Details

Autor(en) / Beteiligte

• Cutolo, Maurizio
• Straub, Rainer H.

Titel

Sex steroids and autoimmune rheumatic diseases: state of the art

Ist Teil von

• Nature reviews. Rheumatology, 2020-11, Vol.16 (11), p.628-644

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• In autoimmune rheumatic diseases, oestrogens can stimulate certain immune responses (including effects on B cells and innate immunity), but can also have dose-related anti-inflammatory effects on T cells, macrophages and other immune cells. By contrast, androgens and progesterone have predominantly immunosuppressive and anti-inflammatory effects. Hormone replacement therapies and oral contraception (and also pregnancy) enhance or decrease the severity of autoimmune rheumatic diseases at a genetic or epigenetic level. Serum androgen concentrations are often low in men and in women with autoimmune rheumatic diseases, suggesting that androgen-like compounds might be a promising therapeutic approach. However, androgen-to-oestrogen conversion (known as intracrinology) is enhanced in inflamed tissues, such as those present in patients with autoimmune rheumatic diseases. In addition, it is becoming evident that the gut microbiota differs between the sexes (known as the microgenderome) and leads to sex-dependent genetic and epigenetic changes in gastrointestinal inflammation, systemic immunity and, potentially, susceptibility to autoimmune or inflammatory rheumatic diseases. Future clinical research needs to focus on the therapeutic use of androgens and progestins or their downstream signalling cascades and on new oestrogenic compounds such as tissue-selective oestrogen complex to modulate altered immune responses. The effects of sex steroids (oestrogens, androgens and progesterone) on immune responses contribute to the sex bias in autoimmune rheumatic diseases in complex ways. Targeting these effects could hold potential for treating patients with autoimmune rheumatic diseases. Key points Oestrogens have both pro-inflammatory and anti-inflammatory effects, acting as stimulators of B cell-mediated immune responses but inhibitors of pro-inflammatory macrophages and some T cells. In contrast to oestrogens, androgens and progesterone have immunosuppressive and anti-inflammatory effects. In men and postmenopausal women with rheumatic diseases, increased androgen-to-oestrogen conversion in inflamed tissues and local oestrogen metabolite synthesis support disease. Pregnancy, sex hormone replacement therapies and oral contraceptives can negatively or positively affect the severity of autoimmune rheumatic diseases, depending on the respective predominance of oestrogens or androgens (and progesterone). Sex-dependent differences in gut microbiota may lead to genetic or epigenetic changes in local gastrointestinal inflammation, systemic immunity and susceptibility to a range of rheumatic diseases. Therapies with androgens and progestins, selective oestrogen receptor modulators and tissue-selective oestrogen complex need to be tested more rigorously in autoimmune rheumatic diseases.