Role of Sex Hormone Levels and Psychological Stress in the Pathogenesis of Autoimmune Diseases

Abstract

The aim of this review article is to assess the connection between psychological stress and sex hormones and their effect on the development of autoimmune diseases. Psychological stress describes what people feel when they are under mental, physical, or emotional pressure. We searched for online articles using MEDLINE®, Embase, Cochrane Library and Google Scholar. Our research yielded a total of 165 articles out of which 30 articles were considered for further perusal. The articles were reviewed from February 2016 to February 2017. Case reports and patients suffering from hematolymphoid malignancies and active infections were excluded from the review. Estrogen and testosterone are potential physiological regulatory factors for the peripheral development of CD4+CD25+ T regulatory cells. Stress at any age leads to the depletion of estrogen and testosterone stores in the body, leading to the loss of expansion of T regulatory cells, making the immature B cells evade the negative selection at the germinal center, or in other words, leading to the loss of central tolerance, a triggering event in autoimmune diseases like systemic lupus erythematosus. Autoimmune diseases in women are most likely due to changes in estrogen levels during mental, physical, pre-menopausal, post-menopausal, and pregnancy-induced stress. We conclude that modulating estrogen in females (pre-menopausal and post-menopausal) and testosterone in males can be used to treat stress-related immune imbalance resulting in autoimmune diseases in both sexes.

Stress, pseudoallergens, autoimmunity, infection and inflammation in chronic spontaneous urticaria

“…The link between the brain and mast cells within the skin via C fibre sensory nerves is likely involved in the worsening of skin diseases such as atopic dermatitis and CSU with stress [75]. The increased frequency of CSU in women is likely related to oestrogen and progesterone and the ability of these hormones to stimulate autoimmunity [5]. However, recent work also suggests the importance of pituitary adenylate cyclase activating polypeptide in stress circuits and stress responses and which is modulated by oestrogen [76].…”

“…CSU is more frequent in females with a male to female ratio varying between 1.5:1 to 2:1. Such female preponderance is evident in many of the organ specific and systemic autoimmune diseases [5]. While autoimmune disease (21%), chronic infection (29%) and immune dysfunction (4%) may become evident over time, CSU remains idiopathic in 45% even after 10 years of follow-up [6].…”

Molecular and Cellular Bases of Immunosenescence, Inflammation, and Cardiovascular Complications Mimicking “Inflammaging” in Patients with Systemic Lupus Erythematosus

“…Complex etiological factors are involved in lupus pathogenesis, such as genetic predisposition [28,29,30,31], epigenetic post-transcriptional regulation [32,33,34,35,36], sex hormone imbalance [37,38], environmental stimulation [39,40], mental/psychological stresses [38], and other undefined factors [41]. Recently, many authors have demonstrated that mitochondrial dysfunctions [42,43,44,45,46], defective bioenergetics in immune cells, and abnormal immunometabolism [47,48] can induce structural and functional changes of biomolecules (proteins, lipids, nucleic acids, and glycoproteins) by oxidative and nitrosative stresses [49,50].…”

An insight into the role of the death receptor CD95 throughout pregnancy: Guardian, facilitator, or foe

“…The possibility of becoming pregnant had been a concern for patients with autoimmune disease, due to the possibility of the disease worsening and poor gestational outcomes. This concern can be alleviated with maternal counseling, precise detection of the type of autoimmune disease, and with the replacement of teratogenic for safer medication that avoids the emergence of symptoms during the pregnancy (Assad et al, ; Kumru et al, ; Negro & Stagnaro‐Green, ; Perricone, de Carolis, & Perricone, ; Tincani, Dall'Ara, Lazzaroni, Reggia, & Andreoli, ). Autoimmune diseases are negatively correlated with fecundity success; indeed, preclinical stage autoimmune patients (asymptomatic and even those unaware of their disease) have decreased fecundity.…”