Effects of Menopause on Autoimmune Diseases

Miranda A Farage; Kenneth W Miller; Howard I Maibach


Expert Rev of Obstet Gynecol. 2012;7(6):557-571. 

In This Article

Gender & Immunity

Immunosenescence does not affect men and women equally.[11] The dysregulation in T-cell function, for example, that is associated with aging, occurs much more dramatically in women than in men.[24,25]

Gender-specific differences in immunosenescence are at least partly attributable to sex hormones, evidenced by the fact that men and postmenopausal women have reduced T-cell immunity compared with premenopausal women.[26] The fact that men live shorter lives, on average, than women is also partially attributed to the thymic involution produced by higher circulating levels of androgens in men.[27]

Much is known about the influence of sex hormones on immunity in general. Androgens, estrogen, and progesterone all influence immune functions; estrogen in the form of 17b estradiol has been particularly associated with profound influences on the immune system (Table 2).

Females, in general, have superior immune vigilance compared with males, with both humoral and cell-mediated arms mounting more vigorous responses to immune stimulation.[28] Women maintain higher antibody levels than men, as well as higher levels of circulating IL-1, IL-4 and IFN-g[29] and females reject grafts faster.[30] A general pattern is observed in which estrogen enhances humoral immunity while androgens as well as progesterone tend to suppress it.[31] Women respond to antigenic stimulation with a predominantly Th2 response, with increased antibody production.[32] Estrogen stimulates the Th2 response by stimulating Th lymphocytes to secrete type 2 cytokines, which promote the synthesis of antibodies.[33] High estrogen levels associated with pregnancy also produce a shift towards Th2 response.[34]

Conversely, men respond to antigenic stimulation with primarily a Th1 response.[32] Androgens stimulate Th cells to produce type 1 cytokines, which suppress Th2 activity and stimulate CD8 cells,[35] a process that produces inflammation as the predominant immune response.[32]

The fact that estrogen favors a stronger overall immune response, particularly with regard to antibody response in women, is a mixed blessing. Although it produces a superior resistance to infection compared with men it also increases the risk in women of autoimmune disease.[36]