
It is not known exactly what the prevalence of autoimmune diseases is in the general population. There is no mechanism to collect data in this case, as there is for other diseases, such as infectious diseases and cancers. There is no complete and universally acceptable list of autoimmune diseases, so it is difficult to collect data on something that is not clearly defined. The estimate is between 3% and 10%. What is known for sure is that the ratio between men and women is clearly ”in favor” of women. The number of women with autoimmune diseases is 50% to 80% higher than that of men.
Women are more likely to develop autoimmune diseases than men
Why is this happening? It is difficult to say, because the very causes for which autoimmune diseases are triggered have not been fully discovered. It seems that the first factor is genetic, namely the X chromosome, present 2 times in women and only once in men, and the second, the hormonal changes that occur throughout a woman’s life: puberty, childbirth, postpartum period, menopause, post menopause.
Men have more testosterone, women have more estrogen. While in men testosterone levels remain somewhat constant, only late in life slowly starting to decline, in women estrogen has fluctuating levels throughout life. These are natural phenomena, we are not talking about exceptions. Estrogen “explodes” at puberty and during pregnancy, it is “squeamish” in perimenopause, and at menopause it mostly leaves us. Each month, estrogen and progesterone levels change considerably each day during the menstrual cycle. As the life average age increases, almost half of women’s lives are spent in post menopause, i.e. without the protection offered by estrogens.
In particular, in the case of preexisting autoimmune diseases, estrogen and autoimmunity appear to be interrelated. That is, autoimmune diseases influence hormonal changes, but also hormonal changes influence or trigger autoimmune diseases.
What are estrogens and what do they do?
Estrogens are not just sex hormones. Indeed, the ovaries produce most of the estrogen hormones, but the adrenal glands and fat cells also produce small amounts of these hormones. In addition to regulating the menstrual cycle, estrogen affects the reproductive tract, urinary tract, heart and blood vessels, bones, breasts, skin, hair, mucous membranes, pelvic muscles, immune response, and brain.
There are 3 forms of estrogen:
Estradiol. The best-known form of estrogen, it is produced by the body during the reproductive years.
Estriol. It is present during pregnancy, helps the uterus to grow and prepares the body for childbirth.
Estrone. It is present in the body after menopause. It is a weaker form of estrogen, one that the body can convert into estradiol if needed.
Men also produce estrogen, in a much smaller amount than women, just as women produce testosterone in a smaller amount than men. As we have seen, estrogen and testosterone are not only sex hormones, but also have other functions in the body.
The immune system
The immune system is of 2 kinds, innate and adaptive.
The first line of defense against pathogens is the innate or nonspecific immune response. We are born with this immune response and all living organisms have it. The innate immune response consists of physical, chemical and cellular defenses against pathogens. The main purpose of the innate immune response is to immediately prevent the spread and movement of foreign pathogens in the body.
The second line of defense against pathogens is called the adaptive immune response. Adaptive immunity is also called acquired immunity or specific immunity and is found only in vertebrates. We acquire this type of immunity throughout life through exposure to pathogens. If the first time it encounters a certain virus or bacteria this immune response needs more time, the second time it “recognizes” it and neutralizes it much faster.
The adaptive immune response is meant to attack pathogens, but it can sometimes make mistakes and attack its own cells. When this happens, autoimmune diseases can develop.
Estrogen and autoimmunity
Women have stronger immune responses to infections than men. Paradoxically, this stronger immune response comes with a price, which is the high incidence of autoimmune diseases in women. The reasons why women have stronger immunity and a higher incidence of autoimmunity are not fully understood.
From an evolutionary point of view, the primary purpose of all living organisms is the survival, reproduction and propagation of the species. In humans and most vertebrates, the mother has the responsibility of carrying and protecting the offspring from danger. In addition, there is a non-genetic passive transfer of immunity from mother to offspring called “transgenerational immune priming”. Therefore, motherhood may explain a stronger immunity of women so to be able to defend and protect the young. This may also imply that the same immune response changes during pregnancy to “tolerate” the foreign fetus and prevent rejection.
The female predilection of autoimmune diseases ranging from 3:1 for multiple sclerosis to 15:1 for autoimmune thyroiditis clearly implicates female sex and sex hormones in autoimmunity. While progesterone and testosterone are considered immunosuppressive, thus protective, estrogens in general are considered immunostimulatory, thus pathogenic in autoimmune diseases.
Pregnancy
The role of estrogen is complicated and still poorly understood in the connection between pregnancy and autoimmune diseases. In some diseases, estrogens are immunostimulatory, while in others they are inhibitory. While diseases such as systemic lupus erythematosus (SLE) worsen during pregnancy, others, including multiple sclerosis (MS), rheumatoid arthritis (RA), uveitis, and thyroiditis, improve.
Menopause
As for menopause, it represents a period of significant clinical and hormonal changes. Given the incompletely understood relationship between sex hormones and the immune system, it is possible that menopause affects or is affected by the presence of autoimmune disease.
Premature ovarian failure is related to autoimmune factors in some cases, but is not generally associated with autoimmune disease unless secondary to treatment with alkylating agents such as cyclophosphamide. Sex hormones have been suggested to be related to both the onset and activity of certain autoimmune diseases. For patients with systemic lupus erythematosus (SLE), disease activity is lower and damage accumulates more in the postmenopausal years, but the responsible mechanisms may be related to age, disease duration, menopausal changes, long-term effects of therapy, or a combination of these factors. Early menopause is a risk factor for rheumatoid arthritis (RA), and the postmenopausal state is associated with greater injury and disability. Scleroderma and giant cell arteritis (Horton’s arteritis) can also be adversely affected by the onset of menopause.
What is very important is that autoimmune diseases and menopause can have an increased effect on the risk of common comorbidities such as cardiovascular disease and osteoporosis.
Conclusions
Complex interactions of hormones and environmental factors in people genetically susceptible to autoimmune disease lead to immune dysregulation, then to immune-mediated diseases, including autoimmune diseases. We cannot change our genetics and we can only intervene a little in the hormonal activity of our body, but we can intervene in the case of environmental factors, i.e. the causes suspected of triggering an autoimmune disease, in addition to genetics and hormones: don’t smoke, don’t drink in excess, make healthy choices regarding nutrition, exercise and sleep and rest schedules. And build a mindset that helps us implement these habits naturally in our lives.