Increased perinatal intracranial pressure and prediction of early puberty in girls with myelomeningocele

An increased risk of developing precocious puberty has been reported in children with myelomeningocele. In order to evaluate this further and to study factors associated with early or precocious puberty the medical records of all girls with myelomeningocele, born from 1970 onwards (n = 64), who were admitted to our unit were reviewed. Early/precocious puberty (E/PP) was defined as breast development or pubic hair corresponding to Tanner stage 2 before the age of 9.2 years. In 32 out of 62 cases data were sufficient for evaluation of the timing of puberty. Twenty girls had E/PP and 12 girls normal timing of puberty. In the girls who had reached the age of 9.2 years the incidence of E/PP was at least 52%. Girls with E/PP had a higher incidence of hydrocephalus, were treated with intraventricular shunts more often, and had significantly higher frequency of increased intracranial pressure during the perinatal period (p < 0.05, p < 0.01, and p < 0.001, respectively). The group of girls developing E/PP was also more severely disabled with respect to motor and urological function and had more shunt revisions. In conclusion, E/PP in girls with myelomeningocele is strongly associated with increased intracranial pressure particularly during the perinatal period.     

Increased perinatal intracranial pressure and brainstem dysfunction predict early puberty in boys with myelomeningocele

Background: Children with myelomeningocele (MMC) run an increased risk of developing early or precocious puberty (E/PP). Aim: To identify risk factors for E/PP in boys with MMC. Methods: Boys born between 1970 and 1992, treated for MMC at the University Children’s Hospital, Uppsala, were identified. Thirty‐eight boys were eligible to be included. Medical records were examined retrospectively. Early puberty was defined as pubertal signs before the age of 10 years and 2 months. Precocious puberty was defined as the appearance of these signs before 9 years of age. Increased intracranial pressure perinatally was defined as wide sutures, bulging fontanelles and increased/increasing head circumference at birth and/or during the first week after birth. Early brainstem dysfunction was defined as severe and persistent feeding and respiratory problems before the age of 3 months despite proper control of the hydrocephalus. Results: Of the 38 boys, 8 (21%) had E/PP, which was strongly associated with increased intracranial pressure perinatally and also with early brainstem dysfunction. Multivariate regression analysis showed early brainstem dysfunction to have the highest explanatory value regarding the occurrence of early puberty. Conclusion: Increased intracranial pressure perinatally and brainstem dysfunction early in life are strong predictors of E/PP in boys with MMC.     

True precocious puberty in non-tumor hydrocephalus. An analysis of 16 cases

True precocious puberty occurred in 16 children (15 girls and 1 boy) with non tumoral shunted hydrocephalus at a mean age of 6.8 years. They had mild clinical manifestations of precocious puberty, and the other pituitary functions were found to be normal. Except for one child, precocious puberty did not correlate with raised intracranial pressure or lack of cerebral drainage by the shunt. Growth was the main concern in this group as the predicted height fell at a mean value of 1.7 SD below the parental target height, and even more in children with myelomeningocele. This growth retardation is due to an early progression of bone age observed even prior to the appearance of breast or pubic hair. Therefore we suggest that these children might benefit from early treatment by an LHRH analogue as soon as precocious puberty occurs.     

Accelerated pubertal development in patients with shunted hydrocephalus.

OBJECTIVE: To evaluate pubertal development and peripheral concentrations of gonadotrophins and sex hormones in children with shunted hydrocephalus compared with healthy controls. STUDY DESIGN: 114 patients (52 females, 62 males) and 73 healthy controls (35 females, 38 males) aged 5 to 20 years were analysed for stage of puberty, age at menarche, testicular volume, basal serum follicle stimulating hormone (FSH), luteinising hormone (LH), sex hormone binding globulin (SHBG), testosterone and oestradiol concentrations, and free androgen index. RESULTS: Male gonadal and male and female pubic hair development occurred significantly earlier in the patients than in the controls. The mean age at menarche was significantly lower in the female patients than in their controls (11.7 v 13.2 years; p < 0.001), and lower than it had been for their mothers (v 13.1 years; p < 0.001). Relative testicular volume was higher in the male patients than in their controls (1.2 standard deviation score (SDS) v 0.2 SDS; p < 0.001). The prepubertal patients had higher basal LH (0.13 U/l v 0.08 U/l; p < 0.001) and SHBG (132.3 nmol/l v 109.1 nmol/l; p < 0.01) than the controls. Both the prepubertal and pubertal females had significantly higher basal FSH than their controls (1.57 U/l v 1.03 U/l; p < 0.05, and 4.0 U/l v 2.9 U/l; p < 0.01, respectively). CONCLUSIONS: Hydrocephalic children experience accelerated pubertal maturation, reflected in a younger age at menarche in females and an increased testicular volume in males. This may be because of enhanced gonadotrophin secretion, possibly resulting from unphysiological variations in intracranial pressure.     

Study of true precocious puberty in girls using clinical, laboratorial and imaging techniques

This paper reviews the clinical findings, pituitary gonadotrophin reserve, plasma estradiol and androgens, radiological findings and pelvic ultrasound appearance in 17 girls with true precocious puberty (PP), and attempts to asses the value of these tests diagnosis in the clinical management of such patients and better understanding of the pathogenesis of this disorder. As noted in other series, acceleration of growth is one of the earliest features of PP and at the time of diagnosis bone age can be already significantly advanced. In 3 (18%) patients intracranial abnormalities were present. Ultrasound examination showed changes similar to those seen during normal puberty. To conclude, the introduction of high-resolution methods (CT scan and RM) and techniques for ultrasound examination have greatly simplified the clinical investigation of female precocious puberty.     

Pubertal Characteristics in Girls of Qazvin Province,Iran

Objective

Puberty is a critical time between childhood and adulthood. Many studies have reported that the mean age of breast development is decreasing. The aim of this study was to provide updated data on the pubertal development of girls and to evaluate precocious puberty in our population.

Methods

This cross sectional study was conducted in 6 to 16 year old school girls during 2009-2010 in Qazvin. 2240 healthy girls from all geographical regions with every socioeconomic status were selected by a stratified multistage cluster design to obtain representative sample of population. A questionnaire including demographic data, anthropometric measurements, secondary sexual characteristics, menarche status and its onset was filled out for every participant. Secondary sexual characteristics including breast development (B_1–5) and pubic hair (PH_1–5) were evaluated according to Marshal and Tanner recommendation.

Findings

The mean±SD of height, weight, and BMI of participants was 139.7±14.5, 36.1±12.9 and 17.9±3.7 respectively. The mean age (10th – 90th percentile) of B₂ and PH₂ were 9.71(7.67–11.4) and 9.82 years (7.84–11.42) respectively. Mean age of menstruation was 12.52 years. The mean BMI was significantly higher in pubertal females comparing to prepubertal girls (P<0.001). Average duration of puberty (the time from initiation of puberty to menarche) was 2.81 years.

Conclusion

The mean age of pubertal onset in girls living in Qazvin is 9.71 years. Menarche occurs at mean age of 12.52 and onset of puberty earlier than 6.24 years will be precocious. We found that girls in Qazvin had a slightly earlier age of initiation of puberty and of menarche in comparison with other studies in Iran.     

Causes and Types of Precocious Puberty in North-West Iran

Objective

Precocious puberty is of concern because of the underlying disorders, the short adult stature, and the psychosocial difficulties. This study was carried out in order to evaluate the characteristics of children referred to pediatric endocrinology clinic with diagnosis of precocious puberty.

Methods

In a cross-sectional study between February 2007 and September 2009, all of the children referred to pediatric endocrinology clinic in North-West Iran with diagnosis of precocious puberty were recruited.

Findings

Data of 106 girls (82.2%) and 23 boys (17.8%) were analyzed. Mean age of the patients at the time of referral was 6.6±2.8 years (ranging 0.3-14 yr), which was 7±3.9 (ranging 0.3-14 yr) for boys and 6.6±2.5 (ranging 0.8-12 yr) for girls (P=0.6). Out of 129 subjects, 56(43.4%) had precocious puberty, 71.4% (35 cases) of them were due to central precocious puberty and 28.6% (16 cases) were pseudo-precocious puberty. 73 out of 129 subjects (56.6%) were due to normal variants of puberty, normal puberty, and no puberty. 87.5% of subjects with central precocious puberty were idiopathic.

Conclusion

Most of children referred with diagnosis of precocious puberty have benign normal variants. Most of cases with precocious puberty are affected with central precocious puberty, especially with idiopathic form of it.     

Final height in central precocious puberty after long term treatment with a slow release GnRH agonist.

OBJECTIVE: To study the resumption of puberty and the final height achieved in children with central precocious puberty (CPP) treated with the GnRH agonist triptorelin. PATIENTS: 31 girls and five boys with CPP who were treated with triptorelin 3.75 mg intramuscularly every four weeks. Girls were treated for a mean (SD) of 3.4 (1.0) years and were followed up for 4.0 (1.2) years after the treatment was stopped. RESULTS: The rate of bone maturation decreased during treatment and the predicted adult height increased from 158.2 (7.4) cm to 163.9 (7.5) cm at the end of treatment (p < 0.001). When treatment was stopped bone maturation accelerated, resulting in a final height of 161.6 (7.0) cm, which was higher than the predicted adult height at the start of treatment (p < 0.001). Height at the start of treatment was the most important factor positively influencing final height (r = 0.75, p < 0.001). Bone age at cessation of treatment negatively influenced final height (r = -0.52, p = 0.03). A negative correlation between bone age and height increment after discontinuation of treatment was observed (r = -0.85, p = 0.001). Residual growth capacity was optimal when bone age on cessation of treatment was 12 to 12.5 years. Body mass index increased during treatment and remained high on cessation. At final height, the ratio of sitting height to subischial leg length was normal. Menarche occurred at 12.3 (1.1) years, and at a median (range) of 1.1 (0.4 to 2.6) years after treatment was stopped. The ovaries were normal on pelvic ultrasonography. CONCLUSIONS: Treatment of CPP with triptorelin increases final height, with normal body proportions, and seems to increase body mass index. The best results were achieved in girls who were taller at the start of treatment. Puberty was resumed after treatment, without the occurrence of polycystic ovaries.     

The gonadotrophins response to GnRH test is not a predictor of neurological lesion in girls with central precocious puberty

OBJECTIVES: To assess the value of gonadotrophin releasing hormone (GnRH) stimulation test in identifying intracranial abnormality in girls with central precocious puberty (CPP). PATIENTS AND METHODS: A study of 67 girls diagnosed with CPP who underwent cranial MRI scans. Patients were not receiving any therapy and there were no neurological signs or symptoms at presentation. Patients underwent evaluation of GnRH stimulation test and plasma oestradiol levels at presentation. RESULTS: Mean age at onset of puberty was 6.2 years (range 2.0 to 8.0 years). Intracranial abnormalities were present in 10 (15%) patients, while 57 girls (85%) had no abnormalities. No significant difference was shown between girls with intracranial abnormality and girls without intracranial abnormality in basal LH or FSH values, peak LH or FSH values, LH/FSH peak ratios, peak LH/basal LH ratios, peak FSH/ basal FSH ratios at presentation. CONCLUSION: GnRH stimulation test does not identify those with underlying intracranial abnormality at presentation. MRI imaging remains necessary in all cases of central precocious puberty in girls.     

Plasminogen activator inhibitor-1 in girls with precocious pubarche: a premenarcheal marker for polycystic ovary syndrome?

In both obese and nonobese women, polycystic ovary syndrome (PCOS) is essentially a disorder of hyperinsulinemic insulin resistance, and it may be heralded by precocious pubarche (PP; appearance of pubic hair in girls aged <8 y). The risk of progression from PP to PCOS is related to low birth weight, but there are no early biochemical markers of this risk. As increased plasminogen activator-inhibitor type 1 (PAI-1) activity (act) is an early marker of cardiovascular risk in PCOS, we have sought abnormalities in young girls with PP. In 33 young PP girls (age range 6-11 y), PAI-1-act was increased (mean + SEM: 15.6 +/- 1.5 IU/mL) compared with age-, sex-, and pubertal stage-matched controls (n = 13, 10.7 +/- 1.9, p < 0.05). PAI-1-act levels were inversely related to birth weight SD score (r = -0.33, p < 0.05), and PAI-1-act levels were therefore higher in PP girls with low birth weights (n = 14, 19.5 +/- 2.5 IU/mL) than normal birth weights (n = 19, 12.8 +/- 1.5, p < 0.01). During longitudinal observation in 10 PP girls (mean time interval 2.7 y), PAI-1-act levels in early puberty were positively related to postmenarcheal insulin levels (mean serum insulin SDS postoral glucose, r = 0.65, p < 0.05), and showed a similar relationship to postmenarcheal testosterone levels (r = 0.61, p = 0.06). Together with low birth weight, increased plasma PAI-1-act levels in early pubertal PP girls may indicate those girls with greater risk of developing hyperinsulinemic-hyperandrogenism features of PCOS.     

Central precocious puberty: Evaluation by neuroimaging

To evaluate the incidence of abnormal intracranial findings in children with central precocious puberty, 62 children (51 girls, 11 boys) were examined by computerized tomography and/or magnetic resonance imaging (MRI) of the brain. Forty-four had normal examinations; 18 (11 girls, 7 boys) showed intracranial pathologies, including hamartoma of the tuber cinereum (8 cases), parenchymal loss (3 cases), hypothalamicchiasmatic lesions (2 cases), lesions of the corpus callosum (2 cases), suprasellar cyst (1 case), and pineal cyst and mesiotemporal sclerosis (1 case each). Based on the correlation between the clinical and the imaging results of this series, the authors recommend MRI as the imaging method of choice in the investigation of precocious puberty.     

Etiology and age incidence of precocious puberty in girls: a multicentric study

We review the etiology and age incidence of precocious puberty in 438 girls examined between 1988-1998; 428 (97.7%) had central precocious puberty (CPP), the remaining 10 (2.3%) gonadotropin-independent precocious puberty (GIPP) of ovarian origin. The majority of CPP girls (59.6%) were aged between 7-7.9 yr, 22.4% were 6 year olds, and only 18% were under 6 years old. Cranial CT and/or MRI performed in 304/428 girls, showed neurogenic abnormalities in 56/304 (18.4%) CPP girls; 30 (9.9%) were due to previously diagnosed intracranial abnormalities and the remaining 26 (8.5%) were detected at the diagnosis of CPP. The frequency of neurogenic CPP tended to be higher in girls under 4 years of age while the frequency of idiopathic CPP tended to be higher in girls aged between 7-7.9 years, but no statistically significant differences were found. Interestingly, some CNS anomalies either of tumoral or congenital origin were detected at presentation in 7% of the girls aged over 7 years. Other related or coincidental clinical anomalies, mainly due to genetic diseases, were observed in 22/304 (7.2%) patients. History of precocious maternal menarche was found in 12/304 (4%) girls. In conclusion, idiopathic CPP was observed in 74% of the girls in this study. Neurogenic anomalies or other coincidental or related clinical findings were observed in the remaining 26%. The increased frequency of idiopathic CPP in girls aged over 7 years may suggest an early, but otherwise normal onset of puberty in many of these girls as a consequence of the trend towards earlier maturation. Nonetheless, the finding of CNS anomalies also in the older patients, raises the question of whether these patients should undergo a complete diagnostic work-up.     

Growth hormone secretory dynamics in children with precocious puberty

We investigated whether an increase in growth hormone secretion contributed to the growth spurt in children with precocious puberty by measuring the 24-hour profile of serum growth hormone in 51 patients with central precocious puberty. Girls with central precocious puberty had significantly greater mean 24-hour levels of growth hormone in comparison with normal prepubertal girls (5.1 +/- 0.5 SEM vs 3.4 +/- 0.3 ng/mL, P less than 0.005). Mean 24-hour growth hormone levels did not differ significantly between boys with central precocious puberty and normal prepubertal boys (4.4 +/- 1.2 vs 3.0 +/- 0.4 ng/mL). Serum somatomedin C levels were significantly correlated with mean 24-hour growth hormone levels in the girls only. Height age advancement (expressed as height age/chronologic age) was significantly correlated with mean 24-hour growth hormone levels in both boys and girls with central precocious puberty. We conclude that spontaneous 24-hour growth hormone secretion in girls with precocious puberty is greater than that of normal prepubertal girls and may mediate at least in part the increased growth rate in this disorder.     

Outcome of premature thelarche: relation to puberty and final height

BACKGROUND—There is a debate about the possible progression of idiopathic premature thelarche towards precocious or early puberty.
OBJECTIVE—To evaluate height and age at onset of puberty in a group of girls with a history of idiopathic premature thelarche.
STUDY DESIGN—The height and age at onset of puberty of 42 girls now over 10 years of age who were diagnosed with isolated premature thelarche before the age of 3 years were evaluated.
RESULTS—Menarche was reached before or at 11 years of age in 13.5% of this group of girls. This percentage of early menarche was higher than would be expected from historical controls in the general population, but was consistent with maternal age of menarche. The mean (SD) height of the girls (n = 15) who achieved adult height was 162.9 (6.3) cm, which was slightly higher than the mean (SD) relative midparental height (160.7 (6.7) cm).
CONCLUSIONS—Isolated premature thelarche with onset before 3 years of age progresses towards precocious puberty, although this was consistent with the maternal age of menarche. Furthermore, adult height was normal when compared with population norms in all patients.

     

Long-term treatment of central precocious puberty with an intranasal LHRH analogue: control of pituitary function by urinary gonadotropins

Daily subcutaneous doses of luteinizing hormonereleasing hormone (LHRH) analogues are a well-established therapy for gonadotropin-dependent precocious puberty. Reports on intranasally administered analogues, however, are controversial. We studied the effect of intranasal d-Ser (TBU)⁶-LHRH (BUS) on growth rate, skeletal maturation, and urinary gonadotropins in five girls and one boy with central precocious puberty (CPP) who had been treated for 1.4–2.3 years (mean 1.9). Because of the potential antifertility effects of LHRH analogues, testicular histology was analysed in the boy. In the five children with accelerated growth, the bone age-related velocity of heigh gain decreased from 10.58 ±2.77 to 5.82±1.8 cm/year (means±SD, P<0.01), and the ratio of change in bone age to change in chronological age fell below 1. Basal luteinizing hormone (LH), and LHRH-stimulated LH and follicle stimulating-hormone, at pubertal levels before treatment, decreased significantly in all children, normalizing in four (P<0.04). During therapy, pituitary function was best controlled by urinary LH, which correlated with clinical data. After 13 months of therapy, testicular histology showed degenerated Sertoli cells, and absence of B-and Ap-spermatogonia and of primary spermatocytes in the boy. We conclude that: (1) Efficient long-term suppression of central precocious puberty — including accelerated growth and skeletal maturation — can be maintained by intranasal dosage of BUS. (2) Urinary LH reflects pituitary function and proves to be a reliable guide to adjustment of the LHRH-analogue dose regimen. (3) Testicular atrophy after 1 year of continuous therapy with high doses of BUS raises the question of potential infertility in boys with precocious puberty treated with potent analogues of the LHRH.Abbreviations CPP central precocious puberty - LH luteinizing hormone - FSH tollicle-stimulating hormone - LHRH luteinizing hormone-releasing hormone - LHRH_A LHRH analogue - BUS the analogue d-Ser[TBU]⁶-LHRH (Buserelin), HOE 766) - BA bone age - BA/ CA ratio of change in bone age to change in chronological age - SDS standard deviation score - T urinary testosterone - E2 urinary oestradiol     

Isosexual Precocious Puberty in Girls

ABSTRACT. This paper reviews the clinical findings, pituitary gonadotrophin reserve and plasma oestradiol, neurological findings and pelvic ultrasound appearance in 47 girls with precocious puberty starting before the age of 7 years. Of the 39 girls who had air encephalograms or cranial CT scans, 19 showed intracranial abnormalities (hamartomas 11; hydrocephalus 5; optic glioma 2; arachnoid cyst 1). There was no significant difference in the peak serum luteinizing hormone and follicle-stimulating hormone responses to intravenous gonadotrophin stimulating hormone in girls with and without intracranial lesions. Pelvic ultrasound examination showed development of the ovaries, uterus, and vagina similar to that seen in normal puberty. Treatment with cyproterone acetate (50-100 mg/day) in 26 girls resulted in arrest of breast development and suppression of menstruation, but a definite effect on growth was not documented.     

Transient true precocious puberty. A report of five cases

Five girls with idiopathic true precocious puberty are reported who underwent spontaneous regression of sexual development. In all patients the signs of sexual maturation were of moderate degree. Considering the possible spontaneous regression of precocious puberty, in similar cases it seems advisable to defer suppressive central therapy for about 6–12 months.Abbreviations FSH follicle stimulating hormone - Gn-RH gonadotrophin releasing hormone - LH-RH luteinizing hormone releasing hormone     

Neurofibromatosis type 1 and precocious puberty

Since neurofibromatosis type 1 (NF1) is a well known cause of precocious puberty (PP), we reviewed 412 NF1 pediatric patients to evaluate the prevalence of PP, the association with optic pathway tumors (OPT), and other clinical, auxological and hormonal data. Thirty-one of 412 patients had OPT (7.5%), 10/412 PP (2.4%), and in seven of these PP was associated with OPT (7/31, 22.6%). OPT in patients with PP involved the chiasm in four patients, and the optic nerves alone in three patients. The age at the onset of puberty (or better at diagnosis) ranged from 5.2 to 7.5 yr in girls (n=6) and from 7.9 to 8.9 yr in boys (n=4). LHRH agonist therapy was used in only three children because in the others the predicted height at diagnosis was good, treatment was refused or the patients were referred to us too late. The three treated patients attained a final height within the familial range. In the untreated patients the progression of puberty was not too rapid and final height was slightly below the genetic target in four patients; however, three patients had a final height markedly below the familial range. In conclusion, the prevalence of PP is increased in children with NF1, and frequently but not exclusively is associated with OPT. Moreover, sexual precocity does not seem to be necessarily bound to chiasmatic OPT. Treatment seems to be useful in the children with younger age at the onset of puberty or with a progressive decline in predicted final height.     

Ovarian function in girls with McCune-Albright syndrome

We measured plasma estradiol levels and ovarian volumes in eight girls with precocious puberty due to McCune-Albright syndrome. Six girls had gonadotropin-independent ovarian estrogen secretion and two girls had pubertal gonadotropin levels. Mean ovarian volume in all patients was significantly greater than in normal prepubertal girls. Mean ovarian volumes of the girls with McCune-Albright syndrome overlapped the range found in girls with idiopathic central precocious puberty or central precocious puberty associated with central nervous system lesions. However, the degree of asymmetry between the right and left ovaries was significantly greater in girls with McCune-Albright syndrome. Asymmetry was due, for the most part, to the presence of large solitary cysts in the larger of the two ovaries. In the six girls with McCune-Albright syndrome and gonadotropin-independent precocious puberty, both mean ovarian volume and the degree of asymmetry between the right and left ovaries were significantly correlated with plasma estradiol. Serum follicle-stimulating hormone bioactivity was increased in two patients but did not vary with ovarian cyst size. Thyroid-stimulating hormone levels were normal but serum prolactin was slightly elevated in one of the six girls with gonadotropin-independent precocious puberty. Fluctuation in the size of unilateral ovarian cysts appears to result in changes in the plasma estradiol level, leading to advancement and spontaneous regression of secondary sexual characteristics and menses in girls with McCune-Albright syndrome. The cause of the cyst formation is unknown but may be related to periodic elevation of as yet undefined serum factors such as follicle-stimulating hormone bioactive substances.     

The NIH experience with precocious puberty: diagnostic subgroups and response to short-term luteinizing hormone releasing hormone analogue therapy

Between 1979 and 1983, 129 children (95 girls) with precocious puberty were referred to the National Institutes of Health and received treatment for at least 6 months with the long-acting LHRH analogue D-Trp6-Pro9-NEt-LHRH. The majority (107 of 129) of the children had central precocious puberty mediated by activation of the hypothalamic-pituitary-gonadal axis in association with hypothalamic hamartomas (24 of 107) or other central nervous system lesions (21 of 107), or idiopathic precocious puberty (62 of 107). Hypothalamic hamartomas or other central nervous system lesions were a frequent cause of central precocious puberty in girls (27 of 87), but idiopathic precocious puberty was still the most frequent diagnosis (63%). Idiopathic precocious puberty was uncommon in boys (6%). The patients with peripheral precocious puberty included six girls with McCune-Albright syndrome and six boys with familial male precocious puberty. These children had peripheral sex steroid secretion in the absence of hypothalamic-pituitary-gonadal axis maturation. The children with combined peripheral and central precocious puberty included nine children with congenital adrenal hyperplasia and one girl with a virilizing adrenal tumor. In the patients with central precocious puberty or combined peripheral and central precocious puberty, LHRHa therapy caused suppression of gonadotropin and sex steroid levels (P less than 0.001), stabilization or regression of secondary sexual characteristics, and decreases in growth rate and in the rate of bone age maturation (P less than 0.005). Patients with peripheral precocious puberty, however, had no significant change in gonadotropin or sex steroid levels, growth rate, or the rate of bone age maturation, and no improvement in secondary sexual characteristics. Thus, LHRHa is an effective treatment of central precocious puberty and combined peripheral and central precocious puberty, but is ineffective in the therapy of peripheral precocious puberty.