Cardiometabolic risks during anabolic hormone supplementation in older men§

Authors


  • Funding agencies: Primary support for HORMA trial was provided from R01 AG18169 with secondary support from NCRR GCRC M0I RR00043 at USC, the U.S. Department of Agriculture (USDA) ARS Cooperative Agreement 58-1950-9-001, the NCRR GCRC grant M01 RR000054 at Tufts University, the Mass Spectrometry Research Resource at Washington University (RR000954, DK020579, and DK056341), and U01AG14369 and 1R01DK70534 at Boston Medical Center, Boston University of Medicine.

  • Disclosures:Sponsors' Role: The primary funding source was the National Institute of Aging. National Center for Research Resources and United States Department of Agriculture provided funding for the General Clinical Research Centers and Tufts University Metabolic Research Unit, respectively. Study therapies were provided by Solvay Pharmaceuticals Inc, Genentech Inc, and Tap Pharmaceutical Products Inc; industry sponsors provided no monetary support and no input for the design, methods, subject recruitment, data collection or analysis, and did not review this manuscript. FRS, EFB, and SB have received grant support from Solvay Pharmaceuticals.

  • §

    Author Contributions:Study Concept and Design: FRS (PI), SB, RR, KY, and SA (lead statistician) were responsible for the hypotheses, specific aims, and study design. Data Acquisition: EFB, KY, CC-S, ETS, RR, and FRS were responsible for data acquisition. Data Quality and Analysis: SA and FRS created the manual of operations and procedures, case report forms, an electronic data base for web-based data entry, and the manual and electronic screening of data for outliers, quality control, and audits of all data with verification from source documents, and statistical analyses. C-PC assisted with the pathway analysis. Manuscript Preparation: All authors reviewed the data base, analyses and their interpretation, and then reviewed and contributed to the writing of the manuscript.

  • Scientific Meeting Presentation: Paper was presented in part as a poster at Endo Soc 2011 meeting: He J, Bhasin S, Binder EF, Castaneda-Sceppa C, Yarasheski K, Schroeder ET, Roubenoff R, Chou H-P, Azen SP, Sattler FR. Effects of Testosterone and rhGH on Metabolic Syndrome Components in Older Men: the HORMA Study, Abstract P3-208, Endo 2011, June 4-7, 2011, Boston, MA.

Abstract

Objective:

To determine the cardiometabolic risks of testosterone and growth hormone (GH) replacement therapy to youthful levels during aging.

Design and Methods:

A double-masked, partially placebo controlled study in 112 men 65-90 years-old was conducted. Transdermal testosterone (5 g vs. 10 g/day) using a Leydig Cell Clamp and subcutaneous recombinant GH (rhGH) (0 vs. 3 vs. 5 μg/kg/day) were administered for 16-weeks. Measurements included testosterone and IGF-1 levels, body composition by DEXA, and cardiometabolic risk factors (upper body fat, blood pressure, insulin sensitivity, fasting triglycerides, HDL-cholesterol, and serum adiponectin) at baseline and after 16 weeks of treatment.

Results:

Some cardiometabolic factors improved (total and trunk fat, triglycerides, HDL-cholesterol) and others worsened (systolic blood pressure, insulin sensitivity index [QUICKI], adiponectin). Cardiometabolic risk composite scores (CRCSs) improved (−0.69 ± 1.55, P < 0.001). In multivariate analyses, QUICKI, triglycerides, and HDL-cholesterol contributed 33%, 16%, and 14% of the variance in CRCS, respectively. Pathway analyses indicated that changes in fat and lean mass were related to individual cardiometabolic variables and CRCS in a complex manner. Changes in BMI, reflecting composite effects of changes in fat and lean mass, were more robustly associated with cardiometabolic risks than changes in fat mass or LBM individually.

Conclusions:

Testosterone and rhGH administration was associated with diverse changes in individual cardiometabolic risk factors, but in aggregate appeared not to worsen cardiometabolic risk in healthy older men after 4-months. The long-term effects of these and similar anabolic therapies on cardiovascular events should be investigated in populations with greater functional limitations along with important health disabilities including upper body obesity and other cardiometabolic risks.

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