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Adipocytes ESR1 Expression, Body Fat and Response to Testosterone Therapy in Hypogonadal Men Vary According to Estradiol Levels

Department of Medicine, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
Center for Translational Research on Inflammatory Diseases, Michael E. DeBakey VA Medical Center, 2002 Holcombe Blvd, Houston, TX 77030, USA
Department of Internal Medicine, University of New Mexico, Albuquerque, NM 87131, USA
New Mexico VA Health Care System, 1501 San Pedro SE, Albuquerque, NM 87108, USA
Division of Mathematics and Statistics, University of New Mexico School of Medicine, Albuquerque, NM 87108, USA
Department of Endocrinology and Metabolism, University Campus Biomedico of Rome, Via Alvaro del Portillo 21040, 00128 Rome, Italy
Author to whom correspondence should be addressed.
Nutrients 2018, 10(9), 1226;
Received: 30 July 2018 / Revised: 27 August 2018 / Accepted: 31 August 2018 / Published: 4 September 2018
(This article belongs to the Special Issue Steroid Hormones and Human Health)
PDF [1924 KB, uploaded 4 September 2018]


Estradiol (E2), mainly produced from Testosterone (T) in men, promotes visceral lipolysis. However, high visceral fat and hyperestrogenemia are features of obese hypogonadal (HG) men. Our study objectives are to evaluate relationships between circulating E2 and: (1) fat mass; (2) Estrogen Receptor α (ESR1) expression in subcutaneous adipose tissue; (3) changes in body fat after 6 months (M) of T therapy in HG men. Hypotheses: (1) existence of a range of circulating E2 associated with better body composition; (2) serum E2 determines tissue E2 sensitivity which affects response to T therapy. Men 40–74 years old, T < 300 (ng/dL), given T-cypionate for 6 months. Subjects were divided into 4-E2 categories: (1) <10.0; (2) 10.0–15.9; (3) 16.0–19.9; (4) ≥20.0 (pg/mL). Body composition (DXA), fat biopsies (liposuction), gene expression (qPCR), serum E2 and T (LC/MS), at baseline and 6 months. We enrolled 105 men; 90 completed the study. Group 2 had lower total and truncal fat mass (p < 0.01) but higher % lean mass (p < 0.001). ESR1 mRNA was the highest in group 1 (p = 0.01). At 6 months, group 1 had higher reduction in total (p = 0.03) and truncal (p = 0.01) fat. In conclusion, serum E2 = 10–15.9 (pg/mL) is associated with the best body composition profile in HG men; however, those with E2 < 10 (pg/mL) had the best response (greater fat loss) to T replacement possibly because of greater E2 sensitivity. View Full-Text
Keywords: oestrogen receptor α; testosterone; estradiol; fat mass; obesity; hypogonadism oestrogen receptor α; testosterone; estradiol; fat mass; obesity; hypogonadism

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Colleluori, G.; Aguirre, L.E.; Qualls, C.; Chen, R.; Napoli, N.; Villareal, D.T.; Armamento-Villareal, R. Adipocytes ESR1 Expression, Body Fat and Response to Testosterone Therapy in Hypogonadal Men Vary According to Estradiol Levels. Nutrients 2018, 10, 1226.

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