Baseline Testosterone Predicts Body Composition and Metabolic Response to Testosterone Therapy

Fnu Deepika, Elliot Ballato, Georgia Colleluori, Lina Aguirre, Rui Chen, Clifford Qualls, Dennis T Villareal, Reina Armamento-Villareal, Fnu Deepika, Elliot Ballato, Georgia Colleluori, Lina Aguirre, Rui Chen, Clifford Qualls, Dennis T Villareal, Reina Armamento-Villareal

Abstract

Context: Male hypogonadism adversely affects body composition, bone mineral density (BMD), and metabolic health. A previous report showed that pre-treatment testosterone (T) levels of <200 ng/dl is associated with greater improvement in spine BMD with T therapy. However, to date, there is no study that investigates whether baseline T levels also influence body composition and metabolic response to T therapy.

Objective: The aim of this study is to determine if there are differences in the changes in body composition, metabolic profile, and bone turnover markers, in addition to BMD, in response to T therapy in men with a baseline T level of <264 ng/dl compared to those with levels ≥264 ng/dl.

Methods: This is a secondary analysis of a single-arm, open-label clinical trial (NCT01378299) on pharmacogenetics of response to T therapy conducted between 2011 and 2016 involving 105 men (40-74 years old), with average morning T < 300 ng/dl, given intramuscular T cypionate 200 mg every 2 weeks for 18 months. Subjects were divided into those with baseline T levels of <264 ng/dl (N = 43) and those with ≥264 ng/dl (N = 57). T and estradiol (E2) were measured by liquid chromatography/mass spectrometry; serum bone turnover markers (C-telopeptide [CTX], osteocalcin, and sclerostin), adiponectin, and leptin were measured by enzyme-linked immunosorbent assay; glycated hemoglobin (HbA1c) was measured by high-performance liquid chromatography; and areal BMD and body composition was measured by dual-energy x-ray absorptiometry (DXA).

Results: Men with T < 264 ng/dl showed greater increases in total fat-free mass (FFM) at 18 months compared to those with T ≥ 264 ng/dl (4.2 ± 4.1 vs. 2.7 ± 3.8%; p = 0.047) and unadjusted appendicular FFM at 6 and 18 months (8.7 ± 11.5 vs. 4.4 ± 4.3%, 7.3 ± 11.6 vs. 2.4 ± 6.8%; p = 0.033 and p = 0.043, respectively). Men with T ≥ 264 ng/dl showed significant decreases in HbA1c at 12 months (-3.1 ± 9.2 vs. 3.2 ± 13.9%; p = 0.005), fasting glucose at 18 months (-4.2 ± 31.9 vs. 13.0 ± 57.3%; p = 0.040), LDL at 6 months (-6.4 ± 27.5 vs. 12.8 ± 44.1%; p = 0.034), and leptin at 18 months (-40.2 ± 35.1 vs. -27.6 ± 31.0%; p = 0.034) compared to those with T < 264 ng/dl. No significant differences in BMD and bone turnover markers were observed.

Conclusion: T therapy results in improvement in body composition irrespective of baseline T levels but T < 264 ng/dl is associated with greater improvement in FFM, whereas a T level of ≥264 ng/dl favors improvement in metabolic profile.

Keywords: HbA1c; body composition; bone turn over markers (BTM); hypogonadism; testosterone.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Deepika, Ballato, Colleluori, Aguirre, Chen, Qualls, Villareal and Armamento-Villareal.

Figures

Figure 1
Figure 1
Changes (%) in total and appendicular fat free mass with testosterone (T) therapy according to baseline testosterone level. T (A) Total FFM increased in both groups at 6, 12 and 18 months, but the increase at 18 months was greater for those with T < 264 ng/dL compared to those with T ≥264 ng/dL (adjusted p = 0.047). (B) Appendicular FFM increased uniformly in both groups at 6, 12 and 18 months. However, the increase was greater in group with T < 264 ng/dL at 6 months (unadjusted p = 0.033 and adjusted p = 0.034) and 18 months (unadjusted p = 0.043) compared to those with T ≥264 ng/dL.
Figure 2
Figure 2
Changes (%) in glycated haemoglobin (HbA1c), leptin and adiponectin with testosterone (T) therapy according to baseline testosterone level. T (A) Among men with T <264 ng/dL, HbA1c shows a non-significant trend towards increase from baseline value at 6, 12 and 18 months, whereas men with T ≥264 ng/dL show a significant reduction in HbA1c at 12 months (Unadjusted p = 0.030 and adjusted p = 0.005) compared to those with < 264 ng/dL. However this significance is lost at 18 months in those T ≥264 ng/dL. (B) In both groups leptin levels decline from baseline at 6 months and appear to stabilize at 12 months, but at 18 months there is a greater decline in those with T ≥264 ng/dL compared to <264 ng/dL (p = 0.034). (C) Adiponectin levels shows an interesting trend, men in group with T < 264 ng/dL show an initial decline followed by a slight increase and a large decline at 18 months, whereas those with T ≥264 ng/dL show an initial increase in adiponectin followed by a steep decline from 12 to 18 months time point. However, no significant between-groups were seen.

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