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Relative influence of age and menopause on total and regional body composition changes in postmenopausal women
Relative influence of age and menopause on total and regional body composition changes in postmenopausal women Florence A. Tr6mollieres, MD, PhD, Jean-Michel Pouilles, MD, and Claude A. Ribot, MD Toulouse, France OBJECTIVE: We measured total and regional body composition to evaluate the differences in body composition associated with menopause and to determine whether the changes in fat distribution were more related to age or to menopause. STUDY DESIGN: Two hundred five healthy white women who had never received estrogen replacement therapy were studied according to menopausal status and age. Bone mass and body composition were measured by dual x-ray absorptiometry. The proportions of android and gynoid fat were calculated in all women and differences were sought by statistical analysis. RESULTS: Compared with premenopausal women, postmenopausal women were characterized by a significant increase in the proportion of android fat and the ratio trunk fat/leg fat, whereas the absolute amount of body fat mass did not significantly change. The different variables of android fat distribution tended to correlate better with years since menopause than with age. In multiple linear regression, years since menopause was a predictor of body fat mass and fat trunk, whereas age was not a predictor of any of the fat distribution variables. CONCLUSIONS: This study underlines the early changes in body fat distribution with a shift of body fat toward a more central location in postmenopausal women. This change in fat distribution appears to be more related to menopause than to age and might, together with other factors, contribute to explain the increased cardiovascular risk reported in postmenopausal women. (Am J Obstet Gynecol 1996;175:1594600.)
Key words: Body composition, menopause, dual x-ray absorptiometry, body fat distribution
Osteoporosis and cardiovascular diseases are the two major risks associated with the postmenopausal period. 1 It is well established that increased b o n e resorption and b o n e loss are related to estrogen deficiency, and n u m e r ous studies have d o c u m e n t e d the increased incidence of osteoporotic fractures with decreasing b o n e mass after menopause. 2 T h e risk factors for cardiovascular diseases are less well identified. Several factors have b e e n rep o r t e d to be associated with an increased risk for develo p m e n t of coronary heart diseases, such as changes in the lipid-lipoprotein profile, alterations of the arterial wall, and changes in vascular contractility or platelet aggregation. ~-5 In addition, changes in body fat distribution have b e e n related to the increased i n c i d e n c e of cardiovascular risk in postmenopausal women. Many studies have shown that upper-body obesity was associFrom the Unit~ FonctionneUe Mdnopause et Maladies Mdtaboliques, Service d'Endocrinologie, Centre Hospitalier Universitaire Purpan. Received for publication February 21, 1996; revised June 25, 1996; acceptedJune 27, 1996. Reprint requests: Florence Trimollieres, MD, PhD, UF Maladies Osseuses et Mdtaboliques, Service d'Endoerinologie, CHU Purpan, 31059 Toulouse Cedex, France. Copyrigkt © 1996 by Mosby-Year Book, Inc. 0002-9378/96 $5.00 + 0 6/1/76074 1594
ated with increased atherosclerosis risk. 6-8 Moreover, epidemiologic studies have shown that android fat distribution was significantly associated with cardiovascular morbidity and mortality, i n d e p e n d e n t of the degree of obesity. 7 T h e onset of m e n o p a u s e is characterized by changes in body composition. B o n e mass and lean mass decrease, whereas fat mass increases in postmenopausal women. Not only an increase in the a m o u n t of fat but also a m o r e android distribution of fat has b e e n r e p o r t e d in postmenopausal c o m p a r e d with p r e m e n o p a u s a l women. 911 However, f r o m these studies it is n o t completely clear w h e t h e r the changes in fat distribution were m o r e related to age or to menopause. T h e aim of this study was to evaluate the differences in body composition associated with m e n o p a u s e in a large group of w o m e n and to d e t e r m i n e w h e t h e r the observed changes in fat distribution were m o r e related to age or to menopause.
S u b j e c t s and m e t h o d s
Population. T h e study population consisted of 205 healthy white w o m e n aged 45 to 70 years. These w o m e n were selected f r o m those who a t t e n d e d our m e n o p a u s e
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Table I. Demographic characteristics of population Premen@ausal women ( n = 6S)
Age (yr) Height (cm) Weight (kg) BMI (kg/m 2) YSM (yr)
49.3 + 160.9 ± 56.1 ± 21.6 + 0
"Young" postmenopausal women (n = 100)
"Old" postmenopausal women (n = 37)
53.8 -+ 3.1" 160.2 +- 6 55.9 -+ 5.4 21.8 -+ 1.8 3.3 -+ 2.2*
64.1 -+ 4", t 158 ± 5.2 + 56'.6 ± 5.6 22.6 ± 2+,§ 11.2 ± 5.1+,§
3.2 5.9 6.4 1.9
BMI, Body mass index; YSM, years since menopause.
*Significantly different +Significantly different +Significantly different §Significantly different
from from from from
premenopausal women, p < 0.001. "young" postmenopausal women, p < 0.05. premenopausal women, p < 0.05. premenopausal women, p < 0.01.
clinic for a routine health check throughout a 6-month period between January and June 1994. Normality was assessed through interview and after extensive physical and biochemical examinations according to a procedure previously reported. 12'13 Briefly, exclusion criteria included history of disease and medication known to interfere with bone metabolism or body composition, including sex steroid therapy. None of the women exercised regularly, smoked, or had documented alcoholism. Women with obvious osteoarthritis or scoliosis on the scans were excluded. Additional exclusion criteria included history of premature menopause (before 40 years old) or surgical menopause. In addition, overweight women, defined as women with a body mass index (weight/height 2) >25, were excluded. Menopause was defined as amenorrhea of ->6 months' duration and was confirmed by measurements of plasma estradiol concentrations <20 p g / m l and plasma folliclestimulating h o r m o n e levels >30 I U / L . All women gave informed consent to participate in this study. Sixty-eight women (45 to 56 years old) were premenopausal (group 1) and 137 women (46 to 70'years old) were postmenopausal. Among the latter, subjects were classified as "young" postmenopausal women when age was <60 years (group 2, n = 100) or "old" when age was >60 years (group 3, n = 37). Methods. Height was measured to the nearest 0.1 cm with subjects in the erect position without shoes. Weight was measured with an electronic scale to the nearest 0.1 kg with subjects wearing indoor clothes without shoes. Bone mass and body composition were measured by dual x-ray absorptiometry with the Lunar DPX (Lunar, Madison, Wis.). Whole-body scans were performed with a transverse speed of 16 cm/sec, giving an average scan time of 10 to 15 minutes and radiation doses <1.5 txSv. Total body bone mass (in kilograms), lean tissue mass (in kilograms), and fat mass (in kilograms) were measured after daily calibration for the whole body. For regional body composition the default Lunar software readings divide the body into trunk, legs, and arms. The proportion of android fat was determined by the
proportion of fat in the trunk region (area between an upper horizontal border below the chin, a lower border formed by the oblique lines passing through the hip joints, and vertical borders lateral to the ribs), whereas the proportion of gynoid fat was determined by the proportion of fat in the leg region (area below the upper border formed by the oblique lines passing through the hip joints), both expressed as percent of total body fat. Previous studies have demonstrated the validity of dual x-ray absorptiometry determination of regional body fat distribution in the assessment of abdominal fat weight,9, 14 which is highly correlated with intraabdominal fat weight as measured by computerized tomography) 5 In addition, the fat percentage for total body, trunk, and leg was determined by the amount of fat in these regions expressed as percent of total body mass (including fat mass, lean mass, and bone mass). The ratio of the amount of fat in the trunk r e g i o n / f a t in the leg region was used as an index of android obesity. In our laboratory the precision errors (given as coefficient of variation percent and determined from three repeated measurements in 10 volunteer subjects scanned within 1 month) were 0.8% for total body bone mass, 1.4% for lean tissue mass, and 2.6% for fat mass. The precision errors for the regional measurements were as follows: trunk fat 2.8%, leg fat 2.3%, lean trunk 1.4%, and lean leg 2.1%. Statistical analysis. Statistical analyses were performed with Statview II Macintosh software. Analyses of variance together with two-tailed unpaired Student t tests were used to examine differences among groups. Pearson's correlation analyses and multiple linear regression analyses were used to determine whether age and years since menopause were predictors for the body composition variables. Results Demographic data. Demographic characteristics of the three groups are given in Table I. Body weight was comparable within the three groups, whereas height was
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Table II. Body c o m p o s i t i o n a n d relative c h a n g e s in d i s t r i b u t i o n o f b o d y c o m p o s i t i o n in t h r e e g r o u p s o f w o m e n
g
Total BMD (gm/cm ~) TBBM (kg) Lean tissue mass Total (kg) Trunk (kg) Leg (kg) Fat mass Total (kg) Trunk (kg) Leg (kg) Proportion of android fat (%) Proportion of gynoid fat (%) Trunk fat/leg fat
7
Group 3 vs group2 (%)
Group 2 (n = 100)
1.127 ± 0.07 2.35 ± 0.3
1.066 ± 0.07* 2.16 -+ 0.27*
1.015 ± 0.07*,t 1.99 ± 0.25",t
-5.4 -8.1
-4.8 -7.9
36.31 + 3.3 18 ± 2.6 11.8 ± 1.4
36.43 -+ 3.1 18.6 ± 1.7 11.7 _+ 1.2
34.94 ± 3+,§ 18.1 ± 1.8 11.1 ÷ 1§,[]
+0.3 +3.3 -0.85
-4.1 -2.7 -5.1
17.76 8.3 6.02 46.2 34.5 1.37
17.83 8.68 5.82 48.3 33.2 1.49
19.57 9.61 6.49 49 32.9 1.54
+0.3 +4.6 -3.3 +4.5 -3.8 +8.8
+9.7 +10.7 +11.5 + 1.4 -0.9 +3.3
± 4.7 -+ 2.6 -+ 1.3 -+ 4.411 ± 4.3 -+ 0.3 +
Group 3 (n = 37)
Group 2 vs | group 1 ~ (%)
Group l (n=68)
-+ 4.6 + 2.5 -+ 1.4 -+ 4.4 -+ 4.8 _+ 0.3
| 1
% change
-+ 4.8++,§ -+ 2.3§,[I +- 1.9§ ± 5.411 -+ 4.9 ± 0.4[]
BMD, Bone mineral density; TBBM, total body bone mass. *p < 0.001, compared with group 1. tP < 0.001, compared with group 2 (analysis of variance). ++p< 0.05, compared with group 1. §p < 0.05, compared with group 2. liP < 0.01, compared with group 1.
lower in g r o u p 3 c o m p a r e d with g r o u p s 1 a n d 2. Body mass i n d e x was thus h i g h e r in this latter g r o u p . W o m e n in g r o u p s 2 a n d 3 were p o s t m e n o p a u s a l with a m e a n d u r a t i o n o f m e n o p a u s e o f 3.3 _+ 2.2 years a n d 11.2 -+ 5.1 years, respectively.
Menopausal status differences in body composition. A l t h o u g h t h e r e was n o significant difference in b o d y w e i g h t a m o n g the t h r e e groups, b o d y c o m p o s i t i o n was different in p o s t m e n o p a u s a l w o m e n (Table II). Total b o d y mass a n d lean tissue mass were lower, w h e r e a s fat b o d y mass was g r e a t e r in p o s t m e n o p a u s a l w o m e n t h a n in p r e m e n o p a u s a l w o m e n . T h e s e c h a n g e s were significantly a c c e n t u a t e d in "old" p o s t m e n o p a u s a l w o m e n . I n g r o u p 2 b o t h l e a n tissue mass a n d its d i s t r i b u t i o n d i d n o t significantly c h a n g e c o m p a r e d with those o f p r e m e n o p a u s a l w o m e n . I n g r o u p 3 a m e a n significant d e c r e a s e in total lean tissue mass a n d leg lean mass o f 4.1% a n d 5.1%, respectively, was n o t e d c o m p a r e d with "young" p o s t m e n o p a u s a l w o m e n . A l t h o u g h t h e a b s o l u t e a m o u n t o f b o d y fat mass d i d n o t significantly c h a n g e in g r o u p 2 c o m p a r e d with g r o u p 1, t h e d i s t r i b u t i o n o f fat mass was s i g n i f i c a n t l y d i f f e r e n t in t h e f o r m e r g r o u p t h a n in t h e latter. T h e p r o p o r t i o n o f a n d r o i d fat was g r e a t e r in "young" p o s t m e n o p a u s a l w o m e n t h a n in p r e m e n o p a u s a l w o m e n ( + 4 . 5 % , p < 0.001). T h e t r u n k f a t / l e g fat ratio was also i n c r e a s e d in g r o u p 2 c o m p a r e d with g r o u p 1 ( + 8 . 8 % , p < 0.05). I n "old" p o s t m e n o p a u s a l w o m e n ( g r o u p 3) t h e absolute a m o u n t o f fat was significantly i n c r e a s e d c o m p a r e d with "young" p o s t m e n o p a u s a l w o m e n , b u t this i n c r e a s e was a l m o s t similar for t r u n k a n d legs. T h e d i s t r i b u t i o n o f fat
mass was t h e r e f o r e n o t significantly different b e t w e e n t h e two p o s t m e n o p a u s e groups. However, c o m p a r e d with p r e m e n o p a u s a l w o m e n , t h e a n d r o i d fat d i s t r i b u t i o n was a g a i n a c c e n t u a t e d in "old" p o s t m e n o p a u s a l w o m e n .
Changes in body fat composition with age and years since menopause Simple linear regression analyses (Table III). Total b o d y b o n e mass was inversely r e l a t e d to b o t h age (r = - 0 . 3 9 , p < 0.001) a n d years since m e n o p a u s e (r = - 0 . 3 9 , p < 0.001). Also, l e a n mass was inversely r e l a t e d to age (r = - 0 . 1 6 , p < 0.05) a n d years since m e n o p a u s e (r = - 0 . 2 0 , p < 0.01). I n contrast, b o d y fat mass d i d n o t c o r r e l a t e with e i t h e r age or years since m e n o p a u s e . However, w h e n b o t h b o d y fat mass a n d t r u n k fat were e x p r e s s e d as a p e r c e n t a g e of total b o d y mass, t h e s e two variables were m o r e strongly c o r r e l a t e d with years since m e n o p a u s e t h a n with age (r = 0.20 vs r = 0.15 a n d r = 0,24 vs r = 0.18, for b o d y fat mass a n d t r u n k fat, respectively) (Table III). T h e p r o p o r t i o n o f a n d r o i d fat i n c r e a s e d b o t h with age a n d years since m e n o p a u s e ( r = 0.18, p < 0.01 a n d r = 0.19, p < 0.01, respectively), w h e r e a s the absolute a m o u n t of leg fat a n d t h e p r o p o r t i o n o f g y n o i d fat were r e l a t e d n e i t h e r to age n o r to years since m e n o p a u s e . When the relationship between the proportion of a n d r o i d fat a n d years since m e n o p a u s e was tested by stratification in 3-year g r o u p s (Fig. 1), t h e p r o p o r t i o n o f a n d r o i d fat was significantly i n c r e a s e d in all p o s t m e n o pausal g r o u p s c o m p a r e d with t h e p r e m e n o p a u s a l g r o u p (p < 0.05, analysis of variance). W h e n this r e l a t i o n s h i p was tested by stratification in 5-year age groups, a signif-
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Am J Obstet Gynecol
YEARS
AGE
SINCE
MENOPAUfIE
FAT (k s ) Is'
~
II
I
NS
N$ o .......... o . . . . . . . . o ' 1
" ° ......... o
O .............O ............... ~O'......... O ~ I ~ / O
NS
i (411
4~9
(~l|
~.
(-17)
5s:~
121)
~
(14,)
>6s
qvJ
o
(4,g)
(43)
(44)
(21)
~-~1
PM
0-3
3-6
~
)~
I~,J
F A T (%) -;-~
II
4oi 4O
j; i
35
o ............... ~ ............., ~ - ' - - o
~ - ' ~ ' ~ - ~ - O ~.................0 NS
i i
~0
....... o m
i
~q
25
Pm
o:3
3.,
~4
Fig. 1. Relationship between age and years since menopause and (/) trunk fat (closed circles) and leg fat (open circles) expressed in kilograms; I/, proportion of android fat (closed circles) and proportion of gynoid fat (open circles) expressed as percentage of total body fat mass in 205 women aged 45 to 70 years. Numbers in parentheses indicate number of subjects in each group. The p indicates significance of relationship between variables of body composition and age or years since menopause (analysis of variance). Asterisk, p < 0.05 compared with premenopausal women; double dagger, p < 0.05 compared with age 45 to 49 years.
T a b l e III. C o r r e l a t i o n coefficients of b o d y c o m p o s i t i o n variables o n age a n d years since m e n o p a u s e
Variables
With age
With YSM
TMMB (kg) Lean (kg) Fat (kg) Fat (%)§ Trunk fat (kg) Trunk fat (%)§ Proportion of android fat (%)11 Leg fat (kg) Leg fat (%)§ Proportion of gynoid fat (%)]1 Trunk fat/leg fat
-0.39* -0.16t 0.08 0.15~0.12 0.18 + 0-18+ 0.04 0.08 -0.12 0.17]-
-0.39* -0.20 + 0.12 0.20 + 0.16t 0.24 + 0.19+ 0.07 0.12 -0.13 0.195
YSM, Years since menopause; TBBM, total body bone mass. 0.001. t P < 0.05. ++p< 0.01.
• *p <
§As percentage of total body mass. ]lAs percentage of total fat mass.
icantly h i g h e r p r o p o r t i o n o f a n d r o i d fat was f o u n d f r o m t h e 60 to 64 year age g r o u p o n w a r d c o m p a r e d with t h e y o u n g e s t g r o u p (45 to 49 years), N o n e o f t h e s e calculations r e v e a l e d any differences b e t w e e n t h e a b s o l u t e a m o u n t o f a n d r o i d fat a n d g y n o i d fat or t h e p r o p o r t i o n o f g y n o i d fat within t h e different groups.
Multiple regression analyses (Table IV). Years since m e n o p a u s e was a significant p r e d i c t o r o f b o d y fat mass a n d t r u n k fat e x p r e s s e d as p e r c e n t a g e of total b o d y mass, w h e r e a s age was n o t a p r e d i c t o r o f any o f t h e fat d i s t r i b u t i o n variables. O n t h e o t h e r h a n d , age was a significant p r e d i c t o r o f total b o d y b o n e mass (p < 0.05).
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Table IV. Multiple linear regression of body composition variables on age and years since m e n o p a u s e
Variables T B B M (kg) Lean (kg) Fat (kg) Fat (%)+ Trunk fat (kg) Trunk fat (%)+ Proportion of android fat (%)[] Leg fat (kg) Leg fat (%)+ Proportion of gynoid fat (%)]1 Trunk fat/leg fat
Age eoefcient -0.012 0.010 -0.044 -0.065 -0.015 -0.024 0.057 -0.015 -0.021 -0.026 0.003
YSM coefficient
(0.005)* (0.06) (0.09) (0.12) (0.005) (0.07) (0.10) (0.03) (0.04) (0.1) (0.007)
-0.012 (0.007) -0.15 (0.08) 0.17 (0.12) 0.33 (0.16)* 0.10 (0.007) 0.20 (0.09)* 0.13 (0.13) 0.040 (0.04) 0.075 (0.05) -0.11 (0.12) 0.01 (0.009)
o.41t 0.20* 0.13 0.21" 0.16 0.24§ 0.20* 0.08 0.12 0.14 0.20*
YSM, Years since menopause; TBBM, total body bone mass. *p < 0.05. tP < 0.001. ++Aspercentage of total body mass. §p < 0.01. ]]As pcercentage of total fat mass.
Comment We used dual x-ray absorptiometry m e a s u r e m e n t s to study the effect of m e n o p a u s e on body composition in a large group of healthy normal-weight women. A l t h o u g h this study was cross-sectional, which m i g h t n o t allow a robust e x a m i n a t i o n of the effects of m e n o p a u s e on body composition changes, it can be n o t e d that o u r population was very h o m o g e n e o u s so far as the physical characteristics were c o n c e r n e d and most of the w o m e n did n o t differ for > 5 years of age a r o u n d menopause. In a g r e e m e n t with previously published findings, 941' 16 our results indicate that b o n e and lean mass were lower and that fat mass h i g h e r in postmenopausal w o m e n comp a r e d with p r e m e n o p a u s a l women. It is interesting to u n d e r l i n e that these changes, especially those concerning fat mass, were not the c o n s e q u e n c e of increased body weight, because our three groups did n o t significantly differ in body weight. T h e r e f o r e the observed changes in body composition a p p e a r e d to be m o r e related to relative changes in the distribution of the three c o m p o n e n t s of body composition than to a body weight effect. T h e most striking finding was the effect of m e n o p a u s e on fat distribution. T h e r e was an early increase in android fat and a relative reduction in gynoid fat, whereas, at least within the first years after menopause, total fat mass did not significantly increase. In our youngest postmenopausal g r o u p (group 2) with a m e a n years since m e n o p a u s e of 3.3 years, the p r o p o r t i o n of a n d r o i d fat increased t o about 4.5%, whereas the total a m o u n t of fat did n o t change c o m p a r e d with p r e m e n o pausal women. Moreover, all index values of u p p e r body fat distribution were f o u n d to be m o r e strongly correlated with years since m e n o p a u s e than with age. W h e n the relationship between the p r o p o r t i o n of android fat and years since m e n o p a u s e was tested by stratification in
3-year intervals, android fat was f o u n d to be significantly h i g h e r in postmenopausal w o m e n within 3 years of m e n o p a u s e c o m p a r e d with p r e m e n o p a u s a l women. A previous study that was based on dual x-ray absorptiometry m e a s u r e m e n t s had also shown that m e n o p a u s e may affect fat distribution but that the i n d e p e n d e n t effect of age and m e n o p a u s e could n o t be distinguished because there was an age difference of > 2 0 years between the two groups of p r e m e n o p a u s a l and postmenopausal women. 9 In our study there was only a slight difference in age between postmenopausal w o m e n who were within 3 years of m e n o p a u s e and p r e m e n o p a u s a l w o m e n (52.2 + 3.2 years old vs 49.3 _+ 3.3 years old). This strongly suggests that there is a m e n o p a u s e effect on fat distribution rather than an age effect. O n the o t h e r hand, o t h e r studies have r e p o r t e d that a n d r o i d fat distribution significantly correlated with age but n o t with years since menopause.i0, IS, 16 However, only postmenopausal w o m e n were evaluated in these studies, which m i g h t have partly diminished the effect of m e n o p a u s e onset on fat distribution. Finally, h o r m o n a l r e p l a c e m e n t therapy given in early postmenopausal w o m e n has b e e n shown to prevent the shifting of body fat to a m o r e central location. I7 These findings, t o g e t h e r with our own data, therefore strongly support the role of sex h o r m o n e concentrations on body fat distribution. T h e a n d r o i d fat distribution has b e e n linked to hyperinsulinemia resulting from insulin resistance or alteration in lipid profiles, which are factors associated with an increased risk in cardiovascular diseases. ls-2° T h e r e f o r e it is possible that both an increase in fat mass and a shift of body fat toward an u p p e r body location may in part contribute to explain the h i g h e r risk in cardiovascular diseases r e p o r t e d in postmenopausal women.
Volume 175, Number 6 AmJ Obstet GynecoI
In contrast to the increase in fat mass, a r e d u c t i o n in b o t h b o n e mass and lean mass was f o u n d in postmenopausal w o m e n c o m p a r e d with p r e m e n o p a u s a l women. T h e r e d u c t i o n in b o n e mass with aging is well established for the spine and the proximal f e m u r as well as for the whole skeleton. B o n e mass decreases as a n o n l i n e a r function with aging showing an acceleration at m e n o pause. In !ongitudinal studies we have previously shown that, within the first 3 years after m e n o p a u s e , there is an accelerated phase of vertebral and femoral b o n e loss that lasts only a few years. 21' 99 We also f o u n d a significantly h i g h e r r e d u c t i o n in total body mass within the first years after m e n o p a u s e , suggesting that our previous findings m i g h t also apply to the whole skeleton. Only a few studies have d e m o n s t r a t e d a decrease of lean body mass with aging, especially muscle mass as d e t e r m i n e d by the total potassium method. In the study by Aloia et al., 23 the r e d u c t i o n in total body potassium is maximal within the first 3 years after menopause, with a pattern of loss similar to that of total body calcium m e a s u r e d by n e u t r o n activation. In o u r study the decrease in lean mass was h i g h e r for legs, which m i g h t suggest the role of mechanical factors rather than a h o r m o n a l influence. 24 This decrease in lean mass is likely to be the result of an increasingly sedentary lifestyle and r e d u c e d protein intake with increasing age. In sedentary w o m e n it has b e e n hypothesized to explain the r e d u c e d energy e x p e n d i t u r e f o u n d in postmenopausal women, which could contribute, t o g e t h e r with increased energy intake, to the body weight increase r e p o r t e d with aging. 25 Moreover, our results m i g h t be even overestimated in o t h e r populations such as U.S. w o m e n who have a different lifestyle and d i e t t h a n do F r e n c h w o m e n . T h u s m a i n t a i n i n g body w e i g h t a n d d i s t r i b u t i o n t h r o u g h active exercise a n d energy-restrictive diets s h o u l d be advised after m e n o p a u s e to c o n t r i b u t e to r e d u c e the cardiovascular risk a c c e l e r a t i o n that occurs postmenopausally. This c u r r e n t study confirms the changes in body composition f o u n d in postmenopausal women. It underlines the early changes in body fat distribution with a shifting of fat mass toward an u p p e r body location observed even in the absence of a significant change in the total a m o u n t of body fat mass. Changes in fat distribution appear to be m o r e related to m e n o p a u s e than to age, which is m o r e directly c o n f i r m e d by the preventive effect of estrogen r e p l a c e m e n t therapy on the increase in android fat mass. In postmenopausal w o m e n the increase in fat mass and a m o r e android fat distribution m i g h t contribute, together with o t h e r factors, to explain the worsening cardiovascular risk associated with estrogen deficiency. Accordingly, preventive therapy should be initiated as soon as possible after m e n o p a u s e to p r e v e n t this risk.
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REFERENCES
1. Cummings SR, Black DM, Rubin SM. Lifetime risks of hip, Colles', or vertebral fracture and coronary heart disease among white postmenopausal women. Arch Intern Med 1989;149:2445-8. 2. Melton LJ, Atkinson EJ, O'Fallon WM, Wahner HW, Riggs BL. Long-term fracture prediction by bone mineral density assessed at different skeletal sites. J Bone Miner Res 1993;8: 1227-34. 3. Barret-Connor E, Bush TL. Estrogen and coronary heart disease in women. JAMA 1991;265:1861-7. 4. Sarrel PM, Lindsay D, Rosno GMC, Poole-Wilson PA. Angina and normal coronary arteries in women: gynecologic findings. A m J Obstet Gynecol 1992;1687:467-72. 5. Scarabin PY, Bonithon-Kopp C, Bara L, Guize L, Samama M. Relationship between plasminogen activator inhibitor activity and menopausal status. Fibrinolysis 1990;4:233-6. 6. Vague J. The degree of masculine differentiation of obesities: a factor determining predisposition to diabetes, atherosclerosis, gout and uric calculus disease. Am J Clin Nutr 1956;4:20-34. 7. Lapidus L, Bengtsson C, Larsson S, Pennert K, Rybo E, Sjostrom L. Distribution of adipose tissue and risk of cardio-vascular disease and death: a 12-year follow-up of participants in the population study of women in Gothenburg, Sweden. BMJ 1984;289:1257-68. 8. Larsson B, Svarsudd K, Welin L, Wilhelmsem L, Bjorntorp P, Tibblin G. Abdominal adipose tissue distribution, obesity and risk of cardiovascular disease and death: 13 year follow up of participants in the study of men born in 1913. BMJ 1984;288:1401-4. 9. Ley CJ, Lees B, Stevenson JC. Sex- and menopause-associated changes in body-fat distribution. Am J Clin Nutr 1992;53:1378-83. 10. Wang O~ Hassager C, Ravn P, Wang S, Christiansen C. Total and regional body-composition changes in early postmenopausal women: age-related or menopause-related? AmJ Clin Nutr 1994;60:843-8. 11. Lindsay R, Cosman F, Herrington BS, Himmelstein S. Bone mass and body composition in normal women. J Bone Miner Res 1992;7:55-63. 12. Ribot C, Tremollieres F, PouillesJM, LouvetJP, Guiraud R. Influence of the menopause and aging on spinal density in French women. Bone Mineral 1988;5:89-95. 13. Ribot C, Bonneu M, PouillesJM, Tremollieres F. Assessment of the risk of postmenopausal osteoporosis using clinical factors. Clin Endocrinol (Oxf) 1992;36:225-8. 14. Svendsen OL, Hassager C, Christiansen C. Relationships and independence of body composition, sex hormones, fat distribution and other cardiovascular risk factors in overweight women. IntJ Obes 1993;17:459-63. 15. Svendsen OL, Hassager C, Bergmann I, Christiansen C. Measurement of abdominal and intra-abdominal fat in postmenopausal women by dual energy x-ray absorptiometry: comparison with computerized tomography. IntJ Obes 1993;17:45-51. 16. Poehtman ET, Toth MJ, Gardner AW. Changes in energy balance and body composition at menopause: a controlled longitudinal study. Ann Intern Med 1995;123:673-5. 17. Haarbo J, Marslew U, Gotfredsen A, Christiansen C. Postmenopausal hormone replacement therapy prevents central distribution of body fat after menopause. Metabolism 1991;12:1323-6. 18. Lonnroth P. Potential role of adipose tissue for the development of insulin resistance in obesity. Acta Med Scand 1988;723:91-4. 19. Soler JT, Folsom AR, Kaye SA, Prineas RJ. Associations of abdominal adiposity, fasting insulin, and sex hormone binding globulin with lipids and lipoproteins in post-menopausal women. Atherosclerosis 1989;79:21-7. 20. Ostlund RE, Staten M, Kohrt ~rM, SchultzJ, Malley M. The ratio of waist-to-hip circumference, plasma insulin level, and
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glucose intolerance as independent predictors of HDL2 cholesterol level in older adults. N Engl J Med 1990;322: 229-34. 21. Pouilles JM, Tremollieres F, Ribot C. The effects of menopause on longitudinal bone loss from the spine. Calcif Tissue Int 1993;52:340-3. 22. Pouilles JM, Tremollieres F, Ribot C. Effects of menopause on femoral and vertebral bone loss. J Bone Miner Res 1995;10:1531-6.
23. Aloia JF, McGowan DM, Vaswani AN, Ross P, Cohn SH. Relationship of menopause to skeletal and muscle mass. A m J Clin Nutr 1991;53:1378-83. 24. Reid IR, Legge M, Stapleton JP, Evans MC, Grey AB. Regular exercise dissociates fat mass and bone density in premenopausal women. J Clin Endocrinol Metab 1995;80:1764-8. 25. Wing RR, Matthews KA, Kuller LH, Meilahn EN, Plantinga PL. Weight gain at the time of menopause. Arch Intern Med 1991;151:97-102.
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Key words: Body composition, menopause, dual x-ray absorptiometry, body fat distribution
Osteoporosis and cardiovascular diseases are the two major risks associated with the postmenopausal period. 1 It is well established that increased b o n e resorption and b o n e loss are related to estrogen deficiency, and n u m e r ous studies have d o c u m e n t e d the increased incidence of osteoporotic fractures with decreasing b o n e mass after menopause. 2 T h e risk factors for cardiovascular diseases are less well identified. Several factors have b e e n rep o r t e d to be associated with an increased risk for develo p m e n t of coronary heart diseases, such as changes in the lipid-lipoprotein profile, alterations of the arterial wall, and changes in vascular contractility or platelet aggregation. ~-5 In addition, changes in body fat distribution have b e e n related to the increased i n c i d e n c e of cardiovascular risk in postmenopausal women. Many studies have shown that upper-body obesity was associFrom the Unit~ FonctionneUe Mdnopause et Maladies Mdtaboliques, Service d'Endocrinologie, Centre Hospitalier Universitaire Purpan. Received for publication February 21, 1996; revised June 25, 1996; acceptedJune 27, 1996. Reprint requests: Florence Trimollieres, MD, PhD, UF Maladies Osseuses et Mdtaboliques, Service d'Endoerinologie, CHU Purpan, 31059 Toulouse Cedex, France. Copyrigkt © 1996 by Mosby-Year Book, Inc. 0002-9378/96 $5.00 + 0 6/1/76074 1594
ated with increased atherosclerosis risk. 6-8 Moreover, epidemiologic studies have shown that android fat distribution was significantly associated with cardiovascular morbidity and mortality, i n d e p e n d e n t of the degree of obesity. 7 T h e onset of m e n o p a u s e is characterized by changes in body composition. B o n e mass and lean mass decrease, whereas fat mass increases in postmenopausal women. Not only an increase in the a m o u n t of fat but also a m o r e android distribution of fat has b e e n r e p o r t e d in postmenopausal c o m p a r e d with p r e m e n o p a u s a l women. 911 However, f r o m these studies it is n o t completely clear w h e t h e r the changes in fat distribution were m o r e related to age or to menopause. T h e aim of this study was to evaluate the differences in body composition associated with m e n o p a u s e in a large group of w o m e n and to d e t e r m i n e w h e t h e r the observed changes in fat distribution were m o r e related to age or to menopause.
S u b j e c t s and m e t h o d s
Population. T h e study population consisted of 205 healthy white w o m e n aged 45 to 70 years. These w o m e n were selected f r o m those who a t t e n d e d our m e n o p a u s e
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Table I. Demographic characteristics of population Premen@ausal women ( n = 6S)
Age (yr) Height (cm) Weight (kg) BMI (kg/m 2) YSM (yr)
49.3 + 160.9 ± 56.1 ± 21.6 + 0
"Young" postmenopausal women (n = 100)
"Old" postmenopausal women (n = 37)
53.8 -+ 3.1" 160.2 +- 6 55.9 -+ 5.4 21.8 -+ 1.8 3.3 -+ 2.2*
64.1 -+ 4", t 158 ± 5.2 + 56'.6 ± 5.6 22.6 ± 2+,§ 11.2 ± 5.1+,§
3.2 5.9 6.4 1.9
BMI, Body mass index; YSM, years since menopause.
*Significantly different +Significantly different +Significantly different §Significantly different
from from from from
premenopausal women, p < 0.001. "young" postmenopausal women, p < 0.05. premenopausal women, p < 0.05. premenopausal women, p < 0.01.
clinic for a routine health check throughout a 6-month period between January and June 1994. Normality was assessed through interview and after extensive physical and biochemical examinations according to a procedure previously reported. 12'13 Briefly, exclusion criteria included history of disease and medication known to interfere with bone metabolism or body composition, including sex steroid therapy. None of the women exercised regularly, smoked, or had documented alcoholism. Women with obvious osteoarthritis or scoliosis on the scans were excluded. Additional exclusion criteria included history of premature menopause (before 40 years old) or surgical menopause. In addition, overweight women, defined as women with a body mass index (weight/height 2) >25, were excluded. Menopause was defined as amenorrhea of ->6 months' duration and was confirmed by measurements of plasma estradiol concentrations <20 p g / m l and plasma folliclestimulating h o r m o n e levels >30 I U / L . All women gave informed consent to participate in this study. Sixty-eight women (45 to 56 years old) were premenopausal (group 1) and 137 women (46 to 70'years old) were postmenopausal. Among the latter, subjects were classified as "young" postmenopausal women when age was <60 years (group 2, n = 100) or "old" when age was >60 years (group 3, n = 37). Methods. Height was measured to the nearest 0.1 cm with subjects in the erect position without shoes. Weight was measured with an electronic scale to the nearest 0.1 kg with subjects wearing indoor clothes without shoes. Bone mass and body composition were measured by dual x-ray absorptiometry with the Lunar DPX (Lunar, Madison, Wis.). Whole-body scans were performed with a transverse speed of 16 cm/sec, giving an average scan time of 10 to 15 minutes and radiation doses <1.5 txSv. Total body bone mass (in kilograms), lean tissue mass (in kilograms), and fat mass (in kilograms) were measured after daily calibration for the whole body. For regional body composition the default Lunar software readings divide the body into trunk, legs, and arms. The proportion of android fat was determined by the
proportion of fat in the trunk region (area between an upper horizontal border below the chin, a lower border formed by the oblique lines passing through the hip joints, and vertical borders lateral to the ribs), whereas the proportion of gynoid fat was determined by the proportion of fat in the leg region (area below the upper border formed by the oblique lines passing through the hip joints), both expressed as percent of total body fat. Previous studies have demonstrated the validity of dual x-ray absorptiometry determination of regional body fat distribution in the assessment of abdominal fat weight,9, 14 which is highly correlated with intraabdominal fat weight as measured by computerized tomography) 5 In addition, the fat percentage for total body, trunk, and leg was determined by the amount of fat in these regions expressed as percent of total body mass (including fat mass, lean mass, and bone mass). The ratio of the amount of fat in the trunk r e g i o n / f a t in the leg region was used as an index of android obesity. In our laboratory the precision errors (given as coefficient of variation percent and determined from three repeated measurements in 10 volunteer subjects scanned within 1 month) were 0.8% for total body bone mass, 1.4% for lean tissue mass, and 2.6% for fat mass. The precision errors for the regional measurements were as follows: trunk fat 2.8%, leg fat 2.3%, lean trunk 1.4%, and lean leg 2.1%. Statistical analysis. Statistical analyses were performed with Statview II Macintosh software. Analyses of variance together with two-tailed unpaired Student t tests were used to examine differences among groups. Pearson's correlation analyses and multiple linear regression analyses were used to determine whether age and years since menopause were predictors for the body composition variables. Results Demographic data. Demographic characteristics of the three groups are given in Table I. Body weight was comparable within the three groups, whereas height was
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Table II. Body c o m p o s i t i o n a n d relative c h a n g e s in d i s t r i b u t i o n o f b o d y c o m p o s i t i o n in t h r e e g r o u p s o f w o m e n
g
Total BMD (gm/cm ~) TBBM (kg) Lean tissue mass Total (kg) Trunk (kg) Leg (kg) Fat mass Total (kg) Trunk (kg) Leg (kg) Proportion of android fat (%) Proportion of gynoid fat (%) Trunk fat/leg fat
7
Group 3 vs group2 (%)
Group 2 (n = 100)
1.127 ± 0.07 2.35 ± 0.3
1.066 ± 0.07* 2.16 -+ 0.27*
1.015 ± 0.07*,t 1.99 ± 0.25",t
-5.4 -8.1
-4.8 -7.9
36.31 + 3.3 18 ± 2.6 11.8 ± 1.4
36.43 -+ 3.1 18.6 ± 1.7 11.7 _+ 1.2
34.94 ± 3+,§ 18.1 ± 1.8 11.1 ÷ 1§,[]
+0.3 +3.3 -0.85
-4.1 -2.7 -5.1
17.76 8.3 6.02 46.2 34.5 1.37
17.83 8.68 5.82 48.3 33.2 1.49
19.57 9.61 6.49 49 32.9 1.54
+0.3 +4.6 -3.3 +4.5 -3.8 +8.8
+9.7 +10.7 +11.5 + 1.4 -0.9 +3.3
± 4.7 -+ 2.6 -+ 1.3 -+ 4.411 ± 4.3 -+ 0.3 +
Group 3 (n = 37)
Group 2 vs | group 1 ~ (%)
Group l (n=68)
-+ 4.6 + 2.5 -+ 1.4 -+ 4.4 -+ 4.8 _+ 0.3
| 1
% change
-+ 4.8++,§ -+ 2.3§,[I +- 1.9§ ± 5.411 -+ 4.9 ± 0.4[]
BMD, Bone mineral density; TBBM, total body bone mass. *p < 0.001, compared with group 1. tP < 0.001, compared with group 2 (analysis of variance). ++p< 0.05, compared with group 1. §p < 0.05, compared with group 2. liP < 0.01, compared with group 1.
lower in g r o u p 3 c o m p a r e d with g r o u p s 1 a n d 2. Body mass i n d e x was thus h i g h e r in this latter g r o u p . W o m e n in g r o u p s 2 a n d 3 were p o s t m e n o p a u s a l with a m e a n d u r a t i o n o f m e n o p a u s e o f 3.3 _+ 2.2 years a n d 11.2 -+ 5.1 years, respectively.
Menopausal status differences in body composition. A l t h o u g h t h e r e was n o significant difference in b o d y w e i g h t a m o n g the t h r e e groups, b o d y c o m p o s i t i o n was different in p o s t m e n o p a u s a l w o m e n (Table II). Total b o d y mass a n d lean tissue mass were lower, w h e r e a s fat b o d y mass was g r e a t e r in p o s t m e n o p a u s a l w o m e n t h a n in p r e m e n o p a u s a l w o m e n . T h e s e c h a n g e s were significantly a c c e n t u a t e d in "old" p o s t m e n o p a u s a l w o m e n . I n g r o u p 2 b o t h l e a n tissue mass a n d its d i s t r i b u t i o n d i d n o t significantly c h a n g e c o m p a r e d with those o f p r e m e n o p a u s a l w o m e n . I n g r o u p 3 a m e a n significant d e c r e a s e in total lean tissue mass a n d leg lean mass o f 4.1% a n d 5.1%, respectively, was n o t e d c o m p a r e d with "young" p o s t m e n o p a u s a l w o m e n . A l t h o u g h t h e a b s o l u t e a m o u n t o f b o d y fat mass d i d n o t significantly c h a n g e in g r o u p 2 c o m p a r e d with g r o u p 1, t h e d i s t r i b u t i o n o f fat mass was s i g n i f i c a n t l y d i f f e r e n t in t h e f o r m e r g r o u p t h a n in t h e latter. T h e p r o p o r t i o n o f a n d r o i d fat was g r e a t e r in "young" p o s t m e n o p a u s a l w o m e n t h a n in p r e m e n o p a u s a l w o m e n ( + 4 . 5 % , p < 0.001). T h e t r u n k f a t / l e g fat ratio was also i n c r e a s e d in g r o u p 2 c o m p a r e d with g r o u p 1 ( + 8 . 8 % , p < 0.05). I n "old" p o s t m e n o p a u s a l w o m e n ( g r o u p 3) t h e absolute a m o u n t o f fat was significantly i n c r e a s e d c o m p a r e d with "young" p o s t m e n o p a u s a l w o m e n , b u t this i n c r e a s e was a l m o s t similar for t r u n k a n d legs. T h e d i s t r i b u t i o n o f fat
mass was t h e r e f o r e n o t significantly different b e t w e e n t h e two p o s t m e n o p a u s e groups. However, c o m p a r e d with p r e m e n o p a u s a l w o m e n , t h e a n d r o i d fat d i s t r i b u t i o n was a g a i n a c c e n t u a t e d in "old" p o s t m e n o p a u s a l w o m e n .
Changes in body fat composition with age and years since menopause Simple linear regression analyses (Table III). Total b o d y b o n e mass was inversely r e l a t e d to b o t h age (r = - 0 . 3 9 , p < 0.001) a n d years since m e n o p a u s e (r = - 0 . 3 9 , p < 0.001). Also, l e a n mass was inversely r e l a t e d to age (r = - 0 . 1 6 , p < 0.05) a n d years since m e n o p a u s e (r = - 0 . 2 0 , p < 0.01). I n contrast, b o d y fat mass d i d n o t c o r r e l a t e with e i t h e r age or years since m e n o p a u s e . However, w h e n b o t h b o d y fat mass a n d t r u n k fat were e x p r e s s e d as a p e r c e n t a g e of total b o d y mass, t h e s e two variables were m o r e strongly c o r r e l a t e d with years since m e n o p a u s e t h a n with age (r = 0.20 vs r = 0.15 a n d r = 0,24 vs r = 0.18, for b o d y fat mass a n d t r u n k fat, respectively) (Table III). T h e p r o p o r t i o n o f a n d r o i d fat i n c r e a s e d b o t h with age a n d years since m e n o p a u s e ( r = 0.18, p < 0.01 a n d r = 0.19, p < 0.01, respectively), w h e r e a s the absolute a m o u n t of leg fat a n d t h e p r o p o r t i o n o f g y n o i d fat were r e l a t e d n e i t h e r to age n o r to years since m e n o p a u s e . When the relationship between the proportion of a n d r o i d fat a n d years since m e n o p a u s e was tested by stratification in 3-year g r o u p s (Fig. 1), t h e p r o p o r t i o n o f a n d r o i d fat was significantly i n c r e a s e d in all p o s t m e n o pausal g r o u p s c o m p a r e d with t h e p r e m e n o p a u s a l g r o u p (p < 0.05, analysis of variance). W h e n this r e l a t i o n s h i p was tested by stratification in 5-year age groups, a signif-
Tr&nollieres, Pouilles, and Ribot
Volume 175, Number 6
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Am J Obstet Gynecol
YEARS
AGE
SINCE
MENOPAUfIE
FAT (k s ) Is'
~
II
I
NS
N$ o .......... o . . . . . . . . o ' 1
" ° ......... o
O .............O ............... ~O'......... O ~ I ~ / O
NS
i (411
4~9
(~l|
~.
(-17)
5s:~
121)
~
(14,)
>6s
qvJ
o
(4,g)
(43)
(44)
(21)
~-~1
PM
0-3
3-6
~
)~
I~,J
F A T (%) -;-~
II
4oi 4O
j; i
35
o ............... ~ ............., ~ - ' - - o
~ - ' ~ ' ~ - ~ - O ~.................0 NS
i i
~0
....... o m
i
~q
25
Pm
o:3
3.,
~4
Fig. 1. Relationship between age and years since menopause and (/) trunk fat (closed circles) and leg fat (open circles) expressed in kilograms; I/, proportion of android fat (closed circles) and proportion of gynoid fat (open circles) expressed as percentage of total body fat mass in 205 women aged 45 to 70 years. Numbers in parentheses indicate number of subjects in each group. The p indicates significance of relationship between variables of body composition and age or years since menopause (analysis of variance). Asterisk, p < 0.05 compared with premenopausal women; double dagger, p < 0.05 compared with age 45 to 49 years.
T a b l e III. C o r r e l a t i o n coefficients of b o d y c o m p o s i t i o n variables o n age a n d years since m e n o p a u s e
Variables
With age
With YSM
TMMB (kg) Lean (kg) Fat (kg) Fat (%)§ Trunk fat (kg) Trunk fat (%)§ Proportion of android fat (%)11 Leg fat (kg) Leg fat (%)§ Proportion of gynoid fat (%)]1 Trunk fat/leg fat
-0.39* -0.16t 0.08 0.15~0.12 0.18 + 0-18+ 0.04 0.08 -0.12 0.17]-
-0.39* -0.20 + 0.12 0.20 + 0.16t 0.24 + 0.19+ 0.07 0.12 -0.13 0.195
YSM, Years since menopause; TBBM, total body bone mass. 0.001. t P < 0.05. ++p< 0.01.
• *p <
§As percentage of total body mass. ]lAs percentage of total fat mass.
icantly h i g h e r p r o p o r t i o n o f a n d r o i d fat was f o u n d f r o m t h e 60 to 64 year age g r o u p o n w a r d c o m p a r e d with t h e y o u n g e s t g r o u p (45 to 49 years), N o n e o f t h e s e calculations r e v e a l e d any differences b e t w e e n t h e a b s o l u t e a m o u n t o f a n d r o i d fat a n d g y n o i d fat or t h e p r o p o r t i o n o f g y n o i d fat within t h e different groups.
Multiple regression analyses (Table IV). Years since m e n o p a u s e was a significant p r e d i c t o r o f b o d y fat mass a n d t r u n k fat e x p r e s s e d as p e r c e n t a g e of total b o d y mass, w h e r e a s age was n o t a p r e d i c t o r o f any o f t h e fat d i s t r i b u t i o n variables. O n t h e o t h e r h a n d , age was a significant p r e d i c t o r o f total b o d y b o n e mass (p < 0.05).
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Table IV. Multiple linear regression of body composition variables on age and years since m e n o p a u s e
Variables T B B M (kg) Lean (kg) Fat (kg) Fat (%)+ Trunk fat (kg) Trunk fat (%)+ Proportion of android fat (%)[] Leg fat (kg) Leg fat (%)+ Proportion of gynoid fat (%)]1 Trunk fat/leg fat
Age eoefcient -0.012 0.010 -0.044 -0.065 -0.015 -0.024 0.057 -0.015 -0.021 -0.026 0.003
YSM coefficient
(0.005)* (0.06) (0.09) (0.12) (0.005) (0.07) (0.10) (0.03) (0.04) (0.1) (0.007)
-0.012 (0.007) -0.15 (0.08) 0.17 (0.12) 0.33 (0.16)* 0.10 (0.007) 0.20 (0.09)* 0.13 (0.13) 0.040 (0.04) 0.075 (0.05) -0.11 (0.12) 0.01 (0.009)
o.41t 0.20* 0.13 0.21" 0.16 0.24§ 0.20* 0.08 0.12 0.14 0.20*
YSM, Years since menopause; TBBM, total body bone mass. *p < 0.05. tP < 0.001. ++Aspercentage of total body mass. §p < 0.01. ]]As pcercentage of total fat mass.
Comment We used dual x-ray absorptiometry m e a s u r e m e n t s to study the effect of m e n o p a u s e on body composition in a large group of healthy normal-weight women. A l t h o u g h this study was cross-sectional, which m i g h t n o t allow a robust e x a m i n a t i o n of the effects of m e n o p a u s e on body composition changes, it can be n o t e d that o u r population was very h o m o g e n e o u s so far as the physical characteristics were c o n c e r n e d and most of the w o m e n did n o t differ for > 5 years of age a r o u n d menopause. In a g r e e m e n t with previously published findings, 941' 16 our results indicate that b o n e and lean mass were lower and that fat mass h i g h e r in postmenopausal w o m e n comp a r e d with p r e m e n o p a u s a l women. It is interesting to u n d e r l i n e that these changes, especially those concerning fat mass, were not the c o n s e q u e n c e of increased body weight, because our three groups did n o t significantly differ in body weight. T h e r e f o r e the observed changes in body composition a p p e a r e d to be m o r e related to relative changes in the distribution of the three c o m p o n e n t s of body composition than to a body weight effect. T h e most striking finding was the effect of m e n o p a u s e on fat distribution. T h e r e was an early increase in android fat and a relative reduction in gynoid fat, whereas, at least within the first years after menopause, total fat mass did not significantly increase. In our youngest postmenopausal g r o u p (group 2) with a m e a n years since m e n o p a u s e of 3.3 years, the p r o p o r t i o n of a n d r o i d fat increased t o about 4.5%, whereas the total a m o u n t of fat did n o t change c o m p a r e d with p r e m e n o pausal women. Moreover, all index values of u p p e r body fat distribution were f o u n d to be m o r e strongly correlated with years since m e n o p a u s e than with age. W h e n the relationship between the p r o p o r t i o n of android fat and years since m e n o p a u s e was tested by stratification in
3-year intervals, android fat was f o u n d to be significantly h i g h e r in postmenopausal w o m e n within 3 years of m e n o p a u s e c o m p a r e d with p r e m e n o p a u s a l women. A previous study that was based on dual x-ray absorptiometry m e a s u r e m e n t s had also shown that m e n o p a u s e may affect fat distribution but that the i n d e p e n d e n t effect of age and m e n o p a u s e could n o t be distinguished because there was an age difference of > 2 0 years between the two groups of p r e m e n o p a u s a l and postmenopausal women. 9 In our study there was only a slight difference in age between postmenopausal w o m e n who were within 3 years of m e n o p a u s e and p r e m e n o p a u s a l w o m e n (52.2 + 3.2 years old vs 49.3 _+ 3.3 years old). This strongly suggests that there is a m e n o p a u s e effect on fat distribution rather than an age effect. O n the o t h e r hand, o t h e r studies have r e p o r t e d that a n d r o i d fat distribution significantly correlated with age but n o t with years since menopause.i0, IS, 16 However, only postmenopausal w o m e n were evaluated in these studies, which m i g h t have partly diminished the effect of m e n o p a u s e onset on fat distribution. Finally, h o r m o n a l r e p l a c e m e n t therapy given in early postmenopausal w o m e n has b e e n shown to prevent the shifting of body fat to a m o r e central location. I7 These findings, t o g e t h e r with our own data, therefore strongly support the role of sex h o r m o n e concentrations on body fat distribution. T h e a n d r o i d fat distribution has b e e n linked to hyperinsulinemia resulting from insulin resistance or alteration in lipid profiles, which are factors associated with an increased risk in cardiovascular diseases. ls-2° T h e r e f o r e it is possible that both an increase in fat mass and a shift of body fat toward an u p p e r body location may in part contribute to explain the h i g h e r risk in cardiovascular diseases r e p o r t e d in postmenopausal women.
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In contrast to the increase in fat mass, a r e d u c t i o n in b o t h b o n e mass and lean mass was f o u n d in postmenopausal w o m e n c o m p a r e d with p r e m e n o p a u s a l women. T h e r e d u c t i o n in b o n e mass with aging is well established for the spine and the proximal f e m u r as well as for the whole skeleton. B o n e mass decreases as a n o n l i n e a r function with aging showing an acceleration at m e n o pause. In !ongitudinal studies we have previously shown that, within the first 3 years after m e n o p a u s e , there is an accelerated phase of vertebral and femoral b o n e loss that lasts only a few years. 21' 99 We also f o u n d a significantly h i g h e r r e d u c t i o n in total body mass within the first years after m e n o p a u s e , suggesting that our previous findings m i g h t also apply to the whole skeleton. Only a few studies have d e m o n s t r a t e d a decrease of lean body mass with aging, especially muscle mass as d e t e r m i n e d by the total potassium method. In the study by Aloia et al., 23 the r e d u c t i o n in total body potassium is maximal within the first 3 years after menopause, with a pattern of loss similar to that of total body calcium m e a s u r e d by n e u t r o n activation. In o u r study the decrease in lean mass was h i g h e r for legs, which m i g h t suggest the role of mechanical factors rather than a h o r m o n a l influence. 24 This decrease in lean mass is likely to be the result of an increasingly sedentary lifestyle and r e d u c e d protein intake with increasing age. In sedentary w o m e n it has b e e n hypothesized to explain the r e d u c e d energy e x p e n d i t u r e f o u n d in postmenopausal women, which could contribute, t o g e t h e r with increased energy intake, to the body weight increase r e p o r t e d with aging. 25 Moreover, our results m i g h t be even overestimated in o t h e r populations such as U.S. w o m e n who have a different lifestyle and d i e t t h a n do F r e n c h w o m e n . T h u s m a i n t a i n i n g body w e i g h t a n d d i s t r i b u t i o n t h r o u g h active exercise a n d energy-restrictive diets s h o u l d be advised after m e n o p a u s e to c o n t r i b u t e to r e d u c e the cardiovascular risk a c c e l e r a t i o n that occurs postmenopausally. This c u r r e n t study confirms the changes in body composition f o u n d in postmenopausal women. It underlines the early changes in body fat distribution with a shifting of fat mass toward an u p p e r body location observed even in the absence of a significant change in the total a m o u n t of body fat mass. Changes in fat distribution appear to be m o r e related to m e n o p a u s e than to age, which is m o r e directly c o n f i r m e d by the preventive effect of estrogen r e p l a c e m e n t therapy on the increase in android fat mass. In postmenopausal w o m e n the increase in fat mass and a m o r e android fat distribution m i g h t contribute, together with o t h e r factors, to explain the worsening cardiovascular risk associated with estrogen deficiency. Accordingly, preventive therapy should be initiated as soon as possible after m e n o p a u s e to p r e v e n t this risk.
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