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

Expert Commentary

Estrogen rules a women's body. With ERs in every organ system and nearly every tissue and organ, estrogen's actions continue to be catalogued but a comprehensive understanding of its dominion over the physiology of the female has yet to be attained. Estrogen maintains female health, protecting a women's cardiovascular system, maintaining bone health, and preserving neural health and brain function. It ferries her from childhood to motherhood yet eventually brings the curtain down on her fertility. Estrogen can also betray her, promoting cancers in the reproductive organs (breast, ovary and uterus) and causing both mood swings and migraines. It also plays a role in autoimmune disease.

The dramatic preponderance of autoimmune disease in females makes a leading role for estrogen in autoimmune disease nearly certain. The specific contributions that estrogen makes to autoimmunity, however, have been difficult to tease out, due largely to the magnitude of estrogen's influence in female physiology, with seemingly infinite possible actions in multiple biochemical processes. The fact that estrogen, over the lifespan of the human female, shapeshifts also complicates the picture. E2, the predominant form during the reproductive years, is complemented by estriol (E3) during pregnancy and replaced as the dominant form by E1 after menopause. Another complicating factor is existence of dual forms of receptors which act to modulate how estrogen is expressed. Variations in the circulating level of the different forms of estrogen also modulate immune processes, particularly with regard to whether immune response is driven towards cellular (Th1 pathway) or humoral (Th2 pathway) immune responses. A better understanding of the role of estrogen in immune processes is critical for elucidating the role that aging (and its associated estrogen withdrawal in women) plays in both the development and the course of autoimmune disease.