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Bmi in childhood and its association with height gain, timing of puberty, and final height.

No large population-based study has addressed the question of how overnutrition is related to subsequent height gain in childhood, timing of puberty, and final height. The present data represent a large Swedish population-based longitudinal growth study. Height gain in childhood, timing of reaching peak height velocity and height gain during adolescence, and final height were regarded as the short-term, interim, and long-term outcomes of childhood nutritional status, i.e. body mass index (BMI) change between 2 and 8 y. Midparental height was adjusted as the genetic influence on linear growth of the child. Childhood BMI gain was related to an increased height gain during the same period, i.e. an increase of 1 BMI unit was associated with an increase in height of 0.23 cm in boys and 0.29 cm in girls. A higher BMI gain in childhood was related to an earlier onset of puberty; the impact on the timing of puberty was 0.6 y in boys and 0.7 y in girls. Each increased unit of BMI gain in childhood also reduced the height gain in adolescence, 0.88 cm for boys and 0.51 cm for girls. No direct correlation was shown between childhood BMI gain and final height. We conclude that overnutrition between 2 and 8 y of age will not be beneficial from a final height point of view, as the temporary increase in height gain in childhood will be compensated by an earlier pubertal maturity and a subnormal height gain in adolescence.

Body Height↗

Longitudinal study of physiologic insulin resistance and metabolic changes of puberty.

Cross-sectional studies have shown that 1) adolescents are insulin resistant compared with prepubertal children and adults, 2) pubertal insulin resistance is likely mediated by growth hormone (GH), and 3) pubertal insulin resistance is associated with increased fat oxidation and decreased glucose oxidation. The aim of this study was to assess the validity of these cross-sectional observations by performing a longitudinal study in normal children during the prepubertal and pubertal periods. Nine healthy, normal weight, prepubertal children underwent hyperinsulinemic-euglycemic and hyperglycemic clamp studies for evaluation of insulin sensitivity and insulin secretion. Children had repeat evaluations during puberty. Consistent with cross-sectional observations, this longitudinal study demonstrated that during puberty: 1) insulin sensitivity decreased by approximately 50%, 2) the decrease in insulin sensitivity was compensated by a doubling in insulin secretion, and 3) the decrease in insulin sensitivity was independent of changes in percentage of body fat. Puberty was associated with increased total body lipolysis and decreased glucose oxidation. A novel observation is the demonstration of approximately 50% decrease in adiponectin levels at the pubertal time point. These metabolic changes are proposed to be partially mediated by increased GH secretion and are consistent with the Randle cycle of competition between glucose and fat oxidation.

Adiponectin↗

Neurobiological mechanisms of the onset of puberty in primates.

An increase in pulsatile release of LHRH is essential for the onset of puberty. However, the mechanism controlling the pubertal increase in LHRH release is still unclear. In primates the LHRH neurosecretory system is already active during the neonatal period but subsequently enters a dormant state in the juvenile/prepubertal period. Neither gonadal steroid hormones nor the absence of facilitatory neuronal inputs to LHRH neurons is responsible for the low levels of LHRH release before the onset of puberty in primates. Recent studies suggest that during the prepubertal period an inhibitory neuronal system suppresses LHRH release and that during the subsequent maturation of the hypothalamus this prepubertal inhibition is removed, allowing the adult pattern of pulsatile LHRH release. In fact, y-aminobutyric acid (GABA) appears to be an inhibitory neurotransmitter responsible for restricting LHRH release before the onset of puberty in female rhesus monkeys. In addition, it appears that the reduction in tonic GABA inhibition allows an increase in the release of glutamate as well as other neurotransmitters, which contributes to the increase in pubertal LHRH release. In this review, developmental changes in several neurotransmitter systems controlling pulsatile LHRH release are extensively reviewed.

Animals↗

Minireview: the neuroendocrine regulation of puberty: is the time ripe for a systems biology approach?

The initiation of mammalian puberty requires an increase in pulsatile release of GnRH from the hypothalamus. This increase is brought about by coordinated changes in transsynaptic and glial-neuronal communication. As the neuronal and glial excitatory inputs to the GnRH neuronal network increase, the transsynaptic inhibitory tone decreases, leading to the pubertal activation of GnRH secretion. The excitatory neuronal systems most prevalently involved in this process use glutamate and the peptide kisspeptin for neurotransmission/neuromodulation, whereas the most important inhibitory inputs are provided by gamma-aminobutyric acid (GABA)ergic and opiatergic neurons. Glial cells, on the other hand, facilitate GnRH secretion via growth factor-dependent cell-cell signaling. Coordination of this regulatory neuronal-glial network may require a hierarchical arrangement. One level of coordination appears to be provided by a host of unrelated genes encoding proteins required for cell-cell communication. A second, but overlapping, level might be provided by a second tier of genes engaged in specific cell functions required for productive cell-cell interaction. A third and higher level of control involves the transcriptional regulation of these subordinate genes by a handful of upper echelon genes that, operating within the different neuronal and glial subsets required for the initiation of the pubertal process, sustain the functional integration of the network. The existence of functionally connected genes controlling the pubertal process is consistent with the concept that puberty is under genetic control and that the genetic underpinnings of both normal and deranged puberty are polygenic rather than specified by a single gene. The availability of improved high-throughput techniques and computational methods for global analysis of mRNAs and proteins will allow us to not only initiate the systematic identification of the different components of this neuroendocrine network but also to define their functional interactions.

Animals↗

Treatment of central precocious puberty by subcutaneous injections of leuprorelin 3-month depot (11.25 mg).

Depot GnRH agonists are widely used for the treatment of precocious puberty. Leuprorelin 3-month depot is currently used in adults but has not been evaluated in children. We evaluated the efficacy of this new formulation (11.25 mg every 3 months), for the suppression of gonadotropic activation and pubertal signs in children with central precocious puberty. We included 44 children (40 girls) with early-onset pubertal development in a 6-month open trial. The inclusion criteria were clinical pubertal development before the age of 8 (girls) or 10 (boys), advanced bone age, enlarged uterus (>36 mm), testosterone more than 1.7 nmol/liter (boys), and pubertal response of LH to GnRH (peak >5 IU/liter). The principal criterion for efficacy assessment, GnRH-stimulated LH peak less than 3 IU/liter, was met in 81 of 85 (95%) of the tests performed at months 3 and 6. The remaining four values were slightly above the threshold. The levels of sex steroids were also significantly reduced and clinical pubertal development was arrested. Plasma leuprorelin levels, measured every 30 d, were essentially stable after d 60. Local intolerance was noted after 10 of 86 injections (12%), and was mild in four cases, moderate in five cases, and severe in one. Among these 10 events, 4 consisted in local pain at injection's site. In conclusion, leuprorelin 3-month depot efficiently inhibits the gonadotropic axis in 95% of children with central precocious puberty studied for a 6-month period. This regimen allows the reduction of the number of yearly injections from 12 to 4.

Child↗

Association between the insulin resistance of puberty and the insulin-like growth factor-I/growth hormone axis.

To test the hypothesis that the relative insulin resistance of puberty is associated with changes in IGF-I levels, we compared IGF-I, IGF binding protein-3 (IGFBP-3), and IGFBP-1 levels to insulin resistance [M(lbm), milligrams glucose used per kilogram of lean body mass (LBM) per minute] measured during euglycemic, hyperinsulinemic clamp studies in 342 children and adolescents. IGF-I levels rose and fell during the Tanner stages of puberty in a pattern that closely followed the rise and fall of insulin resistance. IGF-I levels were significantly related to M(lbm) in boys (P = 0.0006) and girls (P = 0.02). IGF-I was significantly related to fasting insulin levels only in girls (P = 0.006; boys, P = 0.26), and this relation was significantly influenced in girls by body fat (P = 0.007), with the strongest association between IGF-I and fasting insulin seen in thin girls. IGFBP-1 correlated negatively with insulin resistance in both boys (P = 0.0004) and girls (P = 0.04), whereas IGFBP-3 correlated positively with insulin resistance in boys (P = 0.0004) but not girls (P = 0.85). These data suggest that the GH/IGF-I axis is an important contributor to the insulin resistance of puberty.

Adolescent↗

A single luteinizing hormone determination 2 hours after depot leuprolide is useful for therapy monitoring of gonadotropin-dependent precocious puberty in girls.

Long-acting GnRH analogs represent the standard treatment for gonadotropin-dependent precocious puberty. The aim of this study was to determine the hormonal parameters for monitoring the adequacy of depot leuprolide acetate treatment in girls with clinical and hormonal diagnosis of gonadotropin-dependent precocious puberty. Eighteen girls were treated monthly with 3.75 mg depot leuprolide acetate. Adequate hypothalamic-pituitary-gonadal axis suppression during treatment was achieved in 16 of the 18 girls according to the clinical parameters and prepubertal LH levels. In these 16 well-controlled girls, the LH peak after a classical GnRH test was compared with a single LH measurement obtained 2 h after depot leuprolide acetate administration before and during GnRH analog treatment. Before therapy, the mean +/- sd LH peak after a classical GnRH test was 18.4 +/- 11.2 IU/liter (ranging from 7-41.5 IU/liter), and it was 22.6 +/- 8.3 IU/liter 2 h after the first depot leuprolide dose (ranging from 10-35.3 IU/liter). During therapy, the mean +/- sd of LH peak after classical GnRH test was 1.4 +/- 0.6 IU/liter (ranging from <0.6 to 2.3 IU/liter), and it was 2.7 +/- 1.9 IU/liter (ranging from 0.7-6.6 IU/liter) 2 h after depot leuprolide. The LH peak after a classical GnRH test and that 2 h after depot leuprolide administration correlate significantly before and during treatment. In conclusion, we established the LH cut-off values for an adequate depot leuprolide therapy as an LH peak below 2.3 IU/liter after a classical GnRH test or below 6.6 IU/liter 2 h after depot leuprolide. The latter measurement may replace the classical GnRH test as a reliable and convenient tool for monitoring therapy in female gonadotropin-dependent precocious puberty.

Child↗

Use of percutaneous estrogen gel for induction of puberty in girls with Turner syndrome.

The aim of pubertal induction by estrogen in hypogonadic girls is to achieve physical and psychological development similar to that in natural puberty. We investigated the use of percutaneous estradiol gel for induction of puberty in girls with Turner syndrome (TS).Twenty-three girls with TS and hypogonadism were included in the study. The initial percutaneous dose of 0.1 mg ended as 1.5 mg in the fifth year. The efficacy of the treatment was monitored by measuring height, weight, skeletal age, pubertal status, and serum hormone levels and gynecological ultrasonographic examinations throughout the study. Mean serum estradiol concentrations increased from 22.2 pmol/liter at baseline to 162.2 pmol/liter, and mean FSH levels decreased from 77.4 IU/liter at baseline to 19.2 IU/liter after 5 yr. There were no significant differences between GH users and nonusers with regard to height sd score, weight sd score, bone age acceleration, or adult height. The development of secondary sexual characteristics and uterine growth progressed gradually during the study. All girls reached at least stage B4P4. With percutaneous estradiol gel, the development of secondary sexual characteristics and uterine growth proceeded gradually, mimicking natural puberty. Estradiol gel was safe, easy to use, and well accepted by the subjects and provides an excellent way to individualize pubertal induction.

Administration, Cutaneous↗

The skeletal phenotype of men with previous constitutional delay of puberty.

It is presently unclear whether men with a history of constitutional delay (CD) of puberty are osteopenic. This study compares auxology, bone mass, size, and density of 32 men (age, 21-33 yr) with previous CD with 45 controls. Using dual-energy x-ray absorptiometry, areal bone mineral density (aBMD) and volumetric bone mineral density at the lumbar spine (LS) and femoral neck (FN), hip strength analysis, and total-body and body segment (arms, legs, trunk) measurements were determined. Auxological variables, body composition, the muscle-bone relation, and the effect of prior androgen treatment were studied. Men with previous CD were shorter (P < 0.001) and had shorter height-adjusted arms compared with controls. Height-adjusted total-body bone mineral content (BMC) (P = 0.004), aBMD (P = 0.016), and bone area (P = 0.006) but not lean tissue mass (P = 0.507) were lower in CD men compared with controls; consequently, their BMC to lean tissue mass ratio was reduced (P < 0.001). Segment length-adjusted BMC and bone area of arms (P < 0.001) and legs (P < 0.03), but not trunk were lower in CD men than in controls. They had lower LS aBMD (P = 0.044) but normal LS and FN volumetric bone mineral density. Size-adjusted LS width and the hip cross-sectional area were lower than in controls. There was no difference in anthropometric or dual-energy x-ray absorptiometry results between untreated (n = 15) and androgen-treated (n = 17) CD men.We conclude that men with previous CD have normal LS and FN volumetric density but reduced total-body bone mass, which was explained by reduced limb bone mass and size. Together with the reduced LS bone width and hip crosssectional area, these skeletal characteristics suggest impaired periosteal expansion during puberty. The skeletal phenotype of CD males may be altered by their late onset of puberty.

Adolescent↗

Adult height after ketoconazole treatment in patients with familial male-limited precocious puberty.

Familial male-limited precocious puberty is a rare cause of precocious puberty due to activating mutations of the LH receptor, leading to early onset virilization and short stature. Two therapeutic approaches have been proposed: the P450 cytochrome inhibitor ketoconazole or combined treatment with spironolactone and testolactone. Results on adult heights have not been reported to date after these two treatments, and in this study we present results from five patients treated with ketoconazole at a median dose of 16.2 mg/kg.d for a median of 6.2 yr. Adult height was 173 cm (median; interquartile range, 14), similar to target height (175 cm; interquartile range, 9) and significantly higher than pretreatment predicted height (165 cm; interquartile range, 12; P < 0.01). During treatment, 39 of 58 (68%) testosterone measurements were less than 0.5 ng/ml (1.7 nmol/liter), nine of 58 (15%) were between 0.5 and 1 ng/ml (3.5 nmol/liter), and 10 of 58 (17%) were above 1 ng/ml. We observed a physiological increase in GnRH-stimulated LH levels after the age of 10 yr, and none of the patients had early activation of the gonadotropic axis. Liver tolerance was excellent, and only one patient had a transient and modest increase in serum transaminases. We conclude that ketoconazole is an efficient and well tolerated long-term treatment of familial male-limited precocious puberty that should be proposed as a first line therapy.

Adult↗

Comparison of clinical, ultrasonographic, and biochemical differences at the beginning of puberty in healthy girls born either small for gestational age or appropriate for gestational age: preliminary results.

CONTEXT: There are limited and controversial data concerning puberty characteristics in girls born small for gestational age (SGA). OBJECTIVE: The objective of the study was to document clinical, ultrasonographic, and biochemical characteristics at the beginning of puberty in matched healthy girls born either SGA or appropriate for gestational age (AGA) recruited from the community. PATIENTS: Inclusion criteria were breast Tanner stage II and a body mass index between the 10th and 95th percentiles. INTERVENTIONS: Recruited subjects underwent a complete physical exam, bone age, and ultrasound measurements of the internal genitalia. Hormonal assessment included fasting early morning dehydroepiandrosterone sulfate, androstenedione, SHBG, inhibin-B, FSH, LH, estradiol (E2), 17-hydroxyprogesterone (17OH Prog), and testosterone. Thereafter, a GnRH agonist test (leuprolide 500 microg, sc) was performed with FSH and LH at time 3 and 24 h for E2, 17OH Prog, and testosterone. RESULTS: Sixty-five girls (35 AGA, 30 SGA) with a mean age of 9.9 +/- 1.03 (7.8-12.5) yr, similar bone age/chronological age (1.02 +/- 0.8 in AGA and 1 +/- 0.76 in SGA), median height of 1.35 +/- 0.06 cm, and similar waist to hip ratio were included. No differences in the presence of pubic hair, axillary hair, apocrine odor, or ultrasound measurements were found. SGA girls had increased baseline E2 as well as stimulated E2 and 17OH Prog. CONCLUSIONS: In a preliminary sample of lean, healthy girls recruited from the community born either SGA or AGA, we observed slight hormonal differences at the beginning of puberty. Longitudinal follow-up of this cohort will allow us to understand whether these differences are maintained and have a clinical impact in their pubertal development.

17-alpha-Hydroxyprogesterone↗

Change in cortical bone density and its distribution differs between boys and girls during puberty.

CONCEPT: Postmenarchal girls and premenopausal women have 3-4% higher cortical bone density (CoD, milligrams per cubic centimeter), compared with postpubertal boys and men, respectively. Females' denser cortical bone is thought to serve as a calcium reservoir for reproductive needs. However, prospective data are lacking that describe CoD development and bone mineral density distribution during puberty in both sexes. OBJECTIVE: Thus, our objectives were to assess maturity and sex differences in the 20-month change of CoD and radial distribution of bone mineral density (RDBMD, milligrams per cubic centimeter) in early-, peri-, and postpubertal girls and boys. Maturity groups were based on change in menarcheal status (girls, n = 68) and pubic hair stage (Tanner) (boys, n = 59). Peripheral quantitative computed tomography was used to measure CoD and RDBMD at the tibial middiaphysis. RESULTS: The increase in average CoD was 1.9% [22.8 mg/cm(3); 95% confidence interval (CI), 10-36], 2.8% (33.8 mg/cm(3); 95% CI, 21-47), and 1.5% (55.0 mg/cm(3); 95% CI, 17-93) greater in early, peri-, and postpubertal girls, compared with boys, respectively. Analysis of RDBMD revealed that the change in density distribution varied across pubertal groups in girls. Across puberty, all girls showed an increase in the high density midcortical region, whereas only peripubertal girls showed an increase in the lower density subcortical region. A sex-difference in RDBMD change was noted within early and peripubertal groups. CONCLUSIONS: Our findings of sexual dimorphism in CoD development give support to the hypothesis that female bone deposits calcium for reproductive needs by consolidation of cortical bone during puberty.

Adolescent↗

A note on the bone age at which patients with true isolated growth hormone deficiency enter puberty.

Nineteen boys with true isolated growth hormone deficiency developed the first stages of puberty at an average bone age of 12.0"years" (Tanner Whitehouse Method 2, RUS score). The average chronological age was 15.0 years. Seven similar girls entered puberty at 10.9"years" in bone age and 13.7 years in chronological age. The means and ranges of bone age at beginning of puberty of these patients are very close to those of normal children.

Adolescent↗

Puberty in girls: correlation of serum levels of gonadotropins, prolactin, androgens, estrogens, and progestins with physical changes.

Twenty-seven girls aged 8 to 18 were studied in a longitudinal prospective fashion. Serum samples were collected at 6 month intervals up to 4 years and radioassayed for hormones of pituitary, ovarian, and adrenal origin. A progressive elevation of luteinizing hormone (LH), follicle-stimulating hormone/FSH), estradiol (E2), dehydroepiandrosterone (DHA), and androstenedione (delta4) occurred during puberty and continued until menarche. The onset of puberty occurred concomitantly with an elevation of estrone (E1) dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHAS), and 17-hydroxyprogesterone (17-OH-P). Prolactin (Prol) and progesterone (Prog) concentrations did not change during puberty until after menarche. After menarche, levels of LH and FSH were comparable with menstruating adult females. Concentrations of E2 and Prog were lower during the second half of the cycle among most regularly menstruating subjects than expected during the luteal phase. LH and Prog levels indirectly suggest that ovulation occurs in a few girls within months after menarche.

Adolescent↗

Hyperprolactinemia in girls with idiopathic precocious puberty under prolonged treatment with cyproterone acetate.

Pasma prolactin response to the acute injection of sulpiride (1.5 mg/k BW im) was measured at 0800-0900h in 4 girls with idiopathic precocious puberty before and after 6 to 11 months of continuous therapy with 50 mg daily of cyproterone acetate (CA) orally administered. Two additional girls were examined after 26 and 28 months of therapy, respectively. Mean baseline prolactin concentrations were significantly higher in untreated girls with precocious puberty as compared to that of normal controls of the same chronological age and of a comparable degree of sexual maturation (14.5 +/- 1.9 SE vs. 7.4 +/- 1.8 SE ng/ml and vs. 9.5 +/- 1.8 ng/ml, respectively; P less than .02). Treatment with CA caused a significant further increase of plasma prolactin concentration (P less than .02 as compared to pre-treatment values); no correlation was observed between prolactin concentration and duration of treatment. No significant change in the integrated areas of prlactin response to sulpiride occurred after prolonged CA therapy. The results suggest that in idiopathic precocious puberty the action of CA upon the hypothalamic-hypophyseal complex is not solely antigonadotropic and that prolactin secretion is enhanced in patients given this drug.

Child↗

True precocious puberty complicating congenital adrenal hyperplasia: treatment with a luteinizing hormone-releasing hormone analog.

Congenital adrenal hyperplasia (CAH) is a recognized cause of precocious pseudopuberty. Some children with CAH also develop true precocious puberty with early maturation of the hypothalamic-pituitary-gonadal axis. We have seen four such children (three boys and one girl) who had the diagnosis of CAH made between the ages of 3 and 6 yr. These patients were treated with standard doses of hydrocortisone and fludrocortisone. A diagnosis of true precocious puberty was made because of testicular enlargement in the boys, breast development in the girl, progressive pubic hair development, rapid growth, and rapid bone age maturation. Plasma steroid levels were elevated for age, and gonadotropin levels were within the normal pubertal range, both basally and in response to LHRH stimulation. We treated these children with daily sc injections of a LHRH analog (LHRHa) for 6-18 months in addition to the standard hydrocortisone and fludrocortisone therapy for CAH. LHRHa significantly decreased basal plasma LH and FSH, peak LH and FSH responses to native LHRH, and testosterone levels. Testis size decreased in the males, and breast development regressed in the female. LHRHa therapy led to significant decreases in linear growth rate, ulnar growth rate, and rate of bone age advancement. These results suggest that LHRHa is an effective adjunct to hydrocortisone and fludrocortisone in the treatment of true precocious puberty complicating CAH.

Adrenal Hyperplasia, Congenital↗

Intranasal and subcutaneous treatment of central precocious puberty in both sexes with a long-acting analog of luteinizing hormone-releasing hormone.

The chronic administration of the long-acting LHRH agonist analog D-Ser(TBU)6-LHRH-EA10 (HOE 766, Buserelin) suppresses pituitary gonadotropin secretion. Since a similar analog was shown to be effective in the short term parenteral treatment of idiopathic precocious puberty in girls (10), we used Buserelin both intranasally and sc to treat patients of both sexes with idiopathic and secondary central precocious puberty to test its efficacy, safety, and potential for long term use. Six girls and two boys presented with advanced skeletal maturity, accelerated growth velocity, Tanner stage II-IV pubertal development, and pubertal levels of sex steroids and gonadotropins. Patients were treated for 6 months sc and up to 5 months intranasally. Optimal doses ranged from 10-20 micrograms/kg X day in girls and 30 micrograms/kg X day in boys, with marked individual variation. During sc therapy, there was significant suppression of growth velocity (P less than 0.001), serum gonadotropins (P less than 0.001), 17 beta-estradiol (P less than 0.005), and testosterone as well as clinical and behavioral improvement. The rate of bone maturation was reduced. All effects were reversed after discontinuation of therapy for 1 month in one girl. No reduction in efficacy was seen after changing four girls and one boy to intranasal therapy, but improved acceptability and compliance were reported by parents. Apart from withdrawal bleeding in one girl and transient acceleration of puberty in two patients during the initial phase of treatment, no serious unwanted effects occurred. Antibodies to native LHRH were not detected after 6 months of therapy. These results confirm the efficacy and safety of Buserelin by intranasal and sc routes in patients with sexual precocity and indicate a need for long term studies.

Administration, Intranasal↗

Luteinizing hormone-releasing hormone analog treatment of boys with hypothalamic hamartoma and true precocious puberty.

A long-acting analog of LRH (LRHa) has been shown to suppress pituitary gonadotropin and estradiol secretion to prepubertal levels in girls with idiopathic true precocious puberty. We treated six boys, aged 1-6 yr, with true precocious puberty due to hypothalamic hamartoma for 6-24 months with daily sc injections of LRHa. The patients had enlarged testes (6-25 ml), Tanner stage II-IV pubic hair, facial and axillary hair, increased growth rate, and an advanced bone age. Frequent erections occurred in all patients. Computed tomography of the head showed abnormalities characteristic of hypothalamic hamartoma (0.5-3 cm in diameter) in each boy. Each patient had measurable LH and FSH levels, with pulsed nocturnal secretion, and pubertal LH and FSH responses to LRH. Serum testosterone was in the range for normal adult men (200-600 ng/dl). LRHa significantly decreased basal LH (P less than 0.005) and FSH levels (P less than 0.01), LRH-stimulated gonadotropin levels (P less than 0.005), and serum testosterone levels (P less than 0.005). Testis size decreased significantly (P less than 0.005). Annualized growth velocity (centimeters per yr) decreased significantly compared to the pretreatment growth rate (P less than 0.01). Bone age advancement per yr slowed significantly during the course of LRHa treatment (P less than 0.01). Pubic hair, facial hair, and erections decreased in all patients. LRHa is an effective treatment for boys with precocious puberty associated with hypothalamic hamartoma. Chronic therapy will be required, however, to assess the ultimate effect of LRHa.

Bone Development↗