Autoimmune diseases and reproductive aging

Abstract

As the population ages, more individuals with autoimmune diseases are experiencing reproductive senescence. Understanding the impact of menopause and age-related androgen decline on disease onset and course, as well as the potential for hormonal interventions, is critically important. In men, lupus erythematosis (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS) are associated with lower androgen levels. However, the impact of age-related declines in testosterone, as well as of testosterone replacement, on disease course remains underexplored. In women, the course of all three diseases with onset after the age of menopause differs from that with onset before menopause. Early age at menopause is associated with increased disease risk, and after menopause, disease course changes in SLE and RA. Less is known about MS. This article summarizes what is known about the relationship between reproductive aging and autoimmune diseases in men and women, and highlights areas for further investigation.

Neuropsychiatric systemic lupus erythematosus and cognitive dysfunction: The MRL-lpr mouse strain as a model

“…Systemic lupus erythematosus (SLE) is a chronic multisystem relapsing-remitting autoimmune disease, primarily affecting females [1], which can be influenced by hormonal, genetic and environmental factors [2][3][4][5][6][7]. Clinical studies have shown that neurologic and neuropsychiatric (NP) symptoms occur in up to 75% of patients, a condition representing a particularly severe form of the disease known as NPSLE [8].…”

Patients report worse MS symptoms after menopause: Findings from an online cohort

“…The impact of the menopausal transition (Harlow et al, 2012) on MS course has not been explored. Estrogen has been linked with both inflammation and neuroprotection in animal models of MS (Gold and Voskuhl, 2009b;MacKenzie-Graham et al, 2012), and therefore the loss of ovarian sources of estradiol occurring at menopause could be hypothesized to result in either reduced inflammation, or worse clinical decline (Bove, 2013).…”

Low testosterone is associated with disability in men with multiple sclerosis

“…Age-related declines in male testosterone levels 5 have been hypothesized to partially explain the later onset of MS relative to women. While some studies have found decreased levels of testosterone in men with MS relative to healthy controls 6-8 , these studies had important limitations, including variable definitions of hypogonadism, lack of control for confounding introduced by recent steroid use, circadian variation of testosterone levels, and the inclusion of men with advanced disease, in whom hypogonadism may be caused by chronic disease 9 .…”