Effects of estrogen replacement therapy on estrogen receptor expression and immunoregulatory cytokine secretion in surgically induced menopausal women

To investigate the effect of oral and transdermal estrogen replacement therapy (ERT) on the expression of different estrogen receptor (ER) subtypes and the secretion of immunoregulatory cytokines, we performed a clinical investigation on previously healthy women who had undergone a total hysterectomy and bilateral salpingo-oopherectomy. These women were randomly distributed into two groups: an oral ERT group and transdermal ERT group. Before and after ERT, the serum levels of estradiol (E2) and follicle stimulating hormone (FSH) were measured, ERα and ERβ expression of peripheral blood T lymphocytes was tested, and secretion of specific immunoregulatory cytokines (IFNγ, IL-2 and IL-4) by T lymphocytes was examined. Our results confirm that for both groups, the serum E2 level was increased after ERT (P < 0.01) and the serum FSH level was decreased after ERT (P < 0.01), with no significant difference in hormone levels between the two groups. ERα expression by T lymphocytes was significantly higher after ERT than before (P < 0.01) in both groups. Levels of type 1 cytokines (IL-2 and IFNγ), which were secreted by T helper 1 (Th1), after ERT were substantially decreased. The level of type 2 cytokine (IL-4), which were secreted by T helper 2 (Th2), was significantly increased after ERT (P < 0.01 for the oral group and P < 0.05 for the transdermal group). In summary, both oral and transdermal ERT increased serum E2 levels, decreased serum FSH levels and relieved the effects of peri-menopausal symptoms. These data suggest that both oral and transdermal ERT act to improve the balance of Th1/Th2 cytokines by the effects of estrogen potentially acting in T lymphocytes mainly through ERα.