RHEUMATOID-ARTHRITIS, HLA IDENTITY, AND AGE AT MENARCHE

Objective-To determine whether women with rheumatoid arthritis (RA) ha d differences in obstetric and gynaecological histories when compared with sisters without RA (controls) Methods-Ninety eight RA discordant sister pairs, 36 of whom were identical for histocompatibility locus a ntigen (HLA-A, HLA-B, and HLA-Cw) types, were asked to recall their ag e of menarche, duration of use of contraceptive pill, pregnancy histor y, and age of menopause. Results-The 98 siblings with RA had an older mean age of menarche (13.90 (95% confidence interval (95% CI) 13.56 to 14.24) years) than their sisters (13.49 (95% CI 13.22 to 13.76) years ; mean difference within pairs 0.41, 95% CI 0.09 to 0.73 years, paired t test t=2.54, p=0.013). When the pairs were divided into identical H LA and non-identical HLA groups, the first showed no significant diffe rence (mean difference 0-17 (95% CI -0.40 to 0.73) years), whereas the second did (mean difference 0.55 (95% CI 0.16 to 0-94) years, t=2.80, p=0.007). A multiple regression analysis to predict differences in me narche in the non-identical HLA sibling pairs failed to show any demog raphic or reproductive confounding variables. In 19 RA concordant sibl ing pairs, the seven HLA identical pairs had similar ages of menarche, whereas the 12 non-identical HLA pairs had interpair differences that narrowly missed significance (p=0.054). All other obstetric and gynae cological variables were not significantly different within the pairs. Conclusions-The interpretations of these results are that either dela yed menarche may predispose to or act as a marker of RA, or HLA linked genes are important in determining the age of menarche irrespective o f disease state. This study fails to support a significant role for ot her obstetric and gynaecological variables in RA.