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Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2005-2368
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The Journal of Clinical Endocrinology & Metabolism Vol. 91, No. 9 3377-3381
Copyright © 2006 by The Endocrine Society

Comparison of Clinical, Ultrasonographic, and Biochemical Differences at the Beginning of Puberty in Healthy Girls Born Either Small for Gestational Age or Appropriate for Gestational Age: Preliminary Results

M. I. Hernández, A. Martínez, T. Capurro, V. Peña, L. Trejo, A. Avila, T. Salazar, S. Asenjo, G. Iñiguez and V. Mericq

Institute of Maternal and Child Research (M.I.H., A.M., T.C., V.P., L.T., A.A., T.S., G.I., V.M.), Faculty of Medicine, University of Chile, 226-3, Santiago, Chile; and Department of Pediatric Endocrinology (S.A.), University of Concepción, Concepción, Chile

Address all correspondence and requests for reprints to: Verónica Mericq, M.D., Institute of Maternal and Child Research, University of Chile, Casilla 226-3, Santiago, Chile. E-mail: vmericq{at}med.uchile.cl.


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
Context: There are limited and controversial data concerning puberty characteristics in girls born small for gestational age (SGA).

Objective: The objective of the study was to document clinical, ultrasonographic, and biochemical characteristics at the beginning of puberty in matched healthy girls born either SGA or appropriate for gestational age (AGA) recruited from the community.

Patients: Inclusion criteria were breast Tanner stage II and a body mass index between the 10th and 95th percentiles.

Interventions: Recruited subjects underwent a complete physical exam, bone age, and ultrasound measurements of the internal genitalia. Hormonal assessment included fasting early morning dehydroepiandrosterone sulfate, androstenedione, SHBG, inhibin-B, FSH, LH, estradiol (E2), 17-hydroxyprogesterone (17OH Prog), and testosterone. Thereafter, a GnRH agonist test (leuprolide 500 µg, sc) was performed with FSH and LH at time 3 and 24 h for E2, 17OH Prog, and testosterone.

Results: Sixty-five girls (35 AGA, 30 SGA) with a mean age of 9.9 ± 1.03 (7.8–12.5) yr, similar bone age/chronological age (1.02 ± 0.8 in AGA and 1 ± 0.76 in SGA), median height of 1.35 ± 0.06 cm, and similar waist to hip ratio were included. No differences in the presence of pubic hair, axillary hair, apocrine odor, or ultrasound measurements were found. SGA girls had increased baseline E2 as well as stimulated E2 and 17OH Prog.

Conclusions: In a preliminary sample of lean, healthy girls recruited from the community born either SGA or AGA, we observed slight hormonal differences at the beginning of puberty. Longitudinal follow-up of this cohort will allow us to understand whether these differences are maintained and have a clinical impact in their pubertal development.


   Introduction
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 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
CHILDREN BORN SMALL for gestational age (SGA) are at higher risk for perinatal morbidity, mortality, and a number of chronic diseases in later life, such as glucose intolerance, type 2 diabetes mellitus, and cardiovascular disease. The hallmark for these conditions seems to be decrease in insulin sensitivity (1).

The general accepted hypothesis explaining the development of these long-term alterations relates to the thrifty phenotype as an adaptive response to intrauterine malnutrition and modifications thereof; called "fetal origins" and recently updated to "developmental origins," these include the additional contributions of the growth patterns in infancy and childhood (2, 3, 4).

There are still limited data concerning the effects of being born SGA on the gonadal axis (5). Most of these studies have been performed in a selected cohort (northern Spanish girls), are cross-sectional in design, and show that reduced fetal growth appears to be associated with exaggerated adrenarche (6, 7), early puberty (8), and small ovarian and uterine size (9), with subsequent development of ovarian hyperandrogenism (10).

Studies concerning the timing, duration, and progression of puberty in children born SGA are remarkably scarce, and more importantly the results are difficult to compare due to the various methodologies, definitions, follow-up periods, and inclusion criteria (11, 12, 13). Several authors agree that in children born SGA, puberty appears to start at a normal age or slightly earlier but may have a more rapid progression compromising adult height (11, 14). Phillip and colleagues (11) in Israel and Carrascosa and colleagues (15) in Spain reported that children born SGA who were persistently short had a normal pubertal course with a distinct pubertal growth pattern, compromising final height when compared with their target height.

Because data regarding complete pubertal development and gonadal function in a nonselective SGA cohort followed up prospectively are unavailable, we decided to recruit lean, healthy girls, born either SGA or appropriate for gestational age (AGA) from the community and study their clinical, ultrasonographic, and biochemical characteristics of pubertal development.


   Subjects and Methods
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 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
Subjects

A prospective study was designed by age matching girls between 7 and 12 yr old who attend public schools in the cities of Santiago and Concepción in Chile. They were invited to participate in a study of the impact of birth weight on pubertal progression and gonadal function. In addition, we used different local media to encourage participation in the study (school meetings for parents, local newspapers, magazines, and radio stations).

All girls were evaluated at the Institute of Maternal and Child Research with a complete physical exam performed by one pediatric endocrinologist (A.M.). Data from the newborn period were reported by the parents and confirmed in the child’s health control card. We documented birth weight, length, and gestational age. Birth weight was classified as AGA when ranged between the 10th and 90th percentiles and SGA when the range was below the 10th percentile for the Chilean population adjusted for gender and gestational age (16, 17).

Inclusion criteria were good health (by medical history and physical examination), Tanner stage II of breast development according to the criteria of Tanner (18), and a body mass index (BMI) between the 10th and 95th percentiles (19). None of the girls was receiving medication that could interfere with growth or development.

Study protocol

At baseline, we obtained hand x-rays to determine bone ages by the method of Greulich and Pyle (20) performed by a single observer who was blinded to the patient status.

After an overnight fast, the subjects underwent a complete physical examination by a pediatric endocrinologist. Height and weight were measured by one nurse (A.A.). Height was measured using a wall- mounted Harpenden stadiometer (Holtain, UK). Weight was measured using a manual scale with a 10-g gradation (Seca; Quickmedical, Snoqualme, WA). Pubertal development was assessed according to the method of Marshall and Tanner (21). Hirsutism was evaluated by determining the presence of terminal hair using the modified Ferriman-Gallway score (22). The presence of acne was also determined. Waist and hip circumferences were measured to the nearest 0.5 cm using a flexible measuring tape by a single observer (T.C.). Waist was defined as the narrowest circumference between the inferior costal margin and the iliac crest in the standing position. The hip circumference measurement was obtained at the maximum perimeters at the level of the femoral trochanters.

Thereafter all the individuals underwent a GnRH test with 500 µg of leuprolide acetate injected sc as previously described (23). The test was started between 0800 and 0900 h; three blood samples were obtained before and 3 and 24 h after the injection. Dehydroepiandrosterone sulfate (DHEA-S), androstenedione, FSH, LH, estradiol, testosterone, 17-hydroxyprogesterone (17OH Prog), SHBG, and inhibin-B were analyzed in the basal sample. SHBG and testosterone were used to calculate the free androgen index (FAI) as has been previously reported (24). In the 3-h sample, LH and FSH were measured, and in the 24-h sample estradiol, testosterone, 17OH Prog, and androstenedione were determined.

Transabdominal ultrasound was performed by two ultrasonographists with a 5-MHz transducer in Sonoace 6000 C equipment (Madison Co., Seoul, Korea). Ovarian volume was calculated using the simplified formula for a prolate ellipsoid (25). Uterine cross-sectional area was determined using the following formula: uterine length x uterine anteroposterior diameter (26).

The protocol was approved by the Ethical Committee of the Hospital San Borja Arriarán and the Faculty of Medicine, University of Chile. All parents gave signed informed consent at study entry.

Hormone assays

Serum testosterone, androstenedione, 17OH Prog, DHEA-S, and estradiol were determined by competitive specific binding RIA, and serum LH, FSH, and SHBG were measured by immunoradiometric assays. All kits were supplied by Diagnostic System Laboratories (Webster, TX). Intraassay coefficients of variation were 5.1% for testosterone, 3.2% for androstenedione, 4.2% for 17OH Prog, 3.5% for DHEA-S, 4.1% for estradiol, 6.5% for LH, 3.6% for FSH, and 3.9% for SHBG. Interassay coefficients of variation were 6.4% for testosterone, 6.1% for androstenedione, 5.5% for 17OH Prog, 5.1% for DHEA-S, 6.7% for estradiol, 7.6% for LH, 6.2% for FSH, and 6.9% for SHBG.

Statistical analysis

Results were expressed as mean ± SEM. Statistical analysis was performed using SPSS 10.0 for Windows (SPSS Inc., Chicago, IL). Normality of variables was assessed using the Kolmogorov-Smirnov test. Differences between SGA and AGA groups were assessed by the Student’s t test for normally distributed variables and nonparametric tests (Mann-Whitney U) for nonnormally distributed variables.

To examine the correlations between continuous variables, nonnormally distributed variables were log transformed. Linear correlations were performed and Pearson’s correlation coefficients (r) are displayed. P < 0.05 was considered statistically significant.


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
Two hundred seventy girls were examined, of whom 65 (35 AGA, 30 SGA) with a mean chronological age (CA) of 9.7 ± 0.2 (range 8–12) yr in AGA and 10.2 ± 0.2 (range 7.83–12.5) yr in SGA (P = ns) and a bone age (BA) of 10 ± 0.12 yr in AGA and 10.2 ± 0.16 yr (P = ns) in SGA met the inclusion criteria. Clinical data of recruited girls at study entry are shown in Table 1Go. By definition, SGA girls were significantly lighter and shorter at birth than AGA girls, even after being corrected for gestational age. At the same pubertal stage, the SGA group of girls had achieved a greater catch-up-growth in weight and height calculated from birth, compared with the AGA group of girls. BMI percentiles and height z-score were within normal ranges in all subjects and did not differ significantly between AGA and SGA girls. In addition, no differences in BA/CA, waist circumference, and waist to hip ratio between both groups were observed.


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  		TABLE 1. Clinical characteristics and anthropometric parameters of SGA and AGA groups at birth and at enrollment

 
Pubertal characteristics

No differences in the Tanner staging of pubic hair or the presence of axillary hair/apocrine odor were found between the groups (Table 2Go).


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  		TABLE 2. Pubertal development in AGA and SGA

 
Hormonal assays

In girls born SGA, a higher basal estradiol level was found, compared with AGA girls. Furthermore, after the GnRH stimulation test, SGA girls had higher estradiol and 17OH Prog (Table 3Go). Interestingly, a slightly higher testosterone after GnRH was observed in the AGA group. Basal DHEA-S, androstenedione, inhibin-B, FSH, LH, basal testosterone, and FAI were similar in both groups (data not shown). In both groups a positive correlation (P < 0.001) between basal testosterone and DHEA-S, androstenedione, and FAI was found. Post-GnRH LH was correlated with basal and post-GnRH estradiol. Furthermore, inhibin-B levels were positively correlated with estrogen levels obtained after the GnRH test (P < 0.005). In SGA girls basal LH showed a positive correlation with basal estradiol, 17OH Prog 24 h, and androstenedione and after the GnRH test with basal and post-GnRH test estradiol, basal 17OH Prog, and inhibin-B. In the AGA girls, stimulated 17OH Prog showed a positive correlation with all the measured androgens.


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  		TABLE 3. Hormonal assessment and ultrasound characteristics of SGA and AGA groups

 
Ultrasound findings

At the beginning of puberty, SGA girls had slightly larger uterine lengths, uterine cross-sectional area, ovarian volume, and number of follicles, compared with the AGA girls. The percent of ovaries with a volume larger than 2 cc was not different between AGA and SGA (62.8 vs. 66.6%, respectively, P = ns). A positive correlation was observed between LH and estradiol concentration and average ovarian volume only in the AGA group. In addition, no correlation between the levels of inhibin-B or 17OH Prog and ovarian volume or the number of follicles was found in both groups of girls.


   Discussion
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 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
Herein we report results of clinical findings, gonadal function, and ultrasonographic uterine and ovarian imaging studies obtained at the beginning of puberty in healthy, age-matched girls born either SGA or AGA. As expected, SGA girls were significantly lighter and shorter at birth than the AGA girls, and these girls achieved a greater catch-up growth in weight and height, calculated from birth, compared with the AGA group.

Interestingly, in this cohort of girls recruited from the community who have a history of SGA, no differences in axillary hair, apocrine odor, or pubic hair as well as ultrasound internal genitalia assessment, compared with age-matched AGA girls, were detected. However, we were able to describe slight hormonal differences between the groups. SGA girls displayed higher basal and post-GnRH estradiol and 24-h 17OH Prog, which has not been reported previously. The clinical relevance of such findings will be evaluated throughout the follow-up of this cohort.

Importantly, androgen levels were within the normal range, and only in the AGA girls, a slightly higher testosterone was observed after the GnRH test. Previous studies indicated that prenatal growth restrain may be followed by exaggerated adrenarche and higher dehydroepiandrosterone/DHEA-S levels (6, 12). However, differences in this pattern of exaggerated adrenarche in other SGA cohorts have been reported. Indeed, in discordant twins exaggerated adrenarche depends on postnatal weight gain (27), and in other cohorts ethnicity may play a role in the manifestation of exaggerated adrenarche (28, 29, 30). In a Dutch cohort of SGA children, the incidence of premature pubarche and the levels of serum DHEA-S levels were reported to be comparable with those of chronological and gestational age-matched AGA controls (31, 32). The discrepancies found in the different studies might be explained by the composition of the SGA children studied. Increased DHEA-S levels have been described in SGA children with catch-up growth, whereas normal levels have been described in those short SGA children receiving GH therapy. Nevertheless, in a French cohort of 20-yr-old women having a history of intrauterine growth retardation, no independent effect on serum androgen concentrations was found, even after adjustment for hormonal contraception (33). In addition, in a Chilean cohort of term SGA children (34) who have been followed from birth until 5 yr of age (our unpublished results) and in a preterm cohort evaluated between the ages of 5 and 7 yr, no differences of DHEA-S levels were found (12, 35). In these reports, the girls studied at the age of pubertal development did not show differences in the levels of DHEA-S. Importantly, SGA girls included in this study did not differ in height and BMI, compared with AGA girls. It remains to be elucidated whether during later stages of puberty they will show differences with regard to DHEA-S levels or other androgen levels. The use of a GnRH test allowed us to demonstrate differences in the gonadotropin and gonadal response patterns during this early stage of pubertal development.

In the ovary, leptin stimulates 17,20 lyase (36) and insulin stimulates 3ß- and 17,20 lyase (37). Therefore, the contribution of altered insulin and leptin sensitivity in SGA girls needs future assessment (38, 39, 40). In addition, a new signal transduction pathway for LH, which shows a positive cross-talk between insulin and LH at the level of phosphoinositol 3-kinase/AKT pathway in the rat ovary, was demonstrated (41). Again these findings could support the future development of hyperandrogenism in girls born SGA mainly as a decreased insulin sensitivity consequence.

At the onset of puberty, inhibin-B levels were not different in subjects with SGA, compared with the AGA girls, but as expected, in both groups it was strongly associated with estrogen levels. To our knowledge this is the first report that evaluated inhibin-B as a granulose cell hallmark in SGA girls, compared with AGA girls. Because the aim of this research was to follow these girls throughout pubertal development, we may be able to detect whether any difference in this marker is present at a later stage.

The main strength of the present report is that there is no recruitment bias. It remains to be established whether the slight differences in gonadal function pattern of our subjects will persist, disappear, or exacerbate during pubertal development.

In the last century, trends toward earlier pubertal development including earlier menarche in girls in the United States, Asia, and The Netherlands have been documented with stabilization over the last decades (42). Evidence has suggested that the onset of puberty and menarche may be linked to the intrauterine and postnatal growth patterns (43, 44). Importantly both groups had a similar BMI, waist to hip ratio, and fat percent at the beginning of puberty, implying a catch-up growth has been achieved in most of the SGA girls. Furthermore, they do not start with a different body composition at puberty, which has been speculated to alter gonadal function in these girls. However, no longitudinal data on clinical, gonadal function, and ultrosonographic images have been reported in healthy girls followed up throughout pubertal development. Follow-up of this cohort will allow us to understand whether these early pubertal biochemical differences will have an impact in their pubertal tempo and future gonadal function.


   Footnotes
 
This work was supported by Grant 1030610 from Fondo Nacional de Desarrollo Cientifico y Technológico, Chile.

Disclosure statement: A.A. has received consulting fees from Pfizer. The other authors have no disclosures to report.

First Published Online June 20, 2006

Abbreviations: AGA, Appropriate for gestational age; BA, bone age; BMI, body mass index; CA, chronological age; DHEA-S, dehydroepiandrosterone sulfate; FAI, free androgen index; 17OH Prog, 17-hydroxy progesterone; SGA, small for gestational age.

Received October 28, 2005.

Accepted June 13, 2006.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

  1. McMillen IC, Robinson JS 2005 Developmental origins of the metabolic syndrome: prediction, plasticity, and programming. Physiol Rev 85:571–633[Abstract/Free Full Text]
  2. Hales CN, Barker DJ 2001 The thrifty phenotype hypothesis. Br Med Bull 60:5–20[Abstract/Free Full Text]
  3. Barker DJ 1995 Fetal origins of coronary heart disease. BMJ 311:171–174[Free Full Text]
  4. Bateson P, Barker D, Clutton-Brock T, Deb D, D’Udine B, Foley RA, Gluckman P, Godfrey K, Kirkwood T, Lahr MM, McNamara J, Metcalfe NB, Monaghan P, Spencer HG, Sultan SE 2004 Developmental plasticity and human health. Nature 430:419–421[CrossRef][Medline]
  5. Davies MJ, Norman RJ 2002 Programming and reproductive functioning. Trends Endocrinol Metab 13:386–392[CrossRef][Medline]
  6. Ibanez L, Potau N, Marcos MV, de Zegher F 1999 Exaggerated adrenarche and hyperinsulinism in adolescent girls born small for gestational age. J Clin Endocrinol Metab 84:4739–4741[Abstract/Free Full Text]
  7. Curcio AI, Trenchs V, Ibáñez L, Rodríguez F 2004 Influencia del peso al nacer sobre el inicio y progresión de la pubertad y la talla final en la pubarquia precoz. An Pediatr (Barc) 60:436–439
  8. de Zegher F, Ibanez L 2004 Novel insights into the endocrine-metabolic and reproductive consequences of prenatal growth restraint in girls. Girls-born-small become women-born-small. Verh K Acad Geneeskd Belg 66:353–382 (Review)[Medline]
  9. Ibanez L, Potau N, Enriquez G, de Zegher F 2000 Reduced uterine and ovarian size in adolescent girls born small for gestational age. Pediatr Res 47:575–577[Medline]
  10. Ibanez L, Potau N, Francois I, de Zegher F 1998 Precocious pubarche, hyperinsulinism, and ovarian hyperandrogenism in girls: relation to reduced fetal growth. J Clin Endocrinol Metab 83:3558–3562[Abstract/Free Full Text]
  11. Lazar L, Pollak U, Kalter-Leibovici O, Pertzelan A, Phillip M 2003 Pubertal course of persistently short children born small for gestational age (SGA) compared with idiopathic short children born appropriate for gestational age (AGA). Eur J Endocrinol 149:425–432[Abstract]
  12. Veening MA, van Weissenbruch MM, Roord JJ, de Delemarre-van Waal HA 2004 Pubertal development in children born small for gestational age. J Pediatr Endocrinol Metab 17:1497–1505[Medline]
  13. Hokken-Koelega AC 2002 Timing of puberty and fetal growth. Best Pract Res Clin Endocrinol Metab 16:65–71[CrossRef][Medline]
  14. Ghirri P, Bernardini M, Vuerich M, Cuttano AM, Coccoli L, Merusi I, Ciulli C, D’Accavio L, Bottone U, Boldrini A 2001 Adrenarche, pubertal development, age at menarche and final height of full-term, born small for gestational age (SGA) girls. Gynecol Endocrinol 15:91–97[Medline]
  15. Vicens-Calvet E, Espadero RM, Carrascosa A 2002 Longitudinal study of the pubertal growth spurt in children born small for gestational age without postnatal catch-up growth. J Pediatr Endocrinol Metab 15:381–388[Medline]
  16. Juez G 1989 Intrauterine growth curve for the appropriate diagnosis of intrauterine growth retardation. Rev Med Chil 117:1311
  17. Juez G, Lucero E, Ventura-Junca P 1989 Intrauterine growth according to fetal sex and maternal parity. Rev Chil Pediatr 60:204–207[Medline]
  18. Tanner JM 1981 Growth and maturation during adolescence. Nutr Rev 39:43–55[Medline]
  19. Kuczmarski RJ, Ogden, CL, Grummer-Strawn LM 2000 CDC growth charts: United States. Advance data from vital and health statistics. No. 314. Hyattsville, MD: National Center for Health Statistics
  20. Greulich WW, Pyle SI 1959 Radiographics atlas of skeletal development of the hand and wrist. 2nd ed. Stanford, CA: Stanford University Press
  21. Marshall WA, Tanner JM 1969 Variations in pattern of pubertal changes in girls. Arch Dis Child 44:291–303[Free Full Text]
  22. Ferriman D, Gallwey JD 1961 Clinical assessment of body hair growth in women. J Clin Endocrinol Metab 21:1440–1447[Abstract/Free Full Text]
  23. Ibanez L, Potau N, Zampolli M, Street ME, Carrascosa A 1997 Girls diagnosed with premature pubarche show an exaggerated ovarian androgen synthesis from the early stages of puberty: evidence from gonadotropin-releasing hormone agonist testing. Fertil Steril 6:849–855
  24. Vermeulen A, Verdonck L, Kaufman JM 1999 A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 84:3666–3672[Abstract/Free Full Text]
  25. Swanson M, Sauerbrei EE, Cooperberg PL 1981 Medical implications of ultrasonically detected polycystic ovaries. J Clin Ultrasound 9:219–222[Medline]
  26. Griffin IJ, Cole TJ, Duncan KA, Hollman AS, Donaldson MD 1995 Pelvic ultrasound measurements in normal girls. Acta Paediatr 84:536–543[Medline]
  27. Francois I, de Zegher F 1997 Adrenarche and fetal growth. Pediatr Res 41:440–442[Medline]
  28. Ong KK, Potau N, Petry CJ, Jones R, Ness AR, Honor JW, de Zegher F, Ibanez L, Dunger DB 2004 Avon Longitudinal Study of Parents and Children Study Team. Opposing influences of prenatal and postnatal weight gain on adrenarche in normal boys and girls. J Clin Endocrinol Metab 89:2647–2651[Abstract/Free Full Text]
  29. Silfen ME, Manibo AM, Ferin M, McMahon DJ, Levine LS, Oberfield SE 2002 Elevated free IGF-I levels in prepubertal Hispanic girls with premature adrenarche: relationship with hyperandrogenism and insulin sensitivity. J Clin Endocrinol Metab 87:398–403[Abstract/Free Full Text]
  30. DiMartino-Nardi J 2000 Pre- and postpuberal findings in premature adrenarche. J Pediatr Endocrinol Metab 13(Suppl 5):1265–1269
  31. Boonstra VH, Mulder PG, de Jong FH, Hokken-Koelega AC 2004 Serum dehydroepiandrosterone sulfate levels and pubarche in short children born small for gestational age before and during growth hormone treatment. J Clin Endocrinol Metab 89:712–717[Abstract/Free Full Text]
  32. Boonstra V, van Pareren Y, Mulder P, Hokken-Koelega A 2003 Puberty in growth hormone-treated children born small for gestational age (SGA). J Clin Endocrinol Metab 88:5753–5758[Abstract/Free Full Text]
  33. Jaquet D, Leger J, Chevenne D, Czernichow P, Levy-Marchal C 1999 Intrauterine growth retardation predisposes to insulin resistance but not to hyperandrogenism in young women. J Clin Endocrinol Metab 84:3945–3949[Abstract/Free Full Text]
  34. Mericq V, Ong KK, Bazaes R, Pena V, Avila A, Salazar T, Soto N, Iniguez G, Dunger DB 2005 Longitudinal changes in insulin sensitivity and secretion from birth to age three years in small- and appropriate-for-gestational-age children. Diabetologia 48:2609–2614[CrossRef][Medline]
  35. Bazaes RA, Alegria A, Pittaluga E, Avila A, Iniguez G, Mericq V 2004 Determinants of insulin sensitivity and secretion in very-low-birth-weight children. J Clin Endocrinol Metab 89:1267–1272[Abstract/Free Full Text]
  36. Biason-Lauber A, Zachmann M, Schoenle EJ 2000 Effect of leptin on CYP17 enzymatic activities in human adrenal cells: new insight in the onset of adrenarche. Endocrinology 141:1446–1454[Abstract/Free Full Text]
  37. Mesiano S, Katz SL, Lee JY, Jaffe RB 1997 Insulin-like growth factors augment steroid production and expression of steroidogenic enzymes in human fetal adrenal cortical cells: implications for adrenal androgen regulation. J Clin Endocrinol Metab 82:1390–1396[Abstract/Free Full Text]
  38. Guercio G, Rivarola MA, Chaler E, Maceiras M, Belgorosky A 2002 Relationship between the GH/IGF-I axis, insulin sensitivity, and adrenal androgens in normal prepubertal and pubertal boys. J Clin Endocrinol Metab 87:1162–1169[Abstract/Free Full Text]
  39. Denburg MR, Silfen ME, Manibo AM, Chin D, Levine LS, Ferin M, McMahon DJ, Go C, Oberfield SE 2002 Insulin sensitivity and the insulin-like growth factor system in prepubertal boys with premature adrenarche. J Clin Endocrinol Metab 87:5604–5609[Abstract/Free Full Text]
  40. Burcelin R, Thorens B, Glauser M, Gaillard RC, Pralong FP 2003 Gonadotropin-releasing hormone secretion from hypothalamic neurons: stimulation by insulin and potentiation by leptin. Endocrinology 144:4484–4491[Abstract/Free Full Text]
  41. Carvalho CR, Carvalheira JB, Lima MH, Zimmerman SF, Caperuto LC, Amanso A, Gasparetti AL, Meneghetti V, Zimmerman LF, Velloso LA, Saad MJ 2003 Novel signal transduction pathway for luteinizing hormone and its interaction with insulin: activation of Janus kinase/signal transducer and activator of transcription and phosphoinositol 3-kinase/Akt pathways. Endocrinology 144:638–647[Abstract/Free Full Text]
  42. Kaplowitz PB, Slora EJ, Wasserman RC, Pedlow SE, Herman-Giddens ME 2001 Earlier onset of puberty in girls: relation to increased body mass index and race. Pediatrics 108:347–353[Abstract/Free Full Text]
  43. Koziel S, Jankowska EA 2002 Effect of low versus normal birthweight on menarche in 14-year-old Polish girls. J Paediatr Child Health 38:268–271[CrossRef][Medline]
  44. Ibanez L, Ferrer A, Marcos MV, Hierro FR, de Zegher F 2000 Early puberty: rapid progression and reduced final height in girls with low birth weight. Pediatrics 106:E72



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Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals