The pill, parity, and rheumatoid arthritis

Abstract

We report on a case-control study investigating the relationship of oral contraceptive pill (OCP) use and parity to the development of rheumatoid arthritis (RA). Women with RA were compared with 2 separate control groups, women with osteoarthritis (OA) and women randomly selected from a population-based electoral register. Nulliparity was found to be a risk factor for the development of RA, with age-adjusted odds ratios of 1.82 (95% confidence interval [CI] 1.09-3.03) versus the OA control group and 1.83 (95% CI 1.03-3.06) versus the population control group. Use of OCPs before the age of 35 was negatively associated with RA (odds ratio 0.56, 95% CI 0.29-1.12 versus the OA control group; odds ratio 0.6, 95% CI 0.30-1.17 versus the population control group). Some evidence of a duration-response effect was seen, although the numbers were small. The 2 variables were also multiplicative, with nulliparous non-OCP users having a 4-fold risk of RA compared with parous OCP users. These findings suggest that pregnancy and OCP use have a "protective effect" on the development of RA, although the mechanism remains unclear.-. Epidemiologic and immunologic evidence suggests that hormonal factors may play a role in the etiology and course of rheumatoid arthritis (RA). This hypothesis is based on several observations, including a 2-3-fold excess incidence in women at all ages ( l ) , an amelioration of the disease in 80% of women during pregnancy (2). and reported variations in disease severity during the menstrual cycle (3). It has also been suggested that pregnancy may play a role in the later development of RA. However, the evidence about the direction of this association is contradictory. One large population study indicated that parous women are more likely to develop R A (4). whereas another indicated that nulliparous women are at increased risk ( 5 ) . From theA number of European studies have indicated that women who have used the oral contraceptive pill (OCP) are less likely to develop RA than women who have not used it (6-9). Studics from the United States, however, have failed to show a similar relationship (10.1 1). The reasons for these discrepancies are unclear, but differences in study design, patient selection, and methods of analysis have been implicated (12).We report herein the findings of an investigation into the effects of panty and OCP use on the development of RA. PATIENTS AND METHODSPatients. The study had a case-control design. Two hundred ninety female outpatients (age range 35-70 years) who attended 1 of 6 rheumatology centers in east London were studied. The diagnosis of RA was made by the attending physician, according to the criteria of the American Rheumatism Association (13). The majority of the patients (89%) had used a second-line agent at some time, and 76% were seropositive. Women <35 years old were excluded

Blood transfusion, smoking, and obesity as risk factors for the development of rheumatoid arthritis. Results from a primary care‐based incident case‐control study in Norfolk, England

“…Only 9 cases and 5 controls reported tetanus immunization in the 6 weeks prior to onset, and so the study lacked the power to assess tetanus immunization as a risk factor. The study has also failed to show an association between RA and nulliparity, as has been reported previously (29)(30)(31) (Table 6). None of the previous studies used cases derived from primary care, and it may be that nulliparity is a risk factor for a poor prognosis rather than for disease susceptibility.…”

Timing of Pregnancy in Relation to the Onset of Rheumatoid Arthritis

“…The advantage of selecting the former is the potential for a higher response rate and a reduction in the likelihood of major lifestyle differences that could confound the results obtained. The similarity in cases and controls might have masked a difference in nulliparity, which has been found in other studies (5,6). This similarity, in contrast, would not detract from the positive results of the study of the timing of pregnancy.…”

“…Subsequent investigation both by ourselves (6) and by others (12) suggested that this was not generally true, and that nulliparity might be a risk factor. The results from the current study are therefore compatible with the hypothesis that pregnancy suppresses the onset and activity of rheumatoid arthritis, but that in a group of susceptible women, pregnancy might paradoxically induce disease onset, the presentation of which is delayed.…”

“…There is, however, no increased risk in those who are unmarried (6,7), which suggests that in its subclinical phase, RA affects fertility, rather than fertility having any etiologic importance. It is of interest that the apparent protective effect of oral contraceptive use (8) might be enhanced in parous women (6).…”

The relationship between oral contraceptive use and functional outcome in women with recent‐onset inflammatory polyarthritis: Results from the Norfolk Arthritis Register

“…However, OC use, as recorded at each assessment during followup, did not have a significant effect overall, i.e., taking OCs either before or around the time of symptom onset appears to be of the greatest overall benefit. The composition of OCs has, however, become increasingly less potent since they were first made available in the 1960s (21,22). This may partially explain why, in this longitudinal study that did not start enrolling patients until 30 years after the introduction of OCs, OC use before symptom onset appeared to have a greater impact on disease outcome than use during followup, despite a longer time since exposure to the OC.…”