0021-972X/90/7004-0888$02.00/0 Journal of Clinical Endocrinology and Metabolism Copyright © 1990 by The Endocrine Society
Vol. 70, No. 4 Printed in U.S.A.
Body Fat Mass, Body Fat Distribution, and Plasma Hormones in Early Puberty in Females C. M. DE RIDDER, P. F. BRUNING, M. L. ZONDERLAND, J. H. H. THIJSSEN, J. M. G. BONFRER, M. A. BLANKENSTEIN, I. A. HUISVELD, AND W. B. M. ERICH Janus Jongbloed Research Centre, University of Utrecht (C.M.d.R., M.L.Z., I.A.H., W.B.M.E.), Vondellaan 24, 3521 GG Utrecht; the Netherlands Cancer Institute (Antoni van Leeuwenhoekhuis) (P.F.B., J.M.G.B.), Plesmanlaan 121, 1066 CX Amsterdam; and the Department of Endocrinology, University Hospital Utrecht (J.H.H.T., M.A.B.), Catharijnesingel 101, 3511 GV Utrecht, The Netherlands
estradiol (E2), and testosterone as well as the percentage of available E2 or testosterone. Girls with fat localized predominantly on the hips had the highest levels of sex steroids and gonadotropins. It seems likely that this type of fat distribution is a result of ovarian activity. Girls with predominantly abdominal fat were also more obese and showed increased plasma levels of total E2 and a lower androgen/estrogen ratio in plasma, possibly due to increased aromatization, especially in abdominal adipose tissue. The findings suggest a reciprocal relationship among body fat distribution, plasma sex hormone levels, and availability of sex steroids in early female puberty. (J Clin Endocrinol Metab 70: 888-893, 1990)
ABSTRACT. We examined whether there is a relationship between body fat mass or body fat distribution and hormonal profiles in the plasma of early pubertal girls. Thirty-five apparently healthy Caucasian schoolgirls were selected for Tanner's breast development stage M2; they had all been classified as being stage Ml 6 months earlier. Body fat mass had no relationship with the total plasma sex steroid concentration or gonadotropins. However, body fat mass was correlated with the fraction of testosterone that was not bound to sex hormone-binding globulin and considered the fraction available for biological activity. Body fat distribution, rather than body fat mass, was different in relation to the total concentrations of estrone,
S
do not disprove the original hypothesis (7, 8). The modulating effect of a critical body weight or fat mass on the age at menarche and puberty onset has remained obscure. More recent evidence indicates that advanced maturation of girls is associated with an accentuation of the abdominal accumulation of sc fat (9). As early as 1947 Vague (10) introduced the concept of gynoid and android types of fat distribution, based on established pathology. Lower body fat predominance has been regarded as characteristic in females ("pears") and central body fat in males ("apples") (11, 12). These observations suggested that sex steroids may play an important role in body fat distribution. Evans et al. (13) showed that in healthy premenopausal women an increased localization of fat in the upper body was associated with a continuous decline of plasma SHBG levels and an increase in the percentage of nonSHBG-bound testosterone. Kissebah et al. (14) suggested that a predominance of central body fat storage could play a role in the development of metabolic abnormalities, including an increased flux of FFA into the liver via the portal vein. Bruning and Bonfrer (15) found that the non protein-bound fraction of estradiol in plasma correlated with the total FFA in healthy nonfasting premen-
EX STEROIDS play a major role in sexual maturation, including development of secondary sex characteristics. Testosterone and 17/3-estradiol (E2) are bound to sex hormone-binding globulin (SHBG) with high affinity and to albumin with much lower affinity (1, 2). It has been argued that it is not the total concentration of sex steroids but the fraction not bound to protein that is available for biological activity (3). Because of the very loose binding of sex steroids to albumin, it seems likely that both non protein-bound and albumin-bound steroids are available, i.e. the fraction that is not bound to SHBG. In 1970 Frisch (4) postulated the hypothesis of a direct relationship between a critical body weight and the menarche. More recently, Frisch et al. (5, 6) suggested that, besides weight, fat mass was related to age at menarche and initiation of the growth spurt in girls. The evidence produced remained equivocal, as conclusions were based only on weight and height, and too few girls started to menstruate at the critical weight. However, these facts
Received April 27,1989. Address all correspondence and requests for reprints to: G. M. de Ridder, M.D., Janus Jongbloed Research Centre, University of Utrecht, Vondellaan 24, 3521 CC Utrecht, The Netherlands.
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The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 24 April 2015. at 07:16 For personal use only. No other uses without permission. . All rights reserved.
BODY FAT IN EARLY FEMALE PUBERTY TABLE 1. Characteristics of the sum of skinfold quartiles
No. of subjects Sum of skinfolds (mm) Waist-hip ratio BW (kg) Ht (cm) Pubic hair growth (Tanner stage) Age (yr) Pelvic breadth (cm)
SI
S2
S3
S4
9 26.4 ± 0.9°
9 33.1 ± 1.3°
9 43.2 ± 1.3°
8 86.1 ± 11.6"
the same stage of breast development (M2), acoording to the standards of Tanner (17, 18). For an optimal match it was required that they had been staged Ml by the same investigators 6 months previously. The group was divided in quartiles, according to both the sum of 4 skinfolds (Si, S2, S3, and S4) and waist-hip ratio (Wl, W2, W3, and W4). The characteristics of these subgroups are shown in Tables 1 and 2.Antropometric measurements, staging of breast development and pubic hair growth, and blood sampling were performed on the same day.
0.81 ± 0.012 0.82 ± 0.014 0.81 ± 0.017 0.85 ± 0.019 33.2 ± 0.7 145.2 ± 1.6 2.1 ± 0.3
34.3 ± 1.3 144.7 ± 2.8 1.7 ± 0.2
34.1 ± 1.5" 44.9 ± 3.5° 142.7 ± 1.9 145.4 ± 3.1 1.7 ± 0.2 1.8 ± 0.3
Blood sampling 10.9 ± 0.1 21.4 ± 0.3
11.1 ± 0.2 21.4 ± 0.3
10.9 ± 0.1 21.9 ± 0.5
Venous blood was obtained between 0830-1000 h after an overnight fast. The samples were collected in EDTA-coated tubes and centrifuged at 5000 x g for 10 min. The plasma was distributed in aliquots in small plastic cups, frozen in liguid nitrogen, and stored at —20 C until analysis.
10.7 ± 0.1 23.1 ± 0.9
Values are the mean ± SEM. S1-S4, First to fourth quartiles of the sum of skinfolds. Significance was determined by nonparametric Mann-Whitney test. °P< 0.001. 6
P < 0.05.
c
P
Vol. 70, No. 4 Printed in U.S.A.
Body Fat Mass, Body Fat Distribution, and Plasma Hormones in Early Puberty in Females C. M. DE RIDDER, P. F. BRUNING, M. L. ZONDERLAND, J. H. H. THIJSSEN, J. M. G. BONFRER, M. A. BLANKENSTEIN, I. A. HUISVELD, AND W. B. M. ERICH Janus Jongbloed Research Centre, University of Utrecht (C.M.d.R., M.L.Z., I.A.H., W.B.M.E.), Vondellaan 24, 3521 GG Utrecht; the Netherlands Cancer Institute (Antoni van Leeuwenhoekhuis) (P.F.B., J.M.G.B.), Plesmanlaan 121, 1066 CX Amsterdam; and the Department of Endocrinology, University Hospital Utrecht (J.H.H.T., M.A.B.), Catharijnesingel 101, 3511 GV Utrecht, The Netherlands
estradiol (E2), and testosterone as well as the percentage of available E2 or testosterone. Girls with fat localized predominantly on the hips had the highest levels of sex steroids and gonadotropins. It seems likely that this type of fat distribution is a result of ovarian activity. Girls with predominantly abdominal fat were also more obese and showed increased plasma levels of total E2 and a lower androgen/estrogen ratio in plasma, possibly due to increased aromatization, especially in abdominal adipose tissue. The findings suggest a reciprocal relationship among body fat distribution, plasma sex hormone levels, and availability of sex steroids in early female puberty. (J Clin Endocrinol Metab 70: 888-893, 1990)
ABSTRACT. We examined whether there is a relationship between body fat mass or body fat distribution and hormonal profiles in the plasma of early pubertal girls. Thirty-five apparently healthy Caucasian schoolgirls were selected for Tanner's breast development stage M2; they had all been classified as being stage Ml 6 months earlier. Body fat mass had no relationship with the total plasma sex steroid concentration or gonadotropins. However, body fat mass was correlated with the fraction of testosterone that was not bound to sex hormone-binding globulin and considered the fraction available for biological activity. Body fat distribution, rather than body fat mass, was different in relation to the total concentrations of estrone,
S
do not disprove the original hypothesis (7, 8). The modulating effect of a critical body weight or fat mass on the age at menarche and puberty onset has remained obscure. More recent evidence indicates that advanced maturation of girls is associated with an accentuation of the abdominal accumulation of sc fat (9). As early as 1947 Vague (10) introduced the concept of gynoid and android types of fat distribution, based on established pathology. Lower body fat predominance has been regarded as characteristic in females ("pears") and central body fat in males ("apples") (11, 12). These observations suggested that sex steroids may play an important role in body fat distribution. Evans et al. (13) showed that in healthy premenopausal women an increased localization of fat in the upper body was associated with a continuous decline of plasma SHBG levels and an increase in the percentage of nonSHBG-bound testosterone. Kissebah et al. (14) suggested that a predominance of central body fat storage could play a role in the development of metabolic abnormalities, including an increased flux of FFA into the liver via the portal vein. Bruning and Bonfrer (15) found that the non protein-bound fraction of estradiol in plasma correlated with the total FFA in healthy nonfasting premen-
EX STEROIDS play a major role in sexual maturation, including development of secondary sex characteristics. Testosterone and 17/3-estradiol (E2) are bound to sex hormone-binding globulin (SHBG) with high affinity and to albumin with much lower affinity (1, 2). It has been argued that it is not the total concentration of sex steroids but the fraction not bound to protein that is available for biological activity (3). Because of the very loose binding of sex steroids to albumin, it seems likely that both non protein-bound and albumin-bound steroids are available, i.e. the fraction that is not bound to SHBG. In 1970 Frisch (4) postulated the hypothesis of a direct relationship between a critical body weight and the menarche. More recently, Frisch et al. (5, 6) suggested that, besides weight, fat mass was related to age at menarche and initiation of the growth spurt in girls. The evidence produced remained equivocal, as conclusions were based only on weight and height, and too few girls started to menstruate at the critical weight. However, these facts
Received April 27,1989. Address all correspondence and requests for reprints to: G. M. de Ridder, M.D., Janus Jongbloed Research Centre, University of Utrecht, Vondellaan 24, 3521 CC Utrecht, The Netherlands.
888
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 24 April 2015. at 07:16 For personal use only. No other uses without permission. . All rights reserved.
BODY FAT IN EARLY FEMALE PUBERTY TABLE 1. Characteristics of the sum of skinfold quartiles
No. of subjects Sum of skinfolds (mm) Waist-hip ratio BW (kg) Ht (cm) Pubic hair growth (Tanner stage) Age (yr) Pelvic breadth (cm)
SI
S2
S3
S4
9 26.4 ± 0.9°
9 33.1 ± 1.3°
9 43.2 ± 1.3°
8 86.1 ± 11.6"
the same stage of breast development (M2), acoording to the standards of Tanner (17, 18). For an optimal match it was required that they had been staged Ml by the same investigators 6 months previously. The group was divided in quartiles, according to both the sum of 4 skinfolds (Si, S2, S3, and S4) and waist-hip ratio (Wl, W2, W3, and W4). The characteristics of these subgroups are shown in Tables 1 and 2.Antropometric measurements, staging of breast development and pubic hair growth, and blood sampling were performed on the same day.
0.81 ± 0.012 0.82 ± 0.014 0.81 ± 0.017 0.85 ± 0.019 33.2 ± 0.7 145.2 ± 1.6 2.1 ± 0.3
34.3 ± 1.3 144.7 ± 2.8 1.7 ± 0.2
34.1 ± 1.5" 44.9 ± 3.5° 142.7 ± 1.9 145.4 ± 3.1 1.7 ± 0.2 1.8 ± 0.3
Blood sampling 10.9 ± 0.1 21.4 ± 0.3
11.1 ± 0.2 21.4 ± 0.3
10.9 ± 0.1 21.9 ± 0.5
Venous blood was obtained between 0830-1000 h after an overnight fast. The samples were collected in EDTA-coated tubes and centrifuged at 5000 x g for 10 min. The plasma was distributed in aliquots in small plastic cups, frozen in liguid nitrogen, and stored at —20 C until analysis.
10.7 ± 0.1 23.1 ± 0.9
Values are the mean ± SEM. S1-S4, First to fourth quartiles of the sum of skinfolds. Significance was determined by nonparametric Mann-Whitney test. °P< 0.001. 6
P < 0.05.
c
P
