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

Abstract

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.

Keywords

• oestrogen receptor α
• testosterone
• estradiol
• fat mass
• obesity
• hypogonadism