Spermaturia and serum hormone concentrations at the age of puberty in boys prenatally exposed to polychlorinated biphenyls

OBJECTIVE: To determine whether prenatal exposure to polychlorinated biphenyls (PCBs) with possible hormone-disrupting effects is capable of affecting sexual differentiation in boys at the age of puberty. DESIGN: Following analysis for PCB in their umbilical cords, 196 boys from a Faroese birth cohort were examined for the development of puberty at 14 years of age. METHODS: Physical examination included determination of Tanner stages and testicular size. A morning urine sample was centrifuged and examined for the presence of sperm. Serum was analyzed for sex hormones. RESULTS: twenty boys (10.2%) had abnormalities in testicular development, mainly cryptorchidism. only three of them had a positive spermaturia test, but the level of exposure to pcbs in this group had not been increased. occurrence of spermaturia in 58 of the remaining 176 boys was also not associated with pcb exposure but showed highly significant associations with tanner stages and testicular size. serum concentrations of testosterone, fsh and lh were higher in boys with spermaturia, while sex hormone-binding globulin was lower and no difference occurred in inhibin b. serum hormone parameters showed only weak associations with the level of prenatal pcb exposure. CONCLUSIONS: These findings support the validity of spermaturia as a useful indicator of puberty, although a substantial rate of false negatives must be taken into account. Despite the wide range of exposure to PCB, the findings did not reveal any definite associations with the development of puberty. However, because of the limited size of the cohort, small effects cannot be excluded.     

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

We evaluated the effect of leuprorelin treatment on adult height (AH) and followed recovery of reproductive function in 63 girls and 13 boys with central precocious puberty (CPP). Mean treatment durations were 3.8 +/- 2.0 and 4.1 +/- 2.5 yr, and posttreatment follow-up durations were 3.5 +/- 1.3 and 2.6 +/- 1.1 yr for girls and boys, respectively. AH was 154.5 +/- 5.7 cm for girls, and 89.5% of girls reached AH within their target height range. For boys, AH was 163.2 +/- 13.0 cm, and 90.9% reached target height range. It appeared that the Bayley-Pinneau method, modified for Japanese children, using a table for advanced bone age (BA), overestimated AH in CPP; and this method, using a table for average BA and projected height for BA, was suitable for prediction of AH in CPP. Menarche or remenarche occurred in 96.8% of girls at the age of 13.1 +/- 1.5 yr. Of 11 girls who contributed urine samples, all seven idiopathic and two organic cases were considered to have ovulation. Serum testosterone levels reached normal adult level in all boys. In conclusion, long-term leuprorelin treatment for children with CPP improved AH and had no adverse effects on recovery of reproductive function.     

Somatomedin A in male puberty. Variation with age, maturity, growth and androgens

Bioassayable somatomedin-A (SM-A) and serum concentrations of testosterone (T) and dehydroepiandrosterone (DHEA) were determined longitudinally in 26 normal boys during puberty. The mean trend of SM-A increased in relation to age, pubic hair development and peak height velocity (PHV) and significant correlations were observed with testicular volume, height velocity and T (all P less than 0.001) but not with DHEA. In relation to growth SM-A increased mainly during 12 to 6 months prior to PHV but no further increase was seen in the 6 months thereafter. Thus pubertal growth and development have to be taken into account in the evaluation of changes in bioassayable SM-A concentrations in boys.     

Final height outcome after three years of growth hormone and gonadotropin-releasing hormone agonist treatment in short adolescents with relatively early puberty

OBJECTIVE: Our objective was to assess final height (FH) and adverse effects of combined GH and GnRH agonist (GnRHa) treatment in short adolescents born small for gestational age or with normal birth size (idiopathic short stature). DESIGN AND PATIENTS: Thirty-two adolescents with Tanner stage 2-3, age and bone age (BA) less than 12 yr for girls or less than 13 yr for boys, height sd score (SDS) less than -2.0 SDS or between -1.0 and -2.0 SDS plus a predicted adult height (PAH0) less than -2.0 SDS were randomly allocated to receive GH plus GnRHa (n=17) or no treatment (n=15) for 3 yr. FH was assessed at the age of 18 yr or older in girls or 19 yr or older in boys. RESULTS: FH was not different between treatment and control groups. Treated children had a larger height gain (FH-PAH0) than controls: 4.4 (4.9) and -0.5 (6.4) cm, respectively (P<0.05). FH was higher than PAH0 in 76 and 60% of treated and control subjects, respectively. During follow-up, 50% of the predicted height gain at treatment withdrawal was lost, resulting in a mean gain of 4.9 cm (range, -4.0 to 12.3 cm) compared with controls. Treatment did not affect body mass index or hip bone mineral density. Mean lumbar spine bone mineral density and bone mineral apparent density tended to be lower in treated boys, albeit statistically not significant. CONCLUSION: Given the expensive and intensive treatment regimen, its modest height gain results, and the possible adverse effect on peak bone mineralization in males, GH plus GnRHa cannot be considered routine treatment for children with idiopathic short stature or persistent short stature after being born small for gestational age.     

Transdermal testosterone application: pharmacokinetics and effects on pubertal status, short-term growth, and bone turnover

The aim of the study was to assess the effect of transdermal testosterone on free testosterone concentrations in saliva and on short-term growth and bone turnover in boys with growth or pubertal delay. A prospective, randomized, crossover study was conducted over 26 wk with 4 wk of run-in, 8 wk of treatment I (8 or 12 h), 4 wk of washout, 8 wk of treatment II (8 or 12 h), and 4 wk of final washout. The main outcome measures were salivary testosterone profiles during the different study periods; weekly change in lower leg length (LLL) as measured by knemometry, i.e. LLL velocity; absolute and percentage change in bone alkaline phosphatase (bALP) levels; and deoxypyridinoline cross-links measured in urine. Eight boys who took part in the study had a median age of 13.5 yr (range, 12.4-14.9 yr), testicular volume of 3 ml (range, 2-6 ml), height SD score of -2.4 (range, -1.44 to -3.35), and bone age delay of 2 yr (range, 1-3.2 yr). Median salivary testosterone during 8- and 12-h treatments [179 pg/ml (range, 7-3579 pg/ml) and 150 pg/ml (range, 12-3472 pg/ml) (not significant)] was significantly higher than during the run-in and washout blocks (P < 0.0001) [9 pg/ml (range, <7 to 122 pg/ml) and 13 pg/ml (range, <7 to 285 pg/ml) (not significant)]. LLL velocity in the treatment blocks (median, 0.64 mm/wk; range, 0.1-1.08 mm/wk) was significantly higher than during the run-in and washout periods (median, 0.48 mm/wk; range, -0.06 to 0.92 mm/wk) (P < 0.001). The main rise in bALP occurred during the first treatment block with a median percentage change in bALP of 44.2% (range, -4 to 87%) and a smaller percentage change in bALP at the end of the second treatment block of 9.8% (range, -4 to 55%). The increases in bALP were not significantly different between the 8- and 12-h treatment periods, and there was no significant decline during the washout periods. Overnight transdermal testosterone application, as Virormone (5 mg), may be a potentially acceptable method of induction of puberty and stimulates short-term growth and bone turnover.     

Pubertal Gynecomastia Coincides with Peak Height Velocity

Objective: Pubertal gynecomastia (PG) occurs in up to 65% of adolescent boys. In this study, we investigated the relationship between the ages at which PG and peak height velocity occur in pubertal boys.Methods: This was a prospective study that was designed to detect PG within three months of its emergence. We examined one hundred and six boys who were followed for short stature and/or delayed puberty at three month intervals, and gynecomastia was observed in 43 of these boys (40.5%).Results: PG occurred in the 43 boys within a year of their peak height velocity, and most of these boys were at Tanner stage 3 for pubic hair and had testicular volumes between 8-10 mL.Conclusion: It is recommended that evaluation of height growth be included in the diagnostic approach to PG in boys with short stature and/or delayed puberty. The coincidence of age of peak height velocity and PG suggests a causal relationship between the two events and a role of insulin-like growth factor-1.Conflict of interest:None declared.     

Boys with precocious puberty due to hypothalamic hamartoma: reproductive axis after discontinuation of gonadotropin-releasing hormone analog therapy

Hypothalamic hamartoma is an important cause of precocious puberty in boys. Although the GnRH analogs are known to be effective therapy, there are few studies of the recovery of the pituitary-gonadal axis following long-term treatment. To this end, we studied 11 boys with HH after 8.8+/-3.2 yr (range, 4.0-12.6) of treatment with the GnRH agonist D-Trp6,Pro9,NEt-LHRH. The patients' levels of LH and FSH, testosterone, testis volume, and body mass index were compared with those of six normal boys in pubertal stage IV-V. We found that the patients' mean +/- SD peak GnRH-stimulated LH and FSH had returned to the normal range by 1 yr after stopping therapy. Whereas testosterone returned to normal levels by 1 yr, the patients' testis volume remained smaller than normal until 2 yr after therapy. Ultrasonography revealed diffuse, punctate, echogenic foci in the testicular parenchyma of two patients; these were first observed during GnRH agonist therapy and persisted unchanged after discontinuation of treatment. Neither of these two patients reported pain or testicular discomfort, no mass or irregularity was detected by manual examination in either patient at any time, and levels of beta-hCG and alpha1-fetoprotein were normal. By 4 yr after therapy, all patients had pubertal stage V pubic hair; their body mass index was not different from that of the normal boys at any time point. The dimensions of the patients' hamartomas did not change during or after therapy, and no patient reported new neurological symptoms or signs suggestive of an enlarging lesion at any time during or after discontinuation of treatment. Two families did report episodes of emotional lability and truancy as the patients reentered puberty after discontinuation of treatment.     

Adrenocorticotropin-dependent precocious puberty of testicular origin in a boy with X-linked adrenal hypoplasia congenita due to a novel mutation in the DAX1 gene.

Primary adrenal insufficiency is a rare condition in pediatric age, and its association with precocious sexual development is very uncommon. We report a 2-yr-old Brazilian boy with DAX1 gene mutation whose first clinical manifestation was isosexual gonadotropin-independent precocious puberty. He presented with pubic hair, enlarged penis and testes, and advanced bone age. T levels were elevated, whereas basal and GnRH-stimulated LH levels were compatible with a prepubertal pattern. Chronic GnRH agonist therapy did not reduce T levels, supporting the diagnosis of gonadotropin-independent precocious puberty. Testotoxicosis was ruled out after normal sequencing of exon 11 of the LH receptor gene. At age 3 yr he developed clinical and hormonal features of severe primary adrenal insufficiency. The entire coding region of the DAX1 gene was analyzed through direct sequencing. A nucleotide G insertion between nucleotides 430 and 431 in exon 1, resulting in a novel frameshift mutation and a premature stop codon at position 71 of DAX-1, was identified. Surprisingly, steroid replacement therapy induced a clear decrease in testicular size and T levels to the prepubertal range. These findings suggest that chronic excessive ACTH levels resulting from adrenal insufficiency may stimulate Leydig cells and lead to gonadotropin-independent precocious puberty in some boys with DAX1 gene mutations.     

Pubertal growth and final height in hypopituitary boys: a minor role of bone age at onset of puberty

Twenty-two hypopituitary boys treated with human GH were studied longitudinally before and during puberty. Eight patients entered spontaneous puberty at a mean bone age of 12.4 +/- 1.0 (+/- SD) yr. Height velocity reached a mean peak of 6.8 cm/yr during the second year of spontaneous puberty. In these patients, the mean total height gain throughout puberty was 22.8 +/- 5.2 cm, and the mean final height was 158.6 +/- 7.2 cm. Fourteen patients received testosterone enanthate (100 mg/month, im) starting at a mean bone age of 13.6 +/- 1.1 yr. Height velocity was maximal (7.5 cm/yr) during the first year of therapy. The mean final height was 162.9 +/- 5.0 cm, with a mean pubertal gain of 15.9 +/- 3.8 cm. Genital development, peak height velocity, and increase in plasma testosterone levels occurred earlier during testosterone therapy than during spontaneous puberty. In both groups of patients, there was a positive correlation between the bone age at onset of puberty and the height at onset of puberty (r = 0.65). There was also a negative correlation between bone age and total pubertal height gain (r = -0.73). This reduction in pubertal height increase was less than expected for bone age at onset of puberty, which can be explained by a decrease in bone age velocity in relation to bone age at onset of puberty (r = -0.81). Therefore, advancement in bone age at the onset of testosterone therapy did not impair final height, whereas it may increase height at onset of puberty, which is the major factor in final height. We conclude that in GH- and gonadotropin-deficient boys 1) a reduced dosage of testosterone enanthate (25 mg twice a month, im) should be used to induce pubertal development, and 2) the major criterion to decide when to give testosterone is height reached at that time regardless of bone age.     

Pituitary-gonadal function in boys after high dose testosterone treatment for excessively tall stature

One hundred excessively tall boys with a height prediction of 205.32 +/- 5.28 cm (mean +/- SD) were treated with 500 mg testosterone oenanthate (TE) every 14 days for a period of 14.96 +/- 5.29 months. Following therapy, the hypothalamo-pituitary-gonadal axis was evaluated, using a standardized GnRH-test at median time intervals of 14 days, 6 weeks, 13 weeks, 6 months and 16 months. Basal and stimulated LH- and FSH-values were not measurable or severely suppressed in all boys 14 days after termination of therapy. Starting at 6 weeks, normalization of pituitary-gonadal function was demonstrated in 93 boys (group 1) with follow-up periods of up to 48 months. Six boys (group 2) developed transitory hypergonadotrophic LH- and FSH-secretory patterns for up to 11 months after the last TE-injection. Testosterone and gonadotrophins were within the normal range in all 6 boys, when prospectively re-evaluated at 12 to 27 months after termination of therapy. During TE-administration, testicular volume was reduced in some, and in most boys did not show the normal enlargement occurring during puberty. However, return to normal testicular size was seen several months after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Abnormal puberty in paediatric Cushing's disease: relationship with adrenal androgen, sex hormone binding globulin and gonadotrophin concentrations

OBJECTIVE: Paediatric Cushing's disease is frequently associated with abnormal puberty. We addressed the hypothesis that prepubertal patients show excessive virilization and pubertal patients show suppression of LH and FSH secretion. DESIGN AND MEASUREMENTS: Serum androstenedione (A4), dehydroepiandrosterone sulphate (DHEAS), testosterone (T), and sex hormone binding globulin (SHBG) were determined at diagnosis and converted to standard deviation scores. LH, FSH concentrations were also determined. Severity of CD was assessed from the sleeping midnight cortisol concentration. Puberty was staged and excessive virilization defined as advance in pubic hair stage for breast stage or testicular volume (TV). PATIENTS: Twenty-seven CD patients (17 male, 10 female), median age 13.4 years (range 5.9-17.8) were studied. RESULTS: In the CD group as a whole, A4, DHEAS, T standard deviation scores (SDS) values were normal. SHBG SDS values (n = 19) were low (median -1.93, -4.32-0.86) correlating with BMI (r = -0.49). A4, DHEAS, T, SHBG, LH and FSH did not correlate with midnight cortisol, but A4 and T SDS correlated with ACTH at 09.00 h (both r = 0.51). Thirteen patients (11 male, 2 female) had excessive virilization with increased A4 (P = 0.033), DHEAS (P = 0.008), testosterone (P = 0.033) and decreased SHBG (P = 0.004) compared with subjects without excessive virilization. Pubertal boys (TV > or = 4 ml) (n = 7) and girls (breasts > or = stage 2) (n = 8) had low median LH and FSH. Boys had an LH concentration of 1.2 mU/l (0.3-3.5), FSH, 0.9 mU/l (0.2-6.4) and median T SDS, -1.95 (-3.8-4.65), while girls had an LH concentration of 1 mU/l (0.3-7.4). CONCLUSIONS: Many patients had abnormal puberty and excessive virilization associated with increased adrenal androgens and decreased SHBG. Pubertal patients had low LH and FSH suggesting impaired pituitary-gonadal axis function.     

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.     

SHOX haploinsufficiency and Leri-Weill dyschondrosteosis: prevalence and growth failure in relation to mutation, sex, and degree of wrist deformity

SHOX mutations causing haploinsufficiency were reported in Leri-Weill dyschondrosteosis (LWD), which is characterized by mesomelic short stature and Madelung deformity of the wrists. The aim of this study was to determine the prevalence of SHOX mutations in LWD and to investigate the degree of growth failure in relation to mutation, sex, age of menarche, and wrist deformity. We studied 20 families with 24 affected children (18 females) and nine affected parents (seven females). All patients presented with bilateral Madelung deformity and shortening of the limbs. Height, sitting height, parental height, birth length, age of menarche, and presence of minor abnormalities were recorded. The degree of Madelung deformity was estimated by analysis of left hand radiographs. Microsatellite typing of the SHOX locus was used for detection of SHOX deletions and PCR direct sequencing for the detection of SHOX point mutations. In 14 of 20 families (70%), SHOX mutations were detected, with seven deletions (four de novo) and seven point mutations (one de novo). The latter included five missense mutations of the SHOX homeodomain, one nonsense mutation (E102X) truncating the whole homeodomain, and one point mutation (X293R) causing a C-terminal elongation of SHOX. Median age of the affected children was 13.4 yr (range, 6.1-18.3), mean height sd score (SDS) (sd in parentheses) was -2.85 (1.04), and mean sitting height/height ratio SDS was +3.06 (1.09). Mean birth length SDS was -0.59 (1.26). Growth failure occurred before school age. Height change during a median follow-up of 7.4 yr (range, 2.3-11.3) was insignificant with a mean change in height SDS of -0.10 (0.52). Mean height SDS of affected parents was -2.70 (0.85) vs. -0.91 (1.10) in unaffected parents. Height loss due to LWD was estimated calculating delta height defined by actual height SDS minus target height SDS of the unaffected parent(s). In the children, mean delta height SDS was -2.16 (1.06), the loss being greater in girls at -2.30 (1.02) than in boys at -1.72 (1.09) (P = 0.32). In patients with SHOX deletions, it was -2.14 (1.15) vs. -1.67 (0.73) for the SHOX point mutation group (P = 0.38). Mean delta height SDS was -2.26 (0.68) for the girls with early menarche (<12 yr) vs. -2.08 (0.91) for the other postmenarcheal girls (P = 0.72). Height loss in patients with radiologically severe wrist deformities in comparison with those having milder radiological signs was -2.81 (1.01) vs. -1.70 (1.04) (P = 0.03). GH treatment in five children during a median duration of 3.4 yr (range, 1.5-9.8 yr) with a median dosage of 0.23 mg/kg.wk (range, 0.14-0.25) resulted in a mean height SDS gain of +0.82 (0.34). In conclusion, SHOX defects were the main cause of LWD. Growth failure occurred during the first years of life with a mean height loss of 2.16 SDS whereas pubertal growth may only be mildly or not affected. Children with a severe degree of wrist deformity were significantly shorter than those with mild deformities. No statistically significant effects of type of mutation, age of menarche, or sex on height were observed. The effect of GH therapy varied between individuals and needs to be examined in controlled studies.     

Oxandrolone in constitutionally delayed growth, a longitudinal study up to final height

Twenty-seven prepubertal boys and 9 prepubertal girls with constitutionally delayed growth were treated with the anabolic steroid oxandrolone for 12 months and followed until they reached final height. Sixteen boys were treated with a mean dose of 0.12 mg/kg.day [low dose (LD)] and 11 boys with a mean dose of 0.22 mg/kg.day [high dose (HD)]. The girls were treated with a mean dose of 0.1 mg/kg.day. Thirteen boys and 9 girls served as controls. On oxandrolone the mean height velocity increased from 4.0 to 8.6 (boys, LD), from 4.3 to 8.9 (boys, HD), and from 4.3 to 8.3 cm/yr (girls). The immediate posttreatment height velocity was significantly higher than the pretreatment height velocity (P less than 0.05), regardless of whether the patients had entered puberty. On oxandrolone the mean ratios of change in bone age/change in chronological age were 2.0 (boys, LD), 2.3 (boys, HD), and 2.0 yr/yr (girls) and continued to be accelerated during the 6 months after treatment. Height predictions at the onset of treatment and after 6 months off treatment were calculated by three different methods: Bayley-Pinneau (BP), Roche-Wainer-Thissen (RWT), and Tanner Mark II (T II). In the boys (LD) mean height predictions increased significantly by the methods of BP (3.3 cm) and RWT (2.9 cm), but not by the method of T II (0.6 cm). In the boys (HD) no significant change in height predictions was noted. In the girls mean height predictions remained unchanged by BP and RWT, but decreased significantly by T II (-2.5 cm). The difference between final height and initial height prediction was taken as a measure of the influence of the treatment on adult height. In all three treatment groups the difference between final height and initial height prediction, calculated with all three methods, did not differ from the control group. We conclude that oxandrolone treatment for 1 yr has no effect on adult height. In spite of this, the use of an anabolic steroid such as oxandrolone may still have value, as an increase in height velocity and an earlier onset of puberty may benefit short children suffering from psychological problems due to delay of growth and development.     

Estrone and estradiol concentrations in human ovaries, testes, and adrenals during the first two years of life

To determine the origin of estrogens in infant blood, we measured estrone (E1) and estradiol (E2) in the gonads of 50 girls and 64 boys who died suddenly between birth and 2 yr of age as well as in the adrenals of 18 of these infant girls and 16 of the boys. In the adrenals, E1 [median, 2.8 ng/g (10.4 pmol/g); range, 1.1-4.8 ng/g (4.1-17.8 pmol/g)] and E2 [median, 3.0 ng/g (10.9 pmol/g); range, 1.2-5.3 ng/g (4.4-19.5 pmol/g)] were found in similar concentrations and were independent of age and sex. In the gonads, E2 was the major estrogen, but the concentrations differed markedly between the sexes; E2 exceeded E1 almost 10-fold in the ovaries and 2-fold in the testes. On the average, the gonads of the infant girls had 5 times more E2 and 2 times more E1 than those of the boys. As in plasma, E2 concentrations were highest in the ovaries of 1- to 6-month-old girls [median, 10.5 ng/g (38.5 pmol/g); range, 1.1-55.1 ng/g (4.0-202.0 pmol/g)] and in testes of 1- to 3-month-old boys [median, 1.8 ng/g (6.6 pmol/g); range, 0.6-6.4 ng/g (2.3-23.5 pmol/g)]. Ovarian E2 concentrations declined to less than 3.0 ng/g (11.0 pmol/g) by the end of the first year of life, and testicular E2 declined to less than 1.0 ng/g (3.7 pmol/g) after only 6 months of age. Gonadal estrogen concentrations paralleled changes in gonadal morphology. Ovarian weights varied in a pattern of rise and fall similar to that of ovarian E2 concentrations; the biggest ovaries contained multiple macroscopic cysts. Testicular E2 closely correlated with Leydig cell development and testicular testosterone concentrations. We infer, therefore, that the surge of plasma E2 in infant girls originates from ovarian follicles and that of boys from testicular Leydig cells, and that these both occur as a result of the postnatal surge in gonadotropin secretion. The basal plasma E1 and E2 pool, however, is derived from the adrenals and remains at a comparatively constant level in both sexes.     

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.     

Puberty in boys: correlation of plasma levels of gonadotropins (LH, FSH), androgens (testosterone, androstenedione, dehydroepiandrosterone and its sulfate), estrogens (estrone and estradiol) and progestins (progesterone and 17-hydroxyprogesterone).

Mean serum concentration dehydroepiandrosterone (DHA), DHA sulfate (DHAS), progesterone (P), 17-hydroxyprogesterone (17-OH-P), estrone (E1), estradiol (E2), and androstenedione (A) were compared from 43 boys followed longitudinally for as long as 4 yr during puberty. These data were also compared with serum levels of LH, FSH, and testosterone. Elevation is recognized early in puberty for DHAS, late in puberty for P and A, and gradually throughout puberty for E1, 17-OH-P, and DHA. When compared by age, the same general pattern is apparent with adult levels of E1 reached at age 12, DHAS and E2 by 13, and DHA, P, 17-OH-P, and A not until after age 15. Significant elevations of DHA occurred with the onset of pubic hair and voice change; elevations of DHAS occurred with the onset of genital and axillary hair growth; and testosterone increased with the onset of genital and pubic hair growth and voice change.     

Resumption of puberty after long term luteinizing hormone-releasing hormone agonist treatment of central precocious puberty

To determine whether puberty resumes normally after long term LHRH agonist (LHRHa) treatment, we studied 16 children with central precocious puberty treated with LHRHa (D-Trp6,Pro9,NEt-LHRH) for 1-4 yr (mean, 3.3 yr). Treatment was discontinued at a mean age of 11.6 +/- 1.3 (+/- SD) yr. Plasma hormone levels, growth velocity, rate of bone maturation, and pubertal stage were assessed at the end of treatment and 3 and 12 months later. Basal plasma sex steroid and basal and LHRH-stimulated gonadotropin levels returned to near-pretreatment levels 3 months after discontinuation of therapy and were fully restored to pretreatment levels at 12 months. Growth velocity, which had been 7.8 cm/yr before treatment, was stable after discontinuation of treatment at approximately 2.6 cm/yr. The predicted height, which had increased during treatment (P less than 0.01), remained stable at approximately 5 cm above the pretreatment predicted height. The rate of bone age advancement (delta bone age/delta chronological age) increased gradually from 0.4 at the end of treatment to the normal value of 0.9 12 months posttreatment. Breast and pubic hair pubertal stages, which were stable throughout treatment and were 4.0 +/- 0.8 (+/- SD) and 3.6 +/- 1.0 at the end of treatment, increased to 4.9 +/- 0.2 and 4.5 +/- 1.0. This approximated the normal rate of 1 stage/yr. Menses occurred in 8 of 12 girls within 1 yr after treatment and in an additional 3 by 20 months after treatment. Six of the girls had menstruated before treatment, and all of these menstruated within 14 months after discontinuing therapy. We conclude that gonadotropin and sex steroid secretion and the clinical progression through puberty appear to resume normally after discontinuation of long term LHRHa treatment of central precocious puberty. Long term follow-up will be required, however, to determine whether the improvement in predicted height of these patients will be achieved, and whether adult reproductive function will be normal.     

Plasma LH and FSH response to LRH and plasma testosterone levels in boys with irregular puberty.

Nineteen boys with irregular puberty (IP), defined as a discrepancy of two or more pubertal stages between the criteria for genitalia and that for pubic hair, were subjected to a standard LRH test (50 microng/m2, iv) and the response of gonadotrophins as well as the basal levels of plasma testosterone, LH and FSH were compared to those of boys with normal, regular puberty. When the results were plotted against the pubertal stage for genitalia (Pg), it was found that in the boys with IP the basal plasma testosterone levels were lower and the response of plasma LH to LRH stimulation lesser than in the controls. However, when these parameters were plotted against the pubertal stage for pubic hair (Ph) it was found, that in the boys with IP the plasma testosterone levels were significantly higher and the response of both LH and FSH stimulation greater than in the control group. It was concluded that irregular puberty in boys may be regarded as a normal variation. The delayed development of sexual hair and penile length, and retarded pubertal growth spurt and bone age maturation seen in these boys, with normal testicular development, may be explained by a temporary reduced peripheral sensitivity to androgens and a compensatory effort by the pituitary, manifested in increased secretion of LH and testosterone, relatively to their pubertal stage for pubic hair.     

The influence of gonadal function and the effect of gonadal suppression treatment on final height in growth hormone (GH)-treated GH-deficient children

One hundred and sixty-one children with idiopathic GH deficiency who received GH treatment were followed until they reached their final height. Final height was found to be influenced by gonadal function. In 108 patients who had spontaneous puberty (91 boys and 17 girls; group A), the mean final height was 151.8 +/- 6.6 (+/- SD) cm in boys and 141.7 +/- 7.4 cm in girls. In 29 patients with combined GH and gonadotropin deficiency (23 boys and 6 girls; group C), whose pubertal development was induced artificially at age 19.5 +/- 2.1 yr in the boys and 18.6 +/- 1.8 yr in the girls, the mean final height was 163.7 +/- 3.9 cm in boys and 151.0 +/- 5.1 cm in girls. The differences in final height between groups A and C were significant in both boys and girls. The shorter final height in group A was caused by the shorter pubertal duration and smaller pubertal height gain than those in normal children. In 24 patients (17 boys and 7 girls; group B) who developed early signs of puberty, gonadal suppression therapy with cyproterone acetate and/or medroxyprogesterone acetate was given. The mean SD score of the final height in these 24 patients was -2.1 +/- 0.6, significantly higher than that in group A. This beneficial effect of gonadal suppression treatment on final height was caused by increases in the duration of puberty and the pubertal height gain.