to-day life, but did you know gender biases are also prevalent within our immune system?
Not only do men and women respond differently to infections but gender also impacts our likelihood of getting a chronic disease: we know autoimmune syndromes display a strong female bias – with women 3 times more likely to develop an autoimmune disease and almost 80% of all autoimmune issues in women. Autoimmune diseases occur when the immune system turns on and attacks the body’s own cells or tissues, initiating a chronic cycle that results in damage or destruction of specific organs. But gender it seems can also affect our likelihood to develop allergies, response to medical treatments and even the effectiveness of vaccines.
Men die significantly more often from infectious diseases than women. For instance, men are 1.5 times more likely to die from tuberculosis, and flu. The reasons why are complex and only partially understood. There are suggestions that poorly understood evolutionary reasons are at play: survival of the species may mean men are harder hit by infection. But a woman’s reactive immune system perhaps leaves her more open to tipping over into autoimmunity. Autoimmune diseases are complex and multifactorial – meaning there needs to be a perfects storm of contributing genetics and a plethora of environmental influences. So, this alone cannot explain gender dimorphism. Layered on top are numerous possible biological, social and psychological factors. But unfortunately, these are ill-defined and poorly understood.
All this may reflect a sneaky evolutionary trick used by viruses to enable their survival. Women have developed multiple mechanisms to transmit infections; mainly through passing bugs from mother to child during gestation or birth, or through breastfeeding. So, women are better vessels for viruses. Meanwhile, viruses have singled men out as the weaker sex. While popular culture has come up with the term “man flu”, suggesting men are over-dramatizing flu symptoms, evidence suggests they may in reality be suffering more due to this dampening down of their immune responses.
But with chronic diseases such as autoimmunity on the rise, the importance of approaching treatment and diagnosis through a gender lens is of increasing importance. Unpicking why this is has challenged the medical and scientific community. We are still not fully clear on the mechanisms, but there are some clues
Genetic, hormonal or both?
Genes associated with gender differences impart some known effects on immunity and have each been associated with different antibody responses to vaccines, for example. We don’t yet know whether these variations are due to different genes being selected for in different genders or through environmental triggers switching them on and off. What we do know is that the female X chromosome contains a lot of genes involved in autoimmune disease whereas the male Y chromosome has much less genetic influence on autoimmunity.
But unlike genes, our hormones have distinct developmental influences throughout our life and seem to play a bigger role in triggering autoimmunity. These differences tend to appear after puberty and flare-ups increase during pregnancy. In fact, almost half of women who develop an autoimmune disease have onset after the first year of pregnancy. With huge fluctuations over a relatively short period of time, hormones are a key trigger for this unfortunate legacy of carrying a child. But the full picture of why is still quite unclear. Prolactin, the hormone that tells the body to make breast milk when a person is pregnant or breastfeeding, can also be produced by our immune cells and may exacerbate autoimmune flare-ups. In fact, hyperprolactinemia a state of increased prolactin levels is seen in many autoimmune conditions.
On the contrary, menopause is associated with a lower disease severity. The prevailing hypothesis for these differences between life stage, gender and autoimmune risk is that the main sex hormones, testosterone, oestrogen and progesterone, influence how our different immune cells function. It is not surprising that hormonal changes during the female menstrual cycle underlie monthly cyclical changes in immune function and how susceptible we are to infection or inflammatory disease. But the picture is complicated because hormones do not act alone. For example, they are highly influenced by the level of stress molecules present at a specific time, how much exercise and what we are, or are not eating. And it’s not just how much of any given hormone, but also their combination and their respective ratio which impacts the development and the course of autoimmune condition.
Oestrogen directly impact multiple cells of the immune system, change their behaviour and function Oestrogen is variable during the menstrual cycle, high during pregnancy and low after menopause in females. It seems that the power of oestrogen on the immune system partly reflects these variations. A woman’s immune system is more robust and mounts a stronger inflammatory response during the reproductive years - when oestrogen is its highest. As a woman transitions into menopause, oestrogen declines and a woman’s immune system is more comparable to men. For this reason, some women see a decline in their autoimmune symptoms post-menopause. With regards to autoimmune disease, it is particularly a concern in women who are experiencing oestrogen dominance or excess oestrogen. And it is the spikes and dips of oestrogen that can drive autoimmune disease wild in peri-menopause, before the ovaries have called it quits. If you already a woman who suffers from an autoimmune disease, hormone imbalances can be experienced as a flare in symptoms—sudden joint pain, hair loss, fatigue, changes in skin, and other symptoms. So, it would seem that it’s a bit of a Goldilocks situation — not too much, not too little, but just the right amount of oestrogen is necessary for appropriate immune system regulation. Likewise, progesterone affects many of our immune cells directly. With both stimulatory and suppressive effects on the immune system, it is more typically seen as immunosuppressive, blocking inflammation and protecting from autoimmunity. Androgens, including testosterone, also have an effect on the immune system. It does seem that testosterone offers some level of autoimmune protection, gently tapping the breaks on inflammatory immune responses. In a recent study, we showed that high levels of testosterone in males protect them against their immune system deregulating. But again, the picture is not exactly straight forward. It depends on the type of androgen, the amount of it, and the time when the effect happened if the activity of our immune system will be blocked or activated. For this reason, it’s important to pay attention to your cycles and seek help if you are concerned. There are also many naturally occurring chemicals in our environment that resemble oestrogens (environmental oestrogens) as well as some synthetic compounds resembling oestrogens (xenoestrogens). Some of the foods we eat, detergents, plastics and pesticide contain these chemicals, and once in our body, they accumulate in our fat cells, and this is where they interfere with the immune system.
What else is involved?
One thing most people in the autoimmunity field agree on is that there’s a lack of evidence-based information about specific dietary nutrients in treatments for autoimmune disease. Your mothers diet while you were a developing baby in the uterus also has an impact, particularly more so in girls than boys. postnatally, studies also suggest that breastfeeding may benefit girls’ immune systems more than boys. There is accumulating evidence that vitamins and minerals act differently in males and females, particularly in infancy. A new study has raised the possibility that stress may cause autoimmune disease, such as lupus or rheumatoid arthritis, because it found a higher incidence of autoimmune diseases among people who were previously diagnosed with stress-related disorders. The nutritional management of autoimmune diseases usually emphasizes controlling pain and inflammation, slowing the progression of the disease, and boosting the immune system. And a few promising foods and nutrients are emerging as potentially beneficial including vitamin D status and omega 3 fish oil supplements combined with exercise and an anti-inflammatory style eating pattern plant-rich in phytonutrients. One up-and-coming area of research focuses on the impact of balancing the gut microbiome which might actually be responsible for driving this hormonal-dependent triggering of autoimmunity. Incidence of an upset in your gut microbes and their carefully calibrated community as a causal factor, not merely as a consequence of autoimmune disease, is now confirmed. It is thought that the microbiota may be able to regulate sex hormones and therefore indirectly influence our likelihood of succumbing to autoimmunity. Another reason is attributed to the development of “leaky gut” if you don’t have the right gut bugs present or they are not able to do their job properly. Scientists are currently trying to work how having problems in your gut bugs from antibiotic use for example, may cause problems elsewhere in the body. There is also work emerging into how we can reverse autoimmunity with prebiotic dietary fibres to feed the microbiome or probiotics to enrich the good bacteria.
The bottom line.
Although autoimmune disorders affect people of all genders, races, and ages, there are definitely contributing roles played by genes and gender.It’s clear that women have an increased risk, particularly due to hormonal fluctuations at distinct stages of their life.But each autoimmune disease is different and the exact causes for most are still unclear and probably due to causes you can’t control for. It’s difficult to say whether you can reduce your risk but there are definitely a few things worth trying.Like a sensible lifestyle - not drinking too much, avoiding antibiotics (unless strictly necessary), exercise and staying physically active and cultivating the mental bandwidth to adapt and self-manage the stresses of life. And there is no harm in supporting your body with a diet rich in whole plant foods full of phytonutrients and fibre.Think fruits, vegetables, whole grains, legumes, nuts and seeds not to mention focusing on healthful fat sources such as extra-virgin olive oil, avocado, nuts, and fish; and including tea, dark chocolate, spices and herbs, and of course red wine in moderation.