Temporomandibular disorders (TMD) are common pain conditions that have their highest prevalence among women of reproductive age. The higher prevalence of TMD pain among women, pattern of onset after puberty and lowered prevalence rates in the post-menopausal years suggest that female reproductive hormones may play an etiologic role in TMD. Two epidemiologic studies were designed to assess whether use of exogenous hormones is associated with increased risk of TMD pain. Both used data from automated pharmacy records of women enrolled in a large health maintenance organization to identify prescriptions filled for post-menopausal hormone replacement therapies (Study 1) or for oral contraceptives (OCs) (Study 2). Study 1 employed an age-matched case-control design to compare post-menopausal hormone use among 1291 women over age 40 referred for TMD treatment and 5164 controls not referred. After controlling for health services use, the odds of being a TMD case were approximately 30% higher among those receiving estrogen compared to those not exposed (P = 0.002); a clear dose-response relationship was evident. The relationship of progestin use to TMD was not statistically significant. Study 2 used a similar design to examine the relationship of OC use to referral for TMD care, drawing on data from 1473 cases and 5892 controls aged 15-35. Use of OCs was also associated with referral for TMD care, with an increased risk of TMD of approximately 20% for OC users, after controlling for health services use (P < 0.05). These results suggest that female reproductive hormones may play an etiologic role in orofacial pain. This relationship warrants further investigation through epidemiologic, clinical and basic research.