ReviewHormone replacement and contraceptive therapy in autoimmune diseases
Highlights
► The sex hormones play a significant role in the pathophysiology of autoimmune rheumatic diseases. ► Hormonal therapies (OCs and HRT) are effective in the majority of patients with rheumatic diseases. ► However, their use should be avoided in women with severe active SLE and hypercoaguable states. ► HRT led to an increase in mild to moderate SLE flares in the HRT-SELENA trial. ► OCs may improve RA disease activity and are an effective and safe option for young women with RA.
Section snippets
Estrogens and systemic lupus erythematosus
The major concerns over use of estrogens in systemic lupus erythematosus (SLE) were induction or exacerbation of the disease. Animal data have shown harmful effects of estrogens in SLE models. Estrogens augment murine B-cell survival and autoreactivity and exacerbate murine SLE in some models. However, the effects of estrogens on murine disease are variable [1]. In the NZB/NZW murine SLE model, removal of estrogen or addition of androgen improves survival [2]. In contrast, estrogen has diverse
Estrogens and rheumatoid arthritis
In animal models of arthritis, estrogens have beneficial effects, retarding arthritis progression [60], [61]. In human rheumatoid arthritis, the role of estrogens is less clear as both pro- and anti-inflammatory effects have been reported. Rheumatoid arthritis is two to three times more common in women compared to men. Higher disease activity scores have been reported in women compared to men [62]. On the other hand, rheumatoid arthritis tends to improve during periods of high estrogen levels,
Other autoimmune diseases
The evidence for any beneficial or harmful role for estrogens and other sex hormones is very limited and sometimes contradictory for other autoimmune diseases. Two studies suggested beneficial role of exogenous estrogens (including hormone replacement therapy) on endothelial function in patients with systemic sclerosis [82], [83]. In contrast, one case report described progression of Raynaud’s phenomena to severe systemic sclerosis after use of OCs [84]. Behcet’s disease is associated with
Conclusion
The autoimmune rheumatic diseases affect young women, especially SLE. The pathophysiology of these diseases is complex and sex hormones may have variable effects. Care should be exercised in using hormone replacement therapy in SLE given the increased risk of mild to moderate flare. OCs cannot be recommended for women with SLE with hypercoagulability. Women with active and severe SLE, history of thrombosis, anticardiolipin antibody and/or lupus anticoagulant positivity are at high risk and
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2021, Medical HypothesesCitation Excerpt :The risk of developing SLE increases with greater concentrations of ethinyloestradiol in the pill formulation and is higher in women using first- or second-generation contraceptives that are known to have higher oestrogen doses compared to more modern drug formulations [99,100]. As predicted by our hypothesis, postmenopausal exogenous oestrogen use also increases women’s SLE risk, and randomized, double-blind controlled trial of hormone replacement therapy in SLE patients slightly increases the risk of mild to moderate flares [101–103]. Oestrogen levels therefore influence not only symptoms of autoimmune disease, but might also be a contributing factor to autoimmune disease incidence, possibly by affecting central and peripheral tolerance induction mechanisms.
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