The Roles of Sex Hormones in the Course of Atopic Dermatitis

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by T helper 2 cell (Th2)-shifted abnormal immunity, skin barrier impairment, and pruritus. The prevalence of AD in childhood is slightly higher in boys than in girls; after puberty, the sexual difference is reversed. The female preponderance in all generations exists in intrinsic AD with enhanced Th1 activity and nickel allergy, lacking increased serum IgE or filaggrin mutation. AD is often deteriorated before menstruation. We review the effects of sex hormones on immune responses and skin permeability barrier and propose possible hypotheses for the above phenomena. After puberty, the immune responses of patients are remarkably influenced by sex hormones. Estrogen and progesterone enhance the activities of Th2/regulatory T cell (Treg) but suppress Th1/Th17. Androgens suppress Th1/Th2/Th17 and induce Treg. The skin permeability barrier is fortified by estrogen but is impaired by progesterone and androgens. Dehydroepiandrosterone suppresses Th2 but enhances Th1. The amount of steroid sulfatase converting dehydroepiandrosterone sulfate to dehydroepiandrosterone is higher in women than in men, and thus, women might be more susceptible to the influence of dehydroepiandrosterone. The balance of modulatory effects of sex hormones on immune responses and skin barrier might regulate the course of AD.

Sex and Gender Aspects for Patient Stratification in Allergy Prevention and Treatment

“…After puberty females predominate on males: respectively 8.1% and 5.7% in a study in Japan and 8.01% and 6.04% in a study in Europe and USA [24]. It was suggested that sex hormones may contribute to the higher incidence of AD-like dermatitis in female rats KFRS4/Kyo [77]. In intrinsic AD, in all generations exist a female predominance with increased Th1 activity and high incidence of nickel allergy and without filaggrin mutation or enhanced serum IgE levels.…”

The Connection between Urinary Equol Levels and the Prevalence of Atopic Dermatitis

“…As it was reported that male AD patients have lower levels of estradiol than healthy controls [15], the immune responses of AD patients could be influenced by sex hormones. Furthermore, estrogen and progesterone enhance the activities of Th2/regulatory T cells but suppress Th1/Th17 [28]. The skin permeability barrier is reinforced by estrogen but impaired by progesterone and androgens [28].…”

“…Furthermore, estrogen and progesterone enhance the activities of Th2/regulatory T cells but suppress Th1/Th17 [28]. The skin permeability barrier is reinforced by estrogen but impaired by progesterone and androgens [28]. Thus, the estrogen-like effect of equol may improve AD symptoms in tandem with an anti-oxidative effect.…”

Which Way Do We Go? Complex Interactions in Atopic Dermatitis Pathogenesis

“…Components of the innate immune system contribute significantly to the development of AD skin inflammation, including IL-5 and IL-13 from group 2 innate lymphoid cells, IL-4 from basophils, and IL-25, IL-33, and TSLP from epithelial cells (Divekar and Kita, 2015;Hussain et al, 2018;Mashiko et al, 2017;Salimi et al, 2013). This immune milieu is dependent on a patient's age, sex, and ethnic background, thereby adding to the complexity of this disease Brunner and Guttman-Yassky, 2019;Kanda et al, 2019).…”