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BRIEF REPORT |
Division of Endocrinology, Endocrine Research Unit (A.I., B.A.I., M.L.B., K.R.S., K.S.N.) and Cardiovascular Laboratory Medicine (J.P.M.), Mayo Clinic College of Medicine, Rochester, Minnesota 55905
Address all correspondence and requests for reprints to: Dr. K. Sreekumaran Nair, Mayo Clinic, 200 First Street SW, Joseph 5-194, Rochester, Minnesota 55905. E-mail: nair.sree{at}mayo.edu.
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Abstract |
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Objective: The aim of this study was to determine whether 12 wk of DHEA supplementation (50 mg/d) in postmenopausal women enhances exercise-related changes in body composition, physical performance, and cardiometabolic risk.
Design and Setting: This study was a 12-wk randomized double-blind, placebo-controlled trial and took place at the Mayo Clinic General Clinical Research Center (Rochester, MN).
Participants: Thirty-one sedentary, postmenopausal, Caucasian women (mean ± SEM age 64.6 ± 1.0 yr) completed the study.
Intervention: Participants were randomized to one of two 12-wk interventions: 1) exercise training plus 50 mg/d of DHEA (n = 17), or 2) exercise training plus placebo (n = 14). The exercise intervention consisted of both endurance (4 d/wk) and resistance (3 d/wk) exercise components.
Main Outcome Measures: The main outcomes were measures of body composition, physical performance, and measures of cardiometabolic risk.
Results: DHEA treatment with exercise resulted in increases in circulating sulfated DHEA (650%), total testosterone (100%), estradiol (165%), estrone (85%), and IGF-I (30%) (all P 
0.05, for all within and between treatment comparisons). Although exercise training alone significantly improved physical performance, body composition, and insulin sensitivity, administration of DHEA provided no additional benefits.
Conclusions: Twelve weeks of combined endurance and resistance training significantly improved body composition, physical performance, insulin sensitivity, and low-density lipoprotein cholesterol particle number and size, whereas DHEA had no additional benefits.
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Introduction |
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Exercise training beneficially affects many of the age-related changes in body composition, physical performance, and cardiometabolic risk (5). However, exercise-induced improvements in body composition, in particular skeletal muscle mass, are typically modest in older adults, possibly due to reduced circulating anabolic hormones, including DHEA. DHEA supplementation has been reported to potentiate the effects of heavy resistance training on muscle mass and performance in the elderly (6). Here, we examined whether 12 wk of physiological DHEA replacement in postmenopausal women would potentiate the effects of combined endurance and resistance training on improvements in body composition, physical performance, and cardiometabolic risk.
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Subjects and Methods |
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The Institutional Review Board of the Mayo Foundation approved the present study, and participants provided informed written consent before participating in this 12-wk randomized, double-blind, placebo-controlled trial. Thirty-one sedentary, postmenopausal women (54–72 yr) completed one of two 12-wk treatment conditions: 1) exercise training plus 50 mg/d DHEA (n = 17); or 2) exercise training plus placebo (n = 14).
Participants underwent an initial screening that included a medical history, physical exam, electrocardiogram, treadmill test, and biochemical tests of renal, hepatic, hematologic, and metabolic function (7). Participants with a plasma concentration of DHEA-S greater than 110 µg/ml or with evidence of diseases such as diabetes, cardiovascular disease, or thyroid dysfunction were excluded due to the potential effects these diseases may have on the outcome measures. Participants using psychotropic drugs, progesterone, testosterone, corticosteroids, or DHEA within the preceding 6 months were excluded.
Participants completed one outpatient and one inpatient visits in the Clinical Research Unit (CRU), Mayo Clinic Clinical and Translational Science Activities before and after the 12-wk intervention as described below.
Outpatient visits
At baseline and 1–2 d after training, participants were assessed in the CRU for peak oxygen uptake (VO2Peak), one-repetition maximum (1RM) strength, and body composition by dual-energy x-ray absorptiometry (Lunar DPX-L; Lunar, Madison, WI) and single-slice computed tomography as described previously (7).
Inpatient visits
Participants were admitted to the CRU for testing at baseline and 4 d after training after the last training session. A weight-maintaining diet (55, 30, and 15% for carbohydrate, fat, and protein, respectively) was provided for the 3 d preceding the inpatient visit and were asked to refrain from vigorous physical activity. Participants were provided dinner at 1800 h and a standardized snack (5.5 kcal/kg) at 2200 h and then remained fasting until the completion of the inpatient visit. At 0700 h, a fasting arterialized venous blood sample (8) was obtained for measurement of hormones and metabolites. A hyperinsulinemic-euglycemic clamp was then initiated with a 1.5 mU/[kg fat-free mass (FFM) · min] infusion of insulin (9) Plasma glucose was maintained between 85 and 95 mg/dl with a variable infusion of 40% dextrose. An amino acid solution (10% Travasol) was infused at a constant rate equivalent to 0.9 µmol/ leucine/(kg FFM · min) to prevent hypoaminoacidemia (10).
DHEA therapy
Participants received either 50 mg/d DHEA or placebo (7). The dose of DHEA was chosen to restore circulating DHEA concentrations of older women to a level reported in the second decade of life (11).
Exercise training
Endurance training (cycle ergometery) was performed 4 d/wk. During the first week of training, participants exercised for 20 min/session at an intensity eliciting 70% of their maximal heart rate. The length of each session increased by 5 min each week until reaching a total of 40 min in wk 5. The intensity of each session was increased to 75% of maximal heart rate during wk 5–8. During the last 4 wk of the program, participants exercised at 80% of their maximal heart rate for 40 min/session.
Resistance training was performed 3 d/wk. Eight exercises were selected to target both upper and lower body muscle groups. During the first week of training, participants performed one set of 8–12 repetitions at approximately 50–60% of their 1RM for each exercise. During the second week, two sets of 8–12 repetitions at the same load were performed. From the third week until the end of the training period, the resistance load was increased if 12 or more repetitions per set could be performed repeatedly after two sessions. From wk 5 to 12, subjects performed three sets of each leg exercise.
Hormone and metabolite assays
DHEA-S, total testosterone, estradiol, and estrone were measured by competitive chemiluminescence immunoassays (Diagnostic Products, Los Angeles, CA), plasma insulin by a two-site immunoenzymatic assay (Access; Beckman, Chaska, MN), and IGF-I and IGF-II by two-site immunoradiometric assays after separation from their binding proteins (Diagnostic Systems Laboratories, Webster, TX). Serum glucose concentrations were measured by a glucose oxidase method (Beckman Instruments, Portville, CA). High-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), and triglyceride concentrations were determined by standard enzymatic techniques, and nuclear magnetic resonance (NMR) spectroscopy was used to further characterize the lipid profile (12).
Power analysis
The study was powered to detect significant pretraining to posttraining changes in the primary outcome measures, which were defined as percentage body fat, FFM, VO2Peak, and muscle strength, as measured by the leg press 1RM. With 15 participants per group, two-sided, two-sample t tests had 85% power to detect differences between and within groups (DHEA vs. placebo) of 2.2% body fat, 1.5 kg FFM, 3.6 ml/(kg FFM · min) for VO2Peak and 22.0 kg for leg press 1RM.
Statistical analyses
Statistical analyses were conducted using SAS software (version 9.1; SAS, Cary, NC). Data are presented as mean ± SEM, and pretraining to posttraining percentage change data are presented as mean (Tukey’s corrected 95% confidence interval; P value). Hormones and cardiometabolic measures were log transformed to produce symmetric-shaped distributions before analysis (Table 1
). Pretraining characteristics between treatment groups were compared using two-tailed, unpaired t tests. Mixed-effects ANOVA with repeated measures was used to compare treatment effects over time (13). Tukey’s honestly significant differences criterion was used to maintain the a priori type I error rate at 0.05 accounting for multiple comparisons.
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Results |
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and 2 present the pretraining and posttraining outcome measures by condition. There were no significant pretraining differences between the two groups for any outcome measure, except for IGF-I and testosterone. Greater than 85% of the assigned exercise sessions were completed, and greater than 90% of the prescribed pills were ingested in both groups.
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)DHEA replacement significantly increased DHEA-S by approximately 650%, testosterone by approximately 100%, estradiol by approximately 165%, and estrone by approximately 85%. DHEA replacement also significantly increased IGF-I by approximately 30% as opposed to an approximate 9% reduction in IGF-I observed in the placebo group.
Body composition and physical performance (Table 2)
Exercise training plus DHEA significantly reduced percentage body fat and total fat mass but increased FFM, muscle mass, and total midthigh muscle cross-sectional area. Exercise training plus placebo reduced total abdominal fat cross-sectional area. No significant differences were observed between treatments. Furthermore, pooled analyses revealed significant exercise-induced improvements in 10 of the 11 body composition variables measured.
Exercise training significantly increased VO2Peak, peak power output, and leg press for both groups, although 1RM for chest press did not reach statistical significance (P = 0.098 and P = 0.050 for placebo and DHEA, respectively). No significant differences were observed between treatments.
Cardiometabolic measures (Table 1)
Exercise training significantly increased the glucose infusion rate required to maintain euglycemia during similar rates of insulin infusion, indicating enhanced insulin action, with similar results observed in both treatment groups. Fasting glucose and insulin concentrations were not altered in either treatment condition. The HDL, LDL, and triglycerides concentrations remained unchanged using standard lipid profiling. NMR spectroscopy revealed that exercise training reduced the total number of LDL particles (P = 0.011 for pooled analysis), with a concomitant reduction in the number of small, dense LDL particles (P = 0.011 for pooled analysis).
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Discussion |
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650%), testosterone (100%), estradiol (165%), estrone (85%), and IGF-I (30%), consistent with physiological DHEA replacement (11, 14), DHEA repletion did not potentiate the effects of 12 wk of combined exercise training on body composition, physical performance, or cardiometabolic risk in healthy postmenopausal women. A recent study (6) reported that DHEA enhanced muscle mass and strength adaptations induced after 16 wk of heavy resistance training in the elderly people, but our data could not confirm this effect on 3 months of combined resistance and endurance training program. Here, we selected a program of combined training based on current health recommendations for adults (15). We also limited our study to postmenopausal women, because women are more likely than men to become frail during old age (16).
Exercise training induced favorable changes in body composition, which confirms previous findings that exercise training effectively counteracts many of the deleterious effects of aging on body composition, whereas DHEA provided no additional benefit. Similarly, we recently reported that 2 yr of DHEA supplementation alone had no physiological effect on body composition in postmenopausal women (7).
Endurance training consistently elicits improvements in insulin sensitivity and glucose tolerance (17), whereas the effect of resistance training on insulin sensitivity and glucose tolerance remains less certain (18). Previous reports indicate that DHEA replacement modestly improves insulin sensitivity in hypoadrenal women who lack endogenous DHEA production (19) and in elderly people (20). However, we recently reported that DHEA replacement for 2 yr in nonexercising elderly adults had no physiologic effect on insulin sensitivity (7). Little is known about the combined effects of exercise training and DHEA on measures of glucose metabolism. Using the euglycemic clamp, we found that exercise training alone improved insulin sensitivity, whereas DHEA provided no additional effect on insulin action.
Neither exercise training nor DHEA had an effect on the standard lipid profile. However, NMR spectroscopy revealed exercise-induced reductions in the total number of LDL particles and small, dense LDL particles, indicating that exercise training beneficially affected lipid metabolism, whereas DHEA provided no additional effect on the lipid profile.
In summary, despite significant elevations in DHEA-S, testosterone, estradiol, estrone, and IGF-I concentrations, 50 mg/d DHEA did not potentiate the effects of 12 wk of combined endurance and resistance training on body composition, physical performance, or cardiometabolic risk in healthy postmenopausal women. In contrast, the results strongly support the beneficial effects of the exercise program for improving age-related changes in body composition, physical function, and some parameters of cardiometabolic risk.
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Acknowledgments |
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Footnotes |
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Present address for K.R.S.: Department of Pediatrics/Diabetes and Endocrinology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104.
A.I., B.A.I., M.L.B., K.R.S., J.P.M., and K.S.N. have nothing to declare.
First Published Online November 20, 2007
1 A.I. and B.A.I. contributed equally to this work. 
Abbreviations: CRU, Clinical Research Unit; DHEA, dehydroepiandrosterone; DHEA-S, sulfated form of DHEA; FFM, fat-free mass; HDL, high-density lipoprotein cholesterol; LDL, low-density lipoprotein cholesterol; NMR, nuclear magnetic resonance; 1RM, one-repetition maximum; VO2peak, peak oxygen uptake.
Received May 8, 2007.
Accepted November 9, 2007.
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References |
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