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Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2007-1216
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The Journal of Clinical Endocrinology & Metabolism Vol. 93, No. 1 190-195
Copyright © 2008 by The Endocrine Society

Long-Term Observation of 87 Girls with Idiopathic Central Precocious Puberty Treated with Gonadotropin-Releasing Hormone Analogs: Impact on Adult Height, Body Mass Index, Bone Mineral Content, and Reproductive Function

Anna Maria Pasquino, Ida Pucarelli, Fabiana Accardo, Vitan Demiraj, Maria Segni and Raffaella Di Nardo

Department of Pediatrics, "Sapienza" University, 00161 Rome, Italy

Address all correspondence and requests for reprints to: Anna Maria Pasquino, M.D., Pediatric Department, "Sapienza" University, Viale Regina Elena 324, 00161 Rome, Italy. E-mail: annamaria.pasquino{at}virgilio.it.


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
Objective: We assessed in a retrospective unicenter study the impact of treatment with GnRH analogs (GnRHa) on adult height (AH), body mass index (BMI), bone mineral density (BMD), and reproductive function in girls with idiopathic central precocious puberty (ICPP).

Patients: Eighty-seven ICPP patients were treated with GnRHa for 4.2 ± 1.6 yr (range 3–7.9) and observed for 9.9 ± 2.0 yr (range 4–10.6 yr) after discontinuation of treatment; to estimate the efficacy better, 32 comparable ICPP untreated girls were analyzed.

Results: AH was 159.8 ± 5.3 cm, significantly higher than pretreatment predicted AH (PAH) either for accelerated or for average tables of Bayley and Pinneau. The gain in centimeters between pretreatment PAH and AH was 5.1 ± 4.5 and 9.5 ± 4.6 cm, respectively. Hormonal values and ovarian and uterine dimensions, reduced during treatment, increased to normal after 1 yr without therapy. Age of menarche was 13.6 ± 1.1 yr with an interval of 0.9 ± 0.4 yr after therapy. Menstrual pattern was normal. Six girls became pregnant and delivered normal offspring. BMI SD score for chronological age increased, but not significantly, before, during, and after therapy. BMD at discontinuation of treatment was significantly lower and increased to control values after gonadal activity resumption.

Conclusions: GnRHa treatment in ICPP is safe for the reproductive system, BMD, and BMI and helpful in reaching AH close to target height; however, the variability of individual responses suggests that one choose more parameters than increment in height, especially in girls with pubertal onset over 8 yr of age.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
For more than 20 yr (1), GnRH analogs (GnRHa) have been used in the treatment of central precocious puberty (CPP). The question of adult height (AH) improvement is still controversial, although a considerable number of CPP subjects treated with GnRHa for many years have reached AH. Long-term observations during and after discontinuation of therapy and follow-up studies of big cohorts of CPP patients are reported (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14). In this unicenter retrospective study on a group of 87 girls affected by idiopathic central precocious puberty (ICPP) treated with GnRHa and observed for several years after discontinuation of treatment, we evaluated the impact on AH, body mass index (BMI), bone mineral density (BMD), and reproductive function.


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

Eighty-seven girls with ICPP were treated with GnRHa for 4.2 ± 1.6 yr (range 3–7.9) and observed for 9.9 ± 2.0 yr (range 4–10.6) after discontinuation of treatment (Tables 1Go and 2Go).


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  		TABLE 1. Clinical and auxological characteristics of CPP patients at the start and end of treatment and AH

 

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  		TABLE 2. Clinical and auxological characteristics of group 1 (CA ≤ 7 yr at first observation) and group 2 (CA > 7 yr at first observation) at diagnosis, the start, discontinuation of treatment, and AH

 
Diagnosis of CPP was made according to the following classical criteria: 1) onset of breast development (stage B2 or above according to Tanner) before 8 yr of chronological age (CA), 2) pubertal LH response (>7 IU/liter) to GnRH stimulation test, 3) increment of height velocity and advancement of bone age (BA) by at least 1 yr over CA, 4) uterine length greater than 3.5 cm and ovarian volumes greater than 1.5 cm3 at ultrasound. No evidence of hypothalamic-pituitary organic lesions at magnetic resonance imaging (MRI) allowed us to classify as idiopathic the CPP of these girls. However, throughout the years, MRI was repeated to confirm the initial findings. We repeated MRI in the youngest subjects and those with particularly progressive clinical picture before treatment without following a rule in number and frequency.

Personal history, rate of pubertal progression, and consequent psychological problems were evaluated since the first observation. CA at initial evaluation was 6.5 ± 1.5 yr (range 1.2–7.9), BA was 9.1 ± 2.3 yr (range 2–11). Although CA at initial evaluation was generally older than CA at appearance of the first signs of puberty because this is reported by relatives and generally quite not sufficiently documented, we decided not to consider for statistical evaluation CA at onset of puberty but CA at first observation.

The initial evaluation included measuring height, pubertal stage, BA, basal plasma estradiol levels, and LH and FSH responses to GnRH test. In girls presenting with pubic hair as first sign of puberty and striking advancement of BA, an ACTH iv test was performed to evaluate basal and after stimulation 17{alpha}-hydroxyprogesterone and testosterone levels to exclude the possibly underlying coexistence of nonclassical congenital adrenal hyperplasia.

GnRHa treatment was undertaken after an observation period of at least 6 months to rule out transient or slowly progressive forms of CPP. Patients were treated with depot triptorelin (D-TRP6-LHRH) at a dose of 100–120 µg/kg every 21–25 d im. Cyproterone acetate was given orally at the dose of 100 mg/d, divided into two administrations, for 21 d before and 21 d after the first GnRH analog injection to prevent any stimulatory effect by gonadotropins during this flare-up period. The dose was reduced to 50 mg/d the last week.

CA at the start of therapy was 8.4 ± 1.5 yr (range 1.7–9.5), BA was 11.1 ± 1.6 yr (range 3–12), respectively.

Height, weight, BA, pubertal staging, and LH and FSH levels after standard GnRH test were evaluated every 6 months during treatment to assess the suppression of the pituitary-gonadal axis. The dose of GnRHa was adjusted to maintain complete suppression of the pituitary-gonadal axis, demonstrated by GnRH test and after the change of body weight along treatment.

The girls discontinued treatment at a CA of 12.6 ± 1.0 yr (range 10.2–13.5) and at a BA of 13.1 ± 0.5 yr (range 12–14.2).

During the observation period subsequent to the cessation of therapy, all the girls reached AH. AH was considered to be reached when during the preceding year growth was less than 1 cm with a BA of over 15 yr.

BMI of each subject was calculated before, during, and after treatment (even after more than 5 yr) to verify significant changes.

BMD was evaluated at discontinuation of therapy and yearly afterward.

As to reproductive function, during treatment, FSH and LH levels, uterine length, and ovarian volumes at ultrasound were evaluated every 6 months. After discontinuation of treatment, the resumption of menarche, menstrual cycles, underachievement of pregnancy, and birth of a fetus were documented.

To estimate the treatment efficacy better, we analyzed 32 contemporary untreated girls comparable with those treated (Table 1Go). These patients had refused GnRHa treatment for several reasons, although continuing to remain under observation.

Methods

At each evaluation, height was measured three times by the same observer with a Harpenden’s stadiometer. Pubertal staging was calculated by the standards of Marshall and Tanner (15). BA was determined according to the atlas of Greulich and Pyle (16) by the same two observers. Predicted adult height (PAH) was calculated according to the method of Bayley and Pinneau (17) twice for each patient, as follows: the tables for accelerated girls, in which BA is advanced for CA by 1 yr or more (PAH-BP) and the tables for average girls, in which BA is within 1 yr of CA (PAH-BPav), which was used in all the patients as suggested by Kauli et al. (18) also the tables for average girls, disregarding how advanced BA was, in each girl.

Target height (TH) was calculated as midparental height adjusted for sex (minus 6.5) (19).

BMI was calculated as weight (kilograms)/height (square meters) and was expressed in SD score (SDS) for CA, according to Cacciari et al. (20)

BMD was measured by dual-energy x-ray absorptiometry in the lumbar spine at the L2-L4 level, a site that provides by a measure of integral (cortical plus trabecular) bone, with a QDR 4500 densitometer (Hologic, Bedford, MA). The values were corrected by the vertebral surface scanned and expressed as BMD (grams per square centimeter). Dual-energy x-ray absorptiometry-derived data were used to calculate lumbar spine volumetric BMD (vBMD), expressed in grams per cubic centimeter, taking the vertebral body as an ellipsoid cylinder and dividing bone mineral content obtained by lateral scan (in grams) by body vertebral volume (in cubic centimeters), calculated (p x width/2 x depth/2 x height) to reduce the confounding effect of bone size (21).

Statistical analysis

Data are expressed as the mean ± SD, unless otherwise stated. Statistical analysis of the results was assessed using Student t test, paired and unpaired if required. Correlations between two parameters were determined by Pearson’s correlation coefficient analysis. P < 0.05 was considered significant.


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
At first observation, mean CA was 6.5 ± 1.5 and BA 9.1 ± 2.3 yr; at the start of treatment, CA was 8.4 ± 1.5 and BA 11.1 ± 1.6 yr, height was 134.8 ± 9.3 cm, and BMI 18.5 ± 2.4 kg/m2. AH, reached after GnRHa treatment for a duration of 4.2 ± 1.6 yr, was 159.8 ± 5.3 cm. Because pretreatment PAH was 154.2 ± 5.3 cm (BP accelerated) and 150.1 ± 5.1 (BP average), the gain obtained with treatment on AH was 5.1 ± 4.5 and 9.5 ± 4.6 cm, respectively. Nevertheless, AH was well above TH (P < 0.01). Regression analysis between AH and several parameters (Table 3Go) showed a positive correlation with TH, height at the initiation and end of treatment, and PAH before and at the end of treatment and no correlation with duration of treatment, in agreement with other authors.


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  		TABLE 3. Factors associated with AH (centimeters) in girls treated with GnRHa for precocious puberty

 
To investigate whether growth results could be influenced by the age at onset of puberty, we divided our patients into two groups: group 1 with CA younger than 7 yr (n = 44) and group 2 with CA older than 7 yr (n = 43). No significant difference was found between the two groups as to AH or the gain in centimeters over PAH (Table 2Go).

The comparison between AH of the 87 treated girls and 32 ICPP comparable untreated girls, who served as control group, although not randomized, showed that the untreated subjects had a significant loss in terms of centimeters vs. treated girls’ AH (5.4 cm) vs. their TH (4.3 ± 5.7 cm; P < 0.01) and vs. their average PAH (about 6 cm) and accelerated PAH (about 5 cm; P < 0.001; Table 1Go).

Because BMI in children is age related, either considering the whole group or considering the two groups with onset before or after 7 yr of age, during treatment a marked increase was observed. However, as at the beginning of treatment, BMI SDS for CA was 0.39 ± 0.8, at discontinuation 0.41 ± 0.9, and many years after 0.44 ± 1.0; no significant difference (P = NS) was found. Not all the patients were overweight or obese (14.3 and 9.1%, respectively, at the start of therapy and 11.7% for both categories either at discontinuation of treatment or several years after at AH).

We observed that, besides individual data, on the whole BMI increased, although remaining in the same centile or SDS throughout treatment. Furthermore, patients who were overweight or obese at the end of treatment were in the same position of the beginning. Regression analysis showed BMI SDS for CA at the end of treatment positively correlated with BMI SDS for CA at the start of treatment (P < 0.001; r = 0.332).

BMD was evaluated in 66 of 87 patients. At discontinuation of treatment, mean BMD lumbar spine was 0.82 ± 0.01 g/cm2 and mean vBMD was 0.135 ± 0.03 g/cm3; both values were significantly lower (P < 0.001) than in controls (1.001 ± 0.11 g/cm2 and 0.143 ± 0.03 g/cm3, respectively).

At complete resumption of gonadal activity, mean BMD lumbar spine increased to 1.000 ± 0.11 g/cm2, not significantly different from controls (1.015 ± 0.11 g/cm2); similarly, mean vBMD increased to 0.165 ± 0.01 g/cm3, not significantly different from controls (0.166 ± 0.02 g/cm3).

Plasma FSH and LH peaks after the LHRH test were suppressed during treatment significantly lower than pretreatment (peak LH 0.6 ± 0.7 vs. 24.2 ± 28.3 IU/liter, peak FSH 1.6 ± 1.0 vs. 13.2 ± 7.1 IU/liter, both P < 0.005); by 1 yr after therapy, peak LH arose back to 30.3 ± 16.0 and FSH to 11.5 ± 11.9 IU/liter (P < 0.005). Estradiol basal levels (26.9 ± 5.5 pg/ml) during treatment were significantly lower than pretreatment (8 ± 2.8 pg/ml; P < 0.001) and arose to 64.9 ± 13.6 pg/ml 1 yr after therapy withdrawal (P < 0.001).

Ovarian volumes, reduced from 2.8 ± 1.3 to 1.9 ± 1.0 cm3 during treatment, increased to 5.4 ± 3.2 cm3 (P < 0.001), and uterine length, unchanged during treatment (4.6 ± 0.8 cm), increased to 6.7 ± 0.9 cm (P < 0.001), both already after 1 yr without therapy. Menarche appeared at the age of 13.6 ± 1.1 yr after withdrawal of GnRHa at 0.9 ± 0.4 yr (range 0.3–2 yr). The history of menstrual pattern showed that 82 patients had regular menses; the remaining five showed oligomenorrhea due to intensive sport activity, which within 2–3 yr resolved after decrease of intensive exercise. Six girls (one of them twice) became pregnant and delivered normal offspring (Figs. 1Go and 2Go).


Figure 1
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  		FIG. 1. LH and FSH basal and post-GnRH stimulated levels. Ovarian volume and longitudinal uterine length before treatment, during treatment, and at 1 and 7 yr after treatment in ICPP girls.

 

Figure 2
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  		FIG. 2. Patterns of menses at 1, 2, 3, 4, 5, 6, and 7 yr after therapy in girls with ICPP.

 

   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
ICPP is the most frequent cause of CPP in girls aged 6–8 yr (11, 22). Because these patients represent a relatively homogeneous population, it allows a more accurate evaluation of the impact on AH due to the use of GnRHa than in organic CPP.

Our 87 patients, as a whole, reached or overcame TH, and their AH increased significantly vs. pretreatment PAH (8, 9). The comparison of AH obtained in treated girls vs. AH of the untreated control group shows that in the latter AH is shorter about 5 cm, significantly shorter than 4 cm vs. their TH and has no significant gain vs. their average PAH and no gain vs. accelerated PAH.

Our results (7) confirm that there is no significant difference between the gain on AH over PAH pretreatment obtained in girls with onset of puberty less than 7 yr and those with onset over 7 yr. The division in the two groups below and over 7 yr is justified by the fact that in Italy the cutoff of 8 yr in girls is still maintained for the diagnosis of precocious puberty (23). Of course, more striking results are obtained in younger children, younger than 5–6 yr, in whom the potential height should be restored in the range of TH, in view of a severe loss in AH. The extreme variability observed in the growth response of these patients to GnRHa suggests that other factors besides auxological results should be considered when deciding on whether a patient should be treated.

A debated point is still the BMI pattern during and after treatment. Some authors (13, 24, 25) reported a significant increase all along the observation, others (26) even a reduction during the first period. In our cohort, which had a lesser number of overweight or obese children in comparison with other cohorts reported (8, 13, 24), we observed that, besides individual data, on the whole BMI increased, although remaining in the same centile or SDS throughout treatment. Furthermore, patients who were overweight or obese at the end of treatment were in the same position as at the beginning. In conclusion, GnRHa did not result in a significant BMI increment.

As to the bone mineral content, ovarian activity suppression was previously demonstrated to be the cause of BMD reduction, already 1 yr after the beginning of treatment (27, 28, 29, 30). We observed, some years after the cessation of therapy, at AH and complete resumption of ovarian activity, that mineral content was totally restored and peak bone mass reached, leading to the conclusion that GnRHa inhibits the acquisition of mineral content in the bone during therapy, but mineral content is restored after therapy (8, 31, 32, 33).

No relevant side effects (rash, anaphylaxis) were observed (34). The reactivation of the hypothalamo-pituitary-gonadal axis was prompt and similar for all the patients, as either gonadotropin and estrogen levels or completion of uterine and ovarian development; menarche appeared around 1 yr after the end of treatment with regular cycles and six pregnancies with normal offspring, as observed by other authors (8, 13, 14, 24, 35, 36, 37, 38).

Because treatment leads to reduction of height velocity, together with bone maturation, in turn influenced by hormonal extragonadal (adrenal), nutritional, and genetic factors and height prediction should be considered with caution for the inaccuracy of methods (13, 14, 39), the increment of statural growth with a gain of some centimeters on AH cannot be reasonably considered the aim of GnRHa therapy. The rate of pubertal progression, psychological problems depending on personal sensitivity, and the age of onset well below 7 yr, in which the loss of linear growth for years is unavoidable, seem to be the main factors for deciding to treat girls affected by ICPP with GnRHa.

Furthermore, our experience suggests not to establish fixed rules (BA, CA, height velocity slow-down) for discontinuation of therapy. It is better to consider each individual with respect to height satisfaction, compliance, and quality of life, including the need to sexually develop contemporaneously with their peers.

In conclusion, GnRH treatment in ICPP is safe and reversible for the reproductive system, BMD, and BMI. As to growth, it seems to be helpful in reaching an AH close to TH, but the variability of individual response suggests that one choose other parameters than increment in height, especially in girls with pubertal onset over 8 yr of age.


   Footnotes
 
Disclosure Statement: The authors have nothing to disclose.

First Published Online October 16, 2007

Abbreviations: AH, Adult height; BA, bone age; BMD, bone mineral density; BMI, body mass index; CA, chronological age; CPP, central precocious puberty; GnRHa, GnRH analogs; ICPP, idiopathic CPP; MRI, magnetic resonance imaging; PAH, predicted adult height; PAH-BP, PAH using tables for accelerated girls; PAH-BPav, PAH using tables for average girls; SDS, SD score; TH, target height; vBMD, volumetric BMD.

Received May 31, 2007.

Accepted October 9, 2007.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

  1. Crowley WF, Comite F, Vale W, Rivier J, Loriaux DL, Cutler GB 1981 Therapeutic use of pituitary desensitization with a long-acting LHRH agonist: a potential new treatment for idiopathic precocious puberty. J Clin Endocrinol Metab 52:370–372[Abstract/Free Full Text]
  2. Oerter KE, Manasco P, Barnes KM, Jones J, Hill S, Cutler GB 1991 Adult height in precocious puberty after long-term treatment with deslorelin. J Clin Endocrinol Metab 73:1235–1240[Abstract/Free Full Text]
  3. Kletter GB, Kelch RP 1994 Effects of gonadotropin-releasing hormone analog therapy on adult stature in precocious puberty. J Clin Endocrinol Metab 79:331–334[CrossRef][Medline]
  4. Paul D, Conte FA, Grumbach MM Kaplan SL 1995 Long term effect of gonadotropin-releasing hormone agonist therapy on final and near-final height in 26 children with true precocious puberty treated at a median age of less than 5 years. J Clin Endocrinol Metab 80:546–551[Abstract]
  5. 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]
  6. Arrigo T, Cisternino M, Galluzzi F, Bertelloni S, Pasquino AM, Antoniazzi F, Borrelli P, Crisafulli G, Wasniewska M, De Luca F 1999 Analysis of the factors affecting auxological response to GnRH agonist treatment and final height outcome in girls with idiopathic central precocious puberty. Eur J Endocrinol 141:140–144[Abstract]
  7. Carel JC, Roger M, Ispas S, Tondu F, Lahlou N, Blumberg J, Chaussain JL 1999 Final height after long-term treatment with triptorelin slow release for central precocious puberty: importance of statural growth after interruption of treatment. J Clin Endocrinol Metab 84:1973–1978[Abstract/Free Full Text]
  8. Heger S, Partsch C-J, Sippell WG 1999 Long-term outcome after depot gonadotropin-releasing hormone agonist treatment of central precocious puberty: final height, body proportions, body composition, bone mineral density, and reproductive function. J Clin Endocrinol Metab 84:4583–4590[Abstract/Free Full Text]
  9. Antoniazzi F, Arrigo T, Cisternino M, Galluzzi F, Bertelloni S, Pasquino AM, Borrelli P, Osio D, Mengarda F, De Luca F, Tatò L 2000 End results in central precocious puberty with GnRH analog treatment: the data of the Italian Study Group for Physiopathology of Puberty. J Pediatr Endocrinol Metab 13(Suppl 1):773–780
  10. Mul D, Oostdijk W, Otten BJ, Rouwe C, Jansen M, Delemarre-van de Waal HA, Waelkens JJJ, Drop SLS 2000 Final height after gonadotrophin releasing hormone agonist treatment for central precocious puberty: the Dutch experience. J Pediatr Endocrinol Metab 13:765–772
  11. Klein KO, Barnes KM, Jones JV, Feuillan P, Cutler GB 2001 Increased final height in precocious puberty after long-term treatment with LHRH agonists: the national institutes of health experiences. J Clin Endocrinol Metab 86:4711–4716[Abstract/Free Full Text]
  12. Adan L, Chemaitilly W, Trivin C, Brauner R 2002 Factors predicting adult height in girls with idiopathic central precocious puberty: implications for treatment. Clin Endocrinol (Oxf) 56:297–302[CrossRef][Medline]
  13. Paterson WF, McNeill E, Young D, Donaldson MDC 2004 Auxological outcome and time to menarche following long-acting goserelin therapy in girls with central precocious or early puberty. Clin Endocrinol (Oxf) 61:626–634[CrossRef][Medline]
  14. Tanaka T, Niimi H, Matsuo N, Fujieda K, Tachibana K, Ohyama K, Satoh M, Kugu K 2005 Results of long-term follow-up after treatment of central precocious puberty with leuprorelin acetate: evaluation of effectiveness of treatment and recovery of gonadal function. The TAP-144-SR Japanese Study Group on central precocious puberty. J Clin Endocrinol Metab 90:1371–1376[Abstract/Free Full Text]
  15. Marshall WA, Tanner JM 1969 Variations in pattern of pubertal changes in girls. Arch Dis Child 44:291–303[Free Full Text]
  16. Greulich WW, Pyle SI 1959 Radiographic atlas of skeletal development of the hand and wrist. 2nd ed. Stanford, CA: Stanford University Press
  17. Bayley N, Pinneau SR 1952 Tables for predicting adult height from skeletal age: revised for use with the Greulich and Pyle hand standards. J Pediatr 40:423–441[CrossRef][Medline]
  18. 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. Horm Res 47:54–61[Medline]
  19. Tanner JM, Goldstein H, Whitehouse RH 1970 Standards for children’s height at ages 2–9 allowing for height of parents. Arch Dis Child 45:755–762[Abstract/Free Full Text]
  20. Cacciari E, Milani S, Balsamo A, Spada E, Bona G, Cavallo L, Cerutti F, Gargantini L, Greggio N, Tonini G, Cicognani A 2006 Italian cross-sectional growth charts for height, weight and BMI (2 to 20 yr). J Endocrinol Invest 29:581–593[Medline]
  21. Kroger H, Vainio P, Nieminen J, Kotaniemi A 1995 Comparison of different models for interpreting bone mineral density measurements using DXA and MRI technology. Bone 17:157–159[Medline]
  22. Cisternino M, Arrigo T, Pasquino AM, Tinelli C, Antoniazzi F, Beduschi L, Bindi G, Borrelli P, De Sanctis V, Farello V, Galluzzi F, Gargantini L, Lo Presti D, Sposito M, Tatò L 2000 Etiology and age incidence of precocious puberty in girls: a multicentric study. J Pediatr Endocrinol Metab 13(Suppl 1):695–701
  23. Castellino N, Bellone S, Rapa A, Vercellotti A, Binotti M, Petri A, Bona G 2005 Puberty onset in Northern Italy: a random sample of 3597 Italian children. J Endocrinol Invest 28:589–594[Medline]
  24. Palmert MR, Mansfield MJ, Crowley WF, Crigler JF, Crawford JD, Boepple PA 1999 Is obesity an outcome of gonadotropin-releasing hormone agonist administration? Analysis of growth and body composition in 110 patients with central precocious puberty. J Clin Endocrinol Metab 84:4480–4488[Abstract/Free Full Text]
  25. Traggiai C, Polo Perucchin P, Zerbini K, Gastaldi R, De Biasio P, Lorini R 2005 Outcome after depot gonadotrophin-releasing hormone agonist treatment for central precocious puberty: effects on body mass index and final height. Eur J Endocrinol 152:463–464
  26. Arrigo T, De Luca F, Antoniazzi F, Galluzzi F, Segni M, Rosano M, Messina MF, Lombardo F 2004 Reduction of baseline body mass index under gonadotropin-suppressive therapy in girls with idiopathic precocious puberty. Eur J Endocrinol 150:533–537[Abstract]
  27. Saggese G, Bertelloni S, Baroncelli GI, Battini R, Franchi G 1993 Reduction of bone density: an effect of gonadotropin releasing hormone analogue treatment in central precocious puberty. Eur J Pediatr 152:717–720[CrossRef][Medline]
  28. Verrotti A, Chiarelli F, Montanaro AF, Morgese G 1995 Bone mineral content in girls with precocious puberty treated with gonadotropin-releasing hormone analog. Gynecol Endocrinol 9:277–281[Medline]
  29. Antoniazzi F, Bertoldo F, Zamboni G, Valentini R, Sirpresi S, Cavallo L, Adami S, Tatò L 1995 Bone mineral metabolism in girls with precocious puberty during gonadotrophin-releasing hormone agonist treatment. Eur J Endocrinol 133:412–417[Abstract/Free Full Text]
  30. Boot AM, de Muinck-Keizer-Schrama SMPF, Pols HAP, Krenning EP, Drop SLS 1998 Bone mineral density and body composition before and during treatment with gonadotropin-releasing hormone agonist in children with central precocious and early puberty. J Clin Endocrinol Metab 83:370–373[Abstract/Free Full Text]
  31. 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]
  32. Antoniazzi F, Bertoldo F, Lauriola S, Sirpresi S, Gasperi E, Zamboni G, Tatò L 1999 Prevention of bone demineralization by calcium supplementation in precocious puberty during gonadotropin-releasing hormone agonist treatment. J Clin Endocrinol Metab 84:1992–1996[Abstract/Free Full Text]
  33. Van der Sluis IM, Boot AM, Krenning EP, Drop SLS, De Muinck Keizer-Schrama SMPF 2002 Longitudinal follow-up of bone density and body composition in children with precocious or early puberty before, during and after cessation of GnRH agonist therapy. J Clin Endocrinol Metab 87:506–512[Abstract/Free Full Text]
  34. Tonini G, Lazzerini M 2000 Side effects of GnRH analogue treatment in childhood. J Pediatr Endocrinol Metab 13(Suppl 1):795–803
  35. Manasco PK, Pescovitz OH, Feuillan PP, Hench KD, Barnes KM, Jones J, Hill SC, Loriaux DL, Cutler Jr GB 1988 Resumption of puberty after long term luteinizing hormone-releasing hormone agonist treatment of central precocious puberty. J Clin Endocrinol Metab 67:368–372[Abstract/Free Full Text]
  36. Jay N, Mansfield MJ, Blizzard RM, Crowley WF, Schoenfeld D, Rhubin L, Boepple PA 1992 Ovulation and menstrual function of adolescent girls with central precocious puberty after therapy with gonadotropin-releasing hormone agonists. J Clin Endocrinol Metab 75:890–894[Abstract]
  37. Feuillan PP, Jones JV, Barnes K, Oerter-Klein K, Cutler GB 1999 Reproductive axis after discontinuation of gonadotropin-releasing hormone analog treatment of girls with precocious puberty: long term follow-up comparing girls with hypothalamic hamartoma to those with idiopathic precocious puberty. J Clin Endocrinol Metab 84:44–49[Abstract/Free Full Text]
  38. Arrigo T, De Luca F, Antoniazzi F, Galluzzi F, Iughetti L, Pasquino AM, Salerno MC, Marseglia L, Crisafulli G 2007 Menstrual cycle pattern during the first gynaecological years in girls with precocious puberty following gonadotropin-releasing hormone analogue treatment. Eur J Pediatr 166:73–74[CrossRef][Medline]
  39. Carel JC, Lahlou N, Roger M, Chaussain JC 2004 Precocious puberty and statural growth. Hum Reprod Update 10:135–147[Abstract/Free Full Text]



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