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Clinical Studies |
Department of Obstetrics and Gynecology "Piero Fioretti," University of Pisa, and Medical Department, Schering S.p.A. (R.O.), Milan, Italy
Address all correspondence and requests for reprints to: Marco Gambacciani, M.D., Department of Obstetrics and Gynecology, University of Pisa, Via Roma 67, 56100 Pisa, Italy.
| Abstract |
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| Introduction |
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| Materials and Methods |
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The total body bone mineral (TBBM; milligrams per cm2) was measured in the supine position by dual energy x-ray absorptiometry (DEXA) using a Lunar DPX (Lunar Corp., Madison, WI), as previously reported (13, 14). Lean and adipose tissue weight and abdominal fat weight were determined from the DEXA total body scans (15, 16, 17, 18). The abdominal region of interest was determined by setting the lower horizontal border superior to the iliac crest and the upper horizontal border between T12 and L1. Lateral borders were set just outside the soft tissue. This region (named trunk) included the upper body segment fat and the android fat, excluding the fat from the gynoid regions (hips and thighs), which were measured in the region termed legs. The legs region is defined as the tissue below the oblique line passing through the hip joints. The arms region is defined by the software default readings after adjustment for the definition of legs and trunk regions. The proportion of body fat is reported as an absolute value (kilograms) and as a percentage of the soft tissue. The precision of bone scans and body fat distribution was determined by performing repeated scans in five subjects for 3 consecutive days and is expressed as the coefficient of variation. In our laboratory, the coefficient of variation is less than 1% for TBBM and 2.0% for regional tissue measurements. Body mass index (BMI) was calculated as weight (kilograms) divided by the square of the height (meters). All results are reported as the mean ± SE. Statistical analysis of the results was performed by paired Students t test to compare the variables in the two groups before and after treatment.
| Results |
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| Discussion |
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In addition, the present results show that the postmenopausal increase in body weight parallels an increase in body fat and a change in body fat distribution. The assessment of body fat distribution has been traditionally estimated by anthropometric measurements, such as the waist to hip circumference ratio (WHR). However, the WHR may underestimate the abdominal fat in obese individuals, and the method is subject to errors due to the approximate individual measurements. Recently, total body DEXA measurements have been proposed and validated to measure the distribution of body fat (15, 16, 17, 18). DEXA measurements cannot discriminate between sc and intraabdominal fat. However, it has been recently shown that intraabdominal fat weight measured by computed tomography is highly correlated with abdominal, trunk fat weight measured by DEXA (21). Therefore, DEXA measurement of regional body fat distribution can be considered a useful tool for clinical studies, more valid and precise than WHR and less expensive and invasive than computerized tomography or magnetic resonance imaging (15).
In the present study, longitudinal DEXA measurements of body fat show an increase in the percentage of body fat and a shift to a central, android fat distribution in the early postmenopausal period. In fact, after 12 months of the sole calcium supplementation, early postmenopausal women experienced an increase in total body fat weight that paralleled an increase in trunk and arms (central, android) fat, whereas no augmentation in fat in the legs (gynoid) region was evidenced. This modification of body fat distribution seems to be related at least in part to the endocrinological modifications occurring during the perimenopausal period. In fact, in the EV- plus CPA-treated group after 12 months of treatment, BMI and fat mass showed only a blunted trend to increase, and the difference from basal values was not significant. Indeed, the body fat distribution maintained a typical gynoid pattern; the increase in body fat was located in the gynoid (legs) region, whereas trunk and arms fat did not increase.
As previously reported with similar oral estrogen-progestin preparations (22), the present results confirm that the administration of oral EV and CPA can prevent the effects of postmenopausal status on body fat distribution. Central body fat distribution has been associated with a series of endocrine and metabolic consequences (1, 2, 3, 4) related to an increased risk of cardiovascular disease. In this view, the observed stabilization of body weight and body fat distribution can be seen as a further protective effect of HRT against cardiovascular disease (7, 8, 9, 10). However, CPA is a unique antiandrogen progestin, and the present study cannot ascertain whether the effects on body fat should be ascribed to this specific replacement regimen or might be generalizable to all HRT. In addition, our study was not designed for and has not the power to thoroughly investigate the possible environmental and genetic influences on the individual responses to menopause and/or HRT. However, in untreated early postmenopausal women, the individual increments in trunk fat were negatively correlated with the basal percent fat, suggesting that the subjects with a less prominent android fat distribution in basal conditions are those who develop a major increment in central, android fat after the menopause. No significant correlations between basal regional fat distribution and the final measurements were found in the EV- plus CPA-treated group after 12 months of observations. These observations confirm that the changes are related to the hormonal milieu rather than to the individual basal characteristics of the women included in the two groups. Further studies are needed to ascertain the roles of individual characteristics and environmental influences on the extent and mode of body weight increase in the period immediately following the menopause.
A strong positive relation has been reported between BMD and body weight in untreated postmenopausal women; BMI along with age at menopause and the menopausal component of bone loss are the major factors in determining the extent of the involutional osteopenia at the lumbar spine (13) and the femoral neck (23). Again, the present results indeed confirm that the menopausal component of involutional osteopenia is critical. In fact, untreated postmenopausal women showed a trend to a decrease in bone density that was completely negated by EV and CPA treatement, which, in turn, induced a slight, but significant, increase in TBBM.
The EV plus CPA preparation is effective in relieving subjective symptoms and preventing postmenopausal bone loss and the impairment of lipid profile that characterize the postmenopausal years (24, 25, 26). The present study confirms and extends these data, showing that EV in combination with CPA can exert a positive effect on body fat mass and distribution. Further studies may elucidate whether this effect should be ascribed to the HRT per se or to the combination of the effects of oral EV in association with the peculiar antiandrogenic properties of CPA.
| Acknowledgments |
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Received July 12, 1996.
Revised September 16, 1996.
Accepted October 16, 1996.
| References |
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