The effect of selective estrogen receptor modulators on type 2 diabetes onset in women: Basic and clinical insights

Journal of Diabetes and its Complications

Volumn 31, Issue 4, 2017, Pages 773-779

  Xu, Beibei ^a   Lovre, Dragana ^a   Mauvais Jarvis, Franck ^a  

^a TULANE UNIVERSITY HEALTH SCIENCES CENTER   (United States)

Author keywords

Bazedoxifene; Diabetes; Energy metabolism; Metabolic syndrome; Selective estrogen receptor modulators; Steatosis

Indexed keywords

GLUCOSE; LIPID; SELECTIVE ESTROGEN RECEPTOR MODULATOR; ANTINEOPLASTIC HORMONE AGONISTS AND ANTAGONISTS; BAZEDOXIFENE; BONE DENSITY CONSERVATION AGENT; INDOLE DERIVATIVE; RALOXIFENE; TAMOXIFEN;

BREAST CANCER; FATTY LIVER; FEMALE; FOOD INTAKE; GLUCOSE HOMEOSTASIS; HUMAN; HYPERTRIGLYCERIDEMIA; INSULIN RESISTANCE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; POSTMENOPAUSE; PRIORITY JOURNAL; REVIEW; RODENT MODEL; AGING; ANIMAL; BIOLOGICAL MODEL; CHEMICALLY INDUCED; COMPLICATION; DRUG EFFECTS; ENERGY METABOLISM; METABOLISM;

AGING; ANIMALS; ANTINEOPLASTIC AGENTS, HORMONAL; BONE DENSITY CONSERVATION AGENTS; DIABETES MELLITUS, TYPE 2; ENERGY METABOLISM; FEMALE; HUMANS; INDOLES; INSULIN RESISTANCE; MODELS, BIOLOGICAL; OBESITY; RALOXIFENE HYDROCHLORIDE; SELECTIVE ESTROGEN RECEPTOR MODULATORS; TAMOXIFEN;

EID: 85011551520     PISSN: 10568727     EISSN: 1873460X     Source Type: Journal    
DOI: 10.1016/j.jdiacomp.2016.12.010     Document Type: Review

References (86)

1. Andersson, B., Johannsson, G., Holm, G., Bengtsson, B.A., Sashegyi, A., Pavo, I.,.. Anderson, P.W., Raloxifene does not affect insulin sensitivity or glycemic control in postmenopausal women with type 2 diabetes mellitus: A randomized clinical trial. The Journal of Clinical Endocrinology and Metabolism 87:1 (2002), 122–128.
2. Aoyama, T., Peters, J.M., Iritani, N., Nakajima, T., Furihata, K., Hashimoto, T., Gonzalez, F.J., Altered constitutive expression of fatty acid-metabolizing enzymes in mice lacking the peroxisome proliferator-activated receptor alpha (PPARalpha). The Journal of Biological Chemistry 273:10 (1998), 5678–5684.
3. Archer, D.F., Pinkerton, J.V., Utian, W.H., Menegoci, J.C., de Villiers, T.J., Yuen, C.K.,.. Constantine, G.D., Bazedoxifene, a selective estrogen receptor modulator: Effects on the endometrium, ovaries, and breast from a randomized controlled trial in osteoporotic postmenopausal women. Menopause 16:6 (2009), 1109–1115.
4. Artac, M., Sari, R., Altunbas, H., Karayalcin, U., Asymptomatic acute pancreatitis due to tamoxifen-induced severe hypertriglyceridemia in a patient with diabetes mellitus and breast cancer. Journal of Chemotherapy 14:3 (2002), 309–311.
5. Badman, M.K., Pissios, P., Kennedy, A.R., Koukos, G., Flier, J.S., Maratos-Flier, E., Hepatic fibroblast growth factor 21 is regulated by PPARalpha and is a key mediator of hepatic lipid metabolism in ketotic states. Cell Metabolism 5:6 (2007), 426–437.
6. Barrera, J., Chambliss, K.L., Ahmed, M., Tanigaki, K., Thompson, B., McDonald, J.G.,.. Shaul, P.W., Bazedoxifene and conjugated estrogen prevent diet-induced obesity, hepatic steatosis, and type 2 diabetes in mice without impacting the reproductive tract. American Journal of Physiology. Endocrinology and Metabolism 307:3 (2014), E345–E354.
7. Barrett-Connor, E., Ensrud, K.E., Harper, K., Mason, T.M., Sashegyi, A., Krueger, K.A., Anderson, P.W., Post hoc analysis of data from the Multiple Outcomes of Raloxifene Evaluation (MORE) trial on the effects of three years of raloxifene treatment on glycemic control and cardiovascular disease risk factors in women with and without type 2 diabetes. Clinical Therapeutics 25:3 (2003), 919–930.
8. Black, D., Messig, M., Yu, C.R., Assaf, A.R., Komm, B.S., Mirkin, S., Boucher, M., The effect of conjugated estrogens/bazedoxifene therapy on body weight of postmenopausal women: Pooled analysis of five randomized, placebo-controlled trials. Menopause 23:4 (2016), 376–382.
9. Bramlett, K.S., Burris, T.P., Effects of selective estrogen receptor modulators (SERMs) on coactivator nuclear receptor (NR) box binding to estrogen receptors. Molecular Genetics and Metabolism 76:3 (2002), 225–233.
10. Bruno, S., Maisonneuve, P., Castellana, P., Rotmensz, N., Rossi, S., Maggioni, M.,.. Veronesi, U., Incidence and risk factors for non-alcoholic steatohepatitis: Prospective study of 5408 women enrolled in Italian tamoxifen chemoprevention trial. BMJ, 330(7497), 2005, 932.
11. Cagnacci, A., Paoletti, A.M., Zanni, A., Arangino, S., Ibba, G., Orru, M.,.. Volpe, A., Raloxifene does not modify insulin sensitivity and glucose metabolism in postmenopausal women. The Journal of Clinical Endocrinology and Metabolism 87:9 (2002), 4117–4121.
12. Cakmak, A., Posaci, C., Dogan, E., Caliskan, S., Guclu, S., Altunyurt, S., Raloxifene increases serum leptin levels in postmenopausal women: A prospective study. American Journal of Obstetrics and Gynecology 193:2 (2005), 347–351.
13. Carr, M.C., Knopp, R.H., Brunzell, J.D., Wheeler, B.S., Zhu, X., Lakshmanan, M.,.. Anderson, P.W., Effect of raloxifene on serum triglycerides in women with a history of hypertriglyceridemia while on oral estrogen therapy. Diabetes Care 28:7 (2005), 1555–1561.
14. Cole, L.K., Jacobs, R.L., Vance, D.E., Tamoxifen induces triacylglycerol accumulation in the mouse liver by activation of fatty acid synthesis. Hepatology 52:4 (2010), 1258–1265.
15. Considine, R.V., Sinha, M.K., Heiman, M.L., Kriauciunas, A., Stephens, T.W., Nyce, M.R.,.. Caro, J.F., Serum immunoreactive-leptin concentrations in normal-weight and obese humans. The New England Journal of Medicine 334:5 (1996), 292–295.
16. Coskun, U., Toruner, F.B., Gunel, N., Tamoxifen therapy and hepatic steatosis. Neoplasma 49:1 (2002), 61–64.
17. Cucinelli, F., Soranna, L., Romualdi, D., Muzj, G., Mancuso, S., Lanzone, A., The effect of raloxifene on glyco-insulinemic homeostasis in healthy postmenopausal women: A randomized placebo-controlled study. The Journal of Clinical Endocrinology and Metabolism 87:9 (2002), 4186–4192.
18. de Conti, A., Tryndyak, V., Churchwell, M.I., Melnyk, S., Latendresse, J.R., Muskhelishvili, L.,.. Pogribny, I.P., Genotoxic, epigenetic, and transcriptomic effects of tamoxifen in mouse liver. Toxicology 325 (2014), 12–20.
19. Early Breast Cancer Trialists' Collaborative Group, Tamoxifen for early breast cancer: an overview of the randomised trials. Lancet 351:9114 (1998), 1451–1467.
20. Elisaf, M.S., Nakou, K., Liamis, G., Pavlidis, N.A., Tamoxifen-induced severe hypertriglyceridemia and pancreatitis. Annals of Oncology 11:8 (2000), 1067–1069.
21. Ettinger, B., Black, D.M., Mitlak, B.H., Knickerbocker, R.K., Nickelsen, T., Genant, H.K.,.. Cummings, S.R., Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. JAMA 282:7 (1999), 637–645.
22. Fontana, R., Della Torre, S., Meda, C., Longo, A., Eva, C., Maggi, A.C., Estrogen replacement therapy regulation of energy metabolism in female mouse hypothalamus. Endocrinology 155:6 (2014), 2213–2221.
23. Fornander, T., Rutqvist, L.E., Cedermark, B., Glas, U., Mattsson, A., Silfversward, C.,.. Hjalmar, M., Adjuvant tamoxifen in early breast cancer: occurrence of new primary cancers. Lancet 1:8630 (1989), 117–120.
24. Francucci, C.M., Daniele, P., Iori, N., Camilletti, A., Massi, F., Boscaro, M., Effects of raloxifene on body fat distribution and lipid profile in healthy post-menopausal women. Journal of Endocrinological Investigation 28:7 (2005), 623–631.
25. Gudbrandsen, O.A., Rost, T.H., Berge, R.K., Causes and prevention of tamoxifen-induced accumulation of triacylglycerol in rat liver. Journal of Lipid Research 47:10 (2006), 2223–2232.
26. Gunel, N., Coskun, U., Toruner, F.B., Sancak, B., Yilmaz, E., Cengiz, O.,.. Ozkan, S., Serum leptin levels are associated with tamoxifen-induced hepatic steatosis. Current Medical Research and Opinion 19:1 (2003), 47–50.
27. Hejazi, J., Rastmanesh, R., Association between tamoxifen treatment and diabetes: a population-based study. Cancer, 118(23), 2012, 6012 (author reply 6012-3).
28. Hozumi, Y., Kawano, M., Jordan, V.C., In vitro study of the effect of raloxifene on lipid metabolism compared with tamoxifen. European Journal of Endocrinology 143:3 (2000), 427–430.
29. Hozumi, Y., Kawano, M., Miyata, M., Severe hypertriglyceridemia caused by tamoxifen-treatment after breast cancer surgery. Endocrine Journal 44:5 (1997), 745–749.
30. Hulley, S., Grady, D., Bush, T., Furberg, C., Herrington, D., Riggs, B., Vittinghoff, E., Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. JAMA 280:7 (1998), 605–613.
31. Jacobsen, D.E., Samson, M.M., Emmelot-Vonk, M.H., Verhaar, H.J., Raloxifene and body composition and muscle strength in postmenopausal women: A randomized, double-blind, placebo-controlled trial. European Journal of Endocrinology 162:2 (2010), 371–376.
32. Jialal, I., Amess, W., Kaur, M., Management of hypertriglyceridemia in the diabetic patient. Current Diabetes Reports 10:4 (2010), 316–320.
33. Johansson, H., Gandini, S., Guerrieri-Gonzaga, A., Iodice, S., Ruscica, M., Bonanni, B.,.. Decensi, A., Effect of fenretinide and low-dose tamoxifen on insulin sensitivity in premenopausal women at high risk for breast cancer. Cancer Research 68:22 (2008), 9512–9518.
34. Kim, J., Mauvais-Jarvis, F., The combination of conjugated equine estrogens with bazedoxifene prevents streptozotocin-induced diabetes in ovariectomized female mice. Matters, 2(6), 2016 e201605000017.
35. Kim, J.H., Meyers, M.S., Khuder, S.S., Abdallah, S.L., Muturi, H.T., Russo, L.,.. Mauvais-Jarvis, F., Tissue-selective estrogen complexes with bazedoxifene prevent metabolic dysfunction in female mice. Molecular Metabolism 3:2 (2014), 177–190.
36. Kim, Y.A., Lee, S., Jung, J.W., Kwon, Y.J., Lee, G.B., Shin, D.G.,.. Cho, D.H., Severe acute pancreatitis due to tamoxifen-induced hypertriglyceridemia with diabetes mellitus. Chinese Journal of Cancer Research 26:3 (2014), 341–344.
37. Komm, B.S., Chines, A.A., Bazedoxifene: the evolving role of third-generation selective estrogen-receptor modulators in the management of postmenopausal osteoporosis. Therapeutic Advances in Musculoskeletal Disease 4:1 (2012), 21–34.
38. Komm, B.S., Mirkin, S., Evolution of the tissue selective estrogen complex (TSEC). Journal of Cellular Physiology 228:7 (2013), 1423–1427.
39. Kuiper, G.G., Carlsson, B., Grandien, K., Enmark, E., Haggblad, J., Nilsson, S., Gustafsson, J.A., Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinology 138:3 (1997), 863–870.
40. Lambrinoudaki, I.V., Christodoulakos, G.E., Economou, E.V., Vlachou, S.A., Panoulis, C.P., Alexandrou, A.P.,.. Creatsas, G.C., Circulating leptin and ghrelin are differentially influenced by estrogen/progestin therapy and raloxifene. Maturitas 59:1 (2008), 62–71.
41. Lasco, A., Gaudio, A., Morabito, N., Previti, M., Mileto, A., Frisina, N., Cucinotta, D., Effects of a long-term treatment with raloxifene on insulin sensitivity in postmenopausal women. Diabetologia 47:3 (2004), 571–574.
42. Le May, C., Chu, K., Hu, M., Ortega, C.S., Simpson, E.R., Korach, K.S.,.. Mauvais-Jarvis, F., Estrogens protect pancreatic beta-cells from apoptosis and prevent insulin-deficient diabetes mellitus in mice. Proceedings of the National Academy of Sciences of the United States of America 103:24 (2006), 9232–9237.
43. Lelliott, C.J., Lopez, M., Curtis, R.K., Parker, N., Laudes, M., Yeo, G.,.. Vidal-Puig, A., Transcript and metabolite analysis of the effects of tamoxifen in rat liver reveals inhibition of fatty acid synthesis in the presence of hepatic steatosis. The FASEB Journal 19:9 (2005), 1108–1119.
44. Lipscombe, L.L., Fischer, H.D., Yun, L., Gruneir, A., Austin, P., Paszat, L.,.. Rochon, P.A., Association between tamoxifen treatment and diabetes: A population-based study. Cancer 118:10 (2012), 2615–2622.
45. Liu, C.L., Huang, J.K., Cheng, S.P., Chang, Y.C., Lee, J.J., Liu, T.P., Fatty liver and transaminase changes with adjuvant tamoxifen therapy. Anti-Cancer Drugs 17:6 (2006), 709–713.
46. Lobo, R.A., Pinkerton, J.V., Gass, M.L., Dorin, M.H., Ronkin, S., Pickar, J.H., Constantine, G., Evaluation of bazedoxifene/conjugated estrogens for the treatment of menopausal symptoms and effects on metabolic parameters and overall safety profile. Fertility and Sterility, 2009, 1025–1038 (United States).
47. Lopez, M., Lelliott, C.J., Tovar, S., Kimber, W., Gallego, R., Virtue, S.,.. Vidal-Puig, A.J., Tamoxifen-induced anorexia is associated with fatty acid synthase inhibition in the ventromedial nucleus of the hypothalamus and accumulation of malonyl-CoA. Diabetes 55:5 (2006), 1327–1336.
48. Mauvais-Jarvis, F., Pilot study of Duavee in preventing metabolic dysfunction in postmenopausal women. Available from: https://clinicaltrials.gov/ct2/show/NCT02237079, 2014.
49. Mauvais-Jarvis, F., Clegg, D.J., Hevener, A.L., The role of estrogens in control of energy balance and glucose homeostasis. Endocrine Reviews 34:3 (2013), 309–338.
50. Meli, R., Pacilio, M., Raso, G.M., Esposito, E., Coppola, A., Nasti, A.,.. Di Carlo, R., Estrogen and raloxifene modulate leptin and its receptor in hypothalamus and adipose tissue from ovariectomized rats. Endocrinology 145:7 (2004), 3115–3121.
51. Miller, V., LaRosa, J., Barnabei, V., Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. The Writing Group for the PEPI Trial. JAMA 273:3 (1995), 199–208.
52. Miyashita, T., Toyoda, Y., Tsuneyama, K., Fukami, T., Nakajima, M., Yokoi, T., Hepatoprotective effect of tamoxifen on steatosis and non-alcoholic steatohepatitis in mouse models. The Journal of Toxicological Sciences 37:5 (2012), 931–942.
53. Mosca, L., Harper, K., Sarkar, S., O'Gorman, J., Anderson, P.W., Cox, D.A., Barrett-Connor, E., Effect of raloxifene on serum triglycerides in postmenopausal women: Influence of predisposing factors for hypertriglyceridemia. Clinical Therapeutics 23:9 (2001), 1552–1565.
54. Mu, Y., She, R., Zhang, H., Dong, B., Huang, C., Lin, W.,.. Li, X., Effects of estrogen and androgen deprivation on the progression of non-alcoholic steatohepatitis (NASH) in male Sprague–Dawley rats. Hepatology Research 39:9 (2009), 910–920.
55. Nagamani, M., Szymajda, A., Sepilian, V., Urban, R.J., Gilkison, C., Effects of raloxifene on insulin sensitivity, beta-cell function, and hepatic insulin extraction in normal postmenopausal women. Fertility and Sterility 89:3 (2008), 614–619.
56. Nishino, M., Hayakawa, K., Nakamura, Y., Morimoto, T., Mukaihara, S., Effects of tamoxifen on hepatic fat content and the development of hepatic steatosis in patients with breast cancer: High frequency of involvement and rapid reversal after completion of tamoxifen therapy. AJR. American Journal of Roentgenology 180:1 (2003), 129–134.
57. Ogawa, Y., Murata, Y., Nishioka, A., Inomata, T., Yoshida, S., Tamoxifen-induced fatty liver in patients with breast cancer. Lancet, 351(9104), 1998, 725.
58. Ozet, A., Arpaci, F., Yilmaz, M.I., Ayta, H., Ozturk, B., Komurcu, S.,.. Acikel, C., Effects of tamoxifen on the serum leptin level in patients with breast cancer. Japanese Journal of Clinical Oncology 31:9 (2001), 424–427.
59. Pfaffl, M.W., Lange, I.G., Daxenberger, A., Meyer, H.H., Tissue-specific expression pattern of estrogen receptors (ER): Quantification of ER alpha and ER beta mRNA with real-time RT-PCR. APMIS 109:5 (2001), 345–355.
60. Pinkerton, J.V., Utian, W.H., Constantine, G.D., Olivier, S., Pickar, J.H., Relief of vasomotor symptoms with the tissue-selective estrogen complex containing bazedoxifene/conjugated estrogens: A randomized, controlled trial. Menopause 16:6 (2009), 1116–1124.
61. Purushotham, A., Schug, T.T., Xu, Q., Surapureddi, S., Guo, X., Li, X., Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism and results in hepatic steatosis and inflammation. Cell Metabolism 9:4 (2009), 327–338.
62. Ravussin, E., Tissue selective estrogen complex to prevent metabolic dysfunction in women (TSEC). Available from: https://clinicaltrials.gov/ct2/show/NCT02274571, 2014.
63. Rossouw, J.E., Anderson, G.L., Prentice, R.L., LaCroix, A.Z., Kooperberg, C., Stefanick, M.L.,.. Ockene, J., Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women's Health Initiative randomized controlled trial. JAMA 288:3 (2002), 321–333.
64. Santen, R.J., Kagan, R., Altomare, C.J., Komm, B., Mirkin, S., Taylor, H.S., Current and evolving approaches to individualizing estrogen receptor-based therapy for menopausal women. The Journal of Clinical Endocrinology and Metabolism 99:3 (2014), 733–747.
65. Sato, M., Rippy, M.K., Bryant, H.U., Raloxifene, tamoxifen, nafoxidine, or estrogen effects on reproductive and nonreproductive tissues in ovariectomized rats. The FASEB Journal 10:8 (1996), 905–912.
66. Stevenson, J.C., Chines, A., Pan, K., Ryan, K.A., Mirkin, S., A pooled analysis of the effects of conjugated estrogens/bazedoxifene on lipid parameters in postmenopausal women from the selective estrogens, menopause, and response to therapy (SMART) trials. The Journal of Clinical Endocrinology and Metabolism 100:6 (2015), 2329–2338.
67. Sullivan, E.L., Shearin, J., Koegler, F.H., Cameron, J.L., Selective estrogen receptor modulator promotes weight loss in ovariectomized female rhesus monkeys (Macaca mulatta) by decreasing food intake and increasing activity. American Journal of Physiology. Endocrinology and Metabolism 302:7 (2012), E759–E767.
68. Sun, L.M., Chen, H.J., Liang, J.A., Li, T.C., Kao, C.H., Association of tamoxifen use and increased diabetes among Asian women diagnosed with breast cancer. British Journal of Cancer 111:9 (2014), 1836–1842.
69. Tee, M.K., Rogatsky, I., Tzagarakis-Foster, C., Cvoro, A., An, J., Christy, R.J.,.. Leitman, D.C., Estradiol and selective estrogen receptor modulators differentially regulate target genes with estrogen receptors alpha and beta. Molecular Biology of the Cell 15:3 (2004), 1262–1272.
70. Tiano, J., Mauvais-Jarvis, F., Selective estrogen receptor modulation in pancreatic beta-cells and the prevention of type 2 diabetes. Islets 4:2 (2012), 173–176.
71. Tommaselli, G.A., Di Carlo, C., Nasti, A., Giordano, E., Pisano, G., Pellicano, M.,.. Nappi, C., Effects of bilateral ovariectomy and postoperative hormonal replacement therapy with 17beta-estradiol or raloxifene on serum leptin levels. Menopause 10:2 (2003), 160–164.
72. Tommaselli, G.A., Di Carlo, C., Di Spiezio Sardo, A., Bifulco, G., Cirillo, D., Guida, M.,.. Nappi, C., Serum leptin levels and body composition in postmenopausal women treated with tibolone and raloxifene. Menopause 13:4 (2006), 660–668.
73. van Leeuwen, F.E., Benraadt, J., Coebergh, J.W., Kiemeney, L.A., Gimbrere, C.H., Otter, R.,.. Bontenbal, M., Risk of endometrial cancer after tamoxifen treatment of breast cancer. Lancet 343:8895 (1994), 448–452.
74. Van Pelt, R.E., Gozansky, W.S., Wolfe, P., Kittelson, J.M., Jankowski, C.M., Schwartz, R.S., Kohrt, W.M., Estrogen or raloxifene during postmenopausal weight loss: adiposity and cardiometabolic outcomes. Obesity (Silver Spring) 22:4 (2014), 1024–1031.
75. Velasco, G., Geelen, M.J., Guzman, M., Control of hepatic fatty acid oxidation by 5′-AMP-activated protein kinase involves a malonyl-CoA-dependent and a malonyl-CoA-independent mechanism. Archives of Biochemistry and Biophysics 337:2 (1997), 169–175.
76. Villa, A., Della Torre, S., Stell, A., Cook, J., Brown, M., Maggi, A., Tetradian oscillation of estrogen receptor alpha is necessary to prevent liver lipid deposition. Proceedings of the National Academy of Sciences of the United States of America 109:29 (2012), 11806–11811.
77. Vogel, V.G., Raloxifene: a selective estrogen receptor modulator for reducing the risk of invasive breast cancer in postmenopausal women. Women's Health (London, England) 3:2 (2007), 139–153.
78. Vogel, V.G., Costantino, J.P., Wickerham, D.L., Cronin, W.M., Cecchini, R.S., Atkins, J.N.,.. Wolmark, N., Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial. JAMA 295:23 (2006), 2727–2741.
79. Wade, G.N., Heller, H.W., Tamoxifen mimics the effects of estradiol on food intake, body weight, and body composition in rats. The American Journal of Physiology 264:6 Pt 2 (1993), R1219–R1223.
80. Wallen, W.J., Belanger, M.P., Wittnich, C., Sex hormones and the selective estrogen receptor modulator tamoxifen modulate weekly body weights and food intakes in adolescent and adult rats. The Journal of Nutrition 131:9 (2001), 2351–2357.
81. Walsh, B.W., Schiff, I., Rosner, B., Greenberg, L., Ravnikar, V., Sacks, F.M., Effects of postmenopausal estrogen replacement on the concentrations and metabolism of plasma lipoproteins. The New England Journal of Medicine 325:17 (1991), 1196–1204.
82. Webb, P., Nguyen, P., Kushner, P.J., Differential SERM effects on corepressor binding dictate ERalpha activity in vivo. The Journal of Biological Chemistry 278:9 (2003), 6912–6920.
83. Xu, B., Allard, C., Mauvais-Jarvis, F., Estrogen complexes improve the unfolded protein response and prevent ER stress-induced beta-cell failure in Akita mice in diabetes. 2015, Amer Diabetes Assoc, 1701 N Beauregard St, Alexandria, VA 22311–1717 USA.
84. Yoshii, T., Yamada, M., Minami, T., Tsunoda, T., Sasaki, M., Kondo, Y.,.. Terauchi, Y., The effects of bazedoxifene on bone, glucose, and lipid metabolism in postmenopausal women with type 2 diabetes: An exploratory pilot study. Journal of Clinical Medicine Research 7:10 (2015), 762–769.
85. Yoshikawa, Y., Miyashita, T., Higuchi, S., Tsuneyama, K., Endo, S., Tsukui, T.,.. Yokoi, T., Mechanisms of the hepatoprotective effects of tamoxifen against drug-induced and chemical-induced acute liver injuries. Toxicology and Applied Pharmacology 264:1 (2012), 42–50.
86. Yuchi, Y., Cai, Y., Legein, B., De Groef, S., Leuckx, G., Coppens, V.,.. Van de Casteele, M., Estrogen receptor alpha regulates beta-cell formation during pancreas development and following injury. Diabetes 64:9 (2015), 3218–3228.