Rheumatoid arthritis, the contraceptive pill, and androgens

Abstract

Evidence is accumulating that low androgen concentrations are a cause of rheumatoid arthritis. This would explain a number of established features of the epidemiology of the disease. These include: (a) the variation of disease activity with pregnancy; (b) the variation of age at onset by sex; (c) the variation by sex with HLA-B15; (d) the association with bone mineral density; and (e) the differing time trends in incidence rates by sex. It is argued, moreover, that if one makes a plausible assumption--namely, that women who choose oral contraceptives have high androgen concentrations at the time they first make this choice--then an explanation becomes available for the confusion about the relation between rheumatoid arthritis and oral contraception. Grounds are adduced for that assumption. If this line of reasoning is substantially correct it also has implications for the relations between rheumatoid arthritis and smoking and consumption of alcohol.

PIP: People with rheumatoid arthritis (RA) have lower mean androgen levels than those who do not have it. Evidence suggests that, in males, genetics cause the low mean testosterone levels, as indicated by the low ranking of the B15 gene locus, and these low levels are a precursor of RA. Male RA patients treated with androgens improve. In women with RA, however, the B8 gene locus is associated with low testosterone levels and B15 is either just slightly associated or not associated at all. Low androgen levels may account for a number of features of RA's epidemiology; change of disease activity with pregnancy, age at onset by sex, and by sex with HLA-B15 antigen; the link with lower bone mineral density; and differing time trends in incidence rates by sex. Several studies show that oral contraceptive (OC) use may have a protective effect against RA. 2 researchers reviewing the literature suggest that OC use may be instead a marker for a causal factor. A London-based researcher hypothesizes that factor is androgen levels. He goes on to postulate that low androgen levels are a cause of RA, that women who opt to us OCs initially have higher androgen levels than other women, and that the pharmacological effect of OCs is lowering women's androgen levels. Based on these hypotheses, he poses 5 research proposals. Research should determine whether young women choosing OCs have higher testosterone levels than those not choosing OCs. It should also continue to gather data on the progress of RA in unselected male patients treated with androgens. Research should determine whether pregnancy with a male fetus results in greater improvement of RA than with a female fetus. Other research should examine low testosterone levels' role in RA and personality. Since alcohol and cigarettes also reduce testosterone levels, a longitudinal study would determine whether alcohol and cigarette use are indicators of high testosterone levels.