Journal of Gerontology: MEDICAL SCIENCES 2003, Vol. 58A, No. 3, 266–270

Copyright 2003 by The Gerontological Society of America

Effects of Exercise Training and Hormone Replacement Therapy on Lean and Fat Mass in Postmenopausal Women Arturo Figueroa,1 Scott B. Going,2 Laura A. Milliken,3 Robert M. Blew,2 Sarah Sharp,2 Pedro J. Teixeira,2 and Timothy G. Lohman2 1

Department of Exercise Science, Syracuse University, New York. 2 Department of Physiology, The University of Arizona, Tucson. 3 Department of Human Performance and Fitness, University of Massachusetts, Boston. Background. Menopause is associated with decreases in lean mass and increases in fat mass. Serum hormone levels and hormone replacement therapy (HRT) may modify the effects of exercise training on body composition in postmenopausal women. Methods. We assessed the changes in total body and regional lean soft tissue and fat mass (using dual-energy x-ray absorptiometry) in 94 sedentary postmenopausal women, aged 40–65 years, after 12 months of resistance and weightbearing aerobic exercise training. Women currently on oral HRT (n 5 39) and not on HRT (n 5 55) were randomized within groups to exercise and no exercise, resulting in four groups: exercise 1 HRT (n 5 20), HRT (n 5 22), exercise (n 5 24), and control (n 5 28). Fasting blood samples were measured for resting serum total levels of estrone, estradiol, cortisol, androstenedione, growth hormone, and insulin-like growth factor 1 at baseline and 12 months. Results. We found significant effects of exercise on increases in total body, arm, and leg lean soft tissue mass, and decreases in leg fat mass and percentage of body fat. There were no interaction effects of exercise and HRT on the changes in muscle strength and body composition. No significant changes in total hormone levels were found after 12 months. Conclusions. Exercise training resulted in significant beneficial changes in lean soft tissue and fat mass in early postmenopausal women. These changes in body composition were neither influenced by prolonged HRT use nor accompanied by changes in total levels of the hormones determined in this study.

HETHER the decrease in lean soft mass in postW menopausal women is an effect of aging, decreased physical activity, or a result of declines in estrogens, androgens, growth hormone (GH), and insulin-like growth factor 1 (IGF-1) levels is not entirely clear. Although hormone replacement therapy (HRT), including unopposed estrogen or estrogen plus progestins, has been demonstrated to increase bone mineral density (1,2), its effectiveness for preventing or retarding fat accumulation and for maintaining or increasing lean mass is not clear (3,4). HRT increases GH and estrogen levels (5), so it may have an anabolic effect in postmenopausal women. Although it is well established that resistance and weightbearing aerobic exercise training can increase lean mass and reduce fat mass in postmenopausal women without HRT (6–8), few studies have been conducted that combine exercise and HRT (2,4,9,10). These beneficial changes in body composition may occur with no change in circulating levels of anabolic and catabolic hormones (11). However, the adaptations of hormone levels to exercise training in postmenopausal women that use HRT require further investigation. The present study was conducted to determine the effects of exercise training on lean soft tissue mass and fat mass in early postmenopausal women who did or did not use HRT. We hypothesized that exercise training would result in beneficial changes in soft tissue in both groups of women. 266

Moreover, women who used HRT and exercised were hypothesized to derive greater benefit than women who used HRT and did not exercise, as a result of an additional anabolic effect on lean mass and a reductive effect on fat mass. METHODS

Subjects Study participants were recruited through television, radio, and newspaper advertisements. Ninety-four sedentary women, aged 40–65 years, who were 3–10 years postmenopause were studied. Thirty-nine of the women were already taking oral estrogens, either unopposed (conjugated equine, n 5 10, and micronized estradiol, n 5 4) or plus progestins (conjugated equine, n 5 19, micronized estradiol, n 5 4, and estropipate, n 5 2), for 1–3.9 years. Participants were stratified by HRT status and randomized to no exercise (n 5 50) or exercise (n 5 44) conditions, giving four groups: exercise and HRT (EX/HRT; n 5 20), no exercise and HRT (NEX/HRT; n 5 22), exercise and no HRT (EX/NHRT, n 5 24), and no exercise and no HRT (NEX/NHRT; n 5 28). Participants were screened by medical history, physical examination, and a maximal graded treadmill exercise test, and they were excluded from the study if they had cardiovascular, musculoskeletal, or other conditions that contraindicated exercise or were on

EXERCISE, BODY COMPOSITION, AND HORMONES

medications that affect body composition. All subjects agreed to maintain their eating habits and initial level of physical activity over the duration of study, except for the study exercise regimen. The study was approved by the University of Arizona’s Review Board, and written informed consent was obtained from all subjects.

Muscle Strength Testing Muscle strength was assessed in all participants by using a LIDO isokinetic dynamometer, following standard procedures (Loredan Biomedical, Sacramento, CA). Peak torques at 608/s of the right knee flexion–extension (KF–KE) and elbow flexion–extension (EF–EE) were measured. After familiarization with the procedure, subjects were instructed to work as hard and as fast as possible throughout the range of motion. Subjects performed three sets of five repetitions for KE–KF and EE–EF, with a 1-minute rest period between sets. Peak torque was calculated as the mean of the peak one-repetition torque for the second and third sets. Dynamic muscle strength in exercise subjects was also evaluated with the one-repetition maximum (1-RM) method for all the exercises involved in the training protocol. The 1-RM was defined as the maximum weight that could be lifted one time by using proper technique. Exercise Training Training sessions supervised by exercise physiologists were held 3 nonconsecutive days per week for 12 months at community fitness facilities. The training program consisted of both resistance and weight-bearing exercises. The resistance exercises included leg press, squat, lateral pulldown, seated row, back extension, seated one-arm dumbbell shoulder press, and rotary torso, and they were done with machines and free weights. Subjects performed two sets at 70–80% of 1-RM with 1 minute of rest between sets. The resistance was increased on the basis of the 1-RM test assessed every 6 weeks, or sooner if more than eight repetitions per set were completed for an exercise. Weight-bearing exercise training consisted of warm up walking (5 minutes), stair stepping or climbing stairs while wearing a weighted vest (10 minutes), and horizontal walking wearing the weighted vest (10 minutes). Unweighted walking was combined with skipping, jogging, hopping, and jumping. These activities were performed at an intensity of 50–80% of maximal heart rate. The load in the weighted vest was progressively increased from ;4 to ;14 kg. The entire workout lasted 60–75 minutes per session and is described in detail by Metcalfe and colleagues (12). Body Composition Standing height was measured with a wall-mounted stadiometer. Body weight was obtained by using a beam scale (Metro Equipment Corp., Sunnyvale, CA). Waist circumference was measured at the narrowest torso circumference. The averages of two measurements, measured to the nearest tenth of a centimeter (height and waist) or kilogram (weight), were used in the analyses. Soft tissue composition was estimated from dual-energy x-ray absorptiometry (DXA) scans performed at medium speed with a Lunar DPX-L (Lunar Radiation Corp.,

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Madison,WI) densitometer with software version 1.3y. Total body scans were segmented to obtain estimates of arm, leg, and trunk lean and fat masses and fat percentage (% fat). Subjects were scanned two times within a week at each measurement interval (baseline and 12 months), and the average was used in the analyses to improve the precision of DXA measurements. The technical error, expressed as coefficient of variations, for fat and lean soft tissue mass was 3.3% and 2.2% (total body), 9.8% and 3.5% (arms), 4.7% and 2.9% (legs), and 3.6% and 2.9% (trunk), respectively.

Blood Analyses Resting venous blood samples were taken at baseline and 12 months. Blood samples were obtained between 6 AM and 9 AM after an overnight fast and 24–48 hours after the last exercise session. Blood samples were taken at the same time of day to reduce variation in hormone concentrations. Serum samples were aliquotted and stored at 280oC until assayed. Radioimmunoassays (RIAs) were used to determine total levels of estrone (double antibody), estradiol (double antibody), and androstenedione (coated tubes; Diagnostic Systems Laboratory; Webster, TX). Total GH and cortisol levels were determined by using double-antibody (Nichols Institute Diagnostics, San Juan Capistrano, CA), and coatedtubes (ICN Biomedicals, Costa Mesa, CA) RIA, respectively. Total IGF-1 levels were determined by using a coated-tube immunoradiometric assay (Diagnostic Systems). The assay sensitivities were 1.2 pg/ml, 4.7 pg/ml, 0.03 ng/ml, 0.02 ng/ml, 2.0 ng/ml, and 2.7 lg/dl for estrone, estradiol, androstenedione, GH, IGF-1, and cortisol, respectively. Baseline and 12-month samples from each subject were processed in duplicate in the same assay for each hormone. Samples from all study groups were also analyzed in the same assay. Interassay and intra-assay coefficients of variation for all assays were ,10%. Statistical Analyses Baseline differences in outcome variables between NEX and EX groups in the whole sample and within HRT groups were tested by using nonpaired t tests. Multiple linear regressions with a priori contrast statements (HRT vs NHRT, EX/HRT vs NEX/HRT, and EX/NHRT vs NEX/ NHRT groups), age, years postmenopause, and baseline values of outcomes as independent variables were used to test for significant group differences in changes from baseline to 12 months. In addition, the main effect of exercise on changes in outcomes, and the interaction, Exercise 3 HRT, was evaluated by using 2 3 2 analysis of variance (ANOVA). Pearson correlation coefficients were used to measure associations between variables of interest. A type I error of ,0.05 was chosen for establishing statistical significance. All data were analyzed by using SPSS (Version 8.5, Chicago, IL) and were reported as means 6 SEM. RESULTS Of the 94 original participants, 84 completed the study. Ten subjects (2 control and 8 exercise) were not included

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Table 1. Baseline Characteristics of the Subjects Variable

EX/HRT

NEX/HRT

EX/NHRT

NEX/NHRT

6 0.7 6 3.1 6 2.5

53.7 6 1.1 68.9 6 2.4 82.4 6 2.1

57.4 6 0.9 70.6 6 2.2 84.1 6 2.3

57.8 6 0.9 67.0 6 2.2 80.9 6 2.0

6 1.2 6 0.2 6 0.4

38.8 6 0.9 3.7 6 0.1 12.5 6 0.4

39.7 6 1.0 4.0 6 0.2 12.9 6 0.3

37.7 6 0.8 3.7 6 0.1 12.2 6 0.3

Age (y) 55.2 Body weight (kg) 70.2 Waist circumference 81.6 (cm) LSM Total body (kg) 39.8 Arm (kg) 3.9 Leg (kg) 13.0 Fat mass Total body (kg) 27.5 Arm (kg) 2.5 Leg (kg) 11.2 Trunk (kg) 12.8 Body fat (%) 38.4 Estrone (pg/mL) 128.6 Estradiol (pg/mL) 63.8 GH (ng/mL) 1.92 IGF-1 (ng/mL) 116.0 Androstenedione 1.55 (ng/mL) Cortisol (lg/dL) 24.5

6 6 6 6 6 6 6 6 6 6

2.1 26.6 0.2 2.4 0.8 10.3 1.1 13.0 1.5 37.7 21.4 151.9 9.3 59.2 0.36* 0.94 8.8 120.5 0.16 1.81

6 2.2

6 6 6 6 6 6 6 6 6 6

1.9 0.2 0.7 1.1 1.6 14.8 4.5 0.19 11.5 0.14

29.6 6 1.6

27.7 2.5 10.6 13.5 38.7 21.0 11.5 0.84 151.7 1.72

6 6 6 6 6 6 6 6 6 6

1.7 0.2 0.7 0.9 1.4 2.8 1.6 0.16 11.8 0.13

26.3 2.3 10.6 12.4 38.5 15.6 10.5 0.66 139.1 1.73

20.9 6 1.8

6 6 6 6 6 6 6 6 6 6

1.6 0.2 0.6 0.9 1.1 1.6 1.9 0.12 7.1 0.13

22.8 6 1.5

Notes: EX 5 exercise; NEX 5 no exercise; HRT 5 hormone replacement therapy; NHRT 5 no hormone replacement therapy; LSM 5 lean soft mass; GH 5 growth hormone; IGF-1 5 insulin-like growth factor 1. Values are mean 6 SEM. *Significantly different from NEX/HRT; p , .05.

in the analyses. Reasons for dropout were illness and moving away from the area. There were no exercise-related dropouts. Exercise class attendance during the study was similar (p 5 .11) for the EX/HRT (84.7 6 2.4%) and EX/NHRT (77.1 6 3.6%) groups.

Baseline Measurements There were no differences between NEX and EX groups in outcome variables, except for higher GH levels in the EX/ HRT compared with the NEX/HRT group (Table 1). Muscle Strength There were no differences in isokinetic muscle strength between NEX and EX groups at baseline. Exercise training significantly improved peak torque for KF (16%), KE (20%), EF (9%), and EE (18%). No changes were observed in the NEX group for peak torque.

In addition, no differences in 1-RMs between EX groups were found at baseline. There were similar increases ( p , .001) in 1-RM in both groups for leg press (;87%), squat (;34%), lateral pull-down (;38%), row (;20%), and military press (;34%) (Table 2).

Body Composition There were significant effects of exercise on total body (11.6%), arm (14.7%), and leg (11.0%) lean soft tissue mass, and leg fat mass (24.2%) and % body fat (22.9%) (Table 3; ANOVA). There were no significant exercise and HRT interactions for the changes in body composition. Multiple linear regressions were used to assess the effects of exercise on the changes in body composition and hormone levels within HRT and NHRT groups (Table 4). Significant increases in total body (1.6%), arm (4.4%), and leg (1.0%) lean soft tissue mass were found for EX/NHRT compared with NEX/NHRT groups. The effect of EX/ NHRT on % body fat (21.9%) was also significant (p , .05), with the greatest loss of fat mass from the trunk (p 5 .08). There was a trend for increases in arm (5.1%, p 5 .08) and leg (0.6%, p 5 .09) lean soft tissue mass and for reduction in leg fat mass (3%, p 5 .09) for EX/HRT compared with NEX/HRT groups. Hormone Levels There were no significant changes from baseline to 12 months in total levels of estrone, estradiol, GH, IGF-1, androstenedione, and cortisol. DISCUSSION This study examined changes in DXA-assessed total and regional lean soft tissue mass and fat mass as well as circulating total hormone levels after 12 months of exercise training in postmenopausal women who were or were not on HRT prior to the study. We found that exercise training significantly increased total body and regional lean soft tissue mass and decreased leg fat mass and % body fat independent of HRT use. Previous studies have demonstrated increases in lean mass in response to different modes of exercise in postmenopausal women who were not using HRT (6–9). Consistent with these reports, we observed that 12 months of combined resistance and weight-bearing aerobic exercises resulted in significant increases in total and regional lean soft tissue mass. Although our resistance training did not include upper-arm isolation exercises, the involvement

Table 2. Exercise Training and 1-RM Strength EX/HRT Exercises Leg press (kg) Squat (kg) Lat. pull-down (kg) Seated row (kg) Mil. press (kg)

Baseline 97.1 87.9 38.3 38.4 8.6

6 6 6 6 6

4.9 5.0 1.8 1.1 0.6

12 mo 182.6 111.4 52.8 46.3 12.0

6 6 6 6 6

6.9 5.8 2.0 1.5 0.5

EX/NHRT % Change 88* 27* 43* 21* 40*

Baseline 101.4 83.5 43.5 36.6 9.1

6 6 6 6 6

7.9 8.0 2.2 1.1 0.6

12 mo 187.4 116.8 55.5 43.3 11.6

6 6 6 6 6

9.8 8.4 1.6 1.2 0.5

% Change 85* 40* 33* 19* 27*

Notes: One-repetition maximum (1-RM) strength is determined at baseline and after 12 months of exercise training. Changes after this training are also shown. EX 5 exercise; HRT 5 hormone replacement therapy; NHRT 5 no hormone replacement therapy. Values are means 6 SEM. *Significant ( p , .001) change from baseline to 12 months (analysis of variance).

EXERCISE, BODY COMPOSITION, AND HORMONES

Table 3. Effects of Exercise on Body Composition Changes Variables LST mass Total body (kg) Arm (kg) Leg (kg) Fat mass Total body (kg) Arm (kg) Leg (kg) Trunk (kg) Body fat (%)

NEX Change 20.1 6 0.2 0.0 6 0.0 20.2 6 0.1 0.6 0.1 0.1 0.3 0.5

6 6 6 6 6

0.5 0.1 0.2 0.3 0.4

Table 4. Body Composition Changes in Exercisers and Nonexercisers

EX Change 0.6 6 0.2* 0.2 6 0.0* 0.1 6 0.1* 20.7 0.0 20.5 20.3 21.1

6 6 6 6 6

0.4 0.0 0.2* 0.2 0.4*

Notes: Body composition changes are from baseline to 12 months. EX 5 exercise; NEX 5 no exercise; LST 5 lean soft tissue. Values are mean 6 SEM. *Significant exercise effect, p , .05.

of the arm muscles with the chest, shoulder, and back exercises was sufficient to produce significant gains in the arms. Our results are similar to the findings of previous studies in men and women that have shown that arm muscles respond considerably to the overload imposed by resistance exercise (13,14). In contrast to the results in the arms, we observed small gains in leg lean mass, despite significant strength gains. Previous studies have reported increases in 1-RM of various leg exercises ranging from 28% to 148% after 20 weeks to 18 months of resistance exercise in premenopausal and postmenopausal women (6,15,16). Similar to our study, a poor correlation between strength gain and lean mass has been demonstrated in women (14,17). Thus, the larger increases in strength with little gain in lean mass indicate that this effect is primarily due to neural adaptations rather than muscle hypertrophy (11). In addition, DXA-assessed lean soft tissue mass includes the whole leg, and it is possible that the minor response observed in the legs may be attributed to the inclusion of only two exercises for the thigh musculature and the exclusion of the calf muscles in the exercise program. It is likely that a combination of these factors may explain the small but significant increase in leg lean mass observed in these women. In the present study, exercise training resulted in a significant decrease in whole body % fat with significant reductions in leg fat mass. Significant reductions in fat mass from the trunk and legs in response to resistance (8) and weight-bearing aerobic exercise training (2,9) in postmenopausal women with and without HRT have been reported in previous studies. A greater lipolytic activity in abdominal compared with gluteal adipose tissue during exercise (18) likely explains the preferential decrease from the trunk in response to exercise. However, the decrease of trunk fat mass (0.3 kg) in all the exercisers in our study was not significant. In contrast, the largest decrease in fat mass in our exercise group was from the legs, a result that may seem incongruent with previous exercise studies that found a preferential reduction from the abdomen in older postmenopausal women (2,9). The study population included both HRT users and nonusers because a secondary aim of the study was to examine the influence of HRT on the effects of exercise in

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Variable LST mass Total body (kg) Arm (kg) Leg (kg) Fat mass Total body (kg ) Arm (kg) Leg (kg) Trunk (kg) Body fat (%)

EX/HRT (n 5 16)

NEX/HRT (n 5 22)

EX/NHRT (n 5 20)

NEX/NHRT (n 5 26)

0.6 6 0.3

0.2 6 0.4

0.7 6 0.2*

20.4 6 0.2

0.2 6 0.1** 0.1 6 0.1 0.1 6 0.1*** 20.2 6 0.1

0.2 6 0.1* 0.1 6 0.1*

0.0 6 0.0 20.2 6 0.1

20.9 6 0.7 20.1 20.7 20.2 21.4

6 6 6 6

0.1 6 0.8 20.6 6 0.5

0.1 0.1 6 0.1 0.1 6 0.7 0.2*** 20.0 6 0.2 20.3 6 0.2 0.2 20.0 6 0.3 20.4 6 0.3** 0.8 0.0 6 0.7 20.9 6 0.5*

1.0 6 0.7 0.2 0.2 0.6 1.0

6 6 6 6

0.1 0.2 0.4 0.4

Notes: Body composition changes are from baseline to 12 months, within hormone replacement therapy (HRT) and no hormone replacement therapy (NHRT) groups. EX 5 exercise; NEX 5 no exercise; LST5 lean soft tissue. Values are mean 6 SEM. Multiple linear regression with a priori contrasts (HRT vs NHRT, EX/HRT vs NEX/HRT, and EX/NHRT vs NEX/NHRT) was used to determine differences between groups. *p , .05; **p 5 .08; ***p 5 .09.

body composition. HRT has a proven anabolic effect on bone mass (1,2), but a clear and significant effect on lean and fat mass has not been demonstrated. Our results are in agreement with those of previous studies that have reported no additional effect of HRT on the changes in lean mass observed in response to weight-bearing aerobic exercise in early and older postmenopausal women (4,9,10). However, previous reports have suggested that HRT may enhance the effects of weight-bearing aerobic exercise on reducing total body and arm fat mass in older women (2,9). The conflicting findings with these studies may be due in part to the lack of HRT randomization in our study. Because the counteractive effect of oral HRT on trunk fat mass may be observed at 12 months and not thereafter (3), it is possible that the lack of effect on body composition in the EX/ HRT group may be explained by a longer HRT use in our subjects. One factor that may have influenced the preferential reduction from different fat regions in the EX groups was fat distribution. Although no significant differences were found at baseline, the EX/NHRT and EX/HRT groups had the highest central fat (trunk fat and waist circumference) and leg fat depots, respectively. In previous studies of prolonged caloric deficit (19) or exercise training (9), those subjects with the highest initial level of adiposity lost more fat mass from these regions. Increased GH, IGF-1, androstenedione and estrogens, and/or decreased cortisol were expected to influence positively the responses in lean mass to exercise. Although total levels of these hormones are modified by HRT (5,20), stimulation of hepatic hormone-binding proteins for GH, IGF-1, sex hormones, and cortisol (20,21) would reduce the active free hormone levels, leading to a reduced effect on body composition. Our finding that exercise does not significantly modify circulating total levels of GH, IGF-1, and cortisol is consistent with previous investigations (11, 22). However, the lack of change in total hormone levels does not exclude the possibility of modifications in free hor-

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mones or adaptations in the skeletal muscle. Clearly, further studies with randomization of HRT and determination of hormone-binding proteins are required to determine the role of HRT and free hormone levels on the adaptations to exercise training in postmenopausal women.

Conclusions In conclusion, the results of this study indicate that total body and regional lean soft tissue mass can be increased and fat mass can be decreased with a combination of resistance and weight-bearing aerobic exercise in postmenopausal women. Moreover, these changes in body composition are not influenced by prolonged HRT use and are not accompanied by changes in total serum levels of the hormones determined in this study. The results suggest that isolation exercises for the arms are not required to improve muscle strength and lean soft tissue mass in postmenopausal women when exercises for the trunk musculature are included in the program. ACKNOWLEDGMENTS This study was supported by the National Institutes of Health (Grant AR 39939). We thank the Bone Estrogen Strength Training study staff for the collection of data. Address correspondence to Arturo Figueroa, MD, PhD, Department of Exercise Science, Syracuse University, 820 Comstock Avenue, Room 201, Syracuse, NY 13244-0001. E-mail: [email protected]

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