AbstractMenopause and oophorectomy without estrogen therapy (ED) have been associated with increased production of bone‐active cytokines by peripheral blood mononuclear cells. The current study extended evaluation to gingival crevicular fluid (GCF) levels of interleukin (IL)‐1β and IL–6 in such subjects compared to premenopausal and postmenopausal estrogen‐treated females (ES). 13 ED and 13 ES Caucasians with a history of moderate‐severe adult periodontitis provided GCF from 1–3 clinically identical sites each (5–6 mm probing depth, 5–7 mm clinical attachment loss, bleeding on probing). 30 s GCF samples were obtained and evaluated for IL‐1β and IL‐6 levels using two‐site enzyme‐linked immunosorbent assays (ELISAs). The frequency of GCF IL‐1β‐positive subjects was elevated in ED versus ES (92% versus 23%;p<0.0004, X2; analysis). IL‐6 was detected more frequently in ED subjects (23% versus 8%; not significant); however, the frequency of IL‐6 detection was low in both groups due to short sampling times. These data support the concept that clinical conditions causing low estrogen environments allow increased local production of the bone‐ac