Hormone replacement and contraceptive therapy in autoimmune diseases

Sex hormones, including estrogens, influence the immune system in a complex manner, playing an important role in the pathophysiology of autoimmune diseases. Estrogen receptors can be found in almost all cells, including those of the adaptive and innate immune systems. Depending on the relative preponderance and stimulation of different receptors in various tissues, estrogens may demonstrate pro-inflammatory or anti-inflammatory properties. Traditionally, exogenous estrogens were considered to have the potential of worsening the autoimmune processes and hence were avoided in patients with rheumatic diseases. Recent studies have demonstrated the efficacy of exogenous hormone therapies, either in the form of oral contraceptives or post-menopausal hormonal replacement therapy, in the majority of patients with rheumatic diseases. However, caution needs to be exercised as a higher incidence of mild to moderate flares of systemic lupus erythematosus was noted with hormonal replacement therapy in the large randomized controlled trial, HRT-SELENA. Exogenous estrogens can also increase the risk of thrombosis in patients with positive antiphospholipid antibodies and should be avoided in this subgroup. This review will discuss the current evidence on the efficacy, safety and impact of exogenous sex hormone therapies in patients with autoimmune rheumatic diseases.