Hormonal and pregnancy relationships to rheumatoid arthritis: Convergent effects with immunologic and microvascular systems

Abstract

Objective: To review sex hormones and rheumatoid arthritis (RA) and theinterrelationships between hormonal, immunological, and vascular systems. Data Sources: Publications detailing serum sex hormone levels and their HLAinteractions, steroidogenesis, pregnancy, and therapeutic uses of sex hormones in RA. Study Selection: Controlled studies of sex hormone levels in RA patients not previously treated with glucocorticoids. Data Extraction: Mean (±SD) serum levels of dehydroepiandrosterone sulfate (DHEAS), testosterone (T), and estradiol (E2). Data Synthesis: Mean (±SD) levels were collated into tables for women with pre-versus postmenopausal onsets of disease and men. Data were also ordered across all study groups by increasing mean levels of the control subjects. Pooled data were summarized statistically, and major sources of variation between the studies were identified. Conclusions: Serum DHEAS, an adrenal androgen, was impressively decreasedamong women with premenopausal onset of RA. One study showed such deficiency years before disease onset. Serum T was somewhat decreased in the premenopausal onset group, but could be explained by decreased peripheral conversion of the lower levels of adrenal androgens. Women with postmenopausal onset of RA had modestly decreased serum DHEAS levels overall, but no difference in serum T, compared with controls. Male RA cases had consistently decreased serum levels of T, but not of DHEAS. Serum E2 was comparable in all RA versus control groups. The complex biology of pregnancy was interpreted as an example of vital interactions between hormonal, immunological, and vascular systems, as they may relate to the physiopathology of RA. The major age, sex, and hereditable determinants of RA were compared within a composite table of estimated relative risks. Elucidation of the interacting risk factors offers promising avenues of research in this complex disease.