OBJECTIVES: Disease activity in rheumatoid arthritis (RA) varies substantially during periods when luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels change, for example during pregnancy, postpartum, and menopause. We wanted to investigate whether small fluctuations in these hormones could be associated with similar fluctuations in cytokines and disease activity in RA. METHODS: Disease activity markers, serum LH, FSH, and 24 cytokines were assessed on days 1 and 8 in 20 RA patients (median age 58 years, six males) and 19 controls (median age 56 years, six males). RESULTS: Percentage changes in LH and FSH correlated positively with percentage changes in key proinflammatory cytokines such as tumour necrosis factor (TNF)alpha (LH r = 0.737, p = 0.0007; FSH r = 0.680, p = 0.001) and interleukin (IL)-1beta (LH r = 0.515, p = 0.050; FSH r = 0.749, p = 0.0008). Similar correlations were observed with IL-2, IL-2R, IL-8, monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, and eotaxin, but not with the anti-inflammatory cytokine IL-10, in RA and not in controls. Percentage changes in LH, FSH, and cytokines were not correlated with percentage changes of several disease activity markers but were correlated positively with cross-sectional levels of disease activity markers [erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Visual Analogue Scale (VAS) pain, VAS global (physician/patient), and the modified Health Assessment Questionnaire (MHAQ)]. CONCLUSIONS: The significant associations between percentage changes in LH and FSH and percentage changes in key cytokines and several cross-sectional markers of disease activity may indicate that LH and FSH influence crucial points of the cytokine cascade in RA. This may help to explain, partially, why disease activity initiates or worsens during periods of increased LH and FSH, such as the postpartum period and the menopause.