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Body Fat Distribution and Body Composition During GnRH Agonist Therapy


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Recent evidence indicates that body fat distribution, rather than overall adiposity, influences various endocrine and metabolic abnormalities, including hyperlipidemia, diabetes mellitus, hypertension, and atherosclerosis.1 Several factors affect body fat distribution and body composition (lean and fat mass components). Sex steroids regulate body fat distribution and body composition in part.2–6 Menopause induces upper body fat distribution independent of aging.2,3,5,6 Long-term administration of GnRH agonist induces profound hypoestrogenism and decreased serum androgen levels. Those findings suggest that GnRH agonist therapy might affect body fat distribution and body composition, but little direct information on the possible relationship is available.

In the present study, we investigated changes in body fat distribution and body composition during medical sterilization with GnRH agonist in premenopausal women with uterine leiomyomas.

Materials and Methods

Informed written consent was obtained according to institutional guidelines, and the study was conducted in accordance with the Declaration of Helsinki. We enrolled 15 eugonadal women with uterine leiomyomas whose mean age ± standard deviation (SD) was 42.7 ± 8.4 years (range 32–52 years). Eugonadism was judged by regular menstrual cycles and serum FSH levels less than 30 mIU/mL. Subjects were recruited randomly from the Department of Obstetrics and Gynecology, Faculty of Medicine, Kagoshima University, between November 1999 and September 2000. Uterine leiomyomas were diagnosed using bimanual examination, ultrasonography, or magnetic resonance imaging (MRI). As a preoperative treatment, GnRH agonist (leuprorelin acetate, 3.75 mg; Takeda Co. Ltd., Osaka, Japan) was administered subcutaneously at 28-day intervals for 4 months. All women were physically active but did not practice sports. None was using oral contraceptives. All had sporadic alcohol intake and coffee intake not exceeding three cups a day.

Baseline assessment included age, height, weight, and body mass index (BMI). Body mass index was calculated as weight (kg) divided by height squared (m2). Regional and total body composition, ratio of trunk fat mass amount to leg fat mass amount (trunk-leg fat ratio), and bone mineral density of the lumbar spine and total body were assessed by dual-energy x-ray absorptiometry (QDR 2000/W, Hologic Inc., Waltham, MA).

Uterine volume was measured by transabdominal ultrasonography using a Mochida Sonovista-SL (Model MEU 1577; Mochida Inc., Tokyo, Japan), with 7.5- and 5-Mhz transabdominal transducers. It was calculated as 4π (1/2 diameter)3/3, with the diameter taken as maximal length in the longitudinal plane, and maximal anteroposterior and transverse diameters of the uterine corpus measured on the cross-sectional plane. The intraassay and interassay coefficients of variation were were 4.1% and 4.3%, respectively. Default software readings divided body measurements into areas that corresponded to arms, trunk, and legs. The trunk region was delineated by an upper horizontal border below the chin, vertical borders lateral to the ribs, and a lower border formed by oblique lines through the hip joints. The leg region was defined as tissue below the oblique lines passing through the hip joints (Figure 1). Measurement precision was determined in ten volunteers by five repeated measurements over 8 weeks. Precision of regional fat and lean mass measurements showed coefficients of variation less than 2.0% each. All recordings were made by the same investigator, who was masked to the purpose of the study.

Figure 1
Figure 1:
Default region produced by Hologic software.

Descriptive statistics are presented as mean ± SD. Intragroup comparisons were made by paired Student t test. P < .05 was considered statistically significant. To detect the difference of 0.1 (SD = 6.0) between the two time points with α = 0.05 and β = 0.20, 15 subjects were required.


All subjects became amenorrheic after the initial administration of GnRH agonist. During the observation period there were no changes in life style, daily physical activity, or food intake.

Table 1 presents changes in anthropometric variables, bone mineral density, and uterine volume before and after GnRH agonist therapy. Lean mass of the total body, trunk, and leg decreased significantly, whereas body fat mass, percentage of body fat, and trunk fat mass increased significantly. Trunk-leg fat ratio increased significantly. However, weight, BMI, arm tissue composition (lean and fat mass components), and leg fat mass did not change during 4 months of GnRH agonist therapy. During the same period, bone mineral density of the lumbar spine and total body decreased significantly. Uterine volume also decreased significantly.

Table 1
Table 1:
Anthropometric Variables, Bone Mineral Density, and Uterine Volume Before and After GnRH Agonist Therapy


In the present study, we found that GnRH agonist therapy increased the percentage of body fat and the trunk-leg fat ratio, but decreased lean mass despite no change in body weight. The uterine body was assessed as trunk lean mass by measuring anthropometric characteristics with dual-energy x-ray absorptiometry. Estrogen deficiency induced by GnRH agonist decreased uterine size, as shown by the present study. Thus, decrease in trunk lean mass by GnRH agonist might be partially attributable to decreased uterine size. Leg lean mass, which was not included in the trunk region, significantly decreased during GnRH agonist therapy. Long-term GnRH agonist therapy not only induced upper body fat distribution and overall adiposity, but also induced loss of lean mass. Our observation partially agrees with the report by Revilla et al,7 who found significant increases in body fat mass (9.5%) and weight (1.3%) and significant decreases in fat-free mass (−1.8%) 6 months after GnRH agonist therapy in women with endometriosis. In their study, however, little attention was paid to changes in body fat distribution. Dumesic et al,8 found that 3 months of GnRH agonist therapy increased neither abdomen-to-leg fat ratio nor body fat mass in eugonadal women with endometriosis. They defined the abdominal region as the area between the dome of the diaphragm and the top of the greater trochanter, which was different from the trunk region in our study.

It is important to clarify the reasons why GnRH agonist therapy induces upper body fat distribution and overall adiposity. There is complete and profound suppression of ovarian steroids during leuprorelin acetate administration.9,10 Estrogen deficiency by GnRH agonist might be involved in the underlying mechanism. Several reports indicated a menopause-associated shift from lower to upper body fat distribution.2,3,5,6 Estrogens influence gluteofemoral adiposity, evidenced by preferential gluteofemoral fat deposit with the pubertal onset of ovarian function.11,12 Lipoprotein lipase activity in reproductive-aged women is greater in gluteofemoral adipose tissue than in abdominal adipose tissue. Lipoprotein lipase activity of gluteofemoral adipose tissue decreases with menopause but returns to premenopausal levels with hormone replacement therapy (HRT).11,12

Decreased serum androgen levels also should be considered. Upper body fat distribution is a common feature in women with hyperandrogenic anovulation, as in polycystic ovary syndrome.13,14 From that perspective, decreased androgen levels by GnRH agonist might reduce upper body fat distribution. That information was not found in the present study because it was not designed to differentiate between effects of estrogens and androgens on body fat distribution.

Lean mass and fat mass have a reciprocal relationship to each other.15 The more lean mass decreases, the more fat mass increases. Thus, changes toward upper body fat distribution and overall adiposity might be mediated in part by decreased lean mass by GnRH agonist. It appears that changes in body fat distribution and body composition during GnRH agonist therapy are similar to those in natural menopause.7

The reasons for loss of lean mass by GnRH agonist should be clarified. Menopause induces lean mass loss, independent of age and height.16 Some reports indicate that estrogens regulate lean mass by influencing growth hormone and insulin levels.17,18 Adults with growth hormone deficiency have decreased lean mass and increased fat mass.19,20 Thus, lean mass loss by estrogen deficiency might be mediated partially through growth hormone deficiency. Reduced androgen levels by GnRH agonist also might be associated with lean mass loss. Androgens and anabolic steroids have been used to increase muscle size and strength. Muscle size in women with polycystic ovary syndrome positively correlated with serum androgen levels.21 We could not find any significant changes in arm lean mass during GnRH agonist therapy. Human beings are standing, walking, and handling animals that use the bilateral arms even in advanced age. It is well known that muscular action enhances muscle strength resulting in increased lean mass. Naturally, muscular activity is greater in the arm than the trunk and leg in the general population. Thus, in the arm, frequent muscular actions in daily life appear to offset the hypoestrogenic and hypoandrogenic effects on arm lean mass.

We could not do long-term follow-up after the discontinuation of GnRH agonist therapy; however, changes in anthropometric variables produced by GnRH agonist therapy might be reversible, because hypogonadism induced by GnRH agonist is reversible. There also is a report that hormone HRT minimizes the shift to upper body fat distribution after menopause.4 In women who are not receiving HRT, there is a dramatic decrease in the specific force of the adductor pollicis muscle that was not observed in women receiving HRT.22


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© 2001 The American College of Obstetricians and Gynecologists