Rheumatoid arthritis, the contraceptive pill, and androgens.

Abstract

SummaryEvidence 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 ifone 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. (Ann Rheum Dis 1993; 52: 470-474) This paper consists of two parts. The first section reviews the evidence that a major cause of rheumatoid arthritis (RA) is the presence of low androgen concentrations. If this hypothesis were true, a number of features of the epidemiology of the disease would be explained. In the second part it is argued that this hypothesis, together with a plausible assumption, explains the confusion about the relation between RA and oral contraception.

Hypothesis: Gonadal Hormones Act as Confounders in Epidemiological Studies of the Associations between Some Behavioural Risk Factors and Some Pathological Conditions

“…These e!ects appear to be independent of age and marital status''. The same sort of argument has been used to propose that vasectomy (James, 1994) and oral contraceptive use (James, 1993) also act initially as markers for high steroid hormone levels in men and women, respectively. And*again acknowledging the absence of direct hormonal data*a similar argument could be deployed with regard to women who undergo induced abortion.…”

“…In particular, we may expect bizarre suggestions of cause or amelioration with negative dose responses. Two topics identi"ed by Mayes et al (1988) which are potentially explicable in this fashion are (a) oral contraception vs. rheumatoid arthritis (James, 1993) and (b) oral contraception vs. breast cancer (May et al, 1994).…”

Rheumatoid arthritis, fecundity, and coital rates:comment on the article by Nelson et a1

“…In January 1992 this individual was found to have high-titer antibodies against Borrelia burgdorferi by enzyme-linked immunosorbent assay (ELISA), and 15 bands on Western blot analysis. (Note that this clinical situation is diametrically opposed to the one seen most frequently at our referral center and others [3], where patients arrive with histories of often repetitive treatment, and it is a reasonable basis for diagnosis that is lacking.) Dr. Christian's four specific questions are 1) Should…”

“…Studies to date appear to lack consensus regarding androgen levels in women with established RA (1,2). We look forward to his forthcoming article about androgens in RA (3).…”

Further evidence that low androgen values are a cause of rheumatoid arthritis: the response of rheumatoid arthritis to seriously stressful life events

“…(b) RA is associated with HLA B 15,4-5 which in turn is associated with low androgen values in men 6…”