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Estrogens and Body Weight Regulation in Men

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Sex and Gender Factors Affecting Metabolic Homeostasis, Diabetes and Obesity

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1043))

Abstract

Our understanding of the metabolic roles of sex steroids in men has evolved substantially over recent decades. Whereas testosterone once was believed to contribute to metabolic risk in men, the importance of adequate androgen exposure for the maintenance of metabolic health has been demonstrated unequivocally. A growing body of evidence now also supports a critical role for estrogens in metabolic regulation in men. Recent data from clinical intervention studies indicate that estradiol may be a stronger determinant of adiposity than testosterone in men, and even short-term estradiol deprivation contributes to fat mass accrual. The following chapter will outline findings to date regarding the mechanisms, whereby estrogens contribute to the regulation of body weight and adiposity in men. It will present emergent clinical data as well as preclinical findings that reveal mechanistic insights into estrogen-mediated regulation of body composition. Findings in both males and females will be reviewed, to draw comparisons and to highlight knowledge gaps regarding estrogen action specifically in males. Finally, the clinical relevance of estrogen exposure in men will be discussed, particularly in the context of a rising global prevalence of obesity and expanding clinical use of sex steroid-based therapies in men.

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References

  • Abdelgadir, S. E., Resko, J. A., Ojeda, S. R., Lephart, E. D., McPhaul, M. J., & Roselli, C. E. (1994). Androgens regulate aromatase cytochrome P450 messenger ribonucleic acid in rat brain. Endocrinology, 135, 395–401.

    Article  CAS  PubMed  Google Scholar 

  • Ahima, R. S., Stanley, T. L., Khor, V. K., Zanni, M. V., & Grinspoon, S. K. (2011). Estrogen sulfotransferase is expressed in subcutaneous adipose tissue of obese humans in association with TNF-alpha and SOCS3. The Journal of Clinical Endocrinology and Metabolism, 96, E1153–E1158.

    Article  PubMed  PubMed Central  Google Scholar 

  • Anderson, L. A., McTernan, P. G., Barnett, A. H., & Kumar, S. (2001). The effects of androgens and estrogens on preadipocyte proliferation in human adipose tissue: Influence of gender and site. The Journal of Clinical Endocrinology and Metabolism, 86, 5045–5051.

    Article  CAS  PubMed  Google Scholar 

  • Archer, Z. A., Findlay, P. A., McMillen, S. R., Rhind, S. M., & Adam, C. L. (2004). Effects of nutritional status and gonadal steroids on expression of appetite-regulatory genes in the hypothalamic arcuate nucleus of sheep. The Journal of Endocrinology, 182, 409–419.

    Article  CAS  PubMed  Google Scholar 

  • Armamento-Villareal, R., Aguirre, L. E., Qualls, C., & Villareal, D. T. (2016). Effect of lifestyle intervention on the hormonal profile of frail, obese older men. The Journal of Nutrition, Health & Aging, 20, 334–340.

    Article  CAS  Google Scholar 

  • Ayoub, R., Page, S. T., Swerdloff, R. S., Liu, P. Y., Amory, J. K., Leung, A., Hull, L., Blithe, D., Christy, A., Chao, J. H., Bremner, W. J., & Wang, C. (2016). Comparison of the single dose pharmacokinetics, pharmacodynamics, and safety of two novel oral formulations of dimethandrolone undecanoate (DMAU): A potential oral, male contraceptive. Andrology, 5(2), 278–285.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barros, R. P., Machado, U. F., Warner, M., & Gustafsson, J. A. (2006). Muscle GLUT4 regulation by estrogen receptors ERbeta and ERalpha. Proceedings of the National Academy of Sciences of the United States of America, 103, 1605–1608.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Barros, R. P., Gabbi, C., Morani, A., Warner, M., & Gustafsson, J. A. (2009). Participation of ERalpha and ERbeta in glucose homeostasis in skeletal muscle and white adipose tissue. American Journal of Physiology Endocrinology and Metabolism, 297, E124–E133.

    Article  CAS  PubMed  Google Scholar 

  • Bélanger, C., Hould, F. S., Lebel, S., Biron, S., Brochu, G., & Tchernof, A. (2006). Omental and subcutaneous adipose tissue steroid levels in obese men. Steroids, 71, 674–682.

    Article  CAS  PubMed  Google Scholar 

  • Bhasin, S., Woodhouse, L., & Storer, T. W. (2003). Androgen effects on body composition. Growth Hormone & IGF Research, 13(Suppl A), S63–S71.

    Article  CAS  Google Scholar 

  • Bhasin, S., Cunningham, G. R., Hayes, F. J., Matsumoto, A. M., Snyder, P. J., Swerdloff, R. S., Montori, V. M., & Task Force, E. S. (2010). Testosterone therapy in men with androgen deficiency syndromes: An endocrine society clinical practice guideline. The Journal of Clinical Endocrinology and Metabolism, 95, 2536–2559.

    Article  CAS  PubMed  Google Scholar 

  • Bhattacharya, I., Tarabar, S., Liang, Y., Pradhan, V., Owens, J., & Oemar, B. (2016). Safety, pharmacokinetic, and pharmacodynamic evaluation after single and multiple ascending doses of a novel selective androgen receptor modulator in healthy subjects. Clinical Therapeutics, 38, 1401–1416.

    Article  CAS  PubMed  Google Scholar 

  • Blankenstein, M. A., Szymczak, J., Daroszewski, J., Milewicz, A., & Thijssen, J. H. (1992). Estrogens in plasma and fatty tissue from breast cancer patients and women undergoing surgery for non-oncological reasons. Gynecological Endocrinology, 6, 13–17.

    Article  CAS  PubMed  Google Scholar 

  • Blasko, E., Haskell, C. A., Leung, S., Gualtieri, G., Halks-Miller, M., Mahmoudi, M., Dennis, M. K., Prossnitz, E. R., Karpus, W. J., & Horuk, R. (2009). Beneficial role of the GPR30 agonist G-1 in an animal model of multiple sclerosis. Journal of Neuroimmunology, 214, 67–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brind, J., Strain, G., Miller, L., Zumoff, B., Vogelman, J., & Orentreich, N. (1990). Obese men have elevated plasma levels of estrone sulfate. International Journal of Obesity, 14, 483–486.

    CAS  PubMed  Google Scholar 

  • Brown, L. M., & Clegg, D. J. (2010). Central effects of estradiol in the regulation of food intake, body weight, and adiposity. The Journal of Steroid Biochemistry and Molecular Biology, 122, 65–73.

    Article  CAS  PubMed  Google Scholar 

  • Brown, T. J., Naftolin, F., & Maclusky, N. J. (1992). Sex differences in estrogen receptor binding in the rat hypothalamus: Effects of subsaturating pulses of estradiol. Brain Research, 578, 129–134.

    Article  CAS  PubMed  Google Scholar 

  • Burnett-Bowie, S. A., Roupenian, K. C., Dere, M. E., Lee, H., & Leder, B. Z. (2009). Effects of aromatase inhibition in hypogonadal older men: A randomized, double-blind, placebo-controlled trial. Clinical Endocrinology (Oxf), 70, 116–123.

    Article  CAS  Google Scholar 

  • Cannata, D. H., Kirschenbaum, A., & Levine, A. C. (2012). Androgen deprivation therapy as primary treatment for prostate cancer. The Journal of Clinical Endocrinology and Metabolism, 97, 360–365.

    Article  CAS  PubMed  Google Scholar 

  • Carani, C., Qin, K., Simoni, M., Faustini-Fustini, M., Serpente, S., Boyd, J., Korach, K. S., & Simpson, E. R. (1997). Effect of testosterone and estradiol in a man with aromatase deficiency. The New England Journal of Medicine, 337, 91–95.

    Article  CAS  PubMed  Google Scholar 

  • Carrier, N., Saland, S. K., Duclot, F., He, H., Mercer, R., & Kabbaj, M. (2015). The anxiolytic and antidepressant-like effects of testosterone and estrogen in gonadectomized male rats. Biological Psychiatry, 78, 259–269.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Castanho, T. C., Moreira, P. S., Portugal-Nunes, C., Novais, A., Costa, P. S., Palha, J. A., Sousa, N., & Santos, N. C. (2014). The role of sex and sex-related hormones in cognition, mood and well-being in older men and women. Biological Psychology, 103, 158–166.

    Article  PubMed  Google Scholar 

  • Cederroth, C. R., Vinciguerra, M., Kühne, F., Madani, R., Doerge, D. R., Visser, T. J., Foti, M., Rohner-Jeanrenaud, F., Vassalli, J. D., & Nef, S. (2007). A phytoestrogen-rich diet increases energy expenditure and decreases adiposity in mice. Environmental Health Perspectives, 115, 1467–1473.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cederroth, C. R., Vinciguerra, M., Gjinovci, A., Kühne, F., Klein, M., Cederroth, M., Caille, D., Suter, M., Neumann, D., James, R. W., Doerge, D. R., Wallimann, T., Meda, P., Foti, M., Rohner-Jeanrenaud, F., Vassalli, J. D., & Nef, S. (2008). Dietary phytoestrogens activate AMP-activated protein kinase with improvement in lipid and glucose metabolism. Diabetes, 57, 1176–1185.

    Article  CAS  PubMed  Google Scholar 

  • Chakraborty, S., Sachdev, A., Salton, S. R., & Chakraborty, T. R. (2008). Stereological analysis of estrogen receptor expression in the hypothalamic arcuate nucleus of ob/ob and agouti mice. Brain Research, 1217, 86–95.

    Article  CAS  PubMed  Google Scholar 

  • Chao, J., Rubinow, K. B., Kratz, M., Amory, J. K., Matsumoto, A. M., & Page, S. T. (2016). Short-term estrogen withdrawal increases adiposity in healthy men. The Journal of Clinical Endocrinology and Metabolism, 101, 3724–3731.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Clegg, D. J., Brown, L. M., Woods, S. C., & Benoit, S. C. (2006). Gonadal hormones determine sensitivity to central leptin and insulin. Diabetes, 55, 978–987.

    Article  CAS  PubMed  Google Scholar 

  • Clegg, D. J., Brown, L. M., Zigman, J. M., Kemp, C. J., Strader, A. D., Benoit, S. C., Woods, S. C., Mangiaracina, M., & Geary, N. (2007). Estradiol-dependent decrease in the orexigenic potency of ghrelin in female rats. Diabetes, 56, 1051–1058.

    Article  CAS  PubMed  Google Scholar 

  • Cooke, P. S., Heine, P. A., Taylor, J. A., & Lubahn, D. B. (2001). The role of estrogen and estrogen receptor-alpha in male adipose tissue. Molecular and Cellular Endocrinology, 178, 147–154.

    Article  CAS  PubMed  Google Scholar 

  • Corona, G., Rastrelli, G., Morelli, A., Vignozzi, L., Mannucci, E., & Maggi, M. (2011). Hypogonadism and metabolic syndrome. Journal of Endocrinological Investigation, 34, 557–567.

    Article  CAS  PubMed  Google Scholar 

  • Corona, G., Rastrelli, G., Monami, M., Saad, F., Luconi, M., Lucchese, M., Facchiano, E., Sforza, A., Forti, G., Mannucci, E., & Maggi, M. (2013). Body weight loss reverts obesity-associated hypogonadotropic hypogonadism: A systematic review and meta-analysis. European Journal of Endocrinology, 168, 829–843.

    Article  CAS  PubMed  Google Scholar 

  • Cunningham, M., & Gilkeson, G. (2011). Estrogen receptors in immunity and autoimmunity. Clinical Reviews in Allergy & Immunology, 40, 66–73.

    Article  CAS  Google Scholar 

  • D’Eon, T. M., Souza, S. C., Aronovitz, M., Obin, M. S., Fried, S. K., & Greenberg, A. S. (2005). Estrogen regulation of adiposity and fuel partitioning. Evidence of genomic and non-genomic regulation of lipogenic and oxidative pathways. The Journal of Biological Chemistry, 280, 35983–35991.

    Article  CAS  PubMed  Google Scholar 

  • Dakin, R. S., Walker, B. R., Seckl, J. R., Hadoke, P. W., & Drake, A. J. (2015). Estrogens protect male mice from obesity complications and influence glucocorticoid metabolism. International Journal of Obesity (Lond), 39, 1539–1547.

    Article  CAS  Google Scholar 

  • Davis, K. E., Carstens, E. J., Irani, B. G., Gent, L. M., Hahner, L. M., & Clegg, D. J. (2014). Sexually dimorphic role of G protein-coupled estrogen receptor (GPER) in modulating energy homeostasis. Hormones and Behavior, 66(1), 196–207.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • de Boer, H., Verschoor, L., Ruinemans-Koerts, J., & Jansen, M. (2005). Letrozole normalizes serum testosterone in severely obese men with hypogonadotropic hypogonadism. Diabetes, Obesity & Metabolism, 7, 211–215.

    Article  CAS  Google Scholar 

  • Deslypere, J. P., Verdonck, L., & Vermeulen, A. (1985). Fat tissue: A steroid reservoir and site of steroid metabolism. The Journal of Clinical Endocrinology and Metabolism, 61, 564–570.

    Article  CAS  PubMed  Google Scholar 

  • Dieudonne, M. N., Pecquery, R., Leneveu, M. C., & Giudicelli, Y. (2000). Opposite effects of androgens and estrogens on adipogenesis in rat preadipocytes: Evidence for sex and site-related specificities and possible involvement of insulin-like growth factor 1 receptor and peroxisome proliferator-activated receptor gamma2. Endocrinology, 141, 649–656.

    Article  CAS  PubMed  Google Scholar 

  • Dieudonné, M. N., Leneveu, M. C., Giudicelli, Y., & Pecquery, R. (2004). Evidence for functional estrogen receptors alpha and beta in human adipose cells: Regional specificities and regulation by estrogens. American Journal of Physiology Cell Physiology, 286, C655–C661.

    Article  PubMed  Google Scholar 

  • Dieudonné, M. N., Sammari, A., Dos Santos, E., Leneveu, M. C., Giudicelli, Y., & Pecquery, R. (2006). Sex steroids and leptin regulate 11beta-hydroxysteroid dehydrogenase I and P450 aromatase expressions in human preadipocytes: Sex specificities. The Journal of Steroid Biochemistry and Molecular Biology, 99, 189–196.

    Article  CAS  PubMed  Google Scholar 

  • Ding, E. L., Song, Y., Malik, V. S., & Liu, S. (2006). Sex differences of endogenous sex hormones and risk of type 2 diabetes: A systematic review and meta-analysis. JAMA, 295, 1288–1299.

    Article  CAS  PubMed  Google Scholar 

  • Fan, W., Yanase, T., Nomura, M., Okabe, T., Goto, K., Sato, T., Kawano, H., Kato, S., & Nawata, H. (2005). Androgen receptor null male mice develop late-onset obesity caused by decreased energy expenditure and lipolytic activity but show normal insulin sensitivity with high adiponectin secretion. Diabetes, 54, 1000–1008.

    Article  CAS  PubMed  Google Scholar 

  • Finan, B., Yang, B., Ottaway, N., Stemmer, K., Müller, T. D., Yi, C. X., Habegger, K., et al. (2012). Targeted estrogen delivery reverses the metabolic syndrome. Nature Medicine, 18, 1847–1856.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Finkelstein, J. S., Lee, H., Burnett-Bowie, S. A., Pallais, J. C., Yu, E. W., Borges, L. F., Jones, B. F., Barry, C. V., Wulczyn, K. E., Thomas, B. J., & Leder, B. Z. (2013). Gonadal steroids and body composition, strength, and sexual function in men. The New England Journal of Medicine, 369, 1011–1022.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Flores, R., Shi, J., Fuhrman, B., Xu, X., Veenstra, T. D., Gail, M. H., Gajer, P., Ravel, J., & Goedert, J. J. (2012). Fecal microbial determinants of fecal and systemic estrogens and estrogen metabolites: A cross-sectional study. Journal of Translational Medicine, 10, 253.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Foryst-Ludwig, A., & Kintscher, U. (2010). Metabolic impact of estrogen signalling through ERalpha and ERbeta. The Journal of Steroid Biochemistry and Molecular Biology, 122, 74–81.

    Article  CAS  PubMed  Google Scholar 

  • Foryst-Ludwig, A., Clemenz, M., Hohmann, S., Hartge, M., Sprang, C., Frost, N., Krikov, M., Bhanot, S., Barros, R., Morani, A., Gustafsson, J. A., Unger, T., & Kintscher, U. (2008). Metabolic actions of estrogen receptor beta (ERbeta) are mediated by a negative cross-talk with PPARgamma. PLoS Genetics, 4, e1000108.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Frank, A., Brown, L. M., & Clegg, D. J. (2014). The role of hypothalamic estrogen receptors in metabolic regulation. Frontiers in Neuroendocrinology, 35, 550–557.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gao, Q., Mezei, G., Nie, Y., Rao, Y., Choi, C. S., Bechmann, I., Leranth, C., Toran-Allerand, D., Priest, C. A., Roberts, J. L., Gao, X. B., Mobbs, C., Shulman, G. I., Diano, S., & Horvath, T. L. (2007). Anorectic estrogen mimics leptin’s effect on the rewiring of melanocortin cells and Stat3 signaling in obese animals. Nature Medicine, 13, 89–94.

    Article  CAS  PubMed  Google Scholar 

  • Gerriets, V. A., & MacIver, N. J. (2014). Role of T cells in malnutrition and obesity. Frontiers in Immunology, 5, 379.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gillies, G. E., & McArthur, S. (2010). Estrogen actions in the brain and the basis for differential action in men and women: A case for sex-specific medicines. Pharmacological Reviews, 62, 155–198.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Giudicelli, Y., Dieudonne, M. N., Lacasa, D., Pasquier, Y. N., & Pecquery, R. (1993). Modulation by sex hormones of the membranous transducing system regulating fatty acid mobilization in adipose tissue. Prostaglandins, Leukotrienes, and Essential Fatty Acids, 48, 91–100.

    Article  CAS  PubMed  Google Scholar 

  • Grasa, M. M., Esteve, M., Masanés, R. M., Yubero, P., Blay, M., López-Martí, J., Cabot, C., Vilà, R., Fernández-López, J. A., Remesar, X., & Alemany, M. (2001). Oral gavage of oleoyl-oestrone has a stronger effect on body weight in male Zucker obese rats than in female. Diabetes, Obesity & Metabolism, 3, 203–208.

    Article  CAS  Google Scholar 

  • Hamilton, E. J., Gianatti, E., Strauss, B. J., Wentworth, J., Lim-Joon, D., Bolton, D., Zajac, J. D., & Grossmann, M. (2011). Increase in visceral and subcutaneous abdominal fat in men with prostate cancer treated with androgen deprivation therapy. Clinical Endocrinology, 74, 377–383.

    Article  CAS  PubMed  Google Scholar 

  • Hammoud, A., Carrell, D. T., Meikle, A. W., Xin, Y., Hunt, S. C., Adams, T. D., & Gibson, M. (2010). An aromatase polymorphism modulates the relationship between weight and estradiol levels in obese men. Fertility and Sterility, 94, 1734–1738.

    Article  CAS  PubMed  Google Scholar 

  • Harada, N., Hanaoka, R., Horiuchi, H., Kitakaze, T., Mitani, T., Inui, H., & Yamaji, R. (2016). Castration influences intestinal microflora and induces abdominal obesity in high-fat diet-fed mice. Scientific Reports, 6, 23001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heine, P. A., Taylor, J. A., Iwamoto, G. A., Lubahn, D. B., & Cooke, P. S. (2000). Increased adipose tissue in male and female estrogen receptor-alpha knockout mice. Proceedings of the National Academy of Sciences of the United States of America, 97, 12729–12734.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hemsell, D. L., Grodin, J. M., Brenner, P. F., Siiteri, P. K., & MacDonald, P. C. (1974). Plasma precursors of estrogen. II. Correlation of the extent of conversion of plasma androstenedione to estrone with age. The Journal of Clinical Endocrinology and Metabolism, 38, 476–479.

    Article  CAS  PubMed  Google Scholar 

  • Holland, A. M., Roberts, M. D., Mumford, P. W., Mobley, C. B., Kephart, W. C., Conover, C. F., Beggs, L. A., Balaez, A., Otzel, D. M., Yarrow, J. F., Borst, S. E., & Beck, D. T. (2016). Testosterone inhibits expression of lipogenic genes in visceral fat by an estrogen-dependent mechanism. Journal of Applied Physiology. (1985, 121, 792–805.

    Article  CAS  PubMed  Google Scholar 

  • Homma, H., Kurachi, H., Nishio, Y., Takeda, T., Yamamoto, T., Adachi, K., Morishige, K., Ohmichi, M., Matsuzawa, Y., & Murata, Y. (2000). Estrogen suppresses transcription of lipoprotein lipase gene. Existence of a unique estrogen response element on the lipoprotein lipase promoter. The Journal of Biological Chemistry, 275, 11404–11411.

    Article  CAS  PubMed  Google Scholar 

  • Ihunnah, C. A., Wada, T., Philips, B. J., Ravuri, S. K., Gibbs, R. B., Kirisci, L., Rubin, J. P., Marra, K. G., & Xie, W. (2014). Estrogen Sulfotransferase/SULT1E1 promotes human adipogenesis. Molecular and Cellular Biology, 34, 1682–1694.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Isidori, A. M., Giannetta, E., Greco, E. A., Gianfrilli, D., Bonifacio, V., Isidori, A., Lenzi, A., & Fabbri, A. (2005). Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle-aged men: A meta-analysis. Clinical Endocrinology (Oxf), 63, 280–293.

    Article  CAS  Google Scholar 

  • Jasuja, G. K., Travison, T. G., Davda, M., Murabito, J. M., Basaria, S., Zhang, A., Kushnir, M. M., Rockwood, A. L., Meikle, W., Pencina, M. J., Coviello, A., Rose, A. J., D'Agostino, R., Vasan, R. S., & Bhasin, S. (2013a). Age trends in estradiol and estrone levels measured using liquid chromatography tandem mass spectrometry in community-dwelling men of the Framingham heart study. The Journals of Gerontology Series A, Biological Sciences and Medical Sciences, 68, 733–740.

    Article  CAS  PubMed  Google Scholar 

  • Jasuja, G. K., Travison, T. G., Davda, M., Rose, A. J., Zhang, A., Kushnir, M. M., Rockwood, A. L., Meikle, W., Coviello, A. D., D'Agostino, R., Vasan, R. S., & Bhasin, S. (2013b). Circulating estrone levels are associated prospectively with diabetes risk in men of the Framingham Heart Study. Diabetes Care, 36, 2591–2596.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jones, M. E., Thorburn, A. W., Britt, K. L., Hewitt, K. N., Wreford, N. G., Proietto, J., Oz, O. K., Leury, B. J., Robertson, K. M., Yao, S., & Simpson, E. R. (2000). Aromatase-deficient (ArKO) mice have a phenotype of increased adiposity. Proceedings of the National Academy of Sciences of the United States of America, 97, 12735–12740.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jones, M. E., Thorburn, A. W., Britt, K. L., Hewitt, K. N., Misso, M. L., Wreford, N. G., Proietto, J., Oz, O. K., Leury, B. J., Robertson, K. M., Yao, S., & Simpson, E. R. (2001). Aromatase-deficient (ArKO) mice accumulate excess adipose tissue. The Journal of Steroid Biochemistry and Molecular Biology, 79, 3–9.

    Article  CAS  PubMed  Google Scholar 

  • Jones, M. E., Boon, W. C., Proietto, J., & Simpson, E. R. (2006). Of mice and men: The evolving phenotype of aromatase deficiency. Trends in Endocrinology and Metabolism, 17, 55–64.

    Article  CAS  PubMed  Google Scholar 

  • Jones, T. H., Arver, S., Behre, H. M., Buvat, J., Meuleman, E., Moncada, I., Morales, A. M., Volterrani, M., Yellowlees, A., Howell, J. D., Channer, K. S., & Investigators, T. (2011). Testosterone replacement in hypogonadal men with type 2 diabetes and/or metabolic syndrome (the TIMES2 study). Diabetes Care, 34, 828–837.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Juang, P. S., Peng, S., Allehmazedeh, K., Shah, A., Coviello, A. D., & Herbst, K. L. (2014). Testosterone with dutasteride, but not anastrozole, improves insulin sensitivity in young obese men: A randomized controlled trial. The Journal of Sexual Medicine, 11, 563–573.

    Article  CAS  PubMed  Google Scholar 

  • Kahles, F., Meyer, C., Möllmann, J., Diebold, S., Findeisen, H. M., Lebherz, C., Trautwein, C., Koch, A., Tacke, F., Marx, N., & Lehrke, M. (2014). GLP-1 secretion is increased by inflammatory stimuli in an IL-6-dependent manner, leading to hyperinsulinemia and blood glucose lowering. Diabetes, 63, 3221–3229.

    Article  CAS  PubMed  Google Scholar 

  • Kaminetsky, J., Werner, M., Fontenot, G., & Wiehle, R. D. (2013). Oral enclomiphene citrate stimulates the endogenous production of testosterone and sperm counts in men with low testosterone: comparison with testosterone gel. The Journal of Sexual Medicine, 10, 1628–1635.

    Article  CAS  PubMed  Google Scholar 

  • Kautzky-Willer, A., & Handisurya, A. (2009). Metabolic diseases and associated complications: Sex and gender matter! European Journal of Clinical Investigation, 39, 631–648.

    Article  CAS  PubMed  Google Scholar 

  • Keating, N. L., O’Malley, A. J., & Smith, M. R. (2006). Diabetes and cardiovascular disease during androgen deprivation therapy for prostate cancer. Journal of Clinical Oncology, 24, 4448–4456.

    Article  CAS  PubMed  Google Scholar 

  • Keating, N. L., O’Malley, A., Freedland, S. J., & Smith, M. R. (2012). Diabetes and cardiovascular disease during androgen deprivation therapy: Observational study of veterans with prostate cancer. Journal of the National Cancer Institute, 104, 1518–1523.

    Article  PubMed  Google Scholar 

  • Kellert, B. A., Nguyen, M. C., Nguyen, C., Nguyen, Q. H., & Wagner, E. J. (2009). Estrogen rapidly attenuates cannabinoid-induced changes in energy homeostasis. European Journal of Pharmacology, 622, 15–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Khan, M. J., Gerasimidis, K., Edwards, C. A., & Shaikh, M. G. (2016). Role of gut microbiota in the aetiology of obesity: Proposed mechanisms and review of the literature. Journal of Obesity, 2016, 7353642.

    PubMed  PubMed Central  Google Scholar 

  • Khor, V. K., Tong, M. H., Qian, Y., & Song, W. C. (2008). Gender-specific expression and mechanism of regulation of estrogen sulfotransferase in adipose tissues of the mouse. Endocrinology, 149, 5440–5448.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim, E. D., McCullough, A., & Kaminetsky, J. (2016). Oral enclomiphene citrate raises testosterone and preserves sperm counts in obese hypogonadal men, unlike topical testosterone: Restoration instead of replacement. BJU International, 117, 677–685.

    Article  CAS  PubMed  Google Scholar 

  • Kley, H. K., Deselaers, T., Peerenboom, H., & Krüskemper, H. L. (1980a). Enhanced conversion of androstenedione to estrogens in obese males. The Journal of Clinical Endocrinology and Metabolism, 51, 1128–1132.

    Article  CAS  PubMed  Google Scholar 

  • Kley, H. K., Edelmann, P., & Krüskemper, H. L. (1980b). Relationship of plasma sex hormones to different parameters of obesity in male subjects. Metabolism, 29, 1041–1045.

    Article  CAS  PubMed  Google Scholar 

  • Kovats, S. (2012). Estrogen receptors regulate an inflammatory pathway of dendritic cell differentiation: Mechanisms and implications for immunity. Hormones and Behavior, 62, 254–262.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kovats, S. (2015). Estrogen receptors regulate innate immune cells and signaling pathways. Cellular Immunology, 294, 63–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lacasa, D., Taleb, S., Keophiphath, M., Miranville, A., & Clement, K. (2007). Macrophage-secreted factors impair human adipogenesis: Involvement of proinflammatory state in preadipocytes. Endocrinology, 148, 868–877.

    Article  CAS  PubMed  Google Scholar 

  • Lebherz, C., Kahles, F., Piotrowski, K., Vogeser, M., Foldenauer, A. C., Nassau, K., Kilger, E., Marx, N., Parhofer, K. G., & Lehrke, M. (2016). Interleukin-6 predicts inflammation-induced increase of Glucagon-like peptide-1 in humans in response to cardiac surgery with association to parameters of glucose metabolism. Cardiovascular Diabetology, 15, 21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Loves, S., Ruinemans-Koerts, J., & de Boer, H. (2008). Letrozole once a week normalizes serum testosterone in obesity-related male hypogonadism. European Journal of Endocrinology, 158, 741–747.

    Article  CAS  PubMed  Google Scholar 

  • Loves, S., de Jong, J., van Sorge, A., Telting, D., Tack, C. J., Hermus, A., Westerterp, K., & de Boer, H. (2013). Somatic and psychological effects of low-dose aromatase inhibition in men with obesity-related hypogonadotropic hypotestosteronemia. European Journal of Endocrinology, 169, 705–714.

    Article  CAS  PubMed  Google Scholar 

  • Lu, C., Kumar, P. A., Fan, Y., Sperling, M. A., & Menon, R. K. (2010). A novel effect of growth hormone on macrophage modulates macrophage-dependent adipocyte differentiation. Endocrinology, 151, 2189–2199.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lumeng, C. N., DelProposto, J. B., Westcott, D. J., & Saltiel, A. R. (2008). Phenotypic switching of adipose tissue macrophages with obesity is generated by spatiotemporal differences in macrophage subtypes. Diabetes, 57, 3239–3246.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • MacDonald, A. A., Herbison, G. P., Showell, M., & Farquhar, C. M. (2010). The impact of body mass index on semen parameters and reproductive hormones in human males: A systematic review with meta-analysis. Human Reproduction Update, 16, 293–311.

    Article  CAS  PubMed  Google Scholar 

  • Maffei, L., Rochira, V., Zirilli, L., Antunez, P., Aranda, C., Fabre, B., Simone, M. L., Pignatti, E., Simpson, E. R., Houssami, S., Clyne, C. D., & Carani, C. (2007). A novel compound heterozygous mutation of the aromatase gene in an adult man: Reinforced evidence on the relationship between congenital oestrogen deficiency, adiposity and the metabolic syndrome. Clinical Endocrinology, 67, 218–224.

    Article  CAS  PubMed  Google Scholar 

  • Mah, P. M., & Wittert, G. A. (2010). Obesity and testicular function. Molecular and Cellular Endocrinology, 316, 180–186.

    Article  CAS  PubMed  Google Scholar 

  • Mather, K. J., Kim, C., Christophi, C. A., Aroda, V. R., Knowler, W. C., Edelstein, S. E., Florez, J. C., Labrie, F., Kahn, S. E., Goldberg, R. B., Barrett-Connor, E., & Program, D. P. (2015). Steroid sex hormones, sex hormone-binding globulin, and diabetes incidence in the diabetes prevention program. The Journal of Clinical Endocrinology and Metabolism, 100, 3778–3786.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mathis, D. (2013). Immunological goings-on in visceral adipose tissue. Cell Metabolism, 17, 851–859.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matsumine, H., Hirato, K., Yanaihara, T., Tamada, T., & Yoshida, M. (1986). Aromatization by skeletal muscle. The Journal of Clinical Endocrinology and Metabolism, 63, 717–720.

    Article  CAS  PubMed  Google Scholar 

  • Mauvais-Jarvis, F., Clegg, D. J., & Hevener, A. L. (2013). The role of estrogens in control of energy balance and glucose homeostasis. Endocrine Reviews, 34, 309–338.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Meng, M. V., Grossfeld, G. D., Sadetsky, N., Mehta, S. S., Lubeck, D. P., & Carroll, P. R. (2002). Contemporary patterns of androgen deprivation therapy use for newly diagnosed prostate cancer. Urology, 60, 7–11. discussion 11–12.

    Article  CAS  PubMed  Google Scholar 

  • Merchenthaler, I., Lane, M. V., Numan, S., & Dellovade, T. L. (2004). Distribution of estrogen receptor alpha and beta in the mouse central nervous system: In vivo autoradiographic and immunocytochemical analyses. The Journal of Comparative Neurology, 473, 270–291.

    Article  CAS  PubMed  Google Scholar 

  • Mihalca, R., & Fica, S. (2014). The impact of obesity on the male reproductive axis. Journal of Medicine and Life, 7, 296–300.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Misso, M. L., Murata, Y., Boon, W. C., Jones, M. E., Britt, K. L., & Simpson, E. R. (2003). Cellular and molecular characterization of the adipose phenotype of the aromatase-deficient mouse. Endocrinology, 144, 1474–1480.

    Article  CAS  PubMed  Google Scholar 

  • Monteagudo, P. T., Falcão, A. A., Verreschi, I. T., & Zanella, M. T. (2016). The imbalance of sex-hormones related to depressive symptoms in obese men. The Aging Male, 19, 20–26.

    Article  CAS  PubMed  Google Scholar 

  • Monteiro, R., Teixeira, D., & Calhau, C. (2014). Estrogen signaling in metabolic inflammation. Mediators of Inflammation, 2014, 615917.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morishima, A., Grumbach, M. M., Simpson, E. R., Fisher, C., & Qin, K. (1995). Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens. The Journal of Clinical Endocrinology and Metabolism, 80, 3689–3698.

    CAS  PubMed  Google Scholar 

  • Morton, G. J., & Schwartz, M. W. (2011). Leptin and the central nervous system control of glucose metabolism. Physiological Reviews, 91, 389–411.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Muschamp, J. W., & Hull, E. M. (2007). Melanin concentrating hormone and estrogen receptor-alpha are coexstensive but not coexpressed in cells of male rat hypothalamus. Neuroscience Letters, 427, 123–126.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mystkowski, P., Seeley, R. J., Hahn, T. M., Baskin, D. G., Havel, P. J., Matsumoto, A. M., Wilkinson, C. W., Peacock-Kinzig, K., Blake, K. A., & Schwartz, M. W. (2000). Hypothalamic melanin-concentrating hormone and estrogen-induced weight loss. The Journal of Neuroscience, 20, 8637–8642.

    CAS  PubMed  Google Scholar 

  • Ogawa, S., Chan, J., Gustafsson, J. A., Korach, K. S., & Pfaff, D. W. (2003). Estrogen increases locomotor activity in mice through estrogen receptor alpha: Specificity for the type of activity. Endocrinology, 144, 230–239.

    Article  CAS  PubMed  Google Scholar 

  • Ohlsson, C., Hellberg, N., Parini, P., Vidal, O., Bohlooly-Y, M., Bohlooly, M., Rudling, M., Lindberg, M. K., Warner, M., Angelin, B., & Gustafsson, J. A. (2000). Obesity and disturbed lipoprotein profile in estrogen receptor-alpha-deficient male mice. Biochemical and Biophysical Research Communications, 278, 640–645.

    Article  CAS  PubMed  Google Scholar 

  • Olefsky, J. M., & Glass, C. K. (2010). Macrophages, inflammation, and insulin resistance. Annual Review of Physiology, 72, 219–246.

    Article  CAS  PubMed  Google Scholar 

  • Palin, S. L., McTernan, P. G., Anderson, L. A., Sturdee, D. W., Barnett, A. H., & Kumar, S. (2003). 17Beta-estradiol and anti-estrogen ICI: Compound 182,780 regulate expression of lipoprotein lipase and hormone-sensitive lipase in isolated subcutaneous abdominal adipocytes. Metabolism, 52, 383–388.

    Article  CAS  PubMed  Google Scholar 

  • Pedersen, S. B., Bruun, J. M., Hube, F., Kristensen, K., Hauner, H., & Richelsen, B. (2001). Demonstration of estrogen receptor subtypes alpha and beta in human adipose tissue: Influences of adipose cell differentiation and fat depot localization. Molecular and Cellular Endocrinology, 182, 27–37.

    Article  CAS  PubMed  Google Scholar 

  • Pedersen, S. B., Kristensen, K., Hermann, P. A., Katzenellenbogen, J. A., & Richelsen, B. (2004). Estrogen controls lipolysis by up-regulating alpha2A-adrenergic receptors directly in human adipose tissue through the estrogen receptor alpha. Implications for the female fat distribution. The Journal of Clinical Endocrinology and Metabolism, 89, 1869–1878.

    Article  CAS  PubMed  Google Scholar 

  • Pellitero, S., Olaizola, I., Alastrue, A., Martínez, E., Granada, M. L., Balibrea, J. M., Moreno, P., Serra, A., Navarro-Díaz, M., Romero, R., & Puig-Domingo, M. (2012). Hypogonadotropic hypogonadism in morbidly obese males is reversed after bariatric surgery. Obesity Surgery, 22, 1835–1842.

    Article  PubMed  Google Scholar 

  • Petersen, K. F., Dufour, S., Befroy, D., Lehrke, M., Hendler, R. E., & Shulman, G. I. (2005). Reversal of nonalcoholic hepatic steatosis, hepatic insulin resistance, and hyperglycemia by moderate weight reduction in patients with type 2 diabetes. Diabetes, 54, 603–608.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Phillips, I., Shah, S. I., Duong, T., Abel, P., & Langley, R. E. (2014). Androgen deprivation therapy and the re-emergence of parenteral estrogen in prostate cancer. Oncol Hematol Rev, 10, 42–47.

    PubMed  PubMed Central  Google Scholar 

  • Popkin, B. M., Adair, L. S., & Ng, S. W. (2012). Global nutrition transition and the pandemic of obesity in developing countries. Nutrition Reviews, 70, 3–21.

    Article  PubMed  PubMed Central  Google Scholar 

  • Price, T. M., O’Brien, S. N., Welter, B. H., George, R., Anandjiwala, J., & Kilgore, M. (1998). Estrogen regulation of adipose tissue lipoprotein lipase – possible mechanism of body fat distribution. American Journal of Obstetrics and Gynecology, 178, 101–107.

    Article  CAS  PubMed  Google Scholar 

  • Qiu, Y., Nguyen, K. D., Odegaard, J. I., Cui, X., Tian, X., Locksley, R. M., Palmiter, R. D., & Chawla, A. (2014). Eosinophils and type 2 cytokine signaling in macrophages orchestrate development of functional beige fat. Cell, 157, 1292–1308.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Remesar, X., Tang, V., Ferrer, E., Torregrosa, C., Virgili, J., Masanés, R. M., Fernández-López, J. A., & Alemany, M. (1999). Estrone in food: A factor influencing the development of obesity? European Journal of Nutrition, 38, 247–253.

    Article  CAS  PubMed  Google Scholar 

  • Ribas, V., Drew, B. G., Le, J. A., Soleymani, T., Daraei, P., Sitz, D., Mohammad, L., Henstridge, D. C., Febbraio, M. A., Hewitt, S. C., Korach, K. S., Bensinger, S. J., & Hevener, A. L. (2011). Myeloid-specific estrogen receptor alpha deficiency impairs metabolic homeostasis and accelerates atherosclerotic lesion development. Proceedings of the National Academy of Sciences of the United States of America, 108, 16457–16462.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ribas, V., Drew, B. G., Zhou, Z., Phun, J., Kalajian, N. Y., Soleymani, T., Daraei, P., et al. (2016). Skeletal muscle action of estrogen receptor α is critical for the maintenance of mitochondrial function and metabolic homeostasis in females. Science Translational Medicine, 8, 334ra354.

    Article  CAS  Google Scholar 

  • Riebe, C. J., Hill, M. N., Lee, T. T., Hillard, C. J., & Gorzalka, B. B. (2010). Estrogenic regulation of limbic cannabinoid receptor binding. Psychoneuroendocrinology, 35, 1265–1269.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rogers, N. H., Perfield, J. W., Strissel, K. J., Obin, M. S., & Greenberg, A. S. (2009). Reduced energy expenditure and increased inflammation are early events in the development of ovariectomy-induced obesity. Endocrinology, 150, 2161–2168.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roselli, C. E., Liu, M., & Hurn, P. D. (2009). Brain aromatization: Classic roles and new perspectives. Seminars in Reproductive Medicine, 27, 207–217.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ruan, H., Hacohen, N., Golub, T. R., Van Parijs, L., & Lodish, H. F. (2002). Tumor necrosis factor-alpha suppresses adipocyte-specific genes and activates expression of preadipocyte genes in 3T3-L1 adipocytes: Nuclear factor-kappaB activation by TNF-alpha is obligatory. Diabetes, 51, 1319–1336.

    Article  CAS  PubMed  Google Scholar 

  • Sanchis, D., Balada, F., del Mar, G. M., Virgili, J., Peinado, J., Monserrat, C., Fernández-López, J. A., Remesar, X., & Alemany, M. (1996). Oleoyl-estrone induces the loss of body fat in rats. International Journal of Obesity and Related Metabolic Disorders, 20, 588–594.

    CAS  PubMed  Google Scholar 

  • Sanchis, D., Balada, F., Picó, C., Grasa, M. M., Virgili, J., Farrerons, C., Palou, A., Fernández-López, J. A., Remesar, X., & Alemany, M. (1997). Rats receiving the slimming agent oleoyl-estrone in liposomes (Merlin-2) decrease food intake but maintain thermogenesis. Archives of Physiology and Biochemistry, 105, 663–672.

    Article  CAS  PubMed  Google Scholar 

  • Schneider, G., Kirschner, M. A., Berkowitz, R., & Ertel, N. H. (1979). Increased estrogen production in obese men. The Journal of Clinical Endocrinology and Metabolism, 48, 633–638.

    Article  CAS  PubMed  Google Scholar 

  • Serrano, M., Grasa, M. M., Janer, G., Fernández-López, J. A., & Alemany, M. (2009). Oleoyl-estrone affects lipid metabolism in adrenalectomized rats treated with corticosterone through modulation of SREBP1c expression. The Journal of Steroid Biochemistry and Molecular Biology, 117, 15–22.

    Article  CAS  PubMed  Google Scholar 

  • Shahani, S., Braga-Basaria, M., & Basaria, S. (2008). Androgen deprivation therapy in prostate cancer and metabolic risk for atherosclerosis. The Journal of Clinical Endocrinology and Metabolism, 93, 2042–2049.

    Article  CAS  PubMed  Google Scholar 

  • Simerly, R. B., Chang, C., Muramatsu, M., & Swanson, L. W. (1990). Distribution of androgen and estrogen receptor mRNA-containing cells in the rat brain: an in situ hybridization study. The Journal of Comparative Neurology, 294, 76–95.

    Article  CAS  PubMed  Google Scholar 

  • Simpson, E. R. (1998). Genetic mutations resulting in estrogen insufficiency in the male. Molecular and Cellular Endocrinology, 145, 55–59.

    Article  CAS  PubMed  Google Scholar 

  • Simpson, E. R. (2003). Sources of estrogen and their importance. The Journal of Steroid Biochemistry and Molecular Biology, 86, 225–230.

    Article  CAS  PubMed  Google Scholar 

  • Simpson, E. R. (2004). Aromatase: Biologic relevance of tissue-specific expression. Seminars in Reproductive Medicine, 22, 11–23.

    Article  CAS  PubMed  Google Scholar 

  • Smith, E. P., Boyd, J., Frank, G. R., Takahashi, H., Cohen, R. M., Specker, B., Williams, T. C., Lubahn, D. B., & Korach, K. S. (1994). Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. The New England Journal of Medicine, 331, 1056–1061.

    Article  CAS  PubMed  Google Scholar 

  • Spencer, M., Yao-Borengasser, A., Unal, R., Rasouli, N., Gurley, C. M., Zhu, B., Peterson, C. A., & Kern, P. A. (2010). Adipose tissue macrophages in insulin-resistant subjects are associated with collagen VI and fibrosis and demonstrate alternative activation. American Journal of Physiology Endocrinology and Metabolism, 299, E1016–E1027.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stephens, J. M., Lee, J., & Pilch, P. F. (1997). Tumor necrosis factor-alpha-induced insulin resistance in 3T3-L1 adipocytes is accompanied by a loss of insulin receptor substrate-1 and GLUT4 expression without a loss of insulin receptor-mediated signal transduction. The Journal of Biological Chemistry, 272, 971–976.

    Article  CAS  PubMed  Google Scholar 

  • Stoffel-Wagner, B., Watzka, M., Schramm, J., Bidlingmaier, F., & Klingmüller, D. (1999). Expression of CYP19 (aromatase) mRNA in different areas of the human brain. The Journal of Steroid Biochemistry and Molecular Biology, 70, 237–241.

    Article  CAS  PubMed  Google Scholar 

  • Stout, M. B., Steyn, F. J., Jurczak, M. J., Camporez, J. G., Zhu, Y., Hawse, J. R., Jurk, D., Palmer, A. K., Xu, M., Pirtskhalava, T., Evans, G. L., de Souza, S. R., Frank, A. P., White, T. A., Monroe, D. G., Singh, R. J., Casaclang-Verzosa, G., Miller, J. D., Clegg, D. J., LeBrasseur, N. K., von Zglinicki, T., Shulman, G. I., Tchkonia, T., & Kirkland, J. L. (2017). 17α-Estradiol alleviates age-related metabolic and inflammatory dysfunction in male mice without inducing feminization. The Journals of Gerontology Series A, Biological Sciences and Medical Sciences, 72(1), 3–15.

    Google Scholar 

  • Straub, R. H. (2007). The complex role of estrogens in inflammation. Endocrine Reviews, 28, 521–574.

    Article  CAS  PubMed  Google Scholar 

  • Suganami, T., & Ogawa, Y. (2010). Adipose tissue macrophages: Their role in adipose tissue remodeling. Journal of Leukocyte Biology, 88, 33–39.

    Article  CAS  PubMed  Google Scholar 

  • Tagawa, N., Yuda, R., Kubota, S., Wakabayashi, M., Yamaguchi, Y., Kiyonaga, D., Mori, N., Minamitani, E., Masuzaki, H., & Kobayashi, Y. (2009). 17Beta-estradiol inhibits 11beta-hydroxysteroid dehydrogenase type 1 activity in rodent adipocytes. The Journal of Endocrinology, 202, 131–139.

    Article  CAS  PubMed  Google Scholar 

  • Takeda, K., Toda, K., Saibara, T., Nakagawa, M., Saika, K., Onishi, T., Sugiura, T., & Shizuta, Y. (2003). Progressive development of insulin resistance phenotype in male mice with complete aromatase (CYP19) deficiency. The Journal of Endocrinology, 176, 237–246.

    Article  CAS  PubMed  Google Scholar 

  • Tan, R. B., Guay, A. T., & Hellstrom, W. J. (2014). Clinical use of aromatase inhibitors in adult males. Sex Medicine Review, 2, 79–90.

    Article  Google Scholar 

  • Thirumalai, A., Berkseth, K. E., & Amory, J. K. (2017). Treatment of hypogonadism: Current and future therapies. F1000Research, 6, 68.

    Article  PubMed  PubMed Central  Google Scholar 

  • Titolo, D., Cai, F., & Belsham, D. D. (2006). Coordinate regulation of neuropeptide Y and agouti-related peptide gene expression by estrogen depends on the ratio of estrogen receptor (ER) alpha to ERbeta in clonal hypothalamic neurons. Molecular Endocrinology, 20, 2080–2092.

    Article  CAS  PubMed  Google Scholar 

  • Toda, K., Hayashi, Y., & Saibara, T. (2010). Deletion of tumor necrosis factor-alpha receptor type 1 exacerbates insulin resistance and hepatic steatosis in aromatase knockout mice. Biochimica et Biophysica Acta, 1801, 655–664.

    Article  CAS  PubMed  Google Scholar 

  • Toran-Allerand, C. D., Tinnikov, A. A., Singh, R. J., & Nethrapalli, I. S. (2005). 17alpha-estradiol: A brain-active estrogen? Endocrinology, 146, 3843–3850.

    Article  CAS  PubMed  Google Scholar 

  • Tritos, N. A., Segal-Lieberman, G., Vezeridis, P. S., & Maratos-Flier, E. (2004). Estradiol-induced anorexia is independent of leptin and melanin-concentrating hormone. Obesity Research, 12, 716–724.

    Article  CAS  PubMed  Google Scholar 

  • Van Sinderen, M. L., Steinberg, G. R., Jørgensen, S. B., To SQ, Knower, K. C., Clyne, C. D., Honeyman, J., Chow, J. D., Herridge, K. A., Jones, M. E., Simpson, E. R., & Boon, W. C. (2014). Hepatic glucose intolerance precedes hepatic steatosis in the male aromatase knockout (ArKO) mouse. PLoS One, 9, e87230.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vilà, R., Adán, C., Grasa, M. M., Masanés, R. M., Esteve, M., Cabot, C., Fernández-López, J. A., Remesar, X., & Alemany, M. (1999). Effect of food deprivation on rat plasma estrone fatty acid esters. Diabetes, Obesity & Metabolism, 1, 353–356.

    Article  Google Scholar 

  • Viljanen, A. P., Iozzo, P., Borra, R., Kankaanpää, M., Karmi, A., Lautamäki, R., Järvisalo, M., Parkkola, R., Rönnemaa, T., Guiducci, L., Lehtimäki, T., Raitakari, O. T., Mari, A., & Nuutila, P. (2009). Effect of weight loss on liver free fatty acid uptake and hepatic insulin resistance. The Journal of Clinical Endocrinology and Metabolism, 94, 50–55.

    Article  CAS  PubMed  Google Scholar 

  • Wada, T., Ihunnah, C. A., Gao, J., Chai, X., Zeng, S., Philips, B. J., Rubin, J. P., Marra, K. G., & Xie, W. (2011). Estrogen sulfotransferase inhibits adipocyte differentiation. Molecular Endocrinology, 25, 1612–1623.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang, H., & Ye, J. (2015). Regulation of energy balance by inflammation: Common theme in physiology and pathology. Reviews in Endocrine & Metabolic Disorders, 16, 47–54.

    Article  CAS  Google Scholar 

  • Wang, F., Vihma, V., Soronen, J., Turpeinen, U., Hämäläinen, E., Savolainen-Peltonen, H., Mikkola, T. S., Naukkarinen, J., Pietiläinen, K. H., Jauhiainen, M., Yki-Järvinen, H., & Tikkanen, M. J. (2013). 17β-Estradiol and estradiol fatty acyl esters and estrogen-converting enzyme expression in adipose tissue in obese men and women. The Journal of Clinical Endocrinology and Metabolism, 98, 4923–4931.

    Article  CAS  PubMed  Google Scholar 

  • Weisberg, S. P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R. L., & Ferrante, A. W. (2003). Obesity is associated with macrophage accumulation in adipose tissue. The Journal of Clinical Investigation, 112, 1796–1808.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wiehle, R., Cunningham, G. R., Pitteloud, N., Wike, J., Hsu, K., Fontenot, G. K., Rosner, M., Dwyer, A., & Podolski, J. (2013). Testosterone restoration by enclomiphene citrate in men with secondary hypogonadism: Pharmacodynamics and pharmacokinetics. BJU international, 112(8), 1188–1200.

    Article  CAS  PubMed Central  Google Scholar 

  • Wiehle, R. D., Fontenot, G. K., Wike, J., Hsu, K., Nydell, J., Lipshultz, L., & Group Z-CS. (2014). Enclomiphene citrate stimulates testosterone production while preventing oligospermia: A randomized phase II clinical trial comparing topical testosterone. Fertility and Sterility, 102, 720–727.

    Article  CAS  PubMed  Google Scholar 

  • Wing, R. R., & Group LAR. (2010). Long-term effects of a lifestyle intervention on weight and cardiovascular risk factors in individuals with type 2 diabetes mellitus: Four-year results of the Look AHEAD trial. Archives of Internal Medicine, 170, 1566–1575.

    CAS  PubMed  Google Scholar 

  • Xu, H., Barnes, G. T., Yang, Q., Tan, G., Yang, D., Chou, C. J., Sole, J., Nichols, A., Ross, J. S., Tartaglia, L. A., & Chen, H. (2003). Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. The Journal of Clinical Investigation, 112, 1821–1830.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu, Y., Nedungadi, T. P., Zhu, L., Sobhani, N., Irani, B. G., Davis, K. E., Zhang, X., Zou, F., Gent, L. M., Hahner, L. D., Khan, S. A., Elias, C. F., Elmquist, J. K., & Clegg, D. J. (2011). Distinct hypothalamic neurons mediate estrogenic effects on energy homeostasis and reproduction. Cell Metabolism, 14, 453–465.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ye, J., & McGuinness, O. P. (2013). Inflammation during obesity is not all bad: Evidence from animal and human studies. American Journal of Physiology Endocrinology and Metabolism, 304(5), E466–E477.

    Google Scholar 

  • Zitzmann, M., Rohayem, J., Raidt, J., Kliesch, S., Kumar, N., Sitruk-Ware, R., & Nieschlag, E. (2017). Impact of various progestins with or without transdermal testosterone on gonadotropin levels for non-invasive hormonal male contraception: A randomized clinical trial. Andrology, 5(3), 516–526.

    Article  CAS  PubMed  Google Scholar 

  • Zumoff, B., Miller, L. K., & Strain, G. W. (2003). Reversal of the hypogonadotropic hypogonadism of obese men by administration of the aromatase inhibitor testolactone. Metabolism, 52, 1126–1128.

    Article  CAS  PubMed  Google Scholar 

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    Katya B. Rubinow

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Rubinow, K.B. (2017). Estrogens and Body Weight Regulation in Men. In: Mauvais-Jarvis, F. (eds) Sex and Gender Factors Affecting Metabolic Homeostasis, Diabetes and Obesity. Advances in Experimental Medicine and Biology, vol 1043. Springer, Cham. https://doi.org/10.1007/978-3-319-70178-3_14

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