0944-7113/04/11/04-303 $ 30.00/0  Introduction The bone-protective effects of ipriflavone, a synthetic isoflavone, have been studied for a number of years. The findings of a recent multi-center study (Alexander- sen et al. 2001) raised concern about the lymphocy- topenic potential of ipriflavone in postmenopausal women. This three-year study found that 13.2% of the women who received ipriflavone (600 mg/day) devel- oped sub-clinical lymphocytopenia. An earlier study by Agnusdei et al. (Agnusdei et al. 1997) also observed that 3.66% of elderly osteoporotic women who took 600 mg ipriflavone daily for two years developed ab- normal leukocyte counts. These concerns related to ipriflavone and lymphocy- topenia raise the issue of safety with regard to naturally occurring isoflavones, such as those found in soy. Soy isoflavones have become a popular supplement among postmenopausal women because of their potential health benefits, e.g., cholesterol-lowering (Blum et al. 2003; Jayagopal et al. 2002; Scheiber et al. 2001; Watanabe et al. 2002) and bone-protective effects (Arj- mandi et al. 2003; Chiechi et al. 2002; Scheiber et al. 2001; Watanabe et al. 2002; Yamori et al. 2002). It is therefore necessary to determine whether consumption of soy isoflavones results in abnormal leukocyte counts. The present study was designed to examine whether soy isoflavones alter hematological parame- ters, including total and differential leukocyte counts, using the ovarectomized rat model. Soy isoflavones prevent the ovarian hormone deficiency-associated rise in leukocytes in rats D. Y. Soung, D. A. Khalil, A. B. Arquitt, B. J. Smith, L. J. Hammond, E. A. Droke, E. A. Lucas, L. Devareddy and B. H. Arjmandi Department of Nutritional Sciences, Oklahoma State University, Stillwater, OK 74078, USA Summary Recent reports indicate that ovariectomy (ovx) increases lymphopoiesis. Ipriflavone, a synthetic isoflavone, has been reported to reduce lymphocytes in postmenopausal women. The aim of this study was to investigate whether naturally occurring isoflavones also affect lymphopoiesis in ovar- ian hormone deficiency. The present study was carried out using an ovariectomized (ovx) rat model. To mimic early menopause, forty-eight 12-month-old Sprague-Dawley rats were either sham-operated (sham; 1 group) or ovx (3 groups) and were fed a standard semi-purified diet for 120 days. Thereafter, the ovx groups received one of the three doses of isoflavones: 0 (ovx), 500 (ISO500), or 1000 (ISO1000) mg/kg diet for 100 days. Ovariectomy increased total leukocyte counts significantly (p < 0.05) as a result of increased (p < 0.05) lymphocyte, monocyte, eosinophil, and basophil differential counts. Isoflavones at 500 and 1000 mg/kg diet returned the total leuko- cyte counts, as well as leukocyte subpopulations, to levels comparable to that of sham-operated rats. No other hematological parameters, e.g., red blood cell counts or red cell indices, were affect- ed by ovariectomy or isoflavones. We conclude that soy isoflavones restore normal leukocyte counts elevated in ovarian hormone deficiency. Key words: lymphocytes, ipriflavone, hematopoiesis, lymphocytopenia Phytomedicine 11: 303–308, 2004 http://www.elsevier.de/phymed