Review articleSex hormones and urticaria
Introduction
Urticaria is a common clinical disorder, pathophysiology based on mediators release from mast cells, predominantly histamine and subsequently an inflammatory response [1]. However, in most cases, aetiology of chronic urticaria is unknown; it is referred to as chronic idiopathic urticaria and in over one-third of cases the autoimmune pathogenic mechanism is proposed [2], [3]. Interestingly, altered functions of the neuro-endocrine-immune system due to stress and other factors seem to appear as a very interesting theory for urticaria pathogenesis [4]. Changes in hormones balance and expression may promote the immunological imbalance and skin function responsible for urticaria expression. For example, rare association between primary hyperparathyroidism and chronic urticaria has been described [5]. The association between chronic urticaria and autoimmune thyroiditis is frequent. l-Thyroxine reduces the symptoms of chronic urticaria associated with autoimmune thyroiditis (hypothyroid and euthyroid), suggesting a stimulatory effect of TSH able to produce considerable changes of the immune response and immune tolerance in such patients [6]. Higher expression of corticotropin-releasing hormone receptor-1 in the skin of chronic urticaria patients has been demonstrated [7]. It is known that urticaria may be associated with some diseases and/or triggered by some conditions characterized by sex hormone changes, including menstrual cycle, pregnancy, menopause, and hormonal contraceptives or hormone replacement therapy. However, the role of endogenous and exogenous sex hormones as well as estrogen mimetics in the disease pathogenesis are poorly understood.
Sex hormones are considered to be responsible for gender and menstrual cycle phase-associated differential susceptibility and severity of some immune-mediated and inflammatory diseases, including asthma, atopic dermatitis, and lupus [8], [9], [10], [11].
It is well known that fluctuations in sex hormone level associated with menstrual cycle, pregnancy, menopause and hormone administration can induce oedematous attacks in hereditary angioneurotic oedema (HANO) [12], [13], [14], [15]. Thus, it is important to consider also the possibility of the influence of sex hormones on chronic urticaria expression.
Chronic urticaria occurs approximately twice more frequently in women as compared to men [16], [17], suggesting that sex differences in hormonal milieu may play a role in this phenomenon.
Section snippets
The role of sex hormones in the immune system function and mast cells activity
Receptors for sex hormones have been identified on various immune and inflammatory cells suggesting that these hormones influence directly their functions. Sex hormones are involved in immune response by regulation of maturation, survival, activation and function of diverse immune cells; generally with estrogens as enhancers at least of the humoral immunity and androgens and progesterone as natural immune-suppressors [2], [18], [19], [20]. Estrogens have dose- and cell-type-specific effects on
Urticaria related to the sex hormones fluctuations during the menstrual cycle
It is well known that severity of some diseases varies with the menstrual cycle, suggesting some influence of sex hormones on the diseases expression. Especially, symptoms aggravate during the premenstrual period, however the underlining mechanism is poorly understood [8], [9], [10]. For example, premenstrual deterioration in asthma symptoms was observed in about one-third of asthmatic women [8]. Hormonal fluctuations during the menstrual cycle are also thought to play a role in the urticaria
Sex hormonal changes in chronic idiopathic urticaria and autoimmune chronic urticaria
Information on relation between sex hormonal changes and chronic idiopathic urticaria and chronic autoimmune urticaria is scarce. It has been demonstrated that serum concentration of dehydroepiandrosterone sulfate (DHEA-S) in patients suffering from chronic urticaria is significantly lower than in healthy subjects [48], [49], [50], [51]. It is then interesting to state whether urticaria expression is influenced by dehydroepiandrosterone or by its metabolites?
DHEA and DHEA-S are steroid hormones
Oral contraceptives and hormone replacement therapy
Immune system and skin functions are regulated by sex hormones. Exogenous sex hormones can affect these hormone-dependent functions.
It well documented that hormonal contraceptives influence hereditary angioedema [12], [13], [14], [15]. In addition, a case report describes a patient showing acquired deficiency of C1-INH upon hormone replacement therapy [59]. Decreased plasma concentration of C1 esterase inhibitor has been reported in women taking oral contraceptives [60].
However, it is unclear
Menopause
It is known, that the peak time of life for urticaria to begin is between the age of 11 and 40. Then the frequency of urticaria tends to decrease [67]. However, there are no studies available on prevalence of urticaria in perimenopausal, menopausal and postmenopausal women. Theoretically, the lack in fluctuation in endogenous sex hormones in the postmenopausal period might be responsible for less frequent prevalence of the disease compared to perimenopausal and menopausal period characterized
Pregnancy
Urticaria/angioedema may also occur in pregnant women, worsen with pregnancy in some patients and appear to improve in others [68]. Pruritic urticarial papules and plaques of pregnancy (PUPPP) should also be kept in differential diagnosis in pregnant women, especially in cases of urticarial lesions occurring in the third trimester [69].
Concluding remarks
Data regarding relation between urticaria and sex hormones are scarce. Urticaria may be associated with some diseases and conditions characterized by sex hormone changes, including menstrual cycle, pregnancy, menopause, and hormonal contraceptives or hormone replacement therapy, suggesting that fluctuations in hormonal milieu may play a role in pathogenesis of the disease. In addition, occurrence of chronic urticaria is approximately doubled in women as compared to frequency in men. Such
Conflict of interest statement
All authors declare no conflict of interest.
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