Effects of short-term sex steroid suppression on dietary fat storage patterns in healthy males

Abstract

Hypogonadism in males is associated with increased body fat and altered postprandial metabolism, but mechanisms remain poorly understood. Using a cross-over study design, we investigated the effects of short-term sex hormone suppression with or without testosterone add-back on postprandial metabolism and the fate of dietary fat. Eleven healthy males (age: 29 ± 4.5 year; BMI: 26.3 ± 2.1 kg/m² ) completed two 7-day study phases during which hormone levels were altered pharmacologically to produce a low sex hormone condition (gonadotropin releasing hormone antagonist, aromatase inhibitor, and placebo gel) or a testosterone add-back condition (testosterone gel). Following 7 days of therapy, subjects were administered an inpatient test meal containing 50 μCi of [1-¹⁴ C] oleic acid. Plasma samples were collected hourly for 5 h to assess postprandial responses. Energy metabolism (indirect calorimetry) and dietary fat oxidation (¹⁴ CO₂ in breath) were assessed at 1, 3, 5, 13.5, and 24 h following the test meal. Abdominal and femoral adipose biopsies were taken 24 h after the test meal to determine uptake of the labeled lipid. Postprandial glucose, insulin, free-fatty acid, and triglyceride responses were not different between conditions (P > 0.05). Whole-body energy metabolism was also not different between conditions at any time point (P > 0.05). Dietary fat oxidation trended lower (P = 0.12) and the relative uptake of ¹⁴ C labeled lipid into femoral adipose tissue was greater (P = 0.03) in the low hormone condition. Short-term hormone suppression did not affect energy expenditure or postprandial metabolism, but contributed to greater relative storage of dietary fat in the femoral depot. ClinicalTrials.gov Identifier: NCT03289559.

Keywords: Energy metabolism; hypogonadism; lipid metabolism; postprandial metabolism; testosterone.

Figure 1

Study design.

Figure 2

Glucose (A), insulin (B), FFA (C), and TG (D) responses measured over 5 h (300 min) following administration of the test meal at t = 0 min under conditions of sex hormone suppression (GnRH_ANT  + AI + P) and testosterone add‐back (GnRH_ANT  + AI + T). Values are mean ± SEM.

Figure 3

Resting energy expenditure (A), respiratory quotient (B), whole body fat oxidation (C), and cumulative dietary fat oxidation (D) responses measured for 24 h following administration of a test meal at t = 0 min under conditions of sex hormone suppression (GnRH_ANT  + AI + P) and testosterone add‐back (GnRH_ANT  + AI + T). Values are means ± SEM. REE, resting energy expenditure; RQ, respiratory exchange ratio, FatOx, whole body fat oxidation.

Figure 4

Relative 24‐h dietary fat uptake into abdominal and femoral lipid depots following short‐term sex hormone suppression (GnRH_ANT  + AI + P) and testosterone add‐back (GnRH_ANT  + AI + T). Values are means ± SEM.