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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 ? (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.

SUBMITTER: Colleluori G

PROVIDER: S-EPMC6164305 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Adipocytes <i>ESR1</i> Expression, Body Fat and Response to Testosterone Therapy in Hypogonadal Men Vary According to Estradiol Levels.

Colleluori Georgia G Aguirre Lina E LE Qualls Clifford C Chen Rui R Napoli Nicola N Villareal Dennis T DT Armamento-Villareal Reina R

Nutrients 20180904 9

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 (<i>ESR1)</i> expression in subcutaneous adipose tissue; (3) changes in body fat after 6 months (M) of T therapy in HG men.<h4>Hypotheses</h4>(1) existence of a range of circulating E2 associated wit ...[more]

PMID: 30181488

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Project description:ObjectiveTo assess the relative effects of individual testosterone products among hypogonadal men.DesignSystematic review and network meta-analysis.MethodsWe searched MEDLINE, Embase, Cochrane CENTRAL, and grey literature (25 May 2017) for randomised-controlled trials (RCTs) and non-randomised studies (NRS) that involved hypogonadal men given testosterone replacement therapy (TRT) for ≥3 months. Comparators were placebo, another TRT, or the same product at a different dose. Outcomes were quality of life, depression, libido, erectile function, activities of daily living and testosterone levels, as well as cardiovascular death, myocardial infarction, stroke, prostate cancer, heart disease, diabetes, serious adverse events, withdrawals due to adverse events and erythrocytosis. RCT data were pooled via meta-analysis and network meta-analysis. Risk of bias was assessed using Cochrane's risk of bias tool (RCTs) andScottish Intercollegiate Guidelines Network (SIGN)50 (NRS).ResultsEighty-seven RCTs and 51 NRS were included. Most were at high or unclear risk of bias, with short treatment duration and follow-up. When compared as a class against placebo, TRT improved quality of life (standardised mean difference (SMD) -0.26, 95% CI -0.41 to -0.11), libido (SMD 0.33, 95% CI 0.16 to 0.50), depression (SMD -0.23, 95% CI -0.44 to -0.01) and erectile function (SMD 0.25, 95% CI 0.10 to 0.41). Most individual TRTs were significantly better than placebo at improving libido (6/10). Only one TRT was better than placebo at improving quality of life, and no individual TRTs improved depression or erectile function. There was no increased risk of adverse events, with the exception of withdrawals due to adverse events with the use of some TRTs.ConclusionDespite a class effect of improving quality of life, depression, erectile function and libido, major improvements were not observed with the use of any individual product. We observed no statistically significant increase in the risk of adverse events; however, longer-term high-quality trials are needed to fully assess the risk of harm.Prospero registration numberCRD42014009963.

Project description:BackgroundA novel formulation of oral testosterone undecanoate (TU) was studied in a long- and short-term phase III trial to evaluate safety and efficacy.MethodsHypogonadal men (age 18-65 years; two morning serum testosterone (T) <300 ng/dl with signs/symptoms) were recruited into a 365 day (trial I) or 105 day (trial II), randomized, multicenter trial. Patients were randomized 1:1 to oral TU (n = 161) or T-gel (n = 160) in trial I, and 3:1 to oral TU, twice daily (BID) JATENZO® (n = 166) or a topical T product [Axiron® (n = 56)] in trial II. Dose adjustments were based on average T concentrations (Cavg). Efficacy was assessed based on T levels, body composition and bone density. Safety was assessed by standard clinical measures.ResultsOral TU efficacy (% of patients with eugonadal T Cavg) was 84% (serum Cavg = 628 ± 343 ng/dl) and 87% (serum T equivalent Cavg ≈ 489 ± 155 ng/dl) in trials I and II, respectively. Oral TU significantly (p <0.0001) improved all Psychosexual Daily Questionnaire parameters in trials I and II. In trial I, lean mass increased 3.2 ± 2.7 kg and fat decreased by 2.4 ± 3.6 kg (both p <0.0001) and bone density improved in hip (+0.012 ± 0.0225 g/cm2) and spine (+0.018 ± 0.0422 g/cm2) after 365 days (both p <0.0001). Oral TU-associated adverse effects were consistent with other T-replacement therapies but oral TU patients experienced a greater number of mild gastrointestinal adverse effects. Oral TU subjects in both studies exhibited an increase in mean systolic blood pressure of about 3-5 mmHg. Oral TU was not associated with liver toxicity nor did it cause an elevation in high-sensitivity C-reactive protein or lipoprotein-associated phospholipase A2 (cardiovascular safety biomarkers) after 365 days of therapy.ConclusionA new oral TU formulation was safe and effective and represents a significant therapeutic advance for the treatment of appropriate hypogonadal men.

Dataset Information

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

Publications

Adipocytes <i>ESR1</i> Expression, Body Fat and Response to Testosterone Therapy in Hypogonadal Men Vary According to Estradiol Levels.

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