help button home button Endocrine Society JCEM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2005-1693
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Vottero, A.
Right arrow Articles by Ghizzoni, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vottero, A.
Right arrow Articles by Ghizzoni, L.
Related Collections
Right arrow Neuroendocrinology and Pituitary
Right arrow Pediatric Endocrinology
The Journal of Clinical Endocrinology & Metabolism Vol. 91, No. 4 1284-1287
Copyright © 2006 by The Endocrine Society

Final Height in Girls with Central Idiopathic Precocious Puberty Treated with Gonadotropin-Releasing Hormone Analog and Oxandrolone

Alessandra Vottero, Simona Pedori, Marta Verna, Blandina Pagano, Marco Cappa, Sandro Loche, Sergio Bernasconi and Lucia Ghizzoni

Department of Pediatrics (A.V., S.P., M.V., B.P., S.B., L.G.), University of Parma, 43100 Parma, Italy; Department of Paediatric Medicine (M.C.), Paediatric Hospital Bambin Gesu’, 00165 Rome, Italy; and Department of Pediatric Endocrinology (S.L.), Ospedale Regionale per le Microcitemie, 09121 Cagliari, Italy

Address all correspondence and requests for reprints to: Lucia Ghizzoni, M.D., Department of Pediatrics, University of Parma, Via Gramsci 14, 43100 Parma, Italy. E-mail: lucia.ghizzoni{at}unipr.it.


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
Context: GnRH analogs (GnRHa) are considered the treatment of choice for central precocious puberty (CPP). During GnRHa administration, the suppression of the pituitary-gonadal axis results in decreased rates of linear growth and skeletal maturation and in improved adult height. However, in some patients, the growth deceleration is so marked that the expected improvement in predicted adult height is not achieved.

Objective: The objective of this study was to assess whether the addition of oxandrolone (Ox) may affect the height outcome of patients with CPP and growth deceleration during GnRHa treatment.

Design: This was an open-label, clinical study.

Setting: The study was performed at a pediatric endocrinology referral clinic.

Patients: Twenty patients with CPP and marked growth deceleration during GnRHa treatment were studied.

Interventions: Treatment consisted of GnRHa (Leuprorelina, 3.75 mg im every 28 d) alone (10 patients) or in combination with Ox (0.06 mg/kg·d by mouth) (10 patients).

Main Outcome Measure: The main outcome measure was the patients’ adult height.

Results: The adult height of the patients treated with GnRHa plus Ox was significantly higher than pretreatment predicted adult height (162.6 ± 2.3 vs. 154.8 ± 1.7 cm, mean ± SEM; P < 0.05) and target height (162.6 ± 2.3 vs. 158.0 ± 1.9; P > 0.05). Patients treated with GnRHa alone reached an adult height similar to the pretreatment predicted adult height (151.9 ± 1.2 vs. 155.4 ± 2.1 cm) but significantly lower than target height (151.9 ± 1.2 vs. 156.6 ± 1.4 cm; P < 0.005). No side effects were recorded in either group of patients.

Conclusions: Combined GnRHa and Ox therapy is a viable treatment option for children with CPP and marked growth deceleration during treatment with GnRHa alone.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
CENTRAL PRECOCIOUS PUBERTY (CPP) is defined as the onset of sexual development before the age of 8 yr in girls and 9 in boys. The precocious activation of the hypothalamic-pituitary-gonadal axis results in an early rise in gonadal steroids, which, in turn, is responsible for the accelerated linear growth and bone maturation that leads to impaired final height (1, 2). GnRH analogs (GnRHa) are the treatment of choice in CPP (3). The aims of such therapy are to block pubertal maturation and prevent early menarche as well as to slow bone maturation and improve adult height. In most cases, treatment with GnRHa effectively halts pubertal development and improves final height (4, 5). However, in some patients, treatment does not just normalize height velocity but induces an inappropriate deceleration of the growth rate with ensuing impaired final heights (4, 5, 6, 7). Recent studies showed that in such a subset of patients, the addition of GH to the GnRHa therapy results in increased final height as compared with that of patients treated with GnRHa alone (6, 8).

Oxandrolone (Ox), a nonaromatizable androgen that has a high anabolic to androgenic ratio compared with testosterone (9, 10), has been used to stimulate growth in boys with constitutional delay of growth and puberty (11, 12, 13). The exact mechanism of its growth-promoting effect has not been completely elucidated. An activating effect of Ox on the somatotropic axis via distinct neuroendocrine secretory mechanisms was reported by some authors (14, 15) but not confirmed by others (16, 17). In addition, IGF-I concentrations were unaffected by Ox administration (11), further supporting a somatotropic-independent mechanism of action of the steroid. Because androgen receptors are expressed in the growth plate from the developing bone (18), and androgens regulate both proliferation and differentiation of cultured epiphyseal chondrocytes (19, 20, 21, 22, 23), a direct effect on the growth plate may explain the growth-promoting action of Ox.

This study was designed to assess whether Ox may affect the height outcome in patients with CPP and growth deceleration during GnRHa treatment. Ten girls with idiopathic CPP and severe growth deceleration during GnRHa treatment were treated with combined therapy. Their data were compared with those of 10 idiopathic CPP girls matched for auxological data, duration of treatment, and growth deceleration, treated with GnRHa alone.


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

This study was approved by the Clinical Research Committee of the Department of Pediatrics at the University of Parma (Parma, Italy), and informed consent was obtained from the children and their parents. Ten girls with idiopathic CPP, whose height velocity during GnRHa treatment (Leuprorelina, 3.75 mg im every 28 d) decreased below the 25th centile for chronological age, received 0.06 mg/kg·d of Ox by mouth for 1.7 ± 0.15 (mean ± SEM) yr (group 1). The diagnosis of idiopathic CPP was based on the gonadotropin response to the GnRH stimulation test and normal magnetic resonance imaging of the central nervous system. The auxological features of the patients before and during treatment are reported in Table 1Go. Height velocity deceleration was recorded after 2.8 ± 0.3 yr of GnRHa treatment, and at that time Ox was added to the treatment schedule. The Ox dose was selected based on the data on Ox treatment in Turner’s syndrome (24).


View this table:
[in this window]
[in a new window]
  		TABLE 1. Auxological features of patients treated with GnRHa plus Ox

 
Data from 10 girls with idiopathic CPP (group 2) matched for chronological age, bone age, duration of GnRHa treatment (5.0 ± 0.3 yr), and growth deceleration during GnRHa therapy were compared with those of group 1 to evaluate the effect of Ox supplementation on final height. Their auxological data are reported in Table 2Go.


View this table:
[in this window]
[in a new window]
  		TABLE 2. Auxologial features of patients treated with GnRHa alone

 
All patients were euthyroid, had normal IGF-I plasma concentrations, and were evaluated at the start of treatment and every 6 months thereafter. Bone age was determined by the method of Greulich and Pyle (25) by the same observer, and adult height was predicted according to the Bayley and Pinneau method (26). Pubertal staging was evaluated using the method of Marshall and Tanner (27). Gonadotropin concentrations were measured every 12 months before and 15, 30, 60, 90, and 120 min after the iv administration of 100 µg GnRH. To assess suppression of the pituitary-gonadal axis during treatment, the GnRH stimulation test was performed on d 25 after the last injection of GnRHa. Target height was calculated from the mean height of the parents, adjusted for sex, as described by Tanner et al. (28). Adult height was considered to be attained when the growth velocity during the preceding year was less than 1 cm, and bone age was at least 14 yr.

Hormone assays

Serum IGF-I levels were measured using a RIA (IRMA; Nichols Institute Diagnostic, San Juan Capistrano, CA). The sensitivity of the assay was 0.008 nmol/liter. Mean intra- and interassay coefficients of variation were 1.8 and 5%, respectively.

Statistical analysis

Data are expressed as mean ± SEM. Statistical significance was determined by the Wilcoxon signed rank test or the Wilcoxon rank sum test, as appropriate, and by the Kruskal-Wallis one-way ANOVA on ranks. Statistical significance was set at P < 0.05.


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
Plasma LH and FSH concentrations in response to GnRH stimulation were suppressed in both groups throughout the treatment period and raised to levels appropriate for Tanner stage V of pubertal development within 1.5 yr from discontinuation of therapy. Menarche occurred 18.2 ± 4.0 and 16.3 ± 2.3 months after discontinuation of therapy in girls treated with GnRHa and GnRHa plus Ox, respectively, with subsequent regular menses in both groups. Bone age progressed regularly in both groups of patients until epiphyseal closure without any significant difference between groups. At initiation of GnRHa therapy, predicted adult height (PAH) of patients in group 1 was not significantly different from that computed at the time Ox was added to the treatment. At the end of treatment with GnRHa plus Ox, PAH was significantly higher than that detected at diagnosis and at the start of GnRHa (Table 1Go). In group 1 patients, final height significantly exceeded target height, was similar to the PAH recorded at the end of the treatment, and was significantly higher than that at the beginning of GnRHa (Table 1Go) (Fig. 1Go). In patients in group 2, PAH at initiation of treatment was not significantly different from that at the end of GnRHa therapy (Table 2Go). Final height of these patients was similar to the PAH at both the end and the beginning of treatment (Table 2Go) (Fig. 1Go). Target height was not reached, and it was significantly higher than final height. The difference between final heights and pretreatment PAH of patients in group 1 was significantly different from that in group 2 (7.8 ± 2.3 vs. –3.8 ± 2.3 cm; P < 0.02). The same is true for the difference between final heights and target heights (4.6 ± 1.8 vs. –4.2 ± 1.1 cm, in groups 1 and 2, respectively; P < 0.005). No adverse effects were recorded during either GnRHa or GnRHa plus Ox therapy. IGF-I concentrations were unaffected by treatment in both groups (group 1 at diagnosis, 38.2 ± 6.2 nmol/liter; during GnRHa treatment, 36.9 ± 5.5 nmol/liter; and during Ox treatment, 38.3 ± 4.6 nmol/liter; group 2 at diagnosis, 40.9 ± 6.1 nmol/liter, and during GnRHa therapy, 46.9 ± 5.9 nmol/liter).


Figure 1
View larger version (19K):
[in this window]
[in a new window]
  		FIG. 1. {square}, PAH at start of GnRHa; Figure 1, target height; Figure 1, final height. Results are shown as mean ± SEM. *, P < 0.05 final height of patients treated with GnRHa plus Ox vs. their PAH and target height; &, < 0.05 final height of patients treated with GnRH alone vs. their target height.

 

   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
The results of the present study indicate that in girls with idiopathic CPP and severe growth deceleration during GnRHa treatment, the addition of Ox is able to improve final height without any significant side effect. Combined therapy allowed patients to reach a final height higher than the target height, whereas patients who showed severe growth deceleration but were treated with GnRHa alone attained a final height lower than the target height. This was because of a height gain, computed as the difference between final height and pretreatment PAH, of 7.8 and –3.8 cm in groups 1 and 2, respectively. Bone age progressed at the same rate in the two groups, and menarche occurred approximately 1.5 yr after discontinuation of treatment with subsequent regular menses in both groups of patients.

The primary goal of GnRHa therapy in CPP is to slow pubertal maturation and preserve the height potential. Deceleration in growth is expected during GnRHa therapy, but in some patients the decrease during therapy is so marked as to prevent the expected improvement in height. Even after several years of therapy, patients may fail to reach their target heights (4, 6). This observation led to the use of GH in combination with GnRHa to improve final height in children with CPP (6, 8). The published studies do suggest a real benefit from adding GH to GnRHa therapy in children with suboptimal growth during GnRHa therapy. In the two studies in which the adult height of patients with CPP treated with combined GnRHa and GH therapy was reported (6, 8), the mean adult height was 7.1 and 8.1 cm greater than the pretreatment PAH in the first and second report, respectively, and 3.5 and 4.6 cm greater than the adult height reached by the control groups, respectively. Results of the present study compare favorably with those obtained by the addition of GH to GnRHa treatment, with a mean adult height 7.8 cm greater than the pretreatment PAH and 4.5 cm greater than the adult height reached by the control group. Evaluation of the cost and burden of GH (expensive drug requiring parental administration) vs. Ox (cheap and oral administration) treatment makes the latter unquestionably more convenient to both the patients and the community.

Ox, a nonaromatizable androgen that has a high anabolic to androgenic ratio compared with testosterone (9), has been used to stimulate growth in boys with constitutional delay of growth and puberty (11, 12, 13). Small steroid doses induce a sustained growth acceleration without a disproportionate acceleration of skeletal maturation (29) or pubertal maturation. Furthermore, long-term studies have shown that treatment with Ox does not affect final height (30, 31). The precise mechanism of the growth acceleration induced by Ox is still unclear. Studies on the effect of the steroid on the somatotropic axis have provided conflicting results, with some showing a positive effect (14) and others showing no effect at all (15, 16, 17). Those showing an increase in GH secretion included few patients with highly variable responses (14, 15). In agreement with previous studies (13, 32), in the present study, GnRHa therapy alone or in combination with Ox had no effect on IGF-I concentrations, further supporting a somatotropic-independent mechanism of action of the steroid.

In the growth plate and at sites of endochondral ossification in the osteophytes, androgen receptors are predominantly expressed by hypertrophic chondrocytes (18), and specific dihydrotestosterone binding sites were demonstrated in cultured human fetal epiphyseal chondrocytes (19). It was documented that androgens regulate both proliferation and differentiation of cultured epiphyseal chondrocytes (19, 20, 21, 22, 23), supporting a direct effect of androgens on growth plate cartilage. A direct effect of androgens on epiphyseal growth and maturation is also indicated by the fact that the injection of testosterone into the growth plate of rats increases the growth plate width (33). The growth-promoting action of Ox may therefore be related to its direct effect on the growth plate cartilage rather than to an activating effect on the somatotropic axis.

In conclusion, combined GnRHa and Ox therapy can improve adult height in children with CPP and deceleration in growth during treatment with GnRHa alone. In such a subset of patients, the improvement in adult height together with the absence of significant side effects makes this combination therapy a viable treatment option.


   Acknowledgments
 
We thank Mrs. Loredana Arvasi, Cristina Colombini, and Aurelia Pantaleo for their technical support.


   Footnotes
 
A.V., S.P., M.V., B.P., M.C., S.L., S.B., and L.G. have nothing to declare.

First Published Online January 31, 2006

Abbreviations: CPP, Central precocious puberty; GnRHa, GnRH analog; Ox, oxandrolone; PAH, predicted adult height.

Received July 29, 2005.

Accepted January 20, 2006.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

  1. Bertelloni S, Baroncelli GI, Sorrentino MC, Perri G, Saggese G 1998 Effect of central precocious puberty and gonadotropin-releasing hormone analogue treatment on peak bone mass and final height in females. Eur J Pediatr 157:363–367[CrossRef][Medline]
  2. Shankar RR, Pescovitz OH 1995 Precocious puberty. Adv Endocrinol Metab 6:55–89[Medline]
  3. Partsch CJ, Sippell WG 2002 Treatment of central precocious puberty. Best Pract Res Clin Endocrinol Metab 16:165–189[CrossRef][Medline]
  4. Kauli R, Galatzer A, Kornreich L, Lazar L, Pertzelan A, Laron Z 1997 Final height of girls with central precocious puberty, untreated versus treated with cyproterone acetate or GnRH analogue. A comparative study with re-evaluation of predictions by the Bayley-Pinneau method. Horm Res 47:54–61[Medline]
  5. Oerter KE, Manasco PK, Barnes KM, Jones J, Hill S, Cutler GBJ 1993 Effects of luteinizing hormone-releasing hormone agonists on final height in luteinizing hormone-releasing hormone-dependent precocious puberty. Acta Paediatr 388:62–68
  6. Pasquino AM, Municchi G, Pucarelli I, Segni M, Mancini MA, Troiani S 1996 Combined treatment with gonadotropin-releasing hormone analog and growth hormone in central precocious puberty. J Clin Endocrinol Metab 81:948–951[Abstract]
  7. Oostdijk W, Rikken B, Schreuder S, Otten B, Odink R, Rouwe C, Jansen M, Gerver WJ, Waelkens J, Drop S 1996 Final height in central precocious puberty after long term treatment with a slow release GnRH agonist. Arch Dis Child 75:292–297[Abstract/Free Full Text]
  8. Pucarelli I, Segni M, Ortore M, Arcadi E, Pasquino AM 2003 Effects of combined gonadotropin-releasing hormone agonist and growth hormone therapy on adult height in precocious puberty: a further contribution. J Pediatr Endocrinol Metab 16:1005–1010[Medline]
  9. Fox M, Minot AS, Liddle GW 1962 Oxandrolone: a potent anabolic steroid of novel chemical configuration. J Clin Endocrinol Metab 22:921–924[Abstract/Free Full Text]
  10. Loche S, Pintor C, Cambiaso P, Lampis A, Carta D, Corda R, Cappa M 1991 The effect of short-term growth hormone or low-dose oxandrolone treatment in boys with constitutional growth delay. J Endocrinol Invest 14:747–750[Medline]
  11. Moore DC, Tattoni DS, Limbeck GA, Ruvelcaba RH, Lindner DS, Gareis FJ, Al-Agba S, Kelley VC 1976 Studies of anabolic steroids: v. effect of prolonged oxandrolone administration on growth in children and adolescents with uncomplicated short stature. Pediatrics 58:412–422[Abstract]
  12. Marti-Henneberg C, Niirianen AK, Rappaport R 1975 Oxandrolone treatment of constitutional short stature in boys during adolescence: effect on linear growth, bone age, pubic hair, and testicular development. J Pediatr 86:783–788[CrossRef][Medline]
  13. Malhotra A, Poon E, Tse WY, Pringle PJ, Hindmarsh PC, Brook CG 1993 The effects of oxandrolone on the growth hormone and gonadal axes in boys with constitutional delay of growth and puberty. Clin Endocrinol (Oxf) 38:393–398[Medline]
  14. Loche S, Corda R, Lampis A, Puggioni R, Cella SG, Muller EE, Pintor C 1986 The effect of oxandrolone on the growth hormone response to growth hormone releasing hormone in children with constitutional growth delay. Clin Endocrinol (Oxf) 25:195–200[Medline]
  15. Ulloa-Aguirre A, Blizzard RM, Garcia-Rubi E, Rogol AD, Link K, Christie CM, Johnson ML, Veldhuis JD 1990 Testosterone and oxandrolone, a nonaromatizable androgen, specifically amplify the mass and rate of growth hormone (GH) secreted per burst without altering GH secretory burst duration or frequency or the GH half-life. J Clin Endocrinol Metab 71:846–854[Abstract/Free Full Text]
  16. Link K, Blizzard RM, Evans WS, Kaiser DL, Parker MW, Rogol AD 1986 The effect of androgens on the pulsatile release and the twenty-four-hour mean concentration of growth hormone in peripubertal males. J Clin Endocrinol Metab 62:159–164[Abstract/Free Full Text]
  17. Clayton PE, Shalet SM, Price DA, Addison GM 1988 Growth and growth hormone responses to oxandrolone in boys with constitutional delay of growth and puberty (CDGP). Clin Endocrinol (Oxf) 29:123–130[Medline]
  18. Abu EO, Horner A, Kusec V, Triffitt JT, Compston JE 1997 The localization of androgen receptors in human bone. J Clin Endocrinol Metab 82:3493–3497[Abstract/Free Full Text]
  19. Carrascosa A, Audi L, Ferrandez MA, Ballabriga A 1990 Biological effects of androgens and identification of specific dihydrotestosterone-binding sites in cultured human fetal epiphyseal chondrocytes. J Clin Endocrinol Metab 70:134–140[Abstract/Free Full Text]
  20. Corvol MT, Carrascosa A, Tsagris L, Blanchard O, Rappaport R 1987 Evidence for a direct in vitro action of sex steroids on rabbit cartilage cells during skeletal growth: influence of age and sex. Endocrinology 120:1422–1429[Abstract/Free Full Text]
  21. Somjen D, Weisman Y, Mor Z, Harell A, Kaye AM 1991 Regulation of proliferation of rat cartilage and bone by sex steroid hormones. J Steroid Biochem Mol Biol 40:717–723[CrossRef][Medline]
  22. Schwartz Z, Nasatzky E, Ornoy A, Brooks BP, Soskolne WA, Boyan BD 1994 Gender-specific, maturation-dependent effects of testosterone on chondrocytes in culture. Endocrinology 134:1640–1647[Abstract/Free Full Text]
  23. Blanchard O, Tsagris L, Rappaport R, Duval-Beaupere G, Corvol M 1991 Age-dependent responsiveness of rabbit and human cartilage cells to sex steroids in vitro. J Steroid Biochem Mol Biol 40:711–716[CrossRef][Medline]
  24. Rosenfeld RG, Attie KM, Frane J, Brasel JA, Burstein S, Cara JF, Chernausek S, Gotlin RW, Kuntze J, Lippe BM, Mahoney CP, Moore WV, Saenger P, Johanson AJ 1998 Growth hormone therapy of Turner’s syndrome: beneficial effect on adult height. J Pediatr 132:319–324[CrossRef][Medline]
  25. Greulich WW, Pyle SI 1959 Radiographic atlas of skeletal development of the hand and wrist. 2nd ed. Stanford, CA: Stanford University Press
  26. Bayley N, Pinneau SR 1952 Tables for predicting adult height from skeletal age: revised for use with the Greulich-Pyle hand standards. J Pediatr 40:423–441[CrossRef][Medline]
  27. Marshall WA, Tanner JM 1969 Variations in pattern of pubertal changes in girls. Arch Dis Child 44:291–303[Free Full Text]
  28. Tanner JM, Goldstein H, Whitehouse RH 1970 Standards for children’s height at ages 2–9 years allowing for heights of parents. Arch Dis Child 45:755–762[Abstract/Free Full Text]
  29. Sobel EH 1968 Anabolic steroids. In: Astwood EV, Cassidy CE, eds. Clinical endocrinology. New York: Grune, Stratton; 16–21
  30. Joss EE, Schmidt HA, Zuppinger KA 1989 Oxandrolone in constitutionally delayed growth, a longitudinal study up to final height. J Clin Endocrinol Metab 69:1109–1115[Abstract/Free Full Text]
  31. Tse WY, Buyukgebiz A, Hindmarsh PC, Stanhope R, Preece MA, Brook CG 1990 Long-term outcome of oxandrolone treatment in boys with constitutional delay of growth and puberty. J Pediatr 117:588–591[CrossRef][Medline]
  32. Sklar CA, Rothenberg S, Blumberg D, Oberfield SE, Levine LS, David R 1991 Suppression of the pituitary-gonadal axis in children with central precocious puberty: effects on growth, growth hormone, insulin-like growth factor-I, and prolactin secretion. J Clin Endocrinol Metab 73:734–738[Abstract/Free Full Text]
  33. Ren SG, Malozowski S, Sanchez P, Sweet DE, Loriaux DL, Cassorla F 1989 Direct administration of testosterone increases rat tibial epiphyseal growth plate width. Acta Endocrinol (Copenh) 121:401–405[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 J. Immunol.Home page
G. L. Goldberg, C. G. King, R. A. Nejat, D. Y. Suh, O. M. Smith, J. C. Bretz, R. M. Samstein, J. A. Dudakov, A. P. Chidgey, S. Chen-Kiang, et al.
Luteinizing Hormone-Releasing Hormone Enhances T Cell Recovery following Allogeneic Bone Marrow Transplantation
J. Immunol., May 1, 2009; 182(9): 5846 - 5854.
[Abstract] [Full Text] [PDF]

Home page
 PediatricsHome page
J.-C. Carel, E. A. Eugster, A. Rogol, L. Ghizzoni, M. R. Palmert, and on behalf of the members of the ESPE-LWPES GnRH An
Consensus Statement on the Use of Gonadotropin-Releasing Hormone Analogs in Children
Pediatrics, April 1, 2009; 123(4): e752 - e762.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
J.-C. Carel and J. Leger
Precocious Puberty
N. Engl. J. Med., May 29, 2008; 358(22): 2366 - 2377.
[Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
J. S. Sutherland, L. Spyroglou, J. L. Muirhead, T. S. Heng, A. Prieto-Hinojosa, H. M. Prince, A. P. Chidgey, A. P. Schwarer, and R. L. Boyd
Enhanced Immune System Regeneration in Humans Following Allogeneic or Autologous Hemopoietic Stem Cell Transplantation by Temporary Sex Steroid Blockade
Clin. Cancer Res., February 15, 2008; 14(4): 1138 - 1149.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Vottero, A.
Right arrow Articles by Ghizzoni, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vottero, A.
Right arrow Articles by Ghizzoni, L.
Related Collections
Right arrow Neuroendocrinology and Pituitary
Right arrow Pediatric Endocrinology

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals