Results

Table 1 reports the measurements taken at the first examination in the two groups of patients: chronological age, bone age, height, and target height were similar in the two groups. During 24 months of follow up, the height SD score for bone age, predicted height, bone age/chronological age ratio, and bone age SD score did not change significantly in the two groups. Significant breast development was seen only in group 1, whereas height velocity decreased in both groups, although more significantly in group 1 (table 2). Chronological age at onset of menarche was significantly higher in group 1 than in group 2 (11.9 (1.0) v 10.8 (0.7) years; p < 0.005); height at menarche (152.7 (7.2)v 152.5 (5.7) cm), and growth after menarche (4.9 (3.0) v 5.4 (2.2) cm) were similar in both groups. The mean final height was similar in the two groups and not significantly different from target height (table 3). Fourteen of 20 patients in group 1 and 12 of 18 cases in group 2 had a final height equal to or higher than target height. In both groups there was a significant positive correlation between adult final height and height at first examination and target height (p < 0.005).

Table 4 shows final heights of patients of both groups subdivided according to height prognosis at onset. Final heights of girls with poor initial height prognosis were significantly lower than those of girls with good prognosis (p < 0.005; table 4); however, in patients with the same initial height prognosis, both groups showed similar final heights, not significantly different from their target heights. The percentages of patients with a final height equal to or higher than target height were not significantly different in the various groups. For patients with poor initial height prognosis, final height was higher than target height in only two of the 10 patients in group 2 and five of the 12 patients in group 1. However, this difference was not significant (table 4).

Discussion

Some investigators have suggested that age at pubertal onset might be one of the factors affecting final adult height in central precocious puberty, sometimes independently from treatment.3 12 25-27 Sigurjonsdottir and colleagues25 and Murram et al,26 in studies on spontaneous growth in untreated girls with central precocious puberty, reported that girls who started to develop before the age of 6 years were shorter than those who started after 6 years, and Schoevaart and colleagues3found good final heights in subjects with later pubertal onset. Kletter and Kelch11 reported final adult height not significantly different in patients with pubertal onset at greater than 6 years of age, both untreated patients and those treated with LHRH analogues. Moreover, in all these studies, age at pubertal onset was only one of the factors of height variability in samples of patients that were not homogeneous with regard to sex, diagnosis, type of agonist used, pattern of controls, etc. To our knowledge, our results are the first to be published that derive from the study of a homogeneous population of girls affected exclusively by early puberty. Although a randomised study is the ideal method for assessing the auxological effectiveness of treatment, it might appear ethically questionable.27However, our study was extensively discussed and approved by the ethics committee of the hospital, it did not concern children in the first years of life, and the parents were specifically informed before obtaining their consent. They were also made aware of the controversies concerning the treatment that were a cause of uncertainty for paediatricians and anxiety for the family.

In agreement with Kletter and Kelch,11 we found that the LHRH analogue had little effect on final height in subjects with early puberty; in fact, the auxological follow up and final heights of our patients were similar in the treated and untreated groups. However, in girls examined by Kletter et al, the mean final height remained nearly 1 SD score below the mean target height, whereas we found that the final heights in 69% of patients were equal to or higher than target heights, and did not differ from the current mean adult height observed in the Emilia-Romagna region of Italy.28

Recent studies on large samples of the female population have shown in the past 20 years a trend towards earlier appearance of pubertal signs. This phenomenon does not appear to have a negative influence on adult height.29-32 Herman-Giddens et al,29 in a sample of 15 439 white American girls found that more than 15% began puberty between 7 and 8 years of age. The same authors observed also that the mean heights of the study girls were higher than a national sample of race specific data, collected ∼ 20 years before. Therefore, they suggested that practitioners might need to revise their “historical” criteria for the diagnosis of precocious puberty.

Early puberty could be inserted in to this phenomenon of secular trend as a form with genetically fixed auxological features, and it could be defined as a “paraphysiological” condition. In agreement with this hypothesis, we observed in our patients that final height was significantly affected only by height at pubertal onset and by target height, characteristics that are also described in normal puberty,12 and that treatment did not appear to improve the initial height prognosis. We must point out, however, that these results need confirmation; the small number of patients with poor prognosis at onset, in fact, could blunt positive results.

However, all authors agreed that the age of menarche, in the past 20 years, has remained unchanged, at ∼ 12 years , although there are some slight ethnic differences. Marti-Henneberg and Vizmanos,30 in a sample of 163 girls from north east Spain, found a negative correlation between pubertal onset and its duration, so they concluded that the duration of puberty in girls depended on the timing of its onset. In our study, the untreated girls showed a regular and fairly quick progression of pubertal signs and onset of menarche at a mean age of 10.8 years. However, we assume that these differences in pubertal development between our girls and those examined by Marti-Henneberg and Vizmanos might be determined by ethnic/genetic factors that did not affect the final height. In fact, in our experience, early puberty is associated with a satisfactory height prognosis that is not significantly modified by treatment, except perhaps in some selected cases. In addition, the observation that height at menarche was achieved at different times, but was similar in the two groups, indicates a predetermined auxological destiny in subjects with early puberty, which is unaffected by treatment.

Finally, we have to point out that our study evaluated only the auxological results of LHRH analogue treatment. However, other factors might justify treatment and should be considered by paediatricians when deciding on treatment—for example, important emotional and cognitive difficulties that can sometimes affect girls with precocious pubertal development.