Published online January 4, 2006
PEDIATRICS Vol. 117 No. 1 January 2006, pp. 117-121 (doi:10.1542/peds.2005-0664)
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow P3Rs: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when P3Rs are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via ISI Web of Science (17)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ibáñez, L.
Right arrow Articles by de Zegher, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ibáñez, L.
Right arrow Articles by de Zegher, F.
Related Collections
Right arrow Endocrinology

Early Puberty-Menarche After Precocious Pubarche: Relation to Prenatal Growth

Lourdes Ibáñez, MD, PhDa, Rafael Jiménez, MD, PhDa and Francis de Zegher, MD, PhDb

a Hospital Sant Joan de Déu, University of Barcelona, Barcelona, Spain
b Department of Pediatrics, University of Leuven, Leuven, Belgium


   ABSTRACT
TOP
 ABSTRACT
Methods
 RESULTS
 DISCUSSION
 REFERENCES
 
OBJECTIVE. Girls with precocious pubarche (PP; pubic hair at <8 years of age) as a result of an early or amplified adrenarche (high dehydroepiandrosterone-sulfate [DHEAS]) tend to be hyperinsulinemic, in particular when born with low birth weight (LBW). The objective of this study was to assess the interrelationship among prenatal growth, PP, the timing of puberty-menarche, and adult stature.

METHODS. We studied 187 PP girls longitudinally: (1) at birth, (2) in prepuberty, (3) at onset of puberty, (4) at menarche, and (5) on reaching adult stature. This PP cohort was divided into subgroups of higher birth weight (>0 SD), intermediate birth weight (0 to –2 SD), and lower birth weight (less than –2 SD).

RESULTS. At the time of PP diagnosis, age, bone age, and BMI were similar across birth weight subgroups; circulating sex hormone–binding globulin and body height were reduced in PP girls with lower birth weight, and these remained so throughout pubertal development. Onset of puberty occurred earlier in PP girls with lower birth weight; so did menarche. Adult height differed by an average of 6.5 cm (~1 SD) between the upper and lower birth weight subgroups; this difference was essentially achieved before puberty and even before PP. Menarche before age 12.0 years was twofold more prevalent in PP girls than in control subjects. Among PP girls, age at menarche was advanced by 8 to 10 months in lower versus higher birth weight girls. Menarche before age 12.0 years was threefold more prevalent among LBW-PP girls than in control subjects (~75% vs ~25%).

CONCLUSIONS. The link between prenatal growth restraint and early menarche is herewith extended to PP girls. In particular LBW-PP girls may become a target group for interventions directed toward normalization of pubertal onset and progression.

Key Words: precocious pubarche • adrenarche • birth weight • growth • puberty • height

Abbreviations: PP—precocious pubarche • DHEAS—dehydroepiandrosterone-sulfate • LBW—low birth weight • SHBG—sex hormone–binding globulin • B2—Tanner stage 2 for breast development • SDS—SD score

Girls with precocious pubarche (PP; pubic hair at <8 years of age) as a result of an early or amplified adrenarche (high circulating dehydroepiandrosterone-sulfate [DHEAS])1 tend to be hyperinsulinemic, in particular when born with low birth weight (LBW); this hyperinsulinemia is reflected, for example, by low insulin-like growth factor binding protein-1 and sex hormone–binding globulin (SHBG) levels and also by a central fat excess.1–3

The majority of LBW girls demonstrate vigorous catch-up growth in infancy and, by the age of 1 year, become insulin resistant4; by 2 years of age, they have normalized height and weight,5 and by 3 years of age, they start to have an adipose body composition.6 By 8 years of age, girls with the combination of a birth weight in the lower tertile and an actual weight in the upper tertile develop an amplified adrenarche7 that may be accompanied by PP (depending on background genotype) and that can be followed by hyperinsulinemic hyperandrogenism, so-called polycystic ovary syndrome.1, 8–11

Longitudinal follow-up of girls with PP has shown that, on average, these girls present an early-normal onset and progression of puberty and an adult stature within target height range.12 However, the interrelationships among prenatal growth, PP, the timing of puberty-menarche, and adult stature remain to be defined.


   Methods
TOP
 ABSTRACT
 Methods
RESULTS
 DISCUSSION
 REFERENCES
 
Study Population
We studied the longitudinal data from 187 Catalan (Northern Spanish) girls who had PP and were followed in Barcelona up to adult height. On each girl, information was available at 5 consecutive stages: (1) at birth (medical records); (2) in prepuberty (within 6 months after PP diagnosis); (3) at onset of puberty (Tanner stage 2 for breast development [B2]13); (4) at menarche (within 6 months of first menstrual period); and (5) on reaching adult stature.

The study population consisted only of girls in whom PP was ascribed to amplified adrenarche, as suggested by high serum androstenedione and/or DHEAS levels1; mean delay between pubic hair appearance and diagnostic evaluation was estimated to be in the 6- to 12-month range. None of the girls presented evidence for late-onset adrenal hyperplasia,14, 15 thyroid dysfunction, or diabetes or was receiving medications that are known to affect adrenal or gonadal function or carbohydrate or lipid metabolism.

Auxology
Height was measured with a Harpenden stadiometer and transformed into an SD score (SDS) according to Tanner references,16 which were appropriate for Catalan girls over the time span of follow-up.17 Adult height was considered to be reached when postmenarchal growth velocity had decreased to <0.5 cm/year and/or when bone age was ≥15 years. Target height was defined as midparental height, adjusted for female gender. BMI was calculated as a ratio of weight (in kilograms) to height squared (in meters) and was transformed into SDSs3; bone age was assessed by a single observer, according to the method of Greulich and Pyle.18

Birth weight data were transformed into SDSs for gestational age, as described.1 To assess the effect of birth weight on menarche and on auxologic and biochemical variables, the PP cohort was divided into subgroups of higher birth weight (>0 SD), intermediate birth weight (0 to –2 SD), and lower birth weight (less than –2 SD); at term birth, these SD values correspond to birth weights of approximately >3.4, 3.4 to 2.5, and <2.5 kg.1

Hormonal Assessment and Assays, Statistics, and Ethics
In all girls, serum SHBG levels were assessed by immunochemiluminescence (Immulite 2000; Diagnostic Products, Los Angeles, CA); 17-hydroxyprogesterone was measured by a commercial radioimmunoassay, as described.3 Samples were stored at –20°C until assay.

This study was approved by the institutional review board of Barcelona Hospital. Two-sided t tests (paired or unpaired, as appropriate) were used for comparisons; per variable, only 1 comparison was performed; significance level was set at P < .05. Selected results from part of this study population were previously reported within other contexts.1, 3, 8


   RESULTS
TOP
 ABSTRACT
 Methods
 RESULTS
DISCUSSION
 REFERENCES
 
Table 1 summarizes the sequential characteristics of PP girls, as subgrouped by birth weight for gestational age. At birth, the mean birth weight of PP girls centered around –1 SD, as expected.1 At the time of PP diagnosis, age, bone age, and BMI were similar across birth weight subgroups; circulating SHBG and body height were lower in PP girls with lower birth weight, and these remained so throughout pubertal development. Onset of puberty (B2) occurred earlier in PP girls with lower birth weight and so did menarche. Adult height differed by an average of 6.5 cm (~1 SD) between the upper and lower birth weight subgroups. This difference was essentially achieved before puberty and even before PP; pubertal height gain was strikingly similar in all birth weight groups.


View this table:
[in this window]
[in a new window]
  		TABLE 1 Sequential Characteristics, From Birth Up to Adult Height, in the Total Study Population of Girls With PP, Who Were Subgrouped According to Birth Weight for Gestational Age

 
Figure 1 shows the distribution of age at menarche in PP girls. A comparison with the general distribution of menarcheal age in Barcelona19 discloses that the prevalence of menarche before age 12 or 13 years is strikingly higher among PP girls. At the age of 11 years, ~90% of girls in both the PP and the general population are still premenarcheal. Before the age of 12.0 years, however, the prevalence of menarche doubles in PP girls, as compared with the general population. At the age of 12.8 years, the fraction of premenarcheal girls is fivefold larger in the general population than among PP girls.


Figure 1
View larger version (11K):
[in this window]
[in a new window]
  		FIGURE 1 Distribution of age at menarche in PP girls and in a general population from the same region. At 11 years of age, the fraction of premenarcheal girls is ~90% in both the PP girls and the general population. By the age of 12.8 years, however, the fraction of premenarcheal girls is fivefold larger in the general population than among PP girls. {diamondsuit}, reference; {blacksquare}, PP (n = 187).

 
Figure 2 displays the distributions of menarcheal age in birth weight subgroups of PP girls. Time at menarche was advanced (P < .001) by 8 to 10 months in lower birth weight versus higher birth weight girls, whereas intermediate birth weight girls showed an intermediate pattern. Menarche before age 12.0 years was threefold more prevalent among LBW-PP girls than in the general population (~75% vs ~25%).


Figure 2
View larger version (13K):
[in this window]
[in a new window]
  		FIGURE 2 Distributions of menarcheal age in birth weight subgroups of PP girls. Time at menarche was advanced (P < .001) in lower versus upper birth weight girls; intermediate birth weight girls showed an intermediate pattern. {blacktriangleup}, PP + birth weight less than –2 SD (n = 50); {blacksquare}, PP + birth weight from –2 SD to 0 SD (n = 94); {diamondsuit}, PP + birth weight >0 SD (n = 43).

 

   DISCUSSION
TOP
 ABSTRACT
 Methods
 RESULTS
 DISCUSSION
REFERENCES
 
When the onset of puberty (B2) occurs in the normal age range, an earlier start of puberty tends to be compensated by a longer pubertal course to menarche: the time from B2 to menarche spans on average 3.2 years when B2 occurs at 8 years of age, whereas it spans on average 0.7 years when B2 occurs at 13 years of age.20, 21 This compensation explains why the age of menarche varies less than the age of pubertal onset.20, 21 For unknown reasons, such compensation seems to be less operational in LBW girls: their onset of puberty is advanced by ~6 months, and menarche is also advanced by ~6 months, or by even more.22, 23 Among girls who start puberty at 8 years of age, menarche occurs 1 year earlier in LBW than in non-LBW girls, and such rapid pubertal progression may contribute to shortening adult stature.24 However, the main cause of the relatively short adult stature of LBW-PP girls seems to be their prenatal growth restraint, because most of their height loss occurred before puberty and even before PP.

In population studies, early menarche has been associated with fat excess and with higher fasting levels of insulin.25, 26 Given that both LBW and PP girls are characterized by hyperinsulinemia,27–29 the present findings could be interpreted as suggestive of a stimulatory role for hyperinsulinemia (and/or its correlates) in the tempo of pubertal progression. From prepuberty to postmenarche, LBW-PP girls displayed low levels of circulating SHBG, which is a marker of hyperinsulinemic insulin resistance in nondiabetic girls.30 In LBW-PP girls, not only the low levels of SHBG but also the hyperleptinemia may participate in the acceleration of both the onset and progression of puberty.30, 31

The link between prenatal growth restraint and early menarche, as previously established for girls with early-normal onset of puberty,24 is herewith extended to girls with PP. The described acceleration of pubertal onset and progression remains to be confirmed in ethnic or other populations with a relatively high prevalence of LBW, early pubarche, overweight, and, maybe, high androgen sensitivity.9, 25, 26, 32, 33 If the present findings are confirmed, then LBW-PP girls may become a target group for interventions that are directed not only toward prevention of hyperinsulinemic hyperandrogenism10, 34 but also toward normalization of pubertal onset and progression.


   ACKNOWLEDGMENTS
 
This work was supported by grant PI/021013 from the Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III (Madrid, Spain). Dr de Zegher is a clinical investigator of the Fund for Scientific Research (Flanders, Belgium).

We thank Carme Valls for hormone measurements.


   FOOTNOTES
 
Accepted Apr 8, 2005.

Address correspondence to Lourdes Ibáñez, MD, PhD, Endocrinology Unit, Hospital Sant Joan de Déu, University of Barcelona, Passeig de Sant Joan de Déu, 2, 08950 Esplugues, Barcelona, Spain. E-mail: libanez{at}hsjdbcn.org


   REFERENCES
TOP
 ABSTRACT
 Methods
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Ibáñez L, Potau N, Francois I, de Zegher F. Precocious pubarche, hyperinsulinism and ovarian hyperandrogenism in girls: relation to reduced fetal growth. J Clin Endocrinol Metab. 1998;83 :3558 –3662[Abstract/Free Full Text]
  2. Ibáñez L, Potau N, de Zegher F. Precocious pubarche, dyslipidemia and low IGFBP-1 in girls: relation to reduced prenatal growth. Pediatr Res. 1999;46 :320 –322[ISI][Medline]
  3. Ibáñez L, Ong K, de Zegher F, Marcos MV, del Rio L, Dunger D. Fat distribution in non-obese girls with and without precocious pubarche: central adiposity related to insulinemia and androgenemia from pre-puberty to post-menarche. Clin Endocrinol. 2003;58 :372 –379[CrossRef][Medline]
  4. Soto N, Bazaes RA, Pena V, et al. Insulin sensitivity and secretion are related to catch-up growth in small-for-gestational-age infants at age 1 year: results from a prospective cohort. J Clin Endocrinol Metab. 2003;88 :3645 –3650[Abstract/Free Full Text]
  5. Hokken-Koelega AC, De Ridder MA, Lemmen RJ, et al. Children born small for gestational age: do they catch up? Pediatr Res. 1995;38 :267 –271[ISI][Medline]
  6. de Zegher F, Dunger D, Ibáñez L. The pathway from early growth restraint to later diabetes: body adiposity emerges between age 2 and 3 yr in non-obese, low-birthweight girls [abstract 1707-OR]. Presented at the Endocrine Society Meeting; June 4–7, 2005; San Diego, CA
  7. Ong K, Potau N, Petry CJ, et al. Opposing influences of prenatal and postnatal weight gain on adrenarche in normal boys and girls. J Clin Endocrinol Metab. 2004;89 :2647 –2651[Abstract/Free Full Text]
  8. Ibáñez L, Valls C, Potau N, Marcos MV, de Zegher F. Polycystic ovary syndrome after precocious pubarche: ontogeny of the low birthweight effect. Clin Endocrinol. 2001;55 :667 –672[CrossRef][Medline]
  9. Ibáñez L, Ong K, Mongan N, et al. Androgen receptor gene CAG repeat polymorphism in the development of ovarian hyperandrogenism. J Clin Endocrinol Metab. 2003;88 :3333 –3338[Abstract/Free Full Text]
  10. Ibáñez L, Valls C, Marcos MV, Ong K, Dunger D, de Zegher F. Insulin sensitization for girls with precocious pubarche and with risk for polycystic ovary syndrome: effects of prepubertal initiation and postpubertal discontinuation of metformin. J Clin Endocrinol Metab. 2004;89 :4331 –4337[Abstract/Free Full Text]
  11. Petry CJ, Ong KK, Michelmore KF, et al. Association of aromatase (CYP 19) gene variation with features of hyperandrogenism in two populations of young women. Hum Reprod. 2005;20 :1837 –1843[Abstract/Free Full Text]
  12. Ibáñez L, Virdis R, Potau N, et al. Natural history of premature pubarche: an auxological study. J Clin Endocrinol Metab. 1992;74 :254 –257[Abstract]
  13. Marshall WA, Tanner JM. Variations in the pattern of pubertal changes in girls. Arch Dis Child. 1969;44 :291 –303[ISI][Medline]
  14. New MI, Lorenzen F, Lerner AJ, et al. Genotyping steroid 21-hydroxylase deficiency: hormonal reference data. J Clin Endocrinol Metab. 1983;56 :320 –325[Abstract]
  15. Sakkal-Alkaddour H, Zhang L, Yang X, Chang YT, Kappy M, Slover RS. Studies of 3b-hydroxysteroid dehydrogenase genes in infants and children manifesting premature pubarche and increased adrenocorticotropin-stimulated D5-steroid levels. J Clin Endocrinol Metab. 1996;81 :3961 –3965[Abstract/Free Full Text]
  16. Tanner JM, Whitehouse RH, Takaishi M. Standards from birth to maturity for height, weight, height velocity and weight velocity: British children, 1965. Part II. Arch Dis Child. 1986;41 :613 –635
  17. de la Puente ML, Canela J, Alvarez J, Salleras L, Vicens-Calvet E. Cross-sectional study of the child and adolescent population of Catalonia (Spain). Ann Hum Biol. 1997;24 :435 –452[CrossRef][ISI][Medline]
  18. Greulich WW, Pyle SI. Radiographic Atlas of Skeletal Development of the Hand and Wrist. Stanford, CA: Stanford University Press; 1959
  19. Carrascosa A, Yeste D, Copil A, Gussinye M. Secular growth changes. Weight, height and body mass index values in infant, children, adolescent and young adults from Barcelona population. Med Clin (Barc). 2004;123 :445 –451[CrossRef][Medline]
  20. Martí-Henneberg C, Vizmanos B. The duration of puberty in girls is related to the timing of its onset. J Pediatr. 1997;131 :618 –621[CrossRef][ISI][Medline]
  21. Llop-Viñolas D, Vizmanos B, Closa Monasterolo R, Escribano Subías J, Fernández-Ballart JD, Martí-Henneberg C. Onset of puberty at eight years of age in girls determines a specific tempo of puberty but does not affect adult height. Acta Paediatr. 2004;93 :874 –879[CrossRef][ISI][Medline]
  22. Bhargava SK, Ramji S, Srivastava U, et al. Growth and sexual maturation of low birth weight children: a 14 year follow up. Indian Pediatr. 1995;32 :963 –970[Medline]
  23. Persson I, Ahlsson F, Ewald U, et al. Influence of perinatal factors on the onset of puberty in boys and girls: implications for interpretation of link with risk of long term diseases. Am J Epidemiol. 1999;150 :747 –755[Abstract/Free Full Text]
  24. Ibáñez L, Ferrer A, Marcos MV, Rodriguez Hierro F, de Zegher F. Early puberty: rapid progression and reduced final height in girls with low birthweight. Pediatrics. 2000;106(5) . Available at: www.pediatrics.org/cgi/content/full/106/5/e72
  25. Adair LS, Gordon-Larsen P. Maturation timing and overweight prevalence in US adolescent population girls. Am J Public Health. 2001;91 :642 –644[Abstract]
  26. Frontini MG, Srinivasan SR, Berenson GS. Longitudinal changes in risk variables underlying metabolic syndrome X from childhood to young adulthood in female subjects with a history of early menarche: the Bogalusa Heart study. Int J Obes. 2003;27 :1398 –1404[CrossRef][ISI][Medline]
  27. Ibáñez L, Potau N, Zampolli M, Riqué S, Saenger P, Carrascosa A. Hyperinsulinemia and decreased insulin-like growth factor binding protein-1 are common features in prepubertal and pubertal girls with a history of premature pubarche. J Clin Endocrinol Metab. 1997;82 :2283 –2288[Abstract/Free Full Text]
  28. Veening MA, Van Weissenbruch MM, Delemarre-Van De Waal HA. Glucose tolerance, insulin sensitivity, and insulin secretion in children born small for gestational age. J Clin Endocrinol Metab. 2002;87 :4657 –4661[Abstract/Free Full Text]
  29. Ibáñez L, Potau N, Marcos MV, de Zegher F. Exaggerated adrenarche and hyperinsulinism in adolescent girls born small for gestational age. J Clin Endocrinol Metab. 1999;84 :4739 –4741[Abstract/Free Full Text]
  30. Nestler JE. Sex hormone-binding globulin: a marker for hyperinsulinemia and/or insulin resistance [editorial]? J Clin Endocrinol Metab. 1993;76 :273 –274[CrossRef][ISI][Medline]
  31. Ibáñez L, Potau N, Ong K, Dunger DB, de Zegher F. Increased bone mineral density and serum leptin in non-obese girls with precocious pubarche: relation to low birthweight and hyperinsulinism. Horm Res. 2000;54 :192 –197[CrossRef][ISI][Medline]
  32. Herman-Giddens ME, Slora EJ, Wasserman RC, et al. Secondary sexual characteristics and menses in young girls seen in office practice: a study from the Pediatric Research in Office Settings network. Pediatrics. 1997;99 :505 –512[Abstract/Free Full Text]
  33. Herman-Giddens ME, Kaplowitz PB, Wasserman R. Navigating the recent articles on girls' puberty in Pediatrics: what do we know and where do we go from here? Pediatrics 2004;113 :911 –917[Free Full Text]
  34. Ibáñez L, Ferrer A, Ong K, Amin R, Dunger D, de Zegher F. Insulin sensitization early post-menarche prevents progression from precocious pubarche to polycystic ovary syndrome. J Pediatr. 2004;144 :23 –29[CrossRef][ISI][Medline]
PEDIATRICS (ISSN 1098-4275). ©2006 by the American Academy of Pediatrics



This article has been cited by other articles:


Home page
 J. Clin. Endocrinol. Metab.Home page
L. Ibanez, A. Lopez-Bermejo, M. Diaz, M. V. Marcos, and F. de Zegher
Metformin Treatment for Four Years to Reduce Total and Visceral Fat in Low Birth Weight Girls with Precocious Pubarche
J. Clin. Endocrinol. Metab., May 1, 2008; 93(5): 1841 - 1845.
[Abstract] [Full Text] [PDF]

Home page
 Eur J EndocrinolHome page
K. K Ong, F. de Zegher, A. Lopez-Bermejo, D. B Dunger, and L. Ibanez
Flutamide metformin for post-menarcheal girls with preclinical ovarian androgen excess: evidence for differential response by androgen receptor genotype
Eur. J. Endocrinol., November 1, 2007; 157(5): 661 - 668.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
Y. Zhou, W. Zhu, Z. Guo, Y. Zhao, Z. Song, and J. Xiao
Effects of maternal nuclear genome on the timing of puberty in mice offspring
J. Endocrinol., June 1, 2007; 193(3): 405 - 412.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
P. Saenger, P. Czernichow, I. Hughes, and E. O. Reiter
Small for Gestational Age: Short Stature and Beyond
Endocr. Rev., April 1, 2007; 28(2): 219 - 251.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
R. L. Rosenfield
Identifying Children at Risk for Polycystic Ovary Syndrome
J. Clin. Endocrinol. Metab., March 1, 2007; 92(3): 787 - 796.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
P. E. Clayton, S. Cianfarani, P. Czernichow, G. Johannsson, R. Rapaport, and A. Rogol
Management of the Child Born Small for Gestational Age through to Adulthood: A Consensus Statement of the International Societies of Pediatric Endocrinology and the Growth Hormone Research Society
J. Clin. Endocrinol. Metab., March 1, 2007; 92(3): 804 - 810.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
D. M. Sloboda, R. Hart, D. A. Doherty, C. E. Pennell, and M. Hickey
Age at Menarche: Influences of Prenatal and Postnatal Growth
J. Clin. Endocrinol. Metab., January 1, 2007; 92(1): 46 - 50.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
G. Iniguez, K. Ong, R. Bazaes, A. Avila, T. Salazar, D. Dunger, and V. Mericq
Longitudinal Changes in Insulin-Like Growth Factor-I, Insulin Sensitivity, and Secretion from Birth to Age Three Years in Small-for-Gestational-Age Children
J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4645 - 4649.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
C. S. Tam, F. de Zegher, S. P. Garnett, L. A. Baur, and C. T. Cowell
Opposing Influences of Prenatal and Postnatal Growth on the Timing of Menarche
J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4369 - 4373.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
L. Ibanez, K. Ong, C. Valls, M. V. Marcos, D. B. Dunger, and F. de Zegher
Metformin Treatment to Prevent Early Puberty in Girls with Precocious Pubarche
J. Clin. Endocrinol. Metab., August 1, 2006; 91(8): 2888 - 2891.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow P3Rs: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when P3Rs are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via ISI Web of Science (17)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ibáñez, L.
Right arrow Articles by de Zegher, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ibáñez, L.
Right arrow Articles by de Zegher, F.
Related Collections
Right arrow Endocrinology