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Feedback on LH in Testosterone-Clamped Men Depends on the Mode of Testosterone Administration and Body Composition.

ABSTRACT: Context:Quantitative studies of the short-term feedback of testosterone (T) on luteinizing hormone (LH) secretion in healthy men are relatively rare. Such studies require the shutting down of endogenous T secretion and the imposition of experimentally controlled IV T addback. Objective:To evaluate whether pulsatile and continuous T delivery confers equivalent negative feedback on LH secretion. Design:This was a placebo-controlled, blinded, and prospectively randomized crossover study comprising 16 healthy men [age range 23 to 54 years and a body mass index (BMI) between 22.3 and 34.2 kg/m2]. Subjects received ketoconazole to block endogenous T secretion and received continuous or 90-minute pulses of IV T addback. Setting:The study was performed in a Clinical Translational Research Unit. Interventions:Subjects underwent 14 hours of blood sampling at 10-minute intervals, with a bolus IV injection of 33 ng/kg gonadotropin-releasing hormone (GnRH). Main Outcome Measures:Log-transformed LH and T concentration ratios before and after GnRH administration. Results:Despite higher T concentrations during pulsatile T feedback, LH concentrations and secretion rates, whether driven by endogenous or exogenous GnRH, were similar to those during continuous T infusion, indicating diminished pulsatile T feedback. Feedback correlated negatively with BMI. Under controlled T feedback, basal but not pulsatile LH secretion correlated negatively with CT-estimated visceral fat mass. Conclusion:Feedback by pulsatile T delivery has diminished inhibitory strength compared with continuous infusion. Feedback is negatively correlated with BMI.

SUBMITTER: Roelfsema F

PROVIDER: S-EPMC6320245 | biostudies-other | 2019 Jan

REPOSITORIES: biostudies-other

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Feedback on LH in Testosterone-Clamped Men Depends on the Mode of Testosterone Administration and Body Composition.

Roelfsema Ferdinand F Yang Rebecca J RJ Liu Peter Y PY Takahashi Paul Y PY Veldhuis Johannes D JD

Journal of the Endocrine Society 20181123 1

<h4>Context</h4>Quantitative studies of the short-term feedback of testosterone (T) on luteinizing hormone (LH) secretion in healthy men are relatively rare. Such studies require the shutting down of endogenous T secretion and the imposition of experimentally controlled IV T addback.<h4>Objective</h4>To evaluate whether pulsatile and continuous T delivery confers equivalent negative feedback on LH secretion.<h4>Design</h4>This was a placebo-controlled, blinded, and prospectively randomized cross ...[more]

PMID: 30623162

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Project description:ContextMale 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.ObjectiveThe 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.MethodsThis 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).ResultsMen 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.ConclusionT 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.

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Feedback on LH in Testosterone-Clamped Men Depends on the Mode of Testosterone Administration and Body Composition.

Publications

Feedback on LH in Testosterone-Clamped Men Depends on the Mode of Testosterone Administration and Body Composition.

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