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Reina Villareal, M.D., F.A.C.E. Assistant Professor of Medicine
Dr. Villareal received her medical degree from Cebu Institute of Medicine in Cebu, Phillipines and completed an Internal Medicine residency at Texas Tech, University, Amarillo, TX. She completed a fellowship in Endocrinology, Diabetes, and Metabolism at Washington University School of Medicine and is board-certified in Endocrinology. Her honors include the Sandoz Postdoctoral Fellowship in Bone and the NIH BIRWCH Award. Her areas of interest include women's health, breast cancer and bone loss, and menopause as associated with estrogen loss and replacement therapies. Research Interests Dr. Villareal's main research interests are estrogen metabolism and its role in hormone-related disorders. Her group recently found that estrogen metabolism is an important determinant of bone mineral density and bone loss. Women with preferential estrogen metabolism through the 2-hydroxyl (inactive) pathway have lower bone densities relative to those with preference of the 16-_ hydroxyl (active) pathway. Women with family history of osteoporosis have increased hydroxylation through the 2-hydroxyl pathway. They also found through the 2-hydroxyl that estrogen metabolism modulates the response to estrogen/hormone replacement therapy (ERT/HRT) and that those patients with a preference for 2-hydroxl over the 16-hydroxyl pathway have a better response to ERT/HRT in terms of bone density increments. Her plan is to phenotypically characterize premenopausal and early postmenopausal women with the A allele for this polymorphism to determine if the low bone density of these women is secondary to a low peak adult bone density or to increased postmenopausal bone loss. Dr. Villareal is also exploring other hormone-related disorders affected by estrogen metabolism such as Alzheimer's disease to learn if cognitive function correlates with estrogen metabolism and bone density. In the future Dr. Villareal will be looking at the role of polymorphisms of the CYP19 (aromatase) gene on the skeletal response to aromatase inhibitors in women with breast cancer. While aromatase inhibitors have been gaining recognition as the treatment of choice in women with estrogen receptor-positive breast cancer, there is concern that they increase bone loss and fractures. Her group will be looking at the possibility that a particular genotype or haplotype of the CYP19 gene may prevent bone loss. Villareal Lab 
Selected Publications Armamento-Villareal R, Sheikh S, Nawaz A, Napoli N, Mueller C, Brodt MD, Silva MJ, Galbiati E, Halstead, LR, Caruso PL, Civelli M, Civitelli R. A New Selective Estrogen Receptor Modulator, CHF 4227.01, Preserves Bone Mass and Microarchitecture in Ovariectomized Rats. In Press, Journal of Bone and Mineral Research. Napoli, N, Donepudi, S, Sheikh, Rini, G, and Armamento-Villareal, R. Increased 2- hydroxylation of Estrogen in Women with Family History of Osteoporosis, Journal of Clinical Endocrinology and Metabolism 2005; 90(4):2035-41. Napoli, N, Villareal, DT, Mumm, S, Halstead, LR, Sheikh, S, Cagaanan, M, Battista ,R, and Armamento-Villareal R: The effect of CYP1A1 gene polymorphisms on estrogen metabolism and bone density. Journal of Bone and Mineral Research, 2005; 20(2):232-9. Armamento-Villareal, RC, Napoli,N, Klug, T, and Civitelli R: The oxidative metabolism of estrogen modulates response to ERT/HRT in postmenopausal women. Bone 2004; 35:682-688. Civitelli, R, Pilgram, TK, Dotson, M, Muckerman, J, Lewandowski, N, Armamento-Villareal, R Naoko Yokoyama-Crothers, P, Kardaris, E, Hauser, J, Cohen, S, and Hildebolt, CF. Hormone/Estrogen Replacement Therapy improves alveolar and postcranial bone density in postmenopausal women. Archives of Internal Medicine 2002; 162:1409-1415. Leelawattana, R, Ziambaras, K, Rodman-Weiss, J, Lyss, C, Wagner, D, Klug, T, Armamento-Villareal, R, and Civitelli, R. The oxidative metabolism of estradiol conditions postmenopausal bone loss. J. Bone and Miner. Res. 2000; 15(12):2513-2520. Armamento-Villareal R, Ziambaras K, Abbasi-Jarhomi SH, Dimarogonas A, Halstead, LR, Fausto A, Avioli LV, Civitelli R: An intact N-terminus is required for the anabolic action of parathyroid hormone on adult female rats. J. Bone Miner. Res. 1997; 12:384-392. Whyte, MP, Schranck, FW, and Armamento-Villareal, R. X-Linked Hypophosphatemia: a search for gender, race, anticipation, or parent of origin effects on disease expression in children. J. Clin. Endocrinol. Metab 1996; 81:4075-80. Armamento-Villareal, R and Civitelli, R. Estrogen action on bone mass of postmenopausal women is dependent on body mass and initial bone density. J Clin Endocrinol Metab 1995; 80:776-782. Armamento-Villareal, R, Villareal, DT, Avioli, LV, and Civitelli, R. Estrogen status and genetic potential are major determinants of premenopausal bone mass. J Clin Invest 1992; 90:2464-2471.
Division of Bone & Mineral Diseases
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