This analysis examined how unmeasured confounding affects estimates of the effectiveness of
condoms in preventing
sexually transmitted infections. Data were analyzed from a prospective cohort study of 1,122 female
sexually transmitted disease clinic patients in Alabama (1992-1995), wherein participants were evaluated for
sexually transmitted infections at six 1-month intervals. Associations between
condom use and incident
gonorrhea and
chlamydia infection were compared between case-crossover and cohort analyses. In a case-crossover analysis of 228 follow-up visits ending in
gonorrhea/chlamydia ("case intervals") and 743 self-matched follow-up visits not ending in
gonorrhea/chlamydia ("noncase intervals") (183 women), consistent
condom use without breakage or slippage was associated with significantly reduced risk of
infection relative to nonuse (adjusted risk odds ratio = 0.49, 95% confidence interval: 0.26, 0.92). Conversely, a cohort analysis of 245 case intervals and 3,896 noncase intervals (919 women) revealed no significant reduction in
infection risk from consistent use of
condoms (adjusted risk odds ratio = 0.79, 95% confidence interval: 0.53, 1.17). Dose-response relations between the number of unprotected sex acts and
infection were stronger in the case-crossover analysis (p for trend = 0.009) than in the cohort analysis (p for trend = 0.18). These findings suggest that epidemiologic studies confounded by unmeasured differences between
condom users and nonusers underestimate
condom effectiveness against these
infections. The case-crossover method provides an additional technique for reducing unmeasured confounding in studies of
condom effectiveness.