Seminars .m Arthritis and Rheumatism VOL 25, NO 1 AUGUST 1995 Hormonal and Pregnancy Relationships to Rheumatoid Arthritis: Convergent Effects With Immunologic and Microvascular Systems Alfonse T. Masi, Seth L. Feigenbaum, and Robert T. Chatterton Objective: To review sex hormones and rheumatoid arthritis (RA) and the interrelationships between hormonal, immunological, and vascular systems. Data Sources: Publications detailing serum sex hormone levels and their HLA interactions, 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 decreased among 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 postmeno- pausal 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 vascu- lar systems, as they may relate to the physiopathology of RA. The major age, sex, and hereditable determinants of RA were compared within a composite Alfonse T. Masi, MD, DRPH, FACP, Professor of Medi- cine, University of Illinois College of Medicine at Peoria (UICOM-P); Seth L. Feigenbaum, MPH, MD: Assistant Clinical Professor, Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Fran- cisco; Director, Reproductive Endocrinology, Kaiser Perman- ente Medical Center; Robert T. Chatterton, PhD: Professor, Department of Obstetrics~Gynecology, The Medical School, Northwestern University. Supported in part by grants from Sanofi Winthrop Pharma- ceuticals, HealthCORE Fund of the Methodist Medical Center Foundation, The ProctorFoundation, and The BielfeMt Foun- dation. Address" reprint requests to Alfonse T. Masi, MD, DRPH, FACP, University of lUinois Collegeof Medicine of Peoria, One Illinois Dr, Peoria, IL 61656. Copyright © 1995 by W.B. Saunders Company 0049-0177/95/2501-000155.00/0 Seminars in Arthritis and Rheumatism, Vo125, No 1 (August), 1995: pp 1-27 1