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Relationship between estrogen use and musculoskeletal function in postmenopausal women
Maturitas 42 (2002) 119– 127 www.elsevier.com/locate/maturitas
Relationship between estrogen use and musculoskeletal function in postmenopausal women Debra A. Bemben *, David B. Langdon Bone Density Laboratory, Department of Health and Sport Sciences, Uni6ersity of Oklahoma, Norman, OK 73019, USA Received 20 February 2001; received in revised form 6 December 2001; accepted 18 December 2001
Abstract Objecti6es: The purpose of this study was to examine the relationship between estrogen use and muscle strength, bone mineral density (BMD), and body composition variables in postmenopausal women. Forty healthy, untrained women participated in this study. Subjects (53–65 years) were ] 5 years postmenopausal and were categorized into either estrogen replacement therapy (ERT n=20) or non-estrogen replacement therapy (Non-ERT n = 20) groups. Methods: Muscular strength was measured by 1-RM testing using Cybex isotonic weight machines. Handgrip strength was measured using a handgrip dynamometer. Diagnostic Ultrasound was used to determine cross-sectional areas of the biceps brachii and rectus femoris muscle groups. BMD of the lumbar spine, proximal femur, and total body was assessed by Dual Energy X-Ray Absorptiometry (Lunar DPX-IQ). Body composition variables were obtained from the total body scan. Serum osteocalcin was measured as an indicator of bone remodeling. Results: There were no significant differences (P \0.05) for isotonic muscular strength, muscle cross-sectional areas, handgrip strength, or percent fat between ERT and Non-ERT groups. ERT had significantly higher (PB 0.05) BMD for the total body, femoral neck and Ward’s Area. There were moderate positive relationships between lean body mass and the hip sites (r = 0.61–0.70, PB 0.05). Regression analyses determined that lean body mass was the strongest predictor of the hip BMD sites. Estrogen use also was a significant predictor for the femoral neck and Ward’s Area sites. Conclusion: Women taking estrogen exhibited similar muscular strength, muscle size, and body composition as their estrogen-deficient counterparts. Estrogen use was also associated with higher BMD for the total body and hip sites. Generally, body composition, specifically lean body mass, influenced hip BMD more than muscular strength or estrogen use. © 2002 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Hormone replacement therapy; Bone remodeling; Muscle function
1. Introduction
* Corresponding author. Tel.: +1-405-325-2709; fax: + 1405-325-0594. E-mail address: [email protected] (D.A. Bemben).
It is well known that decreases in bone mass [22], muscle strength [3], and in lean body mass [1] occur with aging in women. The similar timing of the onset of these physiological decrements suggests that decreased estrogen levels after
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menopause may be a causal factor. Osteoporosis, and the resulting disabilities associated with vertebral and hip fractures, is an important public health problem, primarily affecting postmenopausal Caucasian women [13]. Many women use estrogen replacement therapy (ERT) to maintain estrogen levels crucial for the preservation of bone mass in their postmenopausal years. Strategies to prevent these fractures have focused on the prevention of the accelerated bone loss that occurs at the time of the menopause. Recent studies confirm that ERT is effective in increasing bone mass and reducing fracture rates in postmenopausal women [8]. Although it is well-documented that ERT can be used for the prevention of osteoporosis, its effects on muscular function, and body composition are not yet fully understood. Women experience a 15% loss in muscular strength during the perimenopausal years which occurs in addition to age-related decrements in muscular strength [17]. Evidence that estrogen deficiency is associated with impairments in muscle function includes reports that estrogen use either prevented the age-related decreases in strength [12,18] or resulted in an increase in muscular strength [14,26]. However, there have been conflicting cross-sectional [20,24,27] and prospective studies [2,7] which have not documented a positive estrogen effect on muscle function. The exact mechanism for estrogen effects on muscle tissue also is unclear. Estrogen receptors have been identified on rat skeletal muscle membrane [10], suggesting it may exert direct effects on this tissue. Estrogen also may influence muscle metabolism and protein synthesis indirectly by altering secretion patterns of growth hormone and IGF-I [9]. Since estrogen treatment was not found to increase muscle cross-sectional area [26], the increase in muscle strength may the result of improved neural function. The interactions of the age-related changes in musculoskeletal function are of interest. In addition to affecting balance, and risk for falls, decreases in muscular strength may result in bone loss given that voluntary muscular forces affect bone adaptations. Recently, Frost [11] presented
a paradigm where age-related bone loss is explained by disuse-mode remodeling caused by decreases in muscle strength placing decreased loads on bone. A relationship between muscle function and bone metabolism also is supported by observations that female patients with osteoporotic fractures have been shown to have back extensor muscle weakness compared with their non-osteoporotic counterparts [25]. Positive relationships have been reported between bone mineral density (BMD) and body composition [15,21,29] and muscular strength [16,19,23] variables, however, it is not clear whether these variables influence bone independent of estrogen use. The purpose of this study was to examine the relationship between estrogen use and muscle strength, BMD, and body composition variables in healthy, sedentary postmenopausal women.
2. Methods
2.1. Subjects Forty healthy postmenopausal, Caucasian, nonsmoking, women between the ages of 53 and 65 years were recruited from the surrounding communities. The subjects were currently not participating in any regular exercise program, and they had no history of cardiovascular, bone, or muscular disorders. Each subject completed medical history, menstrual history, and calcium intake questionnaires. Current physical activity levels were assessed using the Physical Activity Scale for the Elderly (PASE) self-administered questionnaire, which measures leisure time, household, and work-related physical activities. Washburn et al. [28] reported PASE scores ranged from 0 to 361 in a population of older adults, with a mean of 112.79 64.2 for women 65–69 years of age. Subjects were ] 5 years postmenopausal and estrogen users had been taking estrogen replacement for at least 3 years (range 3– 27 years, mean= 11.3 years). Subjects were grouped into either estrogen replacement (ERT n=20) or nonestrogen replacement therapy (Non-ERT) (n= 20)
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based on their estrogen status. Forty-two percent of the estrogen users were taking a combined estrogen/progestin hormone replacement therapy with the remainder taking only estrogen. Only 21% of the ERT group used a skin patch as the route of administration. The dose ranges were 0.05 – 1.25 mg for estrogen and 1– 5 mg for progestin. Two of the non-estrogen users had previously taken estrogen but had stopped for at least 2 years prior to entering in the study. All subjects provided written informed consent, which was approved by the Institutional Review Board at the University of Oklahoma.
2.2. Muscular strength Muscle strength was assessed by a one repetition maximum test (1RM) for three upper body and five lower body isotonic resistance exercises using Cybex® equipment. The 1RM is defined as the amount of weight that could be lifted once but not twice. After stretching each subject warmedup with 5 –10 repetitions, of a preset lightweight. All subjects were shown proper technique and fitting for each machine before the exercise testing was conducted. Subjects rested for 1 min between each attempt with no more than five attempts being made before the 1RM was achieved. The resistance exercises tested were: (1) Military Press, (2) Elbow Extension, (3) Elbow Flexion, (4) Leg Press, (5) Knee Flexion, (6) Knee Extension, (7) Hip Abduction, and (8) Hip Adduction.
2.3. Grip strength Handgrip strength was measured with a handgrip dynamometer (TEC) for both the right and left hands. The shoulder was in neutral position and adducted, with the elbow unsupported in 90° flexion. The choice of wrist position and grip width was left to the discretion of the subjects. Each subject was allowed to become familiar with the dynamometer, and the hand position. The subjects were instructed to squeeze as hard and fast as possible [5], and then to rest for 1 min. Three trials were performed for each hand with the average of the trials used in subsequent analyses. Force was recorded in kilograms.
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2.4. Bone mineral density Dual Energy X-Ray Absorptiometry (DXA) (Lunar DPX-IQ, software version 4.0) was used to measure the BMD (g/cm2) of the total body, anterio-posterior (AP) lumbar spine (L2–L4), and the proximal femur (femoral neck, Ward’s Area, trochanter, total hip). Regional and total body composition (% body fat, fat mass, lean body mass) was determined from the total body scan. Scanning instructions and procedures were standardized for all subjects. Scan speeds were determined by the measured thickness of the subject’s trunk region. The AP spine and femur scans used the scan modes of Hi-Res Fast 3000 mA, Hi-Res medium 3000 mA, and Hi-Res Medium 750mA for subjects with thickness of 15–26, 26– 30, and 12– 15 cm, respectively. The total body scan required the Fast 150 mA, Medium 150 mA, and Slow 150 mA modes to scan subjects with trunk thickness of 15–26, 22–28, and over 28 cm, respectively. Coefficients of variation for accuracy and precision for the spine phantom are 0.6 and 0.8%, respectively for this laboratory. In vivo short term precision for the proximal femur ranges from 0.7% for the total hip site to 1.3% for Ward’s Area.
2.5. Muscle cross-sectional area Each subject had her right biceps brachii and rectus femoris muscle groups measured by diagnostic ultrasound to obtain the cross-sectional areas. This procedure has been shown to be a reliable and valid method in our laboratory for assessing muscle size as compared with magnetic resonance imaging [6]. Subjects did not participate in any vigorous arm or leg exercises on the days of assessment. The biceps brachii scan was performed at maximal girth with the subject in a supine position with her shoulder in 90° abduction, elbow at 180° extension and hand supinated. The rectus femoris scan required the subject to be in a supine position with a rolled up towel placed under the popliteal fossa of the right leg. To locate the exact evaluation site, the proximal pole of the right patella was marked with indelible ink, then a point 15 cm proximal to the patellar mark,
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following the midline of the anterior surface of the thigh, was also marked. A Fukuda Denshi, model 4500 ultrasound, utilized a 5 Mz transducer (FUT-L104) and water-soluble transmission gel to image both muscles. Care was taken to ensure that the transducer was always placed perpendicular to the anterior surface of the thigh and that no depression of the skin surface occurred. Once the image was obtained, the image was frozen on the screen and with the aid of a track ball the muscle was outlined on the inside edge of the connective tissue that surrounded the muscle to obtain that muscles cross-sectional area. All scans were performed by the same technician. Two trials were obtained during each test session which were averaged for use in further data analyses.
2.6. Osteocalcin Blood samples were obtained in the morning after an overnight fast via venipuncture. Samples were allowed to clot and then centrifuged to separate serum from the cells. Serum samples were pipetted into 1 ml aliquots and kept frozen at − 70 °C for the subsequent assays. Biochemical assays were conducted in the biochemistry area of the Human Performance Laboratory at the University of Oklahoma. Serum osteocalcin, a marker of bone formation, was determined by a commercial immunoradiometric assay kit (Diagnostic Systems Laboratories, Webster TX). The intra assay variation was 53% and the inter assay variation was 13.5%.
2.7. Data analyses All data were reported as means9 standard error (S.E.). All statistical analyses were performed using SPSS version 9.0. Descriptive statistics were computed for the dependent variables. One-way analysis of variance (ANOVA) was used to identify group differences in the dependent variables. Analyses of covariance were used to adjust group differences in BMD for body weight. Zero-order correlation coefficients were used to determine relationships between muscle strength, BMD, and body composition variables. Stepwise multiple regression analysis was used to determine
significant body composition and strength predictors of BMD variables. The level of significance was set at P5 0.05. 3. Results Table 1 shows the physical characteristics of the two groups. As expected, there were no significant group differences in age, number of years postmenopausal, or physical activity scores. The NonERT group tended to be heavier and have a higher BMI than ERT, although not significant.
3.1. Bone mineral density Table 2 presents the unadjusted BMD profiles for the two groups. When BMD was adjusted for body weight, ERT had significantly (PB 0.05) higher BMD than the Non-ERT group for the total body, femoral neck, and Ward’s Area sites. There also was a trend (P= 0.059) for the spine BMD to be higher in the ERT group. In comparison to the young-adult reference population, the Ward’s Area site showed the greatest bone loss for both groups (approximately 26% for NonERT and 16% for ERT). In addition, significant group differences existed in both the young adult% (P= 0.025), and T-score value with the ERT group being higher than the Non-ERT group for this site.
Table 1 Physical characteristics of the ERT and Non-ERT groups Variable
ERT (n= 20)
Non-ERT (n =20)
Age (years) Height (cm) Weight (kg) BMI (kg/m2) Physical activity
58.7 9 0.6 162.8 91.17 67.9 92.9 25.6 91.1 151.9 918.2 (35–285) 1638 9189 14.0 91.8
59.2 9 8 163.8 91.1 73.5 92.7 27.5 91.1 158.9 9 15.3 (42–266) 2103 9 268 12.4 91.4
Calcium intake (mg/day) Years postmenopausal
Values are means 9 S.E., BMI, Body Mass Index; Physical activity, Physical activity score from the PASE questionnaire (range). No significant group differences existed (P\0.05).
D.A. Bemben, D.B. Langdon / Maturitas 42 (2002) 119–127 Table 2 BMD of the ERT and Non-ERT groups BMD site (g/cm2)
ERT (n=20)
Non-ERT (n= 20)
Spine L2–L4 Total hip Femoral neck Ward’s triangle Trochanter Total body
1.1949 0.033a 0.93490.022 0.9049 0.022b 0.7569 0.021c 0.7199 0.024 1.1569 0.011c
1.11190.038 0.9199 0.029 0.863 9 0.023 0.673 9 0.029 0.7539 0.027 1.113 9 0.016
Table 3 Muscular strength and cross-sectional areas for the ERT and Non-ERT groups Variable
Values are means 9S.E., ERT, Estrogen Replacement Therapy; Non-ERT, Non Estrogen Replacement Therapy. a P = 0.059 for group effect adjusting for body weight. b Significant group differences adjusting for body weight (PB0.05). c Significant group differences adjusting for body weight (PB0.01).
Serum osteocalcin concentrations were significantly higher in the Non-ERT than the ERT (PB0.05) group (Fig. 1). There was a negative relationship between osteocalcin and total body BMD (r= − 0.43, P B0.05). Total calcium intake including calcium supplements, was not significantly different (P \0.05) between the two groups nor was calcium intake significantly related (P \ 0.05) to any bone density site measured.
3.2. Muscle strength Table 3 shows the descriptive statistics for the isotonic and isometric strength variables and muscle cross-sectional areas for ERT and Non-ERT. There were no significant differences (P \ 0.05) in
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ERT (n =20)
Non-ERT (n =20)
Isotonic Strength (kg) Biceps 16.08 91.06 Triceps 20.19 90.75 Military press 27.06 9 1.20 Leg extension 42.81 9 2.05 Leg flexion 44.51 9 1.75 Leg press 85.00 93.73 Hip abduction 37.37 9 1.85 Hip adduction 34.40 91.70
18.19 90.98 21.76 90.75 24.41 91.45 44.53 92.67 47.40 91.59 91.81 94.65 37.37 91.42 33.08 91.52
Handgrip strength (kg) Right hand 28.12 90.85 Left hand 25.75 90.95
27.65 9 1.20 25.09 9 1.09
Muscle CSA (cm2) Biceps Rectus femoris
4.58 9 0.21 3.58 9 0.19
4.55 90.27 3.39 90.18
Values are means 9S.E. No significant group differences existed (P\0.05). CSA, cross-sectional area.
isotonic muscular strength between the two groups, even when adjusted for differences in body weight or lean body mass. Handgrip strength also was similar for ERT and Non-ERT and there were no significant differences (P\ 0.05) in right and left handgrip strength within each group. There was no significant differences (P\ 0.05) between the groups for biceps brachii or rectus femoris CSA.
3.3. Body composition 6ariables Table 4 shows the means9S.E. for the total body and regional body composition variables. Total body percent fat, fat mass and lean body mass were similar for the two groups. The only significant group difference for regional body composition was a lower trunk lean body mass (PB 0.05) for the ERT group.
3.4. Relationships between BMD, body composition and strength 6ariables Fig. 1. Serum osteocalcin levels (ng/ml) for ERT, and NonERT groups. *, significant difference (P B0.05) between groups.
There were no significant correlations between spine BMD and body composition or muscular strength variables. As shown in Table 5, the hip
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Table 4 Regional and total body composition variables of the ERT and Non-ERT groups Body region
ERT (n= 20)
Non-ERT (n=20)
Total body % fat Total LBM (kg) Total fat mass (kg) Arm % fat Arm LBM (kg) Arm fat mass (kg) Trunk % fat Trunk fat mass (kg) Trunk LBM (kg) Leg % fat Leg fat mass (kg) Leg LBM (kg)
39.139 1.61 37.219 0.96 26.539 2.08 35.35 9 2.16 3.669 0.23 2.29 9 0.19 36.9291.79 11.98 91.09 18.5290.54a 42.599 1.59 10.479 0.74 12.739 0.32
41.13 9 1.86 39.07 9 0.99 30.219 2.13 38.869 2.09 3.959 0.16 2.84 90.25 40.0191.96 14.7591.15 20.2490.61 43.44 9 1.89 10.989 0.83 12.86 9 0.31
Table 6 Multiple regression analyses for hip BMD sites against estrogen use, lean body mass (LBM), fat mass (FM), and lower body strength variables Prediction models by BMD site
Beta
P
Femoral neck LBM Estrogen use Hip adduction Model R 2
0.658 0.305 0.244 0.549
0.000 0.013 0.043
Trochanter LBM FM Model R 2
0.540 0.294 0.516
0.000 0.040
Values given as mean 9S.E. a ERT significantly lower than Non-ERT at (PB0.05).
Ward’s area LBM Estrogen use Model R 2
0.468 0.447 0.311
0.002 0.004
sites were moderately positively related to lean body mass, fat mass and hip adductor strength. Moderate positive relationships also existed between total body BMD and fat mass (r= 0.47) and lean body mass (r = 0.45). Spine BMD was not predicted by estrogen use or by any of the body composition or muscular strength variables. Table 6 shows the stepwise multiple regression models for the hip BMD sites with estrogen use, fat mass, lean body and muscular strength as the independent variables. Lean body mass was entered first into the prediction models for the femoral neck, trochanter, Ward’s Area, and total hip indicating it was the strongest predictor variable for all the hip BMD sites. Estrogen use was included in the model for the femoral neck and Ward’s Area sites. Hip adduction was the only strength measure entered into the prediction models, where it was a signifi-
Total hip LBM Hip adduction Model R 2
0.558 0.299 0.427
0.000 0.028
R 2 —adjusted R 2 for each model.
cant predictor for the femoral neck and total hip sites.
4. Discussion The purpose of this study was to compare BMD, muscular strength, and body composition in estrogen-deficient and estrogen-replete postmenopausal women. In contrast to previous studies, we selected subjects within a relatively narrow age range (53– 65 years) whose estrogen status should have been stabilized based on the number
Table 5 Zero-order correlations between BMD and body composition/muscular strength variables BMD Site Spine L2–L4 Total hip Femoral neck Ward’s triangle Trochanter
FM 0.03 0.38a 0.25 0.03 0.58b
LBM 0.26 0.61a 0.65a 0.40 0.69b
Military press
Leg press
Hip abduction
Hip adduction
0.29 – – – –
– 0.24 0.21 0.21 0.19
– 0.20 0.12 0.13 0.12
– 0.40a 0.38a 0.29 0.32
P, 50.05; bP, 50.01. FM, fat mass; LBM, lean body mass.
a
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of years post menopause and duration of estrogen use. Additional strengths of our study include the assessments of muscle cross-sectional area, isotonic muscular strength for a variety of upper and lower body muscle groups and physical activity patterns. The results showed that while the estrogen-deficient women clearly had lower bone density than the estrogen users, muscle function and lean body mass were similar in the two groups. Thus, in contrast to its strong effects on bone tissue, long-term estrogen deficiency did not appear to negatively impact the muscular fitness and body composition of postmenopausal women. It is possible that our findings differ from previous studies reporting positive effects of estrogen treatment on muscle function, because, our subjects were older, well past perimenopause when the greatest loss of muscle strength occurs [17]. In addition, physical activity patterns, often not examined in previous studies, were similar for the two groups in this study. There have been a limited number of studies, which have examined the influence of estrogen use on muscular function in postmenopausal women. An equivocal number of studies have reported a positive effect [14,18,26] and no effect of ERT [2,12,20,24,27] on muscular strength. The findings of Phillips et al. [18] stimulated interest in the potential benefit of estrogen use in preventing the age-related decrease in muscle strength. They reported that the specific force (strength/cross-sectional area) of the adductor pollicis muscle decreased at the time of menopause in women not taking estrogen, whereas strength was maintained at the premenopausal levels in the estrogen users. Similarly, a prospective study by Skelton et al. [26] found a significant 12.4% increase in the strength of the adductor pollicis muscle with 12 months of hormone replacement therapy. Muscle hypertrophy did not account for the strength improvements as muscle cross-sectional area did not increase over the treatment period. Estrogen-related changes in non-contractile tissue, neural factors such as motor unit recruitment, and force production at the cross-bridge level have been proposed as possible explanations [17,26]. Other prospective studies reporting benefits of estrogen treatment on skeletal muscle function also in-
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cluded exercise programs as part of the intervention [14]. Although positive effects of estrogen treatment on muscle strength have been reported, the significance of these changes is not clear as the increases are relatively small ( 15%) compared with those observed in resistance training studies. For example, we have documented much larger increases (30%) in muscle strength and in muscle cross-sectional areas in early postmenopausal women not taking estrogen after 24 weeks of resistance training [4]. Thus, it seems that exercise programs easily counteract potential losses in muscle mass and strength associated with menopause. The ERT group had higher bone density than Non-ERT, significant at the total body, femoral neck and Ward’s Area sites when adjusted for body weight. A slower rate of bone turnover in ERT, as indicated by lower serum osteocalcin levels, also was documented. Although limited by the cross-sectional nature of the study, these results are in agreement with other studies [8] which indicated ERT is beneficial for increasing BMD and the prevention of osteoporosis. When examining variables that influenced BMD, it was surprising that the muscular strength variables in our study were not related to the BMD sites, with the exception of hip adduction strength. Conversely, other studies have found significant positive relationships between muscular strength and BMD [16,19,23] and that strength variables were significant predictors of BMD [16,19]. Quadriceps strength was reported to be a better predictor of tibial BMD than age, weight or height in women ranging in age from 21 to 78 years [16]. Similarly, Pocock et al. [19] found that femoral neck BMD was predicted by quadriceps strength in women 20– 75 years of age. Both of those studies included premenopausal and postmenopausal women, thus the correlations in our study likely were affected by the restricted age range of the subjects. The influence of body composition variables on bone mass is controversial as both fat mass and lean body mass have been found to be related to BMD. According to Reid et al. [21], the rate of bone loss in postmenopausal women was inversely related to fat mass and not to lean body mass. However, other researchers [15,29] have reported that the lean component of body weight also is a
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determinant of bone mass. Khosla et al. [15] found that both lean body mass and fat mass were important predictors of the spine and total hip BMD in postmenopausal women not taking estrogen. We found that lean body mass, not fat mass, was the most important predictor of all the hip BMD sites independent of estrogen use. In conclusion, estrogen use in postmenopausal women was associated with higher BMD and suppressed bone remodeling rates. However, body composition and muscular strength were similar for the ERT and non-estrogen replacement therapy groups, suggesting that long-term estrogen deficiency in these women did not negatively impact their muscular function. Acknowledgements This research was supported in part by Faculty Research Grants provided by the College of Arts and Sciences, and Research Administration at the University of Oklahoma. References [1] Aloia JF, McGowan D, Vaswani AN, Ross P, Cohn SH. Relationship of menopause to skeletal and muscle mass. Am J Clin Nutr 1991;53:1378 –83. [2] Armstrong AL, Oborne J, Coupland CA, MacPherson MB, Bassey EJ, Wallace WA. Effects of hormone replacement therapy on muscle performance and balance in post-menopausal women. Clin Sci 1996;91:685 –90. [3] Bassey EJ, Harries UJ. Normal values for hangrip strength in 920 men and women aged over 75 years, and longitudinal changes over 4 years in 620 survivors. Clin Sci 1993;84:331 – 7. [4] Bemben DA, Fetters NL, Bemben MG, Nabavi N, Koh ET. Musculoskeletal responses to high and low intensity resistance training in postmenopausal women. Med Sci Sports Exercise 2000;32:1949 –57. [5] Bemben MG, Clasey JL, Massey BH. The effect of the rate of muscle contraction on the force –time curve parameters of male and female subjects. Res Q Exercise Sport 1990;61:96 – 9. [6] Bemben MG, Stratemeier P. Reliability and validity of diagnostic ultrasound for assessing muscle size. Med Sci Sports Exercise 1999;31:S114. [7] Brown M, Birge SJ, Kohrt WM. Hormone replacement therapy does not augment gains in muscle strength or fat-free mass in response to weight-bearing exercise. J Gerontol Biol Sci 1997;52:B166 –70.
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enced by oestrogen status. Age Ageing 1995;24:329 – 33. [28] Washburn RA, Smith KW, Jette AM, Janney CA. The physical activity scale for the elderly (PASE): development and evaluation. J Clin Epidemiol 1993;46:153 – 62. [29] Zhen Z, Lohman TG, Stini WA, Ritenbaugh C, Aickin M. Fat or lean tissue mass: which one is the major determinant of bone mineral mass in health postmenopausal women? J Bone Miner Res 1997;12: 144 – 51.
Relationship between estrogen use and musculoskeletal function in postmenopausal women Debra A. Bemben *, David B. Langdon Bone Density Laboratory, Department of Health and Sport Sciences, Uni6ersity of Oklahoma, Norman, OK 73019, USA Received 20 February 2001; received in revised form 6 December 2001; accepted 18 December 2001
Abstract Objecti6es: The purpose of this study was to examine the relationship between estrogen use and muscle strength, bone mineral density (BMD), and body composition variables in postmenopausal women. Forty healthy, untrained women participated in this study. Subjects (53–65 years) were ] 5 years postmenopausal and were categorized into either estrogen replacement therapy (ERT n=20) or non-estrogen replacement therapy (Non-ERT n = 20) groups. Methods: Muscular strength was measured by 1-RM testing using Cybex isotonic weight machines. Handgrip strength was measured using a handgrip dynamometer. Diagnostic Ultrasound was used to determine cross-sectional areas of the biceps brachii and rectus femoris muscle groups. BMD of the lumbar spine, proximal femur, and total body was assessed by Dual Energy X-Ray Absorptiometry (Lunar DPX-IQ). Body composition variables were obtained from the total body scan. Serum osteocalcin was measured as an indicator of bone remodeling. Results: There were no significant differences (P \0.05) for isotonic muscular strength, muscle cross-sectional areas, handgrip strength, or percent fat between ERT and Non-ERT groups. ERT had significantly higher (PB 0.05) BMD for the total body, femoral neck and Ward’s Area. There were moderate positive relationships between lean body mass and the hip sites (r = 0.61–0.70, PB 0.05). Regression analyses determined that lean body mass was the strongest predictor of the hip BMD sites. Estrogen use also was a significant predictor for the femoral neck and Ward’s Area sites. Conclusion: Women taking estrogen exhibited similar muscular strength, muscle size, and body composition as their estrogen-deficient counterparts. Estrogen use was also associated with higher BMD for the total body and hip sites. Generally, body composition, specifically lean body mass, influenced hip BMD more than muscular strength or estrogen use. © 2002 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Hormone replacement therapy; Bone remodeling; Muscle function
1. Introduction
* Corresponding author. Tel.: +1-405-325-2709; fax: + 1405-325-0594. E-mail address: [email protected] (D.A. Bemben).
It is well known that decreases in bone mass [22], muscle strength [3], and in lean body mass [1] occur with aging in women. The similar timing of the onset of these physiological decrements suggests that decreased estrogen levels after
0378-5122/02/$ - see front matter © 2002 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 3 7 8 - 5 1 2 2 ( 0 2 ) 0 0 0 3 3 - 6
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menopause may be a causal factor. Osteoporosis, and the resulting disabilities associated with vertebral and hip fractures, is an important public health problem, primarily affecting postmenopausal Caucasian women [13]. Many women use estrogen replacement therapy (ERT) to maintain estrogen levels crucial for the preservation of bone mass in their postmenopausal years. Strategies to prevent these fractures have focused on the prevention of the accelerated bone loss that occurs at the time of the menopause. Recent studies confirm that ERT is effective in increasing bone mass and reducing fracture rates in postmenopausal women [8]. Although it is well-documented that ERT can be used for the prevention of osteoporosis, its effects on muscular function, and body composition are not yet fully understood. Women experience a 15% loss in muscular strength during the perimenopausal years which occurs in addition to age-related decrements in muscular strength [17]. Evidence that estrogen deficiency is associated with impairments in muscle function includes reports that estrogen use either prevented the age-related decreases in strength [12,18] or resulted in an increase in muscular strength [14,26]. However, there have been conflicting cross-sectional [20,24,27] and prospective studies [2,7] which have not documented a positive estrogen effect on muscle function. The exact mechanism for estrogen effects on muscle tissue also is unclear. Estrogen receptors have been identified on rat skeletal muscle membrane [10], suggesting it may exert direct effects on this tissue. Estrogen also may influence muscle metabolism and protein synthesis indirectly by altering secretion patterns of growth hormone and IGF-I [9]. Since estrogen treatment was not found to increase muscle cross-sectional area [26], the increase in muscle strength may the result of improved neural function. The interactions of the age-related changes in musculoskeletal function are of interest. In addition to affecting balance, and risk for falls, decreases in muscular strength may result in bone loss given that voluntary muscular forces affect bone adaptations. Recently, Frost [11] presented
a paradigm where age-related bone loss is explained by disuse-mode remodeling caused by decreases in muscle strength placing decreased loads on bone. A relationship between muscle function and bone metabolism also is supported by observations that female patients with osteoporotic fractures have been shown to have back extensor muscle weakness compared with their non-osteoporotic counterparts [25]. Positive relationships have been reported between bone mineral density (BMD) and body composition [15,21,29] and muscular strength [16,19,23] variables, however, it is not clear whether these variables influence bone independent of estrogen use. The purpose of this study was to examine the relationship between estrogen use and muscle strength, BMD, and body composition variables in healthy, sedentary postmenopausal women.
2. Methods
2.1. Subjects Forty healthy postmenopausal, Caucasian, nonsmoking, women between the ages of 53 and 65 years were recruited from the surrounding communities. The subjects were currently not participating in any regular exercise program, and they had no history of cardiovascular, bone, or muscular disorders. Each subject completed medical history, menstrual history, and calcium intake questionnaires. Current physical activity levels were assessed using the Physical Activity Scale for the Elderly (PASE) self-administered questionnaire, which measures leisure time, household, and work-related physical activities. Washburn et al. [28] reported PASE scores ranged from 0 to 361 in a population of older adults, with a mean of 112.79 64.2 for women 65–69 years of age. Subjects were ] 5 years postmenopausal and estrogen users had been taking estrogen replacement for at least 3 years (range 3– 27 years, mean= 11.3 years). Subjects were grouped into either estrogen replacement (ERT n=20) or nonestrogen replacement therapy (Non-ERT) (n= 20)
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based on their estrogen status. Forty-two percent of the estrogen users were taking a combined estrogen/progestin hormone replacement therapy with the remainder taking only estrogen. Only 21% of the ERT group used a skin patch as the route of administration. The dose ranges were 0.05 – 1.25 mg for estrogen and 1– 5 mg for progestin. Two of the non-estrogen users had previously taken estrogen but had stopped for at least 2 years prior to entering in the study. All subjects provided written informed consent, which was approved by the Institutional Review Board at the University of Oklahoma.
2.2. Muscular strength Muscle strength was assessed by a one repetition maximum test (1RM) for three upper body and five lower body isotonic resistance exercises using Cybex® equipment. The 1RM is defined as the amount of weight that could be lifted once but not twice. After stretching each subject warmedup with 5 –10 repetitions, of a preset lightweight. All subjects were shown proper technique and fitting for each machine before the exercise testing was conducted. Subjects rested for 1 min between each attempt with no more than five attempts being made before the 1RM was achieved. The resistance exercises tested were: (1) Military Press, (2) Elbow Extension, (3) Elbow Flexion, (4) Leg Press, (5) Knee Flexion, (6) Knee Extension, (7) Hip Abduction, and (8) Hip Adduction.
2.3. Grip strength Handgrip strength was measured with a handgrip dynamometer (TEC) for both the right and left hands. The shoulder was in neutral position and adducted, with the elbow unsupported in 90° flexion. The choice of wrist position and grip width was left to the discretion of the subjects. Each subject was allowed to become familiar with the dynamometer, and the hand position. The subjects were instructed to squeeze as hard and fast as possible [5], and then to rest for 1 min. Three trials were performed for each hand with the average of the trials used in subsequent analyses. Force was recorded in kilograms.
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2.4. Bone mineral density Dual Energy X-Ray Absorptiometry (DXA) (Lunar DPX-IQ, software version 4.0) was used to measure the BMD (g/cm2) of the total body, anterio-posterior (AP) lumbar spine (L2–L4), and the proximal femur (femoral neck, Ward’s Area, trochanter, total hip). Regional and total body composition (% body fat, fat mass, lean body mass) was determined from the total body scan. Scanning instructions and procedures were standardized for all subjects. Scan speeds were determined by the measured thickness of the subject’s trunk region. The AP spine and femur scans used the scan modes of Hi-Res Fast 3000 mA, Hi-Res medium 3000 mA, and Hi-Res Medium 750mA for subjects with thickness of 15–26, 26– 30, and 12– 15 cm, respectively. The total body scan required the Fast 150 mA, Medium 150 mA, and Slow 150 mA modes to scan subjects with trunk thickness of 15–26, 22–28, and over 28 cm, respectively. Coefficients of variation for accuracy and precision for the spine phantom are 0.6 and 0.8%, respectively for this laboratory. In vivo short term precision for the proximal femur ranges from 0.7% for the total hip site to 1.3% for Ward’s Area.
2.5. Muscle cross-sectional area Each subject had her right biceps brachii and rectus femoris muscle groups measured by diagnostic ultrasound to obtain the cross-sectional areas. This procedure has been shown to be a reliable and valid method in our laboratory for assessing muscle size as compared with magnetic resonance imaging [6]. Subjects did not participate in any vigorous arm or leg exercises on the days of assessment. The biceps brachii scan was performed at maximal girth with the subject in a supine position with her shoulder in 90° abduction, elbow at 180° extension and hand supinated. The rectus femoris scan required the subject to be in a supine position with a rolled up towel placed under the popliteal fossa of the right leg. To locate the exact evaluation site, the proximal pole of the right patella was marked with indelible ink, then a point 15 cm proximal to the patellar mark,
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following the midline of the anterior surface of the thigh, was also marked. A Fukuda Denshi, model 4500 ultrasound, utilized a 5 Mz transducer (FUT-L104) and water-soluble transmission gel to image both muscles. Care was taken to ensure that the transducer was always placed perpendicular to the anterior surface of the thigh and that no depression of the skin surface occurred. Once the image was obtained, the image was frozen on the screen and with the aid of a track ball the muscle was outlined on the inside edge of the connective tissue that surrounded the muscle to obtain that muscles cross-sectional area. All scans were performed by the same technician. Two trials were obtained during each test session which were averaged for use in further data analyses.
2.6. Osteocalcin Blood samples were obtained in the morning after an overnight fast via venipuncture. Samples were allowed to clot and then centrifuged to separate serum from the cells. Serum samples were pipetted into 1 ml aliquots and kept frozen at − 70 °C for the subsequent assays. Biochemical assays were conducted in the biochemistry area of the Human Performance Laboratory at the University of Oklahoma. Serum osteocalcin, a marker of bone formation, was determined by a commercial immunoradiometric assay kit (Diagnostic Systems Laboratories, Webster TX). The intra assay variation was 53% and the inter assay variation was 13.5%.
2.7. Data analyses All data were reported as means9 standard error (S.E.). All statistical analyses were performed using SPSS version 9.0. Descriptive statistics were computed for the dependent variables. One-way analysis of variance (ANOVA) was used to identify group differences in the dependent variables. Analyses of covariance were used to adjust group differences in BMD for body weight. Zero-order correlation coefficients were used to determine relationships between muscle strength, BMD, and body composition variables. Stepwise multiple regression analysis was used to determine
significant body composition and strength predictors of BMD variables. The level of significance was set at P5 0.05. 3. Results Table 1 shows the physical characteristics of the two groups. As expected, there were no significant group differences in age, number of years postmenopausal, or physical activity scores. The NonERT group tended to be heavier and have a higher BMI than ERT, although not significant.
3.1. Bone mineral density Table 2 presents the unadjusted BMD profiles for the two groups. When BMD was adjusted for body weight, ERT had significantly (PB 0.05) higher BMD than the Non-ERT group for the total body, femoral neck, and Ward’s Area sites. There also was a trend (P= 0.059) for the spine BMD to be higher in the ERT group. In comparison to the young-adult reference population, the Ward’s Area site showed the greatest bone loss for both groups (approximately 26% for NonERT and 16% for ERT). In addition, significant group differences existed in both the young adult% (P= 0.025), and T-score value with the ERT group being higher than the Non-ERT group for this site.
Table 1 Physical characteristics of the ERT and Non-ERT groups Variable
ERT (n= 20)
Non-ERT (n =20)
Age (years) Height (cm) Weight (kg) BMI (kg/m2) Physical activity
58.7 9 0.6 162.8 91.17 67.9 92.9 25.6 91.1 151.9 918.2 (35–285) 1638 9189 14.0 91.8
59.2 9 8 163.8 91.1 73.5 92.7 27.5 91.1 158.9 9 15.3 (42–266) 2103 9 268 12.4 91.4
Calcium intake (mg/day) Years postmenopausal
Values are means 9 S.E., BMI, Body Mass Index; Physical activity, Physical activity score from the PASE questionnaire (range). No significant group differences existed (P\0.05).
D.A. Bemben, D.B. Langdon / Maturitas 42 (2002) 119–127 Table 2 BMD of the ERT and Non-ERT groups BMD site (g/cm2)
ERT (n=20)
Non-ERT (n= 20)
Spine L2–L4 Total hip Femoral neck Ward’s triangle Trochanter Total body
1.1949 0.033a 0.93490.022 0.9049 0.022b 0.7569 0.021c 0.7199 0.024 1.1569 0.011c
1.11190.038 0.9199 0.029 0.863 9 0.023 0.673 9 0.029 0.7539 0.027 1.113 9 0.016
Table 3 Muscular strength and cross-sectional areas for the ERT and Non-ERT groups Variable
Values are means 9S.E., ERT, Estrogen Replacement Therapy; Non-ERT, Non Estrogen Replacement Therapy. a P = 0.059 for group effect adjusting for body weight. b Significant group differences adjusting for body weight (PB0.05). c Significant group differences adjusting for body weight (PB0.01).
Serum osteocalcin concentrations were significantly higher in the Non-ERT than the ERT (PB0.05) group (Fig. 1). There was a negative relationship between osteocalcin and total body BMD (r= − 0.43, P B0.05). Total calcium intake including calcium supplements, was not significantly different (P \0.05) between the two groups nor was calcium intake significantly related (P \ 0.05) to any bone density site measured.
3.2. Muscle strength Table 3 shows the descriptive statistics for the isotonic and isometric strength variables and muscle cross-sectional areas for ERT and Non-ERT. There were no significant differences (P \ 0.05) in
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ERT (n =20)
Non-ERT (n =20)
Isotonic Strength (kg) Biceps 16.08 91.06 Triceps 20.19 90.75 Military press 27.06 9 1.20 Leg extension 42.81 9 2.05 Leg flexion 44.51 9 1.75 Leg press 85.00 93.73 Hip abduction 37.37 9 1.85 Hip adduction 34.40 91.70
18.19 90.98 21.76 90.75 24.41 91.45 44.53 92.67 47.40 91.59 91.81 94.65 37.37 91.42 33.08 91.52
Handgrip strength (kg) Right hand 28.12 90.85 Left hand 25.75 90.95
27.65 9 1.20 25.09 9 1.09
Muscle CSA (cm2) Biceps Rectus femoris
4.58 9 0.21 3.58 9 0.19
4.55 90.27 3.39 90.18
Values are means 9S.E. No significant group differences existed (P\0.05). CSA, cross-sectional area.
isotonic muscular strength between the two groups, even when adjusted for differences in body weight or lean body mass. Handgrip strength also was similar for ERT and Non-ERT and there were no significant differences (P\ 0.05) in right and left handgrip strength within each group. There was no significant differences (P\ 0.05) between the groups for biceps brachii or rectus femoris CSA.
3.3. Body composition 6ariables Table 4 shows the means9S.E. for the total body and regional body composition variables. Total body percent fat, fat mass and lean body mass were similar for the two groups. The only significant group difference for regional body composition was a lower trunk lean body mass (PB 0.05) for the ERT group.
3.4. Relationships between BMD, body composition and strength 6ariables Fig. 1. Serum osteocalcin levels (ng/ml) for ERT, and NonERT groups. *, significant difference (P B0.05) between groups.
There were no significant correlations between spine BMD and body composition or muscular strength variables. As shown in Table 5, the hip
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Table 4 Regional and total body composition variables of the ERT and Non-ERT groups Body region
ERT (n= 20)
Non-ERT (n=20)
Total body % fat Total LBM (kg) Total fat mass (kg) Arm % fat Arm LBM (kg) Arm fat mass (kg) Trunk % fat Trunk fat mass (kg) Trunk LBM (kg) Leg % fat Leg fat mass (kg) Leg LBM (kg)
39.139 1.61 37.219 0.96 26.539 2.08 35.35 9 2.16 3.669 0.23 2.29 9 0.19 36.9291.79 11.98 91.09 18.5290.54a 42.599 1.59 10.479 0.74 12.739 0.32
41.13 9 1.86 39.07 9 0.99 30.219 2.13 38.869 2.09 3.959 0.16 2.84 90.25 40.0191.96 14.7591.15 20.2490.61 43.44 9 1.89 10.989 0.83 12.86 9 0.31
Table 6 Multiple regression analyses for hip BMD sites against estrogen use, lean body mass (LBM), fat mass (FM), and lower body strength variables Prediction models by BMD site
Beta
P
Femoral neck LBM Estrogen use Hip adduction Model R 2
0.658 0.305 0.244 0.549
0.000 0.013 0.043
Trochanter LBM FM Model R 2
0.540 0.294 0.516
0.000 0.040
Values given as mean 9S.E. a ERT significantly lower than Non-ERT at (PB0.05).
Ward’s area LBM Estrogen use Model R 2
0.468 0.447 0.311
0.002 0.004
sites were moderately positively related to lean body mass, fat mass and hip adductor strength. Moderate positive relationships also existed between total body BMD and fat mass (r= 0.47) and lean body mass (r = 0.45). Spine BMD was not predicted by estrogen use or by any of the body composition or muscular strength variables. Table 6 shows the stepwise multiple regression models for the hip BMD sites with estrogen use, fat mass, lean body and muscular strength as the independent variables. Lean body mass was entered first into the prediction models for the femoral neck, trochanter, Ward’s Area, and total hip indicating it was the strongest predictor variable for all the hip BMD sites. Estrogen use was included in the model for the femoral neck and Ward’s Area sites. Hip adduction was the only strength measure entered into the prediction models, where it was a signifi-
Total hip LBM Hip adduction Model R 2
0.558 0.299 0.427
0.000 0.028
R 2 —adjusted R 2 for each model.
cant predictor for the femoral neck and total hip sites.
4. Discussion The purpose of this study was to compare BMD, muscular strength, and body composition in estrogen-deficient and estrogen-replete postmenopausal women. In contrast to previous studies, we selected subjects within a relatively narrow age range (53– 65 years) whose estrogen status should have been stabilized based on the number
Table 5 Zero-order correlations between BMD and body composition/muscular strength variables BMD Site Spine L2–L4 Total hip Femoral neck Ward’s triangle Trochanter
FM 0.03 0.38a 0.25 0.03 0.58b
LBM 0.26 0.61a 0.65a 0.40 0.69b
Military press
Leg press
Hip abduction
Hip adduction
0.29 – – – –
– 0.24 0.21 0.21 0.19
– 0.20 0.12 0.13 0.12
– 0.40a 0.38a 0.29 0.32
P, 50.05; bP, 50.01. FM, fat mass; LBM, lean body mass.
a
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of years post menopause and duration of estrogen use. Additional strengths of our study include the assessments of muscle cross-sectional area, isotonic muscular strength for a variety of upper and lower body muscle groups and physical activity patterns. The results showed that while the estrogen-deficient women clearly had lower bone density than the estrogen users, muscle function and lean body mass were similar in the two groups. Thus, in contrast to its strong effects on bone tissue, long-term estrogen deficiency did not appear to negatively impact the muscular fitness and body composition of postmenopausal women. It is possible that our findings differ from previous studies reporting positive effects of estrogen treatment on muscle function, because, our subjects were older, well past perimenopause when the greatest loss of muscle strength occurs [17]. In addition, physical activity patterns, often not examined in previous studies, were similar for the two groups in this study. There have been a limited number of studies, which have examined the influence of estrogen use on muscular function in postmenopausal women. An equivocal number of studies have reported a positive effect [14,18,26] and no effect of ERT [2,12,20,24,27] on muscular strength. The findings of Phillips et al. [18] stimulated interest in the potential benefit of estrogen use in preventing the age-related decrease in muscle strength. They reported that the specific force (strength/cross-sectional area) of the adductor pollicis muscle decreased at the time of menopause in women not taking estrogen, whereas strength was maintained at the premenopausal levels in the estrogen users. Similarly, a prospective study by Skelton et al. [26] found a significant 12.4% increase in the strength of the adductor pollicis muscle with 12 months of hormone replacement therapy. Muscle hypertrophy did not account for the strength improvements as muscle cross-sectional area did not increase over the treatment period. Estrogen-related changes in non-contractile tissue, neural factors such as motor unit recruitment, and force production at the cross-bridge level have been proposed as possible explanations [17,26]. Other prospective studies reporting benefits of estrogen treatment on skeletal muscle function also in-
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cluded exercise programs as part of the intervention [14]. Although positive effects of estrogen treatment on muscle strength have been reported, the significance of these changes is not clear as the increases are relatively small ( 15%) compared with those observed in resistance training studies. For example, we have documented much larger increases (30%) in muscle strength and in muscle cross-sectional areas in early postmenopausal women not taking estrogen after 24 weeks of resistance training [4]. Thus, it seems that exercise programs easily counteract potential losses in muscle mass and strength associated with menopause. The ERT group had higher bone density than Non-ERT, significant at the total body, femoral neck and Ward’s Area sites when adjusted for body weight. A slower rate of bone turnover in ERT, as indicated by lower serum osteocalcin levels, also was documented. Although limited by the cross-sectional nature of the study, these results are in agreement with other studies [8] which indicated ERT is beneficial for increasing BMD and the prevention of osteoporosis. When examining variables that influenced BMD, it was surprising that the muscular strength variables in our study were not related to the BMD sites, with the exception of hip adduction strength. Conversely, other studies have found significant positive relationships between muscular strength and BMD [16,19,23] and that strength variables were significant predictors of BMD [16,19]. Quadriceps strength was reported to be a better predictor of tibial BMD than age, weight or height in women ranging in age from 21 to 78 years [16]. Similarly, Pocock et al. [19] found that femoral neck BMD was predicted by quadriceps strength in women 20– 75 years of age. Both of those studies included premenopausal and postmenopausal women, thus the correlations in our study likely were affected by the restricted age range of the subjects. The influence of body composition variables on bone mass is controversial as both fat mass and lean body mass have been found to be related to BMD. According to Reid et al. [21], the rate of bone loss in postmenopausal women was inversely related to fat mass and not to lean body mass. However, other researchers [15,29] have reported that the lean component of body weight also is a
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determinant of bone mass. Khosla et al. [15] found that both lean body mass and fat mass were important predictors of the spine and total hip BMD in postmenopausal women not taking estrogen. We found that lean body mass, not fat mass, was the most important predictor of all the hip BMD sites independent of estrogen use. In conclusion, estrogen use in postmenopausal women was associated with higher BMD and suppressed bone remodeling rates. However, body composition and muscular strength were similar for the ERT and non-estrogen replacement therapy groups, suggesting that long-term estrogen deficiency in these women did not negatively impact their muscular function. Acknowledgements This research was supported in part by Faculty Research Grants provided by the College of Arts and Sciences, and Research Administration at the University of Oklahoma. References [1] Aloia JF, McGowan D, Vaswani AN, Ross P, Cohn SH. Relationship of menopause to skeletal and muscle mass. Am J Clin Nutr 1991;53:1378 –83. [2] Armstrong AL, Oborne J, Coupland CA, MacPherson MB, Bassey EJ, Wallace WA. Effects of hormone replacement therapy on muscle performance and balance in post-menopausal women. Clin Sci 1996;91:685 –90. [3] Bassey EJ, Harries UJ. Normal values for hangrip strength in 920 men and women aged over 75 years, and longitudinal changes over 4 years in 620 survivors. Clin Sci 1993;84:331 – 7. [4] Bemben DA, Fetters NL, Bemben MG, Nabavi N, Koh ET. Musculoskeletal responses to high and low intensity resistance training in postmenopausal women. Med Sci Sports Exercise 2000;32:1949 –57. [5] Bemben MG, Clasey JL, Massey BH. The effect of the rate of muscle contraction on the force –time curve parameters of male and female subjects. Res Q Exercise Sport 1990;61:96 – 9. [6] Bemben MG, Stratemeier P. Reliability and validity of diagnostic ultrasound for assessing muscle size. Med Sci Sports Exercise 1999;31:S114. [7] Brown M, Birge SJ, Kohrt WM. Hormone replacement therapy does not augment gains in muscle strength or fat-free mass in response to weight-bearing exercise. J Gerontol Biol Sci 1997;52:B166 –70.
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enced by oestrogen status. Age Ageing 1995;24:329 – 33. [28] Washburn RA, Smith KW, Jette AM, Janney CA. The physical activity scale for the elderly (PASE): development and evaluation. J Clin Epidemiol 1993;46:153 – 62. [29] Zhen Z, Lohman TG, Stini WA, Ritenbaugh C, Aickin M. Fat or lean tissue mass: which one is the major determinant of bone mineral mass in health postmenopausal women? J Bone Miner Res 1997;12: 144 – 51.